id	title	abstract	authors	journal	
207	Prophylactic gamma globulin for prevention of endemic hepatitis. Effects of US gamma globulin upon the incidence of viral hepatitis and other infectious diseases in US Soldiers abroad			Archives of internal medicine
67	[Therapeutic management of purulent meningitis in children. Report of 101 cases]	One hundred and one cases of purulent meningitis without any sign of immediate severity have been prospectively treated. Cefotaxime was given until the results of bacteriological tests; when possible, a randomisation separated one group in which cefotaxime was continued and another group in which cefotaxime was replaced by ampicillin. IV treatment was stopped at the 10th day even in cases with persisting fever. All patients less than or equal to 2 years of age were given phenobarbitone. Serious complications consisted of 4 cases of hypoacousia, equally distributed in either therapeutic group of Haemophilus meningitis. No child developed convulsions when receiving phenobarbitone. Late examination of CSF was uncontributive, even in patients with persisting fever. The following simplifications could be proposed in purulent meningitis with usual clinical picture and course: initial treatment with IIIrd generation cephalosporin; substitution by ampicillin or amoxicillin as soon as bacteriological tests make it possible; discontinuation of IV treatment by the 10th day maximum, without CSF control; prevention of convulsions in young children by phenobarbitone given during the acute stage of meningitis.		Archives françaises de pédiatrie
231	Treatment of severe infectious purpura in children with human plasma from donors immunized with Escherichia coli J5: a prospective double-blind study. J5 study Group	To evaluate the efficacy of anti-J5 serum in the treatment of severe infectious purpura, 73 children were randomized to receive either anti-J5 (40) or control (33) plasma. Age, blood pressure, and biologic risk factors were similar in both groups. At admission, however, tumor necrosis factor serum concentrations were 974 +/- 173 pg/ml compared with 473 +/- 85 pg/ml (P = .023) and interleukin-6 serum concentrations were 129 +/- 45 compared with 19 +/- 5 ng/ml (P = .005) in the control and treated groups, respectively. The duration of shock and the occurrence of complications were similar in both groups. The mortality rate was 36% in the control group and 25% in the treated group (P = .317; odds ratio, 0.76; 95% confidence interval, 0.46-1.26). This trend disappeared after correction for unbalances in risk factors at randomization using a logistic regression model. These results suggest that anti-j5 plasma did not affect the course or mortality of severe infectious purpura in children.		The Journal of infectious diseases
341	Long-acting chloramphenicol for bacterial meningitis			Bulletin of the World Health Organization
379	Combined administration of meningococcal serogroup B outer membrane vesicle vaccine and conjugated serogroup C vaccine indicated for prevention of meningococcal disease is safe and immunogenic	MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	I. S. Aaberge, P. Oster, O. S. Helland, A. C. Kristoffersen, E. Ypma, E. A. Hoiby, B. Feiring and H. Nokleby	Clinical & Diagnostic Laboratory Immunology
16	Comparison of functional immune responses in humans after intranasal and intramuscular immunisations with outer membrane vesicle vaccines against group B meningococcal disease	A serogroup B meningococcal outer membrane vesicle (OMV) vaccine was delivered either intranasally or intramuscularly to 12 and 10 volunteers, respectively. The mucosal vaccine was given as four weekly doses followed by a fifth dose after 5 months; each dose consisted of OMVs equivalent to 250 microg of protein. The intramuscular (i.m.) vaccine, consisting of the same OMVs but adsorbed to Al(OH)(3), was administered as three doses each of 25 microg of protein, with 6 weeks interval between first and second doses and the third dose after 10 months. Both groups of vaccinees demonstrated significant immune responses when measured as specific IgG antibodies against live meningococci, as serum bactericidal activity (SBA) and as opsonophagocytic activity. Two weeks after the last dose, the anti-meningococcal IgG concentrations were significantly higher in the i.m. group (median IgG concentration: 43.1 microg/ml) than in the intranasal group (10.6 microg/ml) (P=0.001). The corresponding opsonophagocytic activity was 7.0 and 3.0 (median log(2) titre) (P=0.001), and the SBA was 5.0 and 2.0 (median log(2) titre) (P=0.005), for the i.m. and intranasal groups, respectively. The last immunisation induced an enhanced immune response in the i.m. group, whereas the intranasal group showed no significant booster response. Accordingly, affinity maturation of anti-OMV-specific IgG antibodies was seen only after i.m. vaccination. The IgG1 subclass dominated the responses in both groups, whereas the significant IgG3 responses observed in the i.m. group were absent in the intranasal group. Although the intranasal OMV vaccination schedule used here induced functional immune responses relevant to protection, an improved vaccine formulation and/or a modified mucosal immunisation regimen may be needed to achieve a systemic effect comparable to that seen after three doses of intramuscular vaccination.	A. Aase, L. M. Naess, R. H. Sandin, T. K. Herstad, F. Oftung, J. Holst, I. L. Haugen, E. A. Høiby and T. E. Michaelsen	Vaccine
211	Adverse events following vaccine or placebo injection in an efficacy trial of an outer membrane vesicle vaccine against group B meningococcal disease in Norwegian secondary schools 1988-1991		P. Aavitsland, G. Bjune, S. Aasen and S. Halvorsen	NIPH annals
626	Profile of enterovirus disease in the first two weeks of life	We studied 57 infants < or = 14 days of age referred for possible enterovirus (EV) infection to assess the accuracy of that clinical diagnosis and describe the natural history of neonatal EV infection. Twenty-nine neonates proved to have EV infection, 23 had illnesses compatible with (but not proven to be) EV infection, and 5 had alternative diagnoses: bacterial infections (2); herpes simplex virus infection (1); and metabolic disorders (2). Neonates with proved EV infection were generally full term and had uncomplicated immediate postnatal periods but high percentages of ill contacts. Neonatal symptoms and signs included fever, irritability, anorexia, lethargy, hypoperfusion, rash, jaundice and respiratory findings. Laboratory abnormalities included cerebrospinal fluid (CSF) pleocytosis, chest radiograph infiltrates, abnormal urinalyses and elevated transaminases. EVs were most commonly isolated from CSF and rectum/stool but also frequently from serum and urine. Five EV-infected patients had severe multisystem disease (pneumonitis, hepatitis, thrombocytopenia, bleeding and meningitis), requiring supportive care and lengthy hospitalizations. All survived, 2 with residual hepatic dysfunction. Markers of severe disease included: early age of illness onset (especially Day 1 of life); maternal viral symptoms at delivery; absence of fever and irritability; tachypnea; lethargy; abdominal distension; hepatomegaly; and positive serum viral culture. These data support conservative management of ill infants < or = 2 weeks of age and suggest that antiviral therapy for neonatal EV infection would be optimally targeted at infants with early onset illness, multisystem disease and/or viremia.	M. J. Abzug, M. J. Levin and H. A. Rotbart	The Pediatric infectious disease journal
540	Adult tuberculous meningitis: comparative study of different chemotherapeutic regimens		V. N. Acharya, B. T. Kudva, V. J. Retnam and P. J. Mehta	Journal of the Association of Physicians of India
376	Antigenuria in Gambian infants following immunization with a Haemophilus influenzae type b polyribosylribitol phosphate-tetanus toxoid protein conjugate (PRP-T) vaccine	During a Haemophilus influenzae type b (Hib)-conjugate vaccine trial, the prevalence and duration of antigenuria after vaccination was studied in 102 Gambian infants aged 51 to 175 days. Urine samples were collected at 0, 1, 3, 7, 14, 21 and 28 days postvaccination and tested for Hib antigen by latex agglutination using Biomérieux and Directigen reagent kits. Biomérieux positive reactions were found in 6 of 247 (2.4%) samples from vaccinated children and in 8 of 199 (4.0%) from nonvaccinated children (chi 2 = 0.47; 1 df; p = 0.5). In contrast, Directigen positive reactions were obtained with 86/242 samples (35.5%) from vaccinated children and from 28/190 (14.7%) from non-vaccinated children (chi 2 = 22.7; 1 df; p < 0.0001). The highest rate of antigenuria was detected in samples collected on Day 7 after vaccination when 24 of 30 (80%) were positive. Antigenuria following vaccination was frequent and may complicate the use of this test as a means of diagnosing invasive Hib disease in vaccinated children.	R. A. Adegbola, A. Leach, K. Mulholland, S. Hilton, E. Demba, S. Jaffar and B. M. Greenwood	Diagnostic microbiology and infectious disease
210	First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children	BACKGROUND: An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries. METHODS: From March 2009 through January 2011, we enrolled 15,460 children in two age categories--6 to 12 weeks of age and 5 to 17 months of age--for vaccination with either RTS,S/AS01 or a non-malaria comparator vaccine. The primary end point of the analysis was vaccine efficacy against clinical malaria during the 12 months after vaccination in the first 6000 children 5 to 17 months of age at enrollment who received all three doses of vaccine according to protocol. After 250 children had an episode of severe malaria, we evaluated vaccine efficacy against severe malaria in both age categories. RESULTS: In the 14 months after the first dose of vaccine, the incidence of first episodes of clinical malaria in the first 6000 children in the older age category was 0.32 episodes per person-year in the RTS,S/AS01 group and 0.55 episodes per person-year in the control group, for an efficacy of 50.4% (95% confidence interval [CI], 45.8 to 54.6) in the intention-to-treat population and 55.8% (97.5% CI, 50.6 to 60.4) in the per-protocol population. Vaccine efficacy against severe malaria was 45.1% (95% CI, 23.8 to 60.5) in the intention-to-treat population and 47.3% (95% CI, 22.4 to 64.2) in the per-protocol population. Vaccine efficacy against severe malaria in the combined age categories was 34.8% (95% CI, 16.2 to 49.2) in the per-protocol population during an average follow-up of 11 months. Serious adverse events occurred with a similar frequency in the two study groups. Among children in the older age category, the rate of generalized convulsive seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine provided protection against both clinical and severe malaria in African children. (Funded by GlaxoSmithKline Biologicals and the PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov number, NCT00866619 .).	S. T. Agnandji, B. Lell, S. S. Soulanoudjingar, J. F. Fernandes, B. P. Abossolo, C. Conzelmann, B. G. Methogo, Y. Doucka, A. Flamen, B. Mordmüller, S. Issifou, P. G. Kremsner, J. Sacarlal, P. Aide, M. Lanaspa, J. J. Aponte, A. Nhamuave, D. Quelhas, Q. Bassat, S. Mandjate, E. Macete, P. Alonso, S. Abdulla, N. Salim, O. Juma, M. Shomari, K. Shubis, F. Machera, A. S. Hamad, R. Minja, A. Mtoro, A. Sykes, S. Ahmed, A. M. Urassa, A. M. Ali, G. Mwangoka, M. Tanner, H. Tinto, U. D'Alessandro, H. Sorgho, I. Valea, M. C. Tahita, W. Kaboré, S. Ouédraogo, Y. Sandrine, R. T. Guiguemdé, J. B. Ouédraogo, M. J. Hamel, S. Kariuki, C. Odero, M. Oneko, K. Otieno, N. Awino, J. Omoto, J. Williamson, V. Muturi-Kioi, K. F. Laserson, L. Slutsker, W. Otieno, L. Otieno, O. Nekoye, S. Gondi, A. Otieno, B. Ogutu, R. Wasuna, V. Owira, D. Jones, A. A. Onyango, P. Njuguna, R. Chilengi, P. Akoo, C. Kerubo, J. Gitaka, C. Maingi, T. Lang, A. Olotu, B. Tsofa, P. Bejon, N. Peshu, K. Marsh, S. Owusu-Agyei, K. P. Asante, K. Osei-Kwakye, O. Boahen, S. Ayamba, K. Kayan, R. Owusu-Ofori, D. Dosoo, I. Asante, G. Adjei, G. Adjei, D. Chandramohan, B. Greenwood, J. Lusingu, S. Gesase, A. Malabeja, O. Abdul, H. Kilavo, C. Mahende, E. Liheluka, M. Lemnge, T. Theander, C. Drakeley, D. Ansong, T. Agbenyega, S. Adjei, H. O. Boateng, T. Rettig, J. Bawa, J. Sylverken, D. Sambian, A. Agyekum, L. Owusu, F. Martinson, I. Hoffman, T. Mvalo, P. Kamthunzi, R. Nkomo, A. Msika, A. Jumbe, N. Chome, D. Nyakuipa, J. Chintedza, W. R. Ballou, M. Bruls, J. Cohen, Y. Guerra, E. Jongert, D. Lapierre, A. Leach, M. Lievens, O. Ofori-Anyinam, J. Vekemans, T. Carter, D. Leboulleux, C. Loucq, A. Radford, B. Savarese, D. Schellenberg, M. Sillman, P. Vansadia and Rts	The New England journal of medicine
649	Have cranio-vertebral junction anomalies been overlooked as a cause of vertebro-basilar insufficiency?	STUDY DESIGN: A prospective controlled study using single photon emission computed tomography (SPECT) to assess cerebellar perfusion in a cohort of 19 patients with congenital cranio-vertebral junction (CVJ) anomalies, with or without vertebro-basilar insufficiency (VBI). OBJECTIVE: To correlate symptoms of VBI with the presence of posterior circulation ischemia in patients with congenital CVJ anomalies, using technetium 99m ethylene cystine dimer SPECT. SUMMARY OF BACKGROUND DATA: Patients with VBI are rarely investigated for CVJ anomalies, despite the fact that a significant number of patients with congenital CVJ anomalies has VBI. There are also no studies quantifying outcome of surgical interventions, such as like occipito-cervical fusion, in patients with VBI and CVJ anomalies. METHODS: There were 19 consecutive patients with congenital CVJ anomalies who were scheduled for combined transoral odontoidectomy and occipito-cervical fusion were included in the study. Technetium 99m ethylene cystine dimer brain SPECT and clinical assessment of all patients was performed in the preoperative period and at 4 weeks after surgery. Before surgery, patients were divided into 2 groups depending on the clinical findings: (1) symptomatic group, consisting of 12 patients having features suggestive of VBI (drop attacks, episodic vertigo, visual disturbances and dysarthria); and (2) control group, consisting of 7 patients without symptoms of VBI. RESULTS: SPECT showed decreased cerebellar perfusion in 75% (n = 9) of patients in the symptomatic group compared to 14% (n = 1) in the control group before surgery (Fisher exact 2-tailed test, P = 0.019). Following surgery, 8 patients (88.9%) in the symptomatic group and none in the control group had improvement in cerebellar perfusion. Two patients in the symptomatic group who had meningitis develop during the postoperative period had a decrease in cerebellar perfusion on follow-up SPECT. Clinically, all patients with improvement in cerebellar perfusion had improvement in the symptoms of VBI at 1 month of follow-up. CONCLUSIONS: A significant number of patients with congenital CVJ anomalies who have symptoms of VBI develop have decreased cerebellar perfusion shown by SPECT. Rigid internal fixation of the CVJ may alleviate symptoms and improve posterior circulation in some of these patients.	D. Agrawal, N. K. Gowda, C. S. Bal, S. S. Kale and A. K. Mahapatra	Spine
427	Haemophilus influenzae type b conjugate vaccine (meningococcal protein conjugate) (PedvaxHIB): clinical evaluation	Although systemic infections caused by Haemophilus influenzae type b occur worldwide, detailed epidemiologic data are available in but a few countries. The public health impact of morbidity, mortality, and serious sequelae from disease caused by H influenzae type b has stimulated the search for control strategies. In the United States now, active immunoprophylaxis is largely favored over treatment of prophylaxis with antibiotics. This preference stems from three major observations: that high mortality and morbidity persist despite the availability of potent antimicrobial agents, that antibiotic-resistant strains of H influenzae type b have emerged, and that implementation of antimicrobial prophylaxis on a large scale has been unsatisfactory. Moreover, universal vaccination has been projected as offering a higher economic benefit than other control strategies. A matter of more proximate importance, however, is the search for H influenzae type b vaccines that will confer protection to all age groups, including infants younger than 18 months of age and subpopulations specifically at risk for invasive disease caused by H influenzae type b. Haemophilus b conjugate vaccine (meningococcal protein conjugate), PedvaxHIB (PRP-OMPC), is a conjugate H influenzae type b vaccine developed at Merck Sharp & Dohme Research Laboratories that now is undergoing extensive clinical evaluation to assess its prospects for disease control when first administered in early infancy. This is an interim report of results obtained in studies conducted in diverse locations throughout the United States.	V. I. Ahonkhai, L. J. Lukacs, L. C. Jonas, H. Matthews, P. P. Vella, R. W. Ellis, J. M. Staub, K. T. Dolan, C. M. Rusk and G. B. Calandra	Pediatrics
519	Human antibody responses to the meningococcal factor H binding protein (LP2086) during invasive disease, colonization and carriage		D. A. Ala'aldeen, M. Flint, N. J. Oldfield, S. A. Omer, L. K. McNeil, Q. Jiang, E. Murphy, P. C. Giardina, E. G. Novikova, I. L. Dodge-Scully, C. D. Bayliss, D. P. Turner, K. R. Neal, S. K. Hoiseth, K. U. Jansen and A. S. Anderson	Vaccine
382	Meningococcal carrier rate before and after hajj pilgrimage: effect of single dose ciprofloxacin on carriage	We determined the carriage rate of Neisseria meningitidis before and after haij pilgrimage among a group (1) of 674 randomly selected Iranian pilgrims, and the effect of 500 mg of ciprofloxacin given 24 hours before return on the reduction of meningococcal carriers among another group (2) of 123 randomly selected Iranian pilgrims. Throat specimens taken 1 hour before departure on the haji and immediately on return were cultured. Carriage rates of N. meningitidis in group 1 were 5.2% before and 4.6% after pilgrimage (P = 0.65); 3 new serogroups (Z, Z and A) were identified on return. In group 2, the carriage rate decreased from 8.1 % to zero before and after pilgrimage. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Alborzi, S. Oskoee, B. Pourabbas, S. Alborzi, B. Astaneh, M. M. Gooya and M. J. Kaviani	Eastern Mediterranean Health Journal
32	Reactogenicity and safety of meningococcal A and C vaccine in Saudi children	During an outbreak caused by group A Neisseria meningitidis in March 1992, groups A and C meningococcal polysaccharide vaccine was administered to 1,168 children aged from 2 to 18 years. Parents were surveyed to ascertain reactions of children to the vaccine and development of invasive group A meningococcal disease after immunization. The most common reactions were mild local pain (21.9%), erythema (12.2%), and swelling at the injection site (7.2%). Only 1.7% of the children experienced fever and 3.7% displayed irritability. The vaccine was well tolerated and all adverse reactions disappeared within 24-48 hours of immunization. No cases of meningitis or sepsis caused by group A meningococci were seen in the 1st 12 months of observation among the vaccinated children.	Y. A. al-Eissa	Annals of tropical paediatrics
35	Serologic responses to ACYW135 polysaccharide meningococcal vaccine in Saudi children under 5 years of age	An immunization campaign with meningococcal ACYW135 polysaccharide vaccine was conducted in 2003 by the Saudi Arabian Ministry of Health and included a study to evaluate the immune responses in children under 5 years of age in the Al Qassim region of Saudi Arabia. Children who were >/=24 months old were given one dose of tetravalent polysaccharide vaccine, while younger children were given two doses with an interval of 2 to 3 months. Blood samples were collected prevaccination and 1 month after the second dose for children younger than 24 months old and 1 month after the single dose for older children. Serogroup-specific antibody responses were determined by serum bactericidal antibody (SBA) assays and a tetraplex immunoglobulin G (IgG) bead assay. Significant increases in the proportions of individuals who were >/=24 months old with SBA titers of >/=8 were observed pre- to postvaccination for all serogroups. Age-dependent increases in the percentage of individuals with SBA titers of >/=8 1 month postvaccination were observed for each serogroup. Age-dependent increases in postvaccination IgG levels were observed for serogroup A (menA), serogroup W135 (menW), and serogroup Y (menY) but not for serogroup C (menC). Two doses of tetravalent polysaccharide vaccine in individuals who were </=18 months old were poorly immunogenic for menC, menW, and menY. However, for menA, 42% of the children who were 18 months old were putatively protected with SBA titers of >/=8. A high percentage of subjects who were >/=2 years of age were putatively protected for menA; a similar level was observed for menY for children who were 4 years of age but not for younger children. However, for menC and menW poor levels of putative protection were still evident at 4 years of age.	Y. Al-Mazrou, M. Khalil, R. Borrow, P. Balmer, J. Bramwell, G. Lal, N. Andrews and M. Al-Jeffri	Infection and immunity
168	Immunogenicity and safety of a meningococcal quadrivalent conjugate vaccine in Saudi Arabian adolescents previously vaccinated with one dose of bivalent and quadrivalent meningococcal polysaccharide vaccines: a phase III, controlled, randomized, and modified blind-observer study	Reduced immune responses to repeated polysaccharide vaccination have been previously reported, but there are limited immunogenicity data on the use of meningococcal polysaccharide vaccine (PSV) followed by meningococcal conjugate vaccine. Saudi Arabian adolescents (aged 16 to 19 years) who had previously been vaccinated with ?1 dose of bivalent meningococcal polysaccharide vaccine and 1 dose of quadrivalent meningococcal polysaccharide (MPSV4) were enrolled in a controlled, randomized, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomized to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (n = 145 PSV-exposed/MCV4 group) or MPSV4 (n = 142 PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4 (n = 163). Serum samples collected prevaccination and 28 days postvaccination were measured by baby rabbit serum bactericidal antibody (rSBA) assay, and vaccine tolerability and safety were also evaluated. For each serogroup, the postvaccination geometric mean titers (GMTs) were significantly higher in the PSV-naïve group than in either group comprised of the PSV-exposed participants. The postvaccination serogroup C rSBA GMT was significantly higher in the PSV-MCV4 group than in the PSV-MPSV4 group after adjusting for prevaccination GMTs. Although not statistically significant, similar differences were observed for serogroups A, Y, and W-135. No worrisome safety signals were detected. This study demonstrated MCV4 to be safe and immunogenic in those who had previously received polysaccharide vaccination, and it suggests that conjugate vaccine can partially compensate for the hyporesponsiveness seen with repeated doses of polysaccharide vaccine.	Y. Al-Mazrou, M. Khalil, H. Findlow, H. Chadha, V. Bosch Castells, D. R. Johnson and R. Borrow	Clinical and vaccine immunology : CVI
242	[Absence of meningitis caused by Haemophilus influenzae type b in The Netherlands following twofold vaccination]	OBJECTIVE: To determine the two-year results of nationwide vaccination with Haemophilus influenzae type b (Hib) vaccine on the occurrence of Hib meningitis in the Netherlands.DESIGN: Retrospective controlled study.SETTING: The Netherlands.METHOD: Children born since April 1, 1993 are vaccinated at the age of 3, 4, 5 and 11 months to protect them from infections with Hib. The number of Hib meningitis patients in the period 1 April, 1993 to 1 April, 1995, among infants born in this period who were offered the Hib vaccine (study group), was compared with the number of Hib meningitis patients in the period 1 April, 1991 to 1 April, 1993 among children born in last-mentioned period (control group).RESULTS: Twenty-one cases of meningitis by Hib were observed in the study group. Twelve children who, as a consequence of their age, had only been vaccinated once or not at all; 7 children were not vaccinated for several reasons. In addition one patient was infected by H. influenzae type f strain and one by a non-typable strain. In the control group 185 cases of Hib meningitis occurred.CONCLUSION: Hib meningitis was not observed among infants who had been vaccinated at least twice.	L. Alphen, L. Spanjaard, A. Ende and J. Dankert	Nederlands tijdschrift voor geneeskunde
362	Changes in the distribution of Haemophilus influenzae type b clones associated with widespread infant vaccination in Finland	Isolates from 646 consecutive Finnish Haemophilus influenzae type b (Hib) patients with systemic disease, collected before and during large-scale vaccinations with Hib conjugate vaccines, were analyzed by major outer membrane protein (OMP) subtyping, lipopolysaccharide (LPS) serotyping, and biotyping (BT). Strains with OMP-BT-LPS combinations (clones) 1-I-1 and 1c-I-1 disappeared at the same rate as the disease they were associated with. A preferential decrease in the number of isolates of clone 1-II-1 was recorded, whereas the reduction in disease caused by strains of clone 1-II-9 occurred at a lower rate than expected. The latter clone occurred mainly in the most densely populated area of Finland. Strains belonging to all the common Hib clones were isolated from the 16 infants who acquired Hib disease despite being (partially) vaccinated. Thus, Hib clones disappeared during mass vaccination with conjugate vaccines, although at different rates.	L. Alphen, A. K. Takala, L. Geelen-van den Broek, J. Dankert and J. Eskola	The Journal of infectious diseases
505	Effect of chemoprophylaxis on the meningococcal carrier state after systemic infection		F. Alvez, A. Aguilera, A. Garcia-Zabarte and M. Castro-Gago	Pediatric Infectious Disease Journal
381	Passive immunization against disease due to Haemophilus influenzae type b: concentrations of antibody to capsular polysaccharide in high-risk children	From the pooled plasma of 54 adult donors immunized with Haemophilus influenzae type b capsular polysaccharide (CP), a human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) was prepared. The pharmacokinetics of antibody to H. influenzae type b CP in high-risk children was compared after BPIG and conventional immune serum globulin (ISG) were administered intramuscularly at a dose of 0.5-0.6 ml/kg. The increase in antibody level four to seven days after injection was ninefold higher with BPIG than with ISG and remained higher throughout the three-month follow-up period. The mean half-life of antibody to H. influenzae type b CP was similar after BPIG (27 days) and ISG (29 days). Antibody levels returned to baseline one to two months after ISG but remained significantly above baseline three months after BPIG (mean concentration, 385 ng/ml). Based on the assumption that 150 ng of IgG antibody to H. influenzae type b CP/ml is the minimal protective level, it is concluded that a single intramuscular dose of 0.5 ml of BPIG/kg will protect children for four months.	D. M. Ambrosino, S. H. Landesman, C. C. Gorham and G. R. Siber	The Journal of infectious diseases
344	Accurate diagnosis of tuberculosis meningitis using polymerase chain reaction		A. G. Amin, A. K. Garg, K. Chopra and P. Khandekar	International journal of leprosy and other mycobacterial diseases : official organ of the International Leprosy Association
352	[The late results of intensive chemotherapy (9 months) in severe forms of tuberculosis in children]	The short-course chemotherapy (9 months) in the severe forms of tuberculosis in children is a very modern item. It was very few approached on an international level and relatively short time ago in our country. There were applied the following therapeutical regimens: 3 HRZ2 6 HR2 (in the experimental group) and 3 HR/3 HR2/6 H2 (in the control group). In the granulias and the caseous forms the late results, at 5 years after treatment end, were very good in 100% of cases in both groups. In meningitis clinical very good results (without sequellae) presented a proportion of 70.1% in the experimental group and of 68.2% in the control group (difference statistically non significant). The main advantage of the intensive short course regimens (9 months) comparatively with the "classical" ones (of at least 12 months) consists in reaching finally the same good results but in at least 3 months shorter time interval.	C. Anastasatu, O. Anastasatu, G. Murgoci and M. Dobre	Pneumoftiziologia : revista Societ?tii Române de Pneumoftiziologie / [Societatea Român? de Pneumoftiziologie]
183	Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants	OBJECTIVE: To evaluate the safety, immunogenicity, and immunologic memory in young infants of a seven-valent (6B, 14, 19F, 23F, 18C, 4, 9V) pneumococcal vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis. VACCINEES: Healthy 2-month-old infants 12- to 15-month-old control infants were recruited from participating private practices. METHODS: Infants (n = 25) were vaccinated at 2, 4, and 6 months of age with the conjugated pneumococcal vaccine, followed by a single dose of licensed pneumococcal polysaccharide vaccine (n = 20) at 12 to 15 months of age. Thirteen infants who had not received the investigational pneumococcal conjugate vaccine served as control subjects and were given a single dose of the licensed pneumococcal polysaccharide vaccine at 12 to 15 months of age. RESULTS: The investigational pneumococcal conjugate vaccine was well tolerated by infants. The vaccine was highly immunogenic in young infants, with significant increases in antibody to all seven serotypes after either two or three injections. At 12 to 15 months of age, infants who had been primed with the investigational pneumococcal conjugate vaccine had a brisk immunologic response to the booster injection of the licensed pneumococcal polysaccharide vaccine. Control infants, who received a single primary injection of the licensed pneumococcal polysaccharide vaccine, had negligible immunologic responses to four of the seven serotypes and low responses to the other three types. CONCLUSION: The investigational seven-valent pneumococcal conjugate vaccine administered to young infants was well tolerated and highly immunogenic and provided immunologic memory to an injection of the licensed pneumococcal polysaccharide vaccine.	E. L. Anderson, D. J. Kennedy, K. M. Geldmacher, J. Donnelly and P. M. Mendelman	The Journal of pediatrics
539	Chemotherapy of tuberculosis meningitis with isoniazid plus rifampicin- interim findings in a trial in children [abstract]	Summaries of the papers presented at the 34th National confernece on tuberculosis & Chest diseases at Jaipur from 28th to 31st October. 1979- A coâ?"operative study in which 6 orthopaedic surgeons of Madras are participating is in progress to assess the efficacy of short-course chemotherapy with or without surgery in tuberculosis of the spine. Nearly 60 patients were admitted to each of the 3 groups. One group was given Rifampicin and INK for 6 months with radical surgery. The second group was given Rifampicin and INH for 6 months without surgery and the third group was given the Same drugs for 9 months without surgery. Surgery consisted of excision of diseased vertebrae and bridging of the resultant gap with bone grafting and was usually performed within a month of admission to the study in the first group. The three groups were comparable in respect of number of vertebra involved, abscess formation and nervous involvement. 65, of the patients had 2 vertebrae involved, 34% had 3 or more vertebrae involved. 2l% had clinical evidence of abscess and/or sinus. 54% had mediastinal or paoas abscess shadows in the xâ?"rays. 85% had kyphosis and 95% had limitation of spinal movements. 17 patients had neurological involvement. 92% of the patients in the surgery group as against 62% in the other two groups showed resolution of the abscess within 3 months. By 9 months resolution bad occurred in all but one patient belonging to the third group. All the patients with nervous involvement recovered completely except that 3 patients in the non surgery group had to undergo surgery for neurological relief. There were 3 post-operative deaths in the surgery group. l4% of the patients had jaundice in the entire series. There is a suggestion that jaundice was more frequent in the surgery group. 56% in group 1, 8% in group 2 and 2% in group 3 had unfavourable response at 18 months. On the available evidence at present the 2 non-surgery groups have behaved practically as well as the surgery group. It is not possible to say at this stage whether the surgery group derived the three benefits of radical surgery (more frequent and early bony union, less kyphosis and more rapid resolution of the abscess) or not.	Anon	Indian Journal of Tuberculosis
633	Early neurologic complications following allogeneic bone marrow transplant for leukemia: a prospective study	BACKGROUND: Bone marrow transplant (BMT) is used for both neoplastic and nonneoplastic diseases. Following BMT, particularly during the first 3 months, patients have a number of neurologic complications. We evaluated the early neurologic complications following BMT and their influence on survival. METHODS: We prospectively followed 115 consecutive patients having BMT for leukemia, for a median period of 90 days after transplantation. RESULTS: Sixty-four patients (56%) had neurologic complications. Sixteen developed more than one complication. Twenty-seven patients (25%) had major neurologic complications: metabolic encephalopathy (8), seizures (8), psychiatric symptoms (3), cerebral hemorrhage (1), cerebral abscess (1), leukemic meningitis (1), peripheral neuropathies (5), and myopathies (2). Forty patients (35%) had minor complications, including headache (16) and tremor (31). Major neurologic complications occurred after engraftment in most patients. Metabolic encephalopathy correlated with graft-versus-host disease (GVHD) (p < 0.03). Seven percent of patients had generalized seizures that occurred without signs of structural cerebral lesions. Probability of survival at day 90 was lower in patients with than in those without major central nervous system complications (63% versus 87.5%, p < 0.01). CONCLUSIONS: Neurologic complications are frequent during the first 3 months following BMT and affect patient survival. Drug neurotoxicity and acute GVHD are the main factors influencing their occurrence.	G. Antonini, V. Ceschin, S. Morino, M. Fiorelli, F. Gragnani, A. Mengarelli, A. P. Iori and W. Arcese	Neurology
550	(Antibiotics for bacterial meningitis in children - results of a Finnish multicentre trial)		M. Anttila, I. Anttolainen, J. Ellmén, J. Eskola, T. Joki, L. Kaartinen, U. Kaski and M. Kataja	Duodecim
353	[Antibiotic treatment of bacterial meningitis in children--results from a Finnish multicenter study]		M. Anttila, I. Anttolainen, J. Ellmén, J. Eskola, T. Joki, L. Kaartinen, U. Kaski, M. Kataja, N. Kojo and M. Korppi	Duodecim; lääketieteellinen aikakauskirja
571	Differences in the avidity of antibodies evoked by four different pneumococcal conjugate vaccines in early childhood	Avidity of antibodies to Streptococcus pneumoniae type 6B, 14, 19F and 23F polysaccharides (PS) evoked by four different pneumococcal conjugate vaccines was compared. Infants were primed with pneumococcal PS conjugated to the variant diphtheria toxin CRM197 (PncCRM), diphtheria toxoid (PncD), tetanus toxoid (PncT) or meningococcal protein complex (PncOMPC) and boosted with the homologous conjugate or PS vaccine. No booster was given to children in the PncOMPC group. Relative antibody avidity was measured by thiocyanate EIA. No vaccine specific differences were found in avidity of anti-14 or -19F antibodies. By contrast, antibody avidity to 6B and 23F differed significantly between the vaccine groups, PncCRM and PncT inducing antibodies of highest avidity.	M. Anttila, J. Eskola, H. Ahman and H. Käyhty	Vaccine
18	Precise quantification of fever in childhood bacterial meningitis	Precise quantity of fever was determined in 191 cases of childhood bacterial meningitis by calculating the areas between the line indicating 37.8 degrees C or 39.5 degrees C temperature and the line connecting all individual temperature values. Temperature measurements were performed rectally one to four times a day throughout the hospitalization. The obtained areas under the curves (AUC), expressed as degree-hours, proved to be a sensitive index for delineating each individual fever pattern and reflected the magnitude of fever more precisely than the traditional fever curves. Children under five had significantly (p less than 0.05) greater AUC than those at five to 15 years; similarly, patients with Haemophilus influenzae meningitis showed greater AUC (i.e., had more fever) than those with meningococcal disease (p less than 0.05). The overall rates of secondary (14%), persistent (16%), and prolonged fever (8%) were virtually identical to previous reports; no drug fever was reported in this study. In cases with prolonged fever, a significantly higher rate (40%) of neurological complications was found compared to those who became afebrile earlier. This method is potentially utilizable in other diseases and conditions where precise measurement of fever is of clinical or scientific relevance.	M. Anttila, J. J. Himberg and H. Peltola	Clinical pediatrics
165	The investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) and the seasonal influenza virus vaccine are immunogenic and well-tolerated when co-administered in adults	Co-administration of meningococcal serogroups A, C, W-135 and Y conjugate vaccine (ACWY-TT) with seasonal influenza vaccine was investigated in a subset of adults enrolled in a larger study evaluating lot-to-lot consistency of ACWY-TT and non-inferiority to licensed tetravalent meningococcal polysaccharide vaccine (MenPS). Subjects in this sub-study were randomized (3:1:1) to receive ACWY-TT alone (ACWY-TT group) or with seasonal influenza vaccine (Coad), or licensed MenPS alone. Serum bactericidal antibodies (rSBA) and serum haemagglutination-inhibition (HI) antibody titers were measured pre- and 1 mo post-vaccination. Non-inferiority of the Coad group compared with ACWY-TT group was demonstrated in terms of rSBA geometric mean antibody titers (GMTs) to serogroups A, W-135 and Y. For serogroup C the pre-defined non-inferiority limit was marginally exceeded. Post-vaccination rSBA GMTs were significantly higher (exploratory analysis) in the Coad group compared with the MenPS group for serogroups A, W-135, and Y and were similar to the MenPS group for serogroup C. Overall, > 97% of subjects achieved rSBA titers ? 1:128 for all serogroups. The Coad group met all criteria defined by the Committee on Human Medicinal Products (CHMP) for seroprotection, seroconversion and seroconversion factor for HI antibodies for all three influenza strains. Grade 3 solicited local/general symptoms were reported by ? 1.9% of subjects in any group. These data support the co-administration of ACWY-TT with seasonal influenza vaccine when protection is needed against both diseases. This study is registered at clinicaltrials.gov NCT00453986.	M. R. Aplasca-De Los Reyes, E. Dimaano, N. Macalalad, G. Dbaibo, V. Bianco, Y. Baine and J. Miller	Human vaccines & immunotherapeutics
567	Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa-HBV-IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa-IPV/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age	An open, randomised, multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio (DTPa-HBV-IPV) vaccine administered in one injection mixed with Haemophilus influenzae type b (Hib) conjugate vaccine (Group 1) with that of a pentavalent DTPa-IPV vaccine mixed with a Hib vaccine (DTPa-IPV/Hib), simultaneously administered with HBV (Group 2) in two injections in opposite thighs, as a primary vaccination course, to healthy infants at 2, 4 and 6 months of age. A total of 235 completed the study, 120 from Group 1 and 115 from Group 2. Blood samples (pre-vaccination and 1 month after the third dose) were obtained from a subset of infants (Group 1: 40; Group 2: 31) to assess the immune response to vaccination. Local and general solicited symptoms were recorded by parents on diary cards. Seven hundred and five diary cards (Group 1: 360; Group 2: 345) were collected. The clinically relevant and most commonly reported local reaction was pain (infant cried when the limb was moved) in 2.5% (Group 1) and 1.2% (Group 2) of diary cards. Fever was more frequently reported in Group 1 (21% of diary cards) than in Group 2 (12% of diary cards). However only 3 and 2% of doses in Groups 1 and 2, respectively, were responsible for a rectal temperature between 38.6 and 39.5 degrees C and only one case (Group 2) had > or =39.5 degrees C. Other clinically relevant general symptoms were rarely recorded: irritability (2-2.8%), loss of appetite (0.3-0.6%) and drowsiness (0.3-0.3%). All subjects included in the immunogenicity analysis had seroprotective titres to diphtheria, tetanus, polio virus types 1 and 3, Hib. Almost all subjects were seroprotected for anti-polio type 2 and hepatitis B (with the exception of 1 subject in Group 1 for each antigen). The vaccines response rates to pertussis antigens were over 97 and 90% in Groups 1 and 2, respectively. This study shows that, from a clinical perspective, the DTPa-HBV-IPV/Hib vaccine given in a single injection has a similar reactogenicity and safety profile to that of two licensed vaccines (DTPa-IPV/Hib, HBV) given in two simultaneous injections to infants at 2, 4 and 6 months of age. This is a valuable advantage, since in some countries, such as Spain and the UK, an additional injection (for the administration of meningococcal C conjugate vaccine) has been recently included in the infants' vaccination calendars.	J. Arístegui, R. Dal-Ré, J. Díez-Delgado, J. Marés, J. M. Casanovas, P. García-Corbeira, E. Frutos, D. Esso, J. Verdaguer, J. Flor, F. Moraga, R. Boceta and J. A. García-Martínez	Vaccine
651	Intrathecally administered baclofen for treatment of children with spasticity of cerebral origin	Management of severe spasticity in children is often a difficult problem. Orally administered medications generally offer limited benefits. This study examines the value of intrathecally administered baclofen in the treatment of 19 children with severe spasticity of cerebral origin: eight of whom sustained brain injury associated with trauma, near drowning, or cardiac arrest; 10 with cerebral palsy (spastic quadriplegia); and one child with Leigh's disease. At the time of entry into the study, patients ranged from 4 to 19 years of age, and all were completely dependent on caretakers for activities of daily living. Children who responded positively to a trial dose of intrathecal baclofen underwent insertion of a drug delivery system for continuous infusion. This was followed by a double-blind trial of baclofen or placebo and follow-up review at 3 and 6 months, and yearly thereafter. Seven children did not undergo pump implantation because of excess sedation or poor response. The 12 remaining children have been followed for a period of 1 to 5 years. Favorable responses were present in all 12 children as determined by the Ashworth Scale, with the greatest benefit being reduction of lower limb tone. Except in the case of one child who had reduction in lower limb tone that resulted in difficulty with transfers, the caretakers all reported significant benefits from intrathecal baclofen, with improvement in muscle tone, behavior, sitting, and general ease of care being most commonly noted. Central side effects were seen in some children who received continuous intrathecal baclofen infusion and included hypotension (two patients), bradycardia (two), apnea or respiratory depression (two), and sedation (one). During a total of 568 months of pump operation there were 10 mechanical complications, including two related to pump or side port failure and eight related to catheter kinks, extrusions, or dislodgment. Pump pocket effusion occurred in five children and a cerebrospinal fluid fistula was seen in one child. Local infection occurred in three children and meningitis in two children. The results demonstrate the potential value of continuous intrathecal baclofen infusion for treatment of severe spasticity of cerebral origin. However, this treatment can result in significant complications and more experience is required before the long-term benefits can be determined.	R. W. Armstrong, P. Steinbok, D. D. Cochrane, S. D. Kube, S. E. Fife and K. Farrell	Journal of neurosurgery
47	Acute respiratory disease and meningococcal infection in army recruits		M. S. Artenstein, J. H. Rust, D. H. Hunter, T. H. Lamson and E. L. Buescher	JAMA : the journal of the American Medical Association
236	Long-term valacyclovir suppressive treatment after herpes simplex virus type 2 meningitis: a double-blind, randomized controlled trial	BACKGROUND: Herpes simplex virus type 2 (HSV-2) is a common cause of acute and recurrent aseptic meningitis. Our aim was to determine the impact of antiviral suppression on recurrence of meningitis and to delineate the full spectrum of neurological complications. METHODS: One hundred and one patients with acute primary or recurrent HSV-2 meningitis were assigned to placebo (n = 51) or 0.5 g of valacyclovir twice daily (n = 50) for 1 year after initial treatment with 1 g of valacyclovir 3 times daily for 1 week in a prospective, placebo-controlled, multicenter trial. The primary outcome was time until recurrence of meningitis. The patients were followed up for 2 years. RESULTS: The first year, no significant difference was found between the valacyclovir and placebo groups. The second year, without study drugs, the risk of recurrence of verified and probable HSV-2 meningitis was significantly higher among patients exposed to valacyclovir (hazard ratio, 3.29 [95% confidence interval, 10.06-10.21]). One-third of the patients experienced 1-4 meningitis episodes during the study period. A considerable morbidity rate, comprising symptoms from the central, peripheral, and autonomous nervous system, was found in both groups. CONCLUSIONS: Suppressive treatment with 0.5 g of valacyclovir twice daily was not shown to prohibit recurrent meningitis and cannot be recommended for this purpose after HSV meningitis in general. Protection against mucocutaneous lesions was observed, but the dosage was probably inappropriate for the prevention of HSV activation in the central nervous system. The higher frequency of meningitis, after cessation of active drug, could be interpreted as a rebound phenomenon.	E. Aurelius, E. Franzen-Röhl, M. Glimåker, O. Akre, L. Grillner, C. Jorup-Rönström and M. Studahl	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
527	Reduction of cerebrospinal fluid rhinorrhea after vestibular schwannoma surgery by reconstruction of the drilled porus acusticus with hydroxyapatite bone cement	OBJECT: Cerebrospinal fluid (CSF) rhinorrhea remains a significant cause of morbidity after resection of vestibular schwannomas (VSs), with rates of rhinorrhea after this procedure reported to range between 0 and 27%. The authors investigated whether reconstruction of the drilled posterior wall of the porus acusticus with hydroxyapatite cement (HAC) would decrease the incidence of postoperative CSF rhinorrhea. METHODS: A prospective observational study of 130 consecutive patients who underwent surgery for reconstruction of the posterior wall of the drilled porus acusticus with HAC was conducted between October 2002 and September 2005. All patients underwent a retrosigmoid transmeatal approach for VS resection and were followed up to document cases of CSF rhinorrhea, incisional CSF leak, meningitis, or rhinorrhea-associated meningitis. A cohort of 150 patients with VSs who were treated with the same surgical approach but without HAC reconstruction served as a control group. RESULTS: The authors found that HAC reconstruction of the porus acusticus wall significantly reduced the rate of postoperative CSF rhinorrhea in their patients. In the patients treated with HAC, rhinorrhea developed in only three patients (2.3%) compared with 18 patients (12%) in the control group. This was a statistically significant finding (p = 0.002, odds ratio = 5.8). CONCLUSIONS: The use of HAC in the reconstruction of the drilled posterior wall of the porus acusticus, occluding exposed air cells, greatly reduces the risk of CSF rhinorrhea.	C. J. Baird, A. Hdeib, I. Suk, H. W. Francis, M. J. Holliday, R. J. Tamargo, H. Brem and D. M. Long	Journal of neurosurgery
471	Effect of home-based neonatal care and management of sepsis on neonatal mortality: field trial in rural India	BACKGROUND: Neonatal care is not available to most neonates in developing countries because hospitals are inaccessible and costly. We developed a package of home- based neonatal care, including management of sepsis (septicaemia, meningitis, pneumonia), and tested it in the field, with the hypothesis that it would reduce the neonatal mortality rate by at least 25% in 3 years. METHODS: We chose 39 intervention and 47 control villages in the Gadchiroli district in India, collected baseline data for 2 years (1993-95), and then introduced neonatal care in the intervention villages (1995-98). Village health workers trained in neonatal care made home visits and managed birth asphyxia, premature birth or low birthweight, hypothermia, and breast-feeding problems. They diagnosed and treated neonatal sepsis. Assistance by trained traditional birth attendants, health education, and fortnightly supervisory visits were also provided. Other workers recorded all births and deaths in the intervention and the control area (1993-98) to estimate mortality rates. FINDINGS: Population characteristics in the intervention and control areas, and the baseline mortality rates (1993-95) were similar. Baseline (1993-95) neonatal mortality rate in the intervention and the control areas was 62 and 58 per 1000 live births, respectively. In the third year of intervention 93% of neonates received home-based care. Neonatal, infant, and perinatal mortality rates in the intervention area (net percentage reduction) compared with the control area, were 25.5 (62.2%), 38.8 (45.7%), and 47.8 (71.0%), respectively (p<0.001). Case fatality in neonatal sepsis declined from 16.6% (163 cases) before treatment, to 2.8% (71 cases) after treatment by village health workers (p<0.01) . Home-based neonatal care cost US$5.3 per neonate, and in 1997-98 such care averted one death (fetal or neonatal) per 18 neonates cared for. INTERPRETATION: Home-based neonatal care, including management of sepsis, is acceptable, feasible, and reduced neonatal and infant mortality by nearly 50% among our malnourished, illiterate, rural study population. Our approach could reduce neonatal mortality substantially in developing countries.	A. T. Bang, R. A. Bang, S. B. Baitule and M. H. Reddy	Lancet
172	Idiopathic hypertrophic pachymeningeal lesions: correlation between clinical patterns and neuroimaging characteristics	Nine patients with intracranial pachymeningeal thickening and enhancement on magnetic resonance imaging (MRI) completed a short-term clinical and MRI follow-up study. Based on clinical pictures, 4 of them were found to have spontaneous intracranial hypotension (SIH) and the remaining 5 had idiopathic intracranial pachymeningitis (IIP). Both groups were compared regarding their clinical and MRI characteristics. In 4 patients with SIH, gadolinium-enhanced T1-weighted images (WI) showed a diffuse and even enhancement of the entire intracranial and spinal dura mater. These thickened dura was slightly hyperintense on T2-WI. They had a favorable prognosis. In 2 patients with IIP, MRI demonstrated a relatively focal and even thickening and enhancement of the intracranial dura which was slightly hyperintense with a central hypointense area on T2-WI. These patients showed a very favorable course with or without steroid pulse therapy. In the remaining 3 patients with IIP, MRI depicted a focal, uneven enhancement of the intracranial dura which was relatively hypointense on T2-WI. Two of them with prolonged symptoms had a remitting and relapsing course, and 1 had a favorable outcome. In spite of current limitations in identifying the underlying causes of idiopathic pachymeningeal abnormalities, MRI can characterize the different patterns of pachymeningeal thickening. These findings may also correlate with the clinical picture and may be useful in predicting the response to treatment and prognosis.	O. Y. Bang, D. I. Kim, S. R. Yoon and I. S. Choi	European neurology
131	Controlled clinical trial of IV cyclophosphamide versus IV methylprednisolone in severe neurological manifestations in systemic lupus erythematosus	BACKGROUND: Severe neurological involvement in systemic lupus erythematosus (NPSLE) is one of the most dreadful complications of the disease. OBJECTIVE: To identify the best drug, dose, and treatment. PATIENTS AND METHODS: The study was a controlled clinical trial at two tertiary care centres of patients with SLE according to the ACR criteria, with incident (no more than 15 days) onset of severe NP manifestations such as seizures, optic neuritis, peripheral or cranial neuropathy, coma, brainstem disease, or transverse myelitis. Induction treatment with 3 g of IV methylprednisolone (MP) followed by either IV monthly cyclophosphamide (Cy) versus IV MP bimonthly every 4 months for 1 year and then IV Cy or IV MP every 3 months for another year. The primary end point was response to treatment: at least 20% improvement from basal conditions on clinical, laboratory, or specific neurological testing variables. RESULTS: Overall, a response rate of 75% was observed. Of the 32 patients studied, 18/19 receiving Cy and 7/13 receiving MP responded to treatment (p<0.03). CONCLUSIONS: Cy seems to be more effective than MP in the treatment of acute, severe NPSLE.	L. Barile-Fabris, R. Ariza-Andraca, L. Olguín-Ortega, L. J. Jara, A. Fraga-Mouret, J. M. Miranda-Limón, J. Fuentes de la Mata, P. Clark, F. Vargas and J. Alocer-Varela	Annals of the rheumatic diseases
452	Cefuroxime versus ceftriaxone for bacterial meningitis (I)	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. W. Bass, D. A. Person and R. J. Fonseca	Journal of Pediatrics
238	Antimicrobial treatment of occult bacteremia: a multicenter cooperative study	This prospective multicenter study was conducted to define more clearly clinical and laboratory criteria that predict a strong probability of occult bacteremia and to evaluate the effect of empiric broad spectrum antimicrobial treatment of these children. Children 3 to 36 months old with fever > or = 40 degrees C (104 degrees F) or, > or = 39.5 degrees C (103 degrees F) with white blood cells (WBC) > or = 15 x 10(9)/liter, and no focus of infection had blood cultures obtained and were randomized to treatment with oral amoxicillin/potassium clavulanate or intramuscular ceftriaxone. Sixty of 519 (11.6%) study patients had positive blood cultures: Streptococcus pneumoniae, 51; Haemophilus influenzae b, 6; Neisseria meningitidis, 2; and Group B Streptococcus, 1. Subgroups of high risk were identified as fever > or = 39.5 degrees C and WBC > or = 15 x 10(9)/liter, 55 of 331 or 16.6% positive with increasing incidence of positive culture with increasing increments of degrees of leukocytosis to WBC > or = 30 x 10(9)/liter where 9 of 21 or 42.9% were positive. Subgroups of significantly lower risk were identified as fever > or = 39.5 degrees C and WBC < 15 x 10(9)/liter, 5 of 182 or 2.7% positive and those with WBC < 10 x 10(9)/liter, 0 of 99 or 0.0% positive. Children with positive cultures who received ceftriaxone were nearly all afebrile after 24 hours whereas a significant number who received amoxicillin/potassium clavulanate remained febrile. In the 459 culture-negative children more amoxicillin/potassium clavulanate-treated children developed diarrhea and had less improvement in clinical scores after 24 hours than ceftriaxone-treated children.(ABSTRACT TRUNCATED AT 250 WORDS)	J. W. Bass, R. W. Steele, R. R. Wittler, M. E. Weisse, V. Bell, A. H. Heisser, J. H. Brien, J. E. Fajardo, G. M. Wasserman and J. M. Vincent	The Pediatric infectious disease journal
449	Results of treatment of meningococcal meningitis in children with a single dose of Sulphanilamido-Dimethoxy-Pyrimidin (Fanasil-Roche)		O. Bedir, O. Ilter and B. Tumay	Monatsschrift fur Kinderheilkunde
442	Comparison of ceftriaxone and cefotaxime in severe pediatric bacterial infection: A multicentric study: <ORIGINAL> EVALUATION DE LA CEFTRIAXONE ET DU CEFOTAXIME DANS L'INFECTION BACTERIENNE SEVERE EN PEDIATRIE: ETUDE MULTICENTRIQUE	319 children with clinical data indicating a probably severe bacterial infection were randomly studied during 9 months in 33 French center. They were treated either with a single daily injection of ceftriaxone at 50 mg/kg/d (100 mg/kg/d for meningitis or typhoid fever) or with 3 to 4 injections of cefotaxime at 100 to 200 mg/kg/d. An aminoglycoside or an imidazole compound could be used as associated therapy according to the severity of infection as well as ampicillin in neonates. The clinical severity criteria and the biological parameters (PCR) were assessed before antibiotic treatment. 233 cases were selected for the comparative study: 22 new-borns, 117 infants, 94 children. 118 were given ceftriaxone and 115 cefotaxime. The infections were documented for 221/233 patients (95%): E. coli (54%), H. influenzae (14%), N. meningitidis (6%), Proteus mirabilis (3.5%), S. pneumoniae (6%), Streptococci (2.6%), Pseudomonas (2.2%), Enterobacter (1.7%), Salmonella typhi (6.7%), miscellaneous (3.3%). The infections treated were pyelonephritis (131), meningitis (36), septic fever (35), and other infections (31). The groups were comparable in age and sex. Results showed no difference for efficacity or bacterial eradication, in any pathology. Tolerance was excellent for the two groups, adverse reactions were rare: 9 for the ceftriaxone group, 10 for the cefotaxime group (no significant difference). The total dose (mg/kg x days of treatment) of cefotaxime was three time higher than the total dose of ceftriaxone used. This trial stressed the easier management and the potential lower cost of ceftriaxone, thanks to a single daily administration. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. Begue, J. Astruc, P. Francois and D. Floret	Medecine Et Maladies Infectieuses
615	Safety and pharmacokinetics of single intravenous dose of MGAWN1, a novel monoclonal antibody to West Nile virus	West Nile Virus (WNV) is a neurotropic flavivirus that can cause debilitating diseases, such as encephalitis, meningitis, or flaccid paralysis. We report the safety, pharmacokinetics, and immunogenicity of a recombinant humanized monoclonal antibody (MGAWN1) targeting the E protein of WNV in a phase 1 study, the first to be performed on humans. A single intravenous infusion of saline or of MGAWN1 at escalating doses (0.3, 1, 3, 10, or 30 mg/kg of body weight) was administered to 40 healthy volunteers (30 receiving MGAWN1; 10 receiving placebo). Subjects were evaluated on days 0, 1, 3, 7, 14, 21, 28, 42, 56, 91, 120, and 180 by clinical assessments, clinical laboratory studies, electrocardiograms (ECGs), and pharmacokinetic and immunogenicity assays. All 40 subjects tolerated the infusion of the study drug, and 39 subjects completed the study. One serious adverse event of schizophrenia occurred in the 0.3-mg/kg cohort. One grade 3 neutropenia occurred in the 3-mg/kg cohort. Six MGAWN1-treated subjects experienced 11 drug-related adverse events, including diarrhea (1 subject), chest discomfort (1), oral herpes (1), rhinitis (1), neutropenia (2), leukopenia (1), dizziness (1), headache (2), and somnolence (1). In the 30-mg/kg cohort, MGAWN1 had a half-life of 26.7 days and a maximum concentration in serum (C(max)) of 953 microg/ml. This study suggests that single infusions of MGAWN1 up to 30 mg/kg appear to be safe and well tolerated in healthy subjects. The C(max) of 953 microg/ml exceeds the target level in serum estimated from hamster studies by 28-fold and should provide excess WNV neutralizing activity and penetration into the brain and cerebrospinal fluid (CSF). Further evaluation of MGAWN1 for the treatment of West Nile virus infections is warranted.	J. H. Beigel, J. L. Nordstrom, S. R. Pillemer, C. Roncal, D. R. Goldwater, H. Li, P. C. Holland, S. Johnson, K. Stein and S. Koenig	Antimicrobial agents and chemotherapy
164	A comparison of amphotericin B alone and combined with flucytosine in the treatment of cryptoccal meningitis	We compared amphotericin B therapy for cryptococcal meningitis with a newer regimen containing both amphotericin B and flucytosine. In 50 patients with 51 courses of therapy adherent to the protocol, 27 courses were with amphotericin B and 24 with the combination. Even though the combination regimen was given for only six weeks and amphotericin B for 10 weeks, the combination cured or improved more patients (16 vs 11), produced fewer failures or relapses (three vs. 11), more rapid sterilization of the cerebrospinal fluid (P less than 0.001) and less nephrotoxicity (P less than 0.05) than did amphotericin B alone. The number of deaths was the same (five) with each regimen. Adverse reactions to flucytosine occurred in 11 of 34 patients but were not life threatening. We conclude that combined flucytosine-amphoericin B therapy is the regimen of choice in cryptococcal meningitis.	J. E. Bennett, W. E. Dismukes, R. J. Duma, G. Medoff, M. A. Sande, H. Gallis, J. Leonard, B. T. Fields, M. Bradshaw, H. Haywood, Z. A. McGee, T. R. Cate, C. G. Cobbs, J. F. Warner and D. W. Alling	The New England journal of medicine
262	Beta-glucuronidase in the diagnosis of bacterial meningitis and response to treatment	AIM: Beta-glucuronidase activity is increased in the cerebrospinal fluid (CSF) of patients with bacterial meningitis. The aim of this study was to investigate the beta-glucuronidase activity in the cell-free CSF of bacterial meningitis and its course during treatment, and compare it with other CSF parameters. METHODS: The beta-glucuronidase activity, cell number, protein concentration and CSF/blood glucose ratio were measured in 43 consecutive infants and children with bacterial meningitis, and 97 control subjects. Patients had one or two follow-up lumbar punctures. RESULTS: The beta-glucuronidase activity was increased early in bacterial meningitis, even when the other CSF parameters were undisturbed. Before treatment, the median activity in affected children was 136 micromoles 4-methylumbelliferone l(-1) h(-1) (range 44-826) and in controls 14 (7-23). In all patients who improved, the activity was lower in the follow-up CSF samples. Six to 12 h after starting treatment, the median activity was already reduced by 59%. The other CSF parameters showed a variability during the first 24 h of treatment independently of the course of the disease. Multiple comparisons of the CSF parameters in 17 patients who had two follow-up punctures showed that the beta-glucuronidase activity was the best prognostic index. CONCLUSION: Beta-glucuronidase activity in the CSF is a reliable indicator of bacterial meningitis, which can identify the response to treatment early in the course of illness. The enzyme activity is increased early in the disease, even when the other laboratory parameters from the CSF remain normal.	N. G. Beratis, M. I. Eliopoulou and G. A. Syrogiannopoulos	Acta paediatrica (Oslo, Norway : 1992)
603	Polymerase chain reaction for diagnosis of varicella zoster virus central nervous system infections without skin manifestations	Varicella zoster virus (VZV) can cause disease in the central nervous system (CNS) during both primary infection and reactivation. Rapid and adequate diagnosis of VZV have previously been hampered by the shortcomings of standard virological methods, such as isolation and serology. Earlier reported cases of CNS manifestations of VZV infection have, therefore, mostly been noted in connection with, or shortly after, onset of vesicular rash. Several studies have recently been described of cases of VZV-induced CNS disease occurring as the only sign of viral reactivation, with the diagnosis aided by polymerase chain reaction (PCR) amplification and other methods of genome detection. A prospective study was performed using PCR on cerebrospinal fluid (CSF) and brain samples received for routine diagnosis of possible VZV infection during a 2-year period. Samples from 8 (7 from CSF, 1 from brain) of the 260 patients investigated (3.1%) were found to be positive for VZV-DNA. All 8 had a presumed reactivated VZV infection according to serological and clinical analysis. Their CNS manifestations ranged from meningitis to severe encephalitis, and only in 3 of these patients was a vesicular rash present. Thus, VZV-DNA detection in the CSF was an unexpected finding for the clinician and, in 2 cases, antiviral treatment with aciclovir was initiated only because of the PCR evidence of CNS infection. VZV should be considered as a possible causative agent of infection in patients with CNS disease of suspected viral origin, even in the absence of skin manifestations. Rapid diagnosis by PCR amplification of VZV-DNA from CSF might allow for early and adequate antiviral treatment.	T. Bergström	Scandinavian journal of infectious diseases. Supplementum
135	Safety and immunogenicity of a tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine in adolescents and adults	The highest incidence of invasive meningococcal disease is in young children, with a second peak in adolescents/young adults. All five major disease-causing serogroups (A, B, C, W-135 and Y) have been described in Asia. Immunogenicity and safety of the investigational meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT, GlaxoSmithKline Biologicals) was evaluated in healthy, meningococcal conjugate vaccine-naïve adolescents in the Philippines, India and Taiwan. 1025 adolescents were randomized (3:1) to receive one dose of ACWY-TT or tetravalent ACWY polysaccharide vaccine (Mencevax?, Men-PS). Serum bactericidal activity using rabbit complement (rSBA) was measured. Local and systemic adverse reactions were recorded for 4 days. Safety data were pooled with results from a second, similarly designed study in adults for evaluation of grade 3 systemic events. The pre-specified immunogenicity criterion for non-inferiority to Men-PS was met. One month post-vaccination, ?85.4%-97.1% had a vaccine response (post-titre ?1:8 in initially seronegative and ?4-fold increase in seropositive), versus 78.0%-96.6% after Men-PS, against each vaccine serogroup. Exploratory comparisons showed statistically significantly higher post-vaccination rSBA geometric mean titres against all serogroups following ACWY-TT versus Men-PS. Exploratory analysis showed no statistically significant differences between groups in grade 3 general symptoms; however, the statistical criterion for non-inferiority between pooled treatment groups in terms of the ratio of incidences of grade 3 general symptoms was not demonstrated. No SAEs were related to vaccination. ACWY-TT was immunogenic in Asian adolescents with a reactogenicity profile that was clinically acceptable and similar to that of licensed Men-PS. The results of this study indicate that ACWY-TT could be used as a third conjugate vaccine in the protection of adolescents against meningococcal disease.	N. Bermal, L. M. Huang, A. P. Dubey, H. Jain, A. Bavdekar, T. Y. Lin, V. Bianco, Y. Baine and J. M. Miller	Human vaccines
498	[Ceftriaxone for the treatment of bacterial meningitis in children]	in English (page 42) - prospective blind comparative study	L. Bernadino and N. Marques	Acta Medica Angolana
574	Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination	Early or low dose antigen exposure can prime the immune system for subsequent responses; the so-called "prime-boost" effect. In the context of a Sudanese measles vaccine trial, we assessed whether or not such early exposure could influence the response to revaccination. Children received either Connaught high titer vaccine (CN: n = 53; 10(4.7)pfu) or meningococcal A + C vaccine as a placebo (MEN: n = 58) at 5 months of age. At 9 months of age, all received standard titer Schwarz vaccine (SCH: 10(3.9)pfu). Neutralizing antibodies were measured before initial vaccination and at 9 months of age (plaque reduction neutralization assay (PRN)) and again at 5 years of age (syncytium inhibition assay (SIA)). Lymphoproliferative responses to measles virus (MV) antigens were evaluated at 5 years of age. Eleven of the 53 CN-SCH children (21%) had sub-protective neutralizing antibody titers prior to revaccination (log PRN 1.5 +/- 0.03 versus 2.9 +/- 0.07 in the remaining 42 children; P < 0.004). Maternal antibody titers at the time of initial vaccination in these 11 were high (PRN 2.44 +/- 0.12 versus 1.9 +/- 0.04; P < 0.0001). At 5 years of age, neutralizing antibodies were comparable in the 11 CN-SCH poor responders (log SIA 2.1 +/- 0.09), the remaining CN-SCH children (2.2 +/- 0.06) and the MEN-SCH group vaccinated only once at 9 months of age (2.25 +/- 0.06). In contrast, 7/11 of the CN-SCH poor responders (64%) had stimulation indices (SI) > 3 in response to MV antigens at 5 years of age (SI 3.1 +/- 0.6) compared with only 14% in the remaining children of the CN-SCH group (2.0 +/- 0.3; P = 0.05) and 8% in the MEN-SCH group (1.4 +/- 0.2; P < 0.0003). These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination.	F. M. Bertley, S. A. Ibrahim, M. Libman and B. J. Ward	Vaccine
276	Use of intrathecal hyaluronidase in the management of tuberculous meningitis with hydrocephalus	A preliminary study to evaluate the efficacy of intrathecal hyaluronidase was carried out in nine children suffering from tuberculous meningitis with communicating hydrocephalus. This was followed by a randomized trial in which five cases were treated with intrathecal hyaluronidase, while six cases were treated by the insertion of a ventriculoperitoneal shunt. No untoward reaction of any significance was noted. The results were judged in terms of improvement in the sensorium and mentation, in specific neurological deficit (e.g., visual impairment and hemiparesis), and in overall functional performance. Although most of the patients receiving hyaluronidase showed some improvement in the sensorium, only one of the nine preliminary cases and one of the five cases in the randomized trial showed a total recovery of function. Two of the six shunted patients, however, showed complete recovery. Shunt insertion led to further improvement in two of the nine preliminary cases who had failed to respond to treatment with hyaluronidase. This preliminary study shows that intrathecal hyaluronidase does, in most cases, lead to an improvement in the sensorium but does not offer any particular advantage over shunt insertion in terms of regression of specific neurological deficit or overall functional improvement.	S. N. Bhagwati and K. George	Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
478	Pathways to infant mortality in urban slums of Delhi, India: implications for improving the quality of community- and hospital-based programmes	The study aimed at obtaining insights into the processes underlying infant deaths to help identify preventive interventions which may bring down infant mortality rates further. Verbal autopsies were performed on 162 deaths of liveborn infants that occurred in a birth cohort in two urban slums of Delhi, India, between February 1995 and August 1996. A structured verbal autopsy form was used for ascertaining the cause of death. The narratives of caretakers on seeking of care and treatment received for illness were reviewed to identify the actions and behaviours that might have contributed to death. Seeking of care was less common (57%) for illnesses that led to death in the first week of life than at later ages. The first-week deaths commonly (61%) occurred within 24 hours of recognition of illness which might have been too a short time for effective interventions by care providers. Only six of 45 neonates who had features of sepsis, pneumonia or meningitis, major congenital malformations, birth asphyxia, or prematurity were advised by primary care providers for hospitalization. Similarly, only 25 (41%) of 61 older infants who had severe malnutrition and sepsis or meningitis, diarrhoea or pneumonia, or other illnesses were referred to hospital. Parenteral antibiotics were prescribed less often than warranted. Only two of 16 neonates with serious bacterial infections and eight of 19 postneonates with features of sepsis or meningitis received parenteral antibiotics. Inappropriate healthcare practices were common among the practitioners of modern and indigenous systems of medicine and registered medical practitioners. Forty percent of the neonates and a little over half of the older infants, advised for hospitalization, were taken to hospital. Fifteen percent of the infants taken to hospital were refused admission. Of 21 hospitalized infants discharged alive, five (23%) died within 48 hours and 13 (62%) within a week of returning home. A major effort is required to improve skills of healthcare providers of the biomedical and indigenous systems of medicine in caring for neonates and infants. Development of home-based treatment regimens for young infants and objective criteria for their hospitalization and discharge should receive a high priority.	N. Bhandari, R. Bahl, S. Taneja, J. Martines and M. K. Bhan	Journal of health, population, and nutrition
538	Role of dexamethasone as adjunctive therapy in acute bacterial meningitis in adults		S. Bhaumik and M. Behari	Neurology India
318	High-dose amphotericin B with flucytosine for the treatment of cryptococcal meningitis in HIV-infected patients: a randomized trial	BACKGROUND: The standard therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis of amphotericin B (AmB; 0.7 mg/kg per day) plus flucytosine frequently takes >2 weeks to sterilize the cerebral spinal fluid, and acute mortality remains high. A dosage range for AmB of 0.7-1 mg/kg per day is noted in current guidelines, but there are no data comparing 0.7 mg/kg per day with 1 mg/kg per day. METHODS: Sixty-four HIV-seropositive, antiretroviral therapy-naive patients in Cape Town, South Africa, who experienced their first episode of cryptococcal meningitis during the period May 2005-June 2006 were randomized to receive either (1) AmB, 0.7 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 1; 30 patients); or (2) AmB, 1 mg/kg per day, plus flucytosine, 25 mg/kg 4 times per day (group 2; 34 patients). Regimens were given for 2 weeks, followed by treatment with oral fluconazole. The primary outcome measure was early fungicidal activity, as determined by results of serial, quantitative cerebral spinal fluid cryptococcal cultures. Secondary outcome measures were safety and mortality. The median duration of follow-up was 1 year. RESULTS: Early fungicidal activity was significantly greater for group 2 than for group 1 (mean +/- SD, -0.56 +/- 0.24 vs. -0.45 +/- 0.16 log cfu/mL of cerebral spinal fluid per day; P = .02). The incidence of renal impairment did not significantly differ between the 2 groups. Anemia was associated with female sex and, less strongly, with membership in group 2. Renal impairment and anemia reversed after the regimen was switched to fluconazole. Two- and 10-week mortality rates were 6% and 24%, respectively, with no difference between groups. CONCLUSIONS: AmB, 1 mg/kg per day, plus flucytosine is more rapidly fungicidal than is standard-dose AmB plus flucytosine. Because of its size, this study provides limited data on any difference in toxicity between the regimens, but toxicities were manageable and reversible. CLINICAL TRIALS REGISTRATION NUMBER: ISRCTN68133435 (http://www.controlled-trials.com).	T. Bicanic, R. Wood, G. Meintjes, K. Rebe, A. Brouwer, A. Loyse, L. G. Bekker, S. Jaffar and T. Harrison	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
660	[Importance of the study of the minimal bactericidal time of serum in the choice of optimal treatment of neonatal septicemias]	Rapid eradication of bacteria in bloodstream is critical for the outcome in neonatal bacterial sepsis. Two groups of neonates with E. coli K1 sepsis without purulent meningitis were studied. Group I (n = 14) received cefotaxime IV (100 mg.kg-1 D-1) plus netilmicin (4 mg.kg-1 D-1); group II (n = 8) received amoxicillin/clavulanic acid IV (100/10 mg.kg-1 D-1) plus netilmicin (4 mg.kg-1 D-1). Both groups were identical. For all strains MICs of cefotaxime, amoxicillin/clavulanic acid, netilmicin were less than 0.2, 4 and 1 mg/l respectively. Serum bactericidal activity (SBA) was determined for each patient (peak sample). The SBA was defined as the greatest dilution in which 99,99% of the inoculum was killed. Time-kill curves were performed with 1:16 dilutions of peak serum samples to measure the kinetic of bacterial killing. The minimal bactericidal time of serum (MBTS) was defined as the minimal time required to observe a decrease of more than 4 log CFU/ml of the bacterial inoculum. Samples (10 microliters) were taken at 1 h intervals over a 6 h period and at 24 h for quantitative culture. All patients cured. Median SBA were respectively 1/128 and 1/64 for group I and II. However, mean MBTS for groups I and II were respectively 1.2 h +/- 0.8 and 3.9 h +/- 1.4. Killing was more rapid in group I (p less than 0.01). The MBTS may be a clinically useful adjunctive test when optimal therapy would be expected.	E. Bingen, N. Lambert-Zechovsky, E. Guihaire, P. Mariani, M. Coache, E. Jacqz, Y. Aujard and H. Mathieu	Pathologie-biologie
518	Early Versus Delayed Antiretroviral Therapy and Cerebrospinal Fluid Fungal Clearance in Adults With HIV and Cryptococcal Meningitis		G. P. Bisson, M. Molefi, S. Bellamy, R. Thakur, A. Steenhoff and N. Tamuhla	Clinical infectious diseases
415	Concentrations of ofloxacin in serum and cerebrospinal fluid of patients without meningitis receiving the drug intravenously and orally	The cerebrospinal fluid (CSF) penetration of ofloxacin given orally or intravenously was studied in cancer patients without meningitis. Each patient was assigned to a different sampling time to assess the relation between time and penetration. Ofloxacin was measured in serum and CSF by high-pressure liquid chromatography and bioassay. In addition, the bactericidal titers were measured in CSF and serum against a set of relevant bacteria. Concentrations measured by high-pressure liquid chromatography and bioassay were well correlated. Peak concentrations in CSF (0.4 to 1 mug/ml) were observed 2 to 4 h after infusion or oral administration. Peak concentrations in serum were observed just after infusion (2 to 3.5 mug/ml) or 1 to 2 h after oral administration (1.7 to 4 mug/ml). Measured bactericidal titers were well correlated with the titers expected from the MBC and concentration. High CSF bactericidal titers were observed against Neisseria meningitidis, Haemophilus influenzae, and Escherichia coli, whereas low or no bactericidal titers were obtained against Staphylococcus aureus, Listeria monocytogenes, and Streptococcus pneumoniae. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	N. Bitar, R. Claes and P. Auwera	Antimicrobial Agents & Chemotherapy
360	Assessing costs and cost effectiveness of pneumococcal disease and vaccination within Kaiser Permanente	Objective: To review studies of the costs of pneumococcal disease and the cost effectiveness of pneumococcal conjugate vaccination conducted in association with the Kaiser Permanente Pneumococcal conjugate Efficacy Trial. Results: for each birth cohort of 3.8 million infants, routine pneumococcal conjugate vaccination program for healthy infants would prevent more than 12000 (78% of potential) meningitis and bacteremia cases, 53000 (69% of potential) pneumonia cases, and 1 million (8% of potential) otitis media episodes. Before accounting for vaccine costs, the vaccination program would reduce the costs of pneumococcal disease by $342 million in medical and $415 million in work-loss and other costs. Vaccination of healthy infants would result in net savings for society if the vaccine cost less than $46 per dose, and net savings for the health care payer if the vaccine cost less than $18 per dose.	S. Black, T. A. Lieu, G. T. Ray, A. Capra and H. R. Shinefield	Vaccine
200	Safety and efficacy of the seven-valent pneumococcal conjugate vaccine: evidence from Northern California	UNLABELLED: Pneumococcal disease remains a significant cause of morbidity among young children. A large-scale efficacy trial in the Northern California Kaiser Permanente system (the KP trial) demonstrated that a seven-valent conjugate vaccine (PCV) is safe and immunogenic in young children and effective in preventing both invasive pneumococcal disease caused by vaccine serotypes (97.4% efficacy) and episodes of otitis media (7.0% efficacy). Since the publication of the results of the KP trial in 2000, we have performed an additional analysis on the safety, immunogenicity, and efficacy of the vaccine in low birth weight (LBW) and preterm (PT) infants, and have examined the efficacy of the vaccine during 1 year of wide-scale post-licensure use. The vaccine was at least as immunogenic in LBW and PT infants as in normal-weight, full-term infants and was 100% effective, although the LBW and PT infants had higher rates of adverse events such as redness and swelling. LBW and PT infants receiving pneumococcal vaccine also had higher rates of adverse events, such as hives, than those receiving control meningococcal vaccine, but these reactions were not severe. When the PCV was used in the general population, the efficacy remained high and there was no corresponding increase in disease caused by nonvaccine serotypes. There was also evidence that vaccine administration led to herd immunity. Febrile illness was the only adverse event seen more frequently after vaccine administration than during a control period. CONCLUSION: the seven-valent conjugate vaccine is safe and effective for use in the general population.	S. Black and H. Shinefield	European journal of pediatrics
457	Efficacy, safety and immunogenicity of heptavalent pneumococcal conjugate vaccine in children	Objective. To determine the efficacy, safety and immunogenicity of the heptavalent CRM197 pneumococcal conjugate vaccine against invasive disease caused by vaccine serotypes and to determine the effectiveness of this vaccine against clinical episodes of otitis media. Methods. The Wyeth Lederle Heptavalent CRM197 (PCV) was given to infants at 2, 4, 6 and 12 to 15 months of age in a double blind trial; 37 868 children were randomly assigned 1:1 to receive either the pneumococcal conjugate vaccine or meningococcus type C CRM197 conjugate. The primary study outcome was invasive disease caused by vaccine serotype. Other outcomes included overall impact on invasive disease regardless of serotype, effectiveness against clinical otitis media visits and episodes, impact against frequent and severe otitis media and ventilatory tube placement. In addition the serotype-specific efficacy against otitis media was estimated in an analysis of spontaneously draining ears. Results. In the interim analysis in August, 1998, 17 of the 17 cases of invasive disease caused by vaccine serotype in fully vaccinated children and 5 of 5 of partially vaccinated cases occurred in the control group for a vaccine efficacy of 100%. Blinded case ascertainment was continued until April, 1999. As of that time 40 fully vaccinated cases of invasive disease caused by vaccine serotype had been identified, all but 1 in controls for an efficacy of 97.4% (95% confidence interval, 82.7 to 99.9%), and 52 cases, all but 3 in controls in the intent-to-treat analysis for an efficacy of 93.9% (95% confidence interval, 79.6 to 98.5%). There was no evidence of any increase of disease caused by nonvaccine serotypes. Efficacy for otitis media against visits, episodes, frequent otitis and ventilatory tube placement was 8.9, 7.0, 9.3 and 20.1% with P < 0.04 for all. In the analysis of spontaneously draining ears, serotype-specific effectiveness was 66.7%. Conclusion. This heptavalent pneumococcal conjugate appears to be highly effective in preventing invasive disease in young children and to have a significant impact on otitis media. Number of References 24. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Black, H. Shinefield, B. Fireman, E. Lewis, P. Ray, J. R. Hansen, L. Elvin, K. M. Ensor, J. Hackell, G. Siber, F. Malinoski, D. Madore, I. Chang, R. Kohberger, W. Watson, R. Austrian, K. Edwards, J. Aguilar, M. Bartlett, R. Bergen, M. Burman, S. Dorfman, W. Easter, A. Finkel, H. Froehlich, J. Glauber, A. Herz, D. Honeychurch, R. Kleinrock, I. Landaw, A. Lavetter, C. Le, S. McMurtry, P. Morozumi, P. Mullin, M. Rehbein, R. Rossin, G. Soe, I. Takahashi, G. Udkow and R. Whitson	Pediatric Infectious Disease Journal
89	The effect of rifampicin on meningococcal carriage in family contacts in northern Nigeria		I. S. Blakebrough and H. M. Gilles	The Journal of infection
77	Failure of meningococcal vaccination to stop the transmission of meningococci in Nigerian schoolboys	A combined group A and group C meningococcal polysaccharide vaccine was given to 438 Nigerian schoolboys shortly before an outbreak of group A meningococcal disease occurred in their school. Four months after vaccination the carriage rate of group A meningococci among vaccinated subjects (11%) was no different from that found among the controls (12%), although a good antibody response to both components of the vaccine was observed. One case of group A meningococcal disease was recorded amongst 438 vaccinated subjects while five cases occurred among 874 controls.	I. S. Blakebrough, B. M. Greenwood, H. C. Whittle, A. K. Bradley and H. M. Gilles	Annals of tropical medicine and parasitology
335	[The effect of antiinflammatory therapy with dexamethasone and dexamethasone with pentoxifylline on the course of bacterial meningitis]	Despite of antimicrobial therapy mortality rate in the bacterial meningitis (BM) is high. The aim of the study was to assess the influence of anti-inflammatory treatment with dexamethasone and dexamethasone with pentoxifylline on the course of this disease and concentration of proinflammatory cytokines TNF-alpha, IL-1 beta, II-8 in the cerebrospinal fluid (CSF). 42 patients with the BM were analysed. They were divided into three groups on the basis of applied therapy: A--treated only with antibiotics, A+D--treated with antibiotics and dexamethasone, A+D+P--treated with antibiotics, dexamethasone and pentoxifylline. Anti-inflammatory therapy did not have impact on the resolution of inflammation (pleocytosis, protein and glucose level) in the CSF. However, it was established that adjuvant treatment with dexa-methasone and pentoxifylline has beneficial effect on the course of the BM. In this group 61.5% of patients recovered, in comparison with 28.6% in the group A+D and 26.7% in the group A. Mortality rate was: in the group A--33%, A+D--21.4%, A+D+P--7.7% (p = 0.01). Correlation between the outcome of the BM in the investigated groups and cytokines concentration in CSF was observed. In the group A+D+P all patients responded to the therapy with decrease of cytokine concentration, and coefficients of variation were low (TNF-alpha--1%, IL-1 beta--23.6%, IL-8--18.9%). Also in the group A+D decrease of cytokines concentration in the CSF was observed, however was not such significant in all cases. In the group of patients treated only with antibiotics concentration of cytokines in the CSF varied, even increased in some of them. Our investigation indicates that inhibition of cytokines production in central nervous system (CNS) with dexamethasone and pentoxifylline improves the outcome of BM and is associated with the reduction of neurological sequels and deaths.	M. Bociaga-Jasik, A. Kalinowska-Nowak, A. Garlicki and T. Mach	Przegla?d lekarski
132	Immediate and longer term immunogenicity of a single dose of the combined haemophilus influenzae type B-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in primed toddlers 12 to 18 months of age	Hib-primed but MenC-naive toddlers (N = 433) were randomized to receive 1 dose of Hib-MenC-TT or separate Hib-TT and MenC-CRM197 vaccines. One month later, noninferiority was demonstrated for serum bactericidal anti-MenC antibodies (rSBA) and Hib antipolyribosylribitol phosphate (PRP) antibodies; >99% in both groups had rSBA titer ? 8 or anti-PRP concentration ? 0.15 ?g/mL. After 12 months, rSBA titer ? 8 persisted in 86.7% and 76.4%, and anti-PRP concentration ? 0.15 ?g/mL persisted in 98.8% and 100% of children, respectively.	R. Booy, P. Richmond, T. Nolan, J. McVernon, H. Marshall, M. Nissen, G. Reynolds, J. B. Ziegler, L. Heron, S. Lambert, M. Caubet, N. Mesaros and D. Boutriau	The Pediatric infectious disease journal
404	Effectiveness of rifampicin in the treatment of carriers of meningococcal infections	Los problemas presentados por las recientes epidemias de meningitis meningococica ocurridas en varios paises, junto a la importancia de los portadores de meningococo en tales epidemias, y la dificultad para encontrar terapias adecuadas, han hecho necesario investigar nuevas y efectivas formas de profilaxis Los autores investigan la eficacia e inocuidad de la Rifampicina(Rimactan) en 2.132 ninos entre 1 y 18 anos de edad que asistian a los jardines infantiles y escuelas basicas de Santiago de Chile. A ellos se les efectuo un frotis faringeo para investigar la condicion de portadores de meningococo. El 12% de ellos catalogados como portador de meningococo y tratados con Rifampicina o placebo de acuerdo con una seleccion aleatoria simple por metodo de doble ciego. Nuevos frotis fueron tomados a los tercero y decimo dias. El 92% de los individuos tratados con Rifampicina fueron negativos al tercer dia, y el 35% de los tratados con placebo presentaron igual situacion El 96% de los individuos tratados con Rifampicina que se negativizaron, mantienen esta condicion al decimo dia de tratamiento. No se observaron signos o sintomas atribuibles al medicamento. No se observo resistencia de las cepas a la Rifampicina.	D. J. Borgono and H. J. I. Rodriguez	Rev Chile Pediatr
167	Influence of prior meningococcal C polysaccharide vaccination on the response and generation of memory after meningococcal C conjugate vaccination in young children	To determine whether the immunological hyporesponsiveness induced by meningococcal AC polysaccharide (MACP) vaccines can be overcome by meningococcal C conjugate (MCC) vaccine in young children, serum bactericidal antibody (SBA) serogroup C-specific IgG and IgG avidity indices were measured in young children who received MACP vaccine, followed 7 months later by MCC vaccine, and their responses were compared with those in age-matched MACP-naive control children, who received a single dose of MCC vaccine. For children <1 year of age at MACP vaccination, the SBA geometric mean titer (GMT) after MCC vaccination was lower (P=.022) and proportions with SBA titers <8 (P=.0083) or <128 (P=.0091) were higher than those in the control children. For older children, there was no difference in the SBA GMTs between the study and control groups (P>.5) or in the proportion with SBA titers <8 (P=1.00) or <128 (P=.98). No increase in avidity occurred after MACP vaccination, whereas avidity increased significantly 1 month after MCC vaccination, with a further increase at 6 months, which indicates that the induction of immunological memory was not impaired.	R. Borrow, D. Goldblatt, N. Andrews, P. Richmond, J. Southern and E. Miller	The Journal of infectious diseases
58	Immunogenicity and safety of three doses of a bivalent (B:4:p1.19,15 and B:4:p1.7-2,4) meningococcal outer membrane vesicle vaccine in healthy adolescents	An experimental bivalent meningococcal outer membrane vesicle (OMV) vaccine (B:4:P1.19,15 and B:4:P1.7-2,4) has been developed to provide wide vaccine coverage particularly of the circulating strains in Europe. A randomized, controlled phase II study (study identification number, 710158/002; ClinicalTrials.gov identifier number, NCT00137917) to evaluate the immunogenicity and safety of three doses of the OMV vaccine when given to healthy 12- to 18-year-olds on a 0-2-4 month (n = 162) or 0-1-6 month schedule (n = 159). A control group received two doses of hepatitis A and one of conjugated meningococcal serogroup C vaccine on a 0-1-6 month schedule (n = 157). Immune response, defined as a fourfold increase in serum bactericidal titer using a range of vaccine-homologous or PorA-related and heterologous strains, was determined for samples taken before and 1 month after vaccination; assays were performed at two laboratories. As measured at the GlaxoSmithKline (GSK) laboratory, the OMV vaccine induced an immune response against homologous or PorA-related strains (in at least 51% of subjects against strains of serosubtype P1.19,15 and at least 66% against strains of serosubtype P1.7-2,4) and against a set of three heterologous strains (in 28% to 46% of subjects). Both laboratories showed consistent results for immune response rates. The OMV vaccine had a similar reactogenicity profile for each schedule. Pain preventing normal activities occurred in approximately one-fifth of the subjects; this was significantly higher than in the control group. The immune responses induced by the bivalent OMV vaccine demonstrated the induction of bactericidal antibodies against the vaccine-homologous/PorA-related strains but also against heterologous strains, indicating the presence of protective antigens in OMVs and confirming the potential of clinical cross-protection.	D. Boutriau, J. Poolman, R. Borrow, J. Findlow, J. D. Domingo, J. Puig-Barbera, J. M. Baldó, V. Planelles, A. Jubert, J. Colomer, A. Gil, K. Levie, A. D. Kervyn, V. Weynants, F. Dominguez, R. Barberá and F. Sotolongo	Clinical and vaccine immunology : CVI
169	A placebo-controlled trial of maintenance therapy with fluconazole after treatment of cryptococcal meningitis in the acquired immunodeficiency syndrome. California Collaborative Treatment Group	BACKGROUND AND METHODS: In patients with the acquired immunodeficiency syndrome (AIDS), the rate of relapse after primary treatment for cryptococcal meningitis remains high. We conducted a controlled, double-blind trial to evaluate the efficacy of maintenance therapy with fluconazole. At entry into the study, all participants had sterile cultures of cerebrospinal fluid, blood, and urine after following a standardized course of therapy for culture-proved cryptococcal meningitis. The patients were randomly assigned to take either fluconazole or placebo as maintenance therapy. The dose of fluconazole was 100 mg daily in the first phase of study and 200 mg daily in the second phase. RESULTS: Of 84 patients initially enrolled, 16 (19 percent) were found to have silent, persistent infection on the basis of cultures that became positive after entry into the study; 7 other patients were lost to follow-up shortly after entry. Of the remaining 61 patients, 10 of 27 assigned to placebo (37 percent) and 1 of 34 assigned to fluconazole (3 percent) had a recurrence of cryptococcal infection at any site (difference in risk, 34 percent; 95 percent confidence interval, 15 to 53). Of the 11 recurrent infections, 7 were detected in urine obtained after prostatic massage. There were four recurrent meningeal infections in the patients taking placebo, but none in those taking fluconazole (mean duration of follow-up, 164 days) (P = 0.03). In multivariate analyses, the best predictors of recurrence-free survival were fluconazole treatment (P = 0.02; relative hazard, 13.2), a lower serum cryptococcal-antigen titer (P = 0.05; relative hazard, 1.2), and more prolonged primary therapy with flucytosine (P = 0.09; relative hazard, 1.1). Survival and toxicity were similar in the two maintenance-treatment groups. CONCLUSIONS: In patients with AIDS, silent persistent infection is common after clinically successful treatment for cryptococcal meningitis. Maintenance therapy with fluconazole is highly effective in preventing recurrent cryptococcal infection.	S. A. Bozzette, R. A. Larsen, J. Chiu, M. A. Leal, J. Jacobsen, P. Rothman, P. Robinson, G. Gilbert, J. A. McCutchan and J. Tilles	The New England journal of medicine
180	Malaria chemoprophylaxis with chloroquine in young Nigerian children. II. Effect on the immune response to vaccination	The immune response of 198 young Nigerian children protected against malaria by chemoprophylaxis with chloroquine to immunization with triple, poliomyelitis, measles, typhoid, meningococcal and BCG vaccines was compared with the immune response to vaccination of 185 control children. Good responses to triple, measles and BCG vaccines were shown by children in both groups; poorer responses were obtained to poliomyelitis, typhoid and meningococcal vaccines. The response to immunization of protected children was similar to that observed among control children for all the vaccines tested except for meningococcal polysaccharide vaccine. Protected children showed a significantly greater antibody response to both group A and group C meningococcal polysaccharides than control children. This finding supports the results of previous studies which have shown that the immune response to meningococcal polysaccharide vaccines is adversely affected both by acute malaria and by asymptomatic malaria parasitaemia.	A. M. Bradley-Moore, B. M. Greenwood, A. K. Bradley, A. Bartlett, D. E. Bidwell, A. Voller, J. Craske, B. R. Kirkwood and H. M. Gilles	Annals of tropical medicine and parasitology
162	Safety and immunogenicity of three lots of meningococcal serogroup C conjugate vaccine administered at 2, 3 and 4 months of age	The reactogenicity and immunogenicity of meningococcal serogroup C conjugate (MenC) vaccine was assessed in 322 infants vaccinated at 2, 3, and 4 months of age, with concomitant administration of mixed diphtheria-tetanus-whole-cell pertussis vaccine and Haemophilus influenzae type b conjugate vaccine (DTwP-Hib) and oral polio vaccine. All infants in whom post-vaccination meningococcal C anticapsular IgG levels were assayed (n = 265) attained > or = 2 microg ml(-1). Serum bactericidal titres were assayed for a proportion of subjects (n = 171), 98% of whom obtained a reciprocal titres > or = 8. Local reactions were less frequent at the MenC injection site than at the DTP-Hib site. Systemic events were frequent, but consistent with established DTwP-Hib experience. The study demonstrates that MenC vaccine is immunogenic and well tolerated in infants at manufacturing scale production levels.	J. C. Bramley, T. Hall, A. Finn, R. B. Buttery, D. Elliman, S. Lockhart, R. Borrow and I. G. Jones	Vaccine
69	Fc gamma receptor IIa (CD32) polymorphism in fulminant meningococcal septic shock in children	Antibodies are essential in host defense against Neisseria meningitidis. Therefore, interactions among IgG and Fc receptors (Fc gamma R) on phagocytes may be crucial. Genetic polymorphic forms of Fc gamma RIIa (CD32) express different functional activities. In a retrospective study, Fc gamma R polymorphisms were determined in 25 children who survived fulminant meningococcal septic shock: 11 had Fc gamma RIIa-R/R131, the poor IgG2-binding allotype, which is a significantly more frequent rate than found in a healthy white population (44% vs. 23%; P = .028; odds ratio = 2.67; 95% confidence interval, 1.09-6.53). The relevance of this finding was further supported by the fact that neutrophils with the Fc gamma RIIa-R/R131 allotype phagocytized N. meningitidis opsonized with polyclonal IgG2 antibodies less effectively than did IIa-H/H131 neutrophils. Our findings suggest an important role for anti-N. meningitidis IgG2 and the Fc gamma RIIa polymorphism in host defense against systemic meningococcal infections.	R. G. Bredius, B. H. Derkx, C. A. Fijen, T. P. Wit, M. Haas, R. S. Weening, J. G. Winkel and T. A. Out	The Journal of infectious diseases
329	Oral versus intravenous flucytosine in patients with human immunodeficiency virus-associated cryptococcal meningitis	In a randomized controlled trial of amphotericin B-based therapy for human immunodeficiency virus (HIV)-associated cryptococcal meningitis in Thailand, we also compared the mycological efficacy, toxicity, and pharmacokinetics of oral versus intravenous flucytosine at 100 mg/kg of body weight/day for the initial 2 weeks. Half of 32 patients assigned to the two arms containing flucytosine were randomized to oral and half to intravenous flucytosine. Early fungicidal activity was determined from serial quantitative cultures of cerebrospinal fluid (CSF), and toxicity was assessed by clinical and laboratory monitoring. Flucytosine and fluorouracil concentrations in plasma and CSF were measured by high-performance liquid chromatography. No significant bone marrow or hepatotoxicity was seen, there was no detectable difference in bone marrow toxicity between patients on intravenous and those on oral formulation, and no patients discontinued treatment. In patients receiving intravenous flucytosine, the median 24-h area under the concentration-time curve was significantly higher than in the oral group. Despite this difference, there was no difference in early fungicidal activity between patients on intravenous compared with patients on oral flucytosine. The results suggest that either formulation can be used safely at this dosage in a developing country setting, without drug concentration monitoring. The bioavailability of the oral formulation may be reduced in late-stage HIV-infected patients in Thailand. Concentrations of flucytosine with intravenous formulation at 100 mg/kg/day may be in excess of those required for maximal fungicidal activity.	A. E. Brouwer, H. J. Kan, E. Johnson, A. Rajanuwong, P. Teparrukkul, V. Wuthiekanun, W. Chierakul, N. Day and T. S. Harrison	Antimicrobial agents and chemotherapy
271	Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial	BACKGROUND: It frequently takes more than 2 weeks for drug treatments for cryptococcal meningitis to sterilise cerebrospinal fluid (CSF). In-vitro and animal studies lend support to the use of combinations of amphotericin B, flucytosine, and fluconazole for treatment of cryptococcosis. We compared the fungicidal activity of combinations of these drugs for initial treatment of patients with cryptococcal meningitis. METHODS: 64 patients with a first episode of HIV-associated cryptococcal meningitis were randomised to initial treatment with: amphotericin B (0.7 mg/kg daily); amphotericin B plus flucytosine (100 mg/kg daily); amphotericin B plus fluconazole (400 mg daily); or triple therapy with amphotericin B, flucytosine, and fluconazole. Our primary endpoint was fungicidal activity, measured by the rate of reduction in CSF cryptococcal colony-forming units (CFU) from serial quantitative CSF cultures on days 3, 7, and 14 of treatment. FINDINGS: Baseline CSF CFU counts were an important prognostic factor. Clearance of cryptococci from the CSF was exponential and was significantly faster with amphotericin B plus flucytosine than with amphotericin B alone (p=0.0006), amphotericin B plus fluconazole ( p=0.02), or triple therapy (p=0.02). INTERPRETATION: At these doses, amphotericin B plus flucytosine is the most rapidly fungicidal regimen. Quantification of CSF cultures provides a powerful new means to accurately assess the fungicidal activity of new treatment regimens for cryptococcal meningitis.	A. E. Brouwer, A. Rajanuwong, W. Chierakul, G. E. Griffin, R. A. Larsen, N. J. White and T. S. Harrison	Lancet
223	Effect of pneumococcal vaccination on quality of life in children with recurrent acute otitis media: a randomized, controlled trial	BACKGROUND: Limited effectiveness of current treatment strategies for recurrent acute otitis media (RAOM) and increasing antibiotic resistance have diverted attention to prevention of AOM by vaccination. Pneumococcal vaccination for AOM seems to have only modest clinical efficacy. Thus far, the effects on health-related quality of life (HRQoL) or functional health status (FHS) have not been studied. OBJECTIVE: To assess the effect of vaccination on HRQoL or FHS. METHODS: In a double-blind, randomized, controlled trial, 383 children 1 to 7 years old with RAOM were vaccinated with either heptavalent pneumococcal conjugate vaccine followed by pneumococcal polysaccharide vaccine (pneumococcal group: n = 190) or with hepatitis A or B vaccines (control group: n = 193). Parents completed validated Dutch versions of 8 HRQoL and FHS instruments assessing generic FHS (Rand, Functional Status Questionnaire specific, and Functional Status Questionnaire generic), otitis media-specific FHS (OM-6), otitis media-specific child HRQoL (Numerical Rating Scale for Child), family functioning (Family Functioning Questionnaire), and otitis media-specific caregiver HRQoL (Numerical Rating Scale for Caregiver). Scores were compared at baseline and at 14 and 26 months' follow-up. RESULTS: At baseline, the average AOM incidence in the pneumococcal and control group was 5.0 (SD: 2.8) and 4.9 (SD: 2.6) episodes per year, respectively, with 38.4% and 36.8% having suffered from > or =6 episodes per year. AOM frequency decreased 4.4 episodes per year in both groups, with a considerable and comparable improvement in HRQoL and FHS. No substantial differences in HRQoL or FHS were found between the pneumococcal and the control group at baseline or at 14 or 26 months' follow-up. CONCLUSION: Pneumococcal vaccination has no beneficial effect compared with control vaccination on either HRQoL or FHS in children 1 to 7 years old with RAOM.	C. N. Brouwer, A. R. Maillé, M. M. Rovers, R. H. Veenhoven, D. E. Grobbee, E. A. Sanders and A. G. Schilder	Pediatrics
669	Thalidomide (celgene corp)	Thalidomide, in development by Celgene, inhibits the effects of elevated TNFalpha and may consequently be of use in a range of diseases including cachexia, bacterial meningitis, rheumatoid arthritis, septic shock, AIDS, tuberculosis, multiple sclerosis, ulcerative colitis, graft-versus-host disease and systemic lupus erythematosus. In July 1998, Celgene received clearance from the US FDA to market and sell Thalomid (thalidomide) for the treatment of erythema nodosum leprosum (a severe and debilitating condition associated with leprosy) [291919], following a recommendation for approval by the FDA advisory committee in September 1997 [261846,263970]. In that same month, Celgene filed an IND for the treatment of the chronic autoimmune disorders Behcet's disease, and aphthosis [264366]. The trial will be conducted by investigators at the Mayo Clinic and Bowman Gray School of Medicine. It will be divided into two phases, the first phase lasting 4 weeks in which patients will receive 100 mg thalidomide or placebo, and a second open-label phase which will call back all patients to receive the same dose of thalidomide over a 24-week period. It will be determined whether the drug significantly reduces existing ulcerations and inhibits the formation of new lesions. Positive results of a National Institute of Allergy and Infectious Diseases trial for aphthous ulceration of the mouth in HIV-infected patients prompted Celgene to commence a pivotal trial for the same indication. A total of 84 patients will be randomized to 100 mg, 200 mg or 400 mg thalidomide/day for 4 weeks. Patients achieving a full response after 4 weeks will be re-randomized on 100 mg thalidomide or placebo for up to another year [248356]. The company has also completed the pivotal phase III trial for AIDS-related cachexia [225437]. Results from a pivotal phase II/III trial showed that the drug significantly increased body weight in AIDS patients, but also increased viral load initially. A total of 99 patients, who had lost more than 10% of their body weight due to HIV infection, received either 100 or 200 mg/day of thalidomide or placebo orally for 8 weeks. Although there was a significant increase in body weight associated with the 100 mg dose (p = 0.025), there was no difference in body weight changes between patients treated with 200 mg doses and those on placebo. There was a 55% dropout rate at the higher dose due to side-effects such as somnolence, rash, neutropenia, neuropathy and dizziness. Viral load was significantly increased after 4 weeks of treatment. However, there was no further increase in viral load at 8 weeks, and patients were not receiving triple combination antiviral therapy [243943]. In April 1996, Celgene initiated a phase II trial of thalidomide in London for the treatment of chronic intractable diarrhea in HIV positive patients. The double-blind, placebo-controlled trial will involve up to 120 patients, aged 18 to 65 inclusive, at three centers for 28 days of therapy; those on drugs will be orally dosed with 100 mg of thalidomide daily at bedtime. The primary endpoint is reduction in the occurrence of diarrhea [205006,206218]. The trial will be conducted in the US, the UK and Mexico [210069]. The company expanded its clinical trial program in June 1996, for use of thalidomide in graft versus host disease and AIDS complications, such as debilitating ulcers of the digestive system [212461]. A phase II trial for the treatment of cachexia in cancer patients was carried out at St George's Hospital, London. Ten patients received thalidomide (100 mg) orally for 8 weeks and ten received placebo. The study was structured to determine the ability of thalidomide to reduce or stabilize the symptoms of cachexia. Quality of life and levels of disease markers will also be assessed. Results showed that after a 3-week treatment period, patients who received thalidomide gained an average 4.5% in overall body weight versus 0.9% with placebo [190161]. Results from a 65 patient multicenter phase II/III trial for cachexia are still awaited [221227]. Celgene is also conducting a double-blind, placebo-controlled pivotal trial for the treatment of rheumatoid arthritis at New York University's Hospital of Joint Diseases. Levels of TNFalpha are increased in patients with rheumatoid arthritis. Indicators for the trial will be joint swelling and pain and levels of serological markers [177618]. A separate study is being conducted by the US National Institute for Allergy and Infectious Diseases, of thalidomide in combination with Chiron's IL-2 for the treatment of HIV infection [192218]. In vitro evidence suggests that thalido-mide can inhibit the replication of HIV type 1 [169245]. In addition to the associated patent, WO-09214455, which discloses the use of thalidomide in TNF-related diseases, another Celgene patent, US-05463063, discloses a scaleable process to make high purity thalidomide [194937]	G. A. Bruyn	IDrugs : the investigational drugs journal
529	Pneumococcal polysaccharide vaccines: indications, efficacy and recommendations	Streptococcus pneumoniae is the primary cause of community-acquired pneumonia, meningitis in adults and otitis media in infants and children and the third cause of meningitis in infants and children. Despite the availability of effective therapeutic agents against this pathogen, mortality has remained high, particularly for infections complicated by bacteremia. For many years, there has been a plea for vaccination. The first steps, using whole bacterial vaccines, were taken during the early decades of this century in the gold mining camps of South Africa, where pneumonia was endemic. The efficacy of purified pneumococcal polysaccharide vaccines has since been demonstrated in young adults, such as gold miners and military recruits, as well as for several other groups at risk, such as institutionalized elderly, patients with sickle cell anemia or those who have undergone a splenectomy, and elderly patients with underlying conditions such as chronic obstructive pulmonary disease and chronic cardiovascular disease, but not in infants and severely immunocompromised patients. Serological studies on the immune response to inoculation of pneumococcal polysaccharide antigens have demonstrated a severely impaired antibody response in the last two groups. Therefore, development of more highly immunogenic vaccines, e.g. by linking pneumococcal polysaccharides or parts of them to protein carriers, should be continued in an attempt to offer adequate protection to those who are insufficiently protected by the current 23-valent polysaccharide vaccine. Opportunities to immunize other patients who are at risk for pneumococcal infection and are capable of responding to the current vaccine should not be missed.	G. A. Bruyn and R. Furth	European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
437	Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials	A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR.	K. Bryant, J. McVernon, C. Marchant, T. Nolan, G. Marshall, P. Richmond, H. Marshall, M. Nissen, S. Lambert, E. Aris, N. Mesaros and J. Miller	Human vaccines & immunotherapeutics
174	Immunogenicity and safety of H influenzae type b-N meningitidis C/Y conjugate vaccine in infants	BACKGROUND: Meningococcal disease incidence is highest in children younger than 2 years of age, yet there is no US-licensed vaccine for this age group. A phase III study evaluated the immunogenicity and safety of an investigational Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY).MATERIALS AND METHODS: A total of 4180 infants were randomly assigned to receive the HibMenCY at the ages of 2, 4, 6, and 12 to 15 months or the licensed Hib tetanus toxoid conjugate vaccine (ActHIB) at 2, 4, and 6 months and Hib conjugated to N meningitidis outer membrane protein (PedvaxHIB) at 12 to 15 months. Routinely scheduled vaccines were coadministered. Serum bactericidal activity using human complement and anti-polyribosylribitol phosphate antibodies were assessed in 991 subjects. Local and systemic adverse reactions were recorded for 4 days after each dose.RESULTS: The percentage of HibMenCY recipients with serum bactericidal assay using human complement titers of 1:8 or higher after dose 3 was 98.8% for N meningitidis serogroup C (MenC) and 95.8% for N meningitidis serogroup Y (MenY). After dose 4, the percentages were 98.5% and 98.8%, respectively. The percentage of HibMenCY recipients with postdose 3 anti-polyribosylribitol phosphate antibody levels of ? 1.0 ?g/mL was noninferior to that of control (96.3% vs 91.2%). After dose 4, MenC and MenY serum bactericidal assay using human complement antibody titers increased 12-fold over pre-dose 4 levels. Incidence of pain, redness, and swelling at the HibMenCY injection sites tended to be lower than with Hib type b after the first 3 doses and after the fourth dose. Rates of systemic symptoms were similar across groups.CONCLUSIONS: The HibMenCY was immunogenic against MenC and MenY and induced anti-polyribosylribitol phosphate antibody levels noninferior to those of licensed Hib conjugate vaccine. The safety profile of the HibMenCY was clinically acceptable and comparable to Hib conjugate vaccine.	K. A. Bryant, G. S. Marshall, C. D. Marchant, N. Pavia-Ruiz, T. Nolan, S. Rinderknecht, M. Blatter, E. Aris, P. Lestrate, D. Boutriau, L. R. Friedland and J. M. Miller	Pediatrics
545	Tuberculous meningitis: results of treatment with streptomycin and intrathecal sulphetrone		W. L. Calnan, J. Rubie and A. F. Mohun	Br Med J
20	Latex particle agglutination test in the diagnosis of Haemophilus influenzae type B, Streptococcus pneumoniae and Neisseria meningitidis A and C meningitis in infants and children	The knowledge of purulent meningitis etiology is essential in deciding the immediate therapy; in developing countries, however, the etiological agent identification does not reach 60% of the cases. A comparative study using the latex particle agglutination test (LPAT) in cerebrospinal fluid (CSF) for the diagnosis of meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae or Neisseria meningitidis A and C was carried out in Belo Horizonte MG, Brazil. CSF culture was used as a gold-standard. Two hundred and ninety-nine children, ranging from 3 months to 14 years of age, were included in the investigation. One hundred and forty-four presented a positive CSF culture for the above mentioned bacteria; the remaining presented meningitis due to other organisms (other bacteria or viral) or a normal CSF. The sensitivity and the specificity of LPAT was 95.7 and 100.0% for N. meningitidis C, 95.2 and 100.0% for H. influenzae type b and 86.5 and 100.0% for S. pneumoniae, respectively. When all three organisms were considered simultaneously, the sensitivity and the specificity was 93.0 and 100.0%, respectively. Taking into consideration a realistic estimate of disease prevalence in the community where the diagnostic test is being used, the positive predictive value and the posttest probability were estimated as 36.7 and 47.1% for children < 5 years and as 21.3 and 35.1% for children < 14 years of age, respectively. LPAT is a useful diagnostic test for meningitis due to the studied pathogens, especially in developing countries where laboratory facilities are limited.	P. A. Camargos, M. S. Almeida, I. Cardoso, G. L. Filho, D. M. Filho, J. I. Martins, K. W. Batista, R. C. Silva and C. M. Antunes	Journal of clinical epidemiology
426	Serologic responses to an Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine in very young Gambian infants	Recent studies in the United States and Europe have shown that Haemophilus influenzae type b polysaccharide-protein conjugate vaccines can induce protective antibody levels in young infants, but it was not clear that this would be the case in African infants, to whom H influenzae vaccines must be given at a very early age to prevent disease caused by H influenzae. Therefore, antibody responses to an H influenzae type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine were measured in very young Gambian infants. In the first group (n = 85), to whom the vaccine was given at the ages of 1 and 3 months, the geometric mean antibody level rose from a prevaccination level of 0.23 microgram/mL to a postvaccination level of 1.27 micrograms/mL, and in the second group (n = 56), vaccinated at the ages of 2 and 4 months, the prevaccination level of 0.16 microgram/mL rose to a postvaccination level of 1.59 micrograms/mL. These two final postvaccination levels did not differ significantly, and interpolation suggests that similar antibody levels were present in both groups of infants at the age of 3 months. This is the age by which protection would need to be achieved to protect against H influenzae meningitis in The Gambia and in other countries where the infection has similar epidemiologic characteristics. No significant side effects of vaccination were noted.	H. Campbell, P. Byass, V. I. Ahonkhai, P. P. Vella and B. M. Greenwood	Pediatrics
696	Administration of antibiotics to patients with rupture of membranes at term: a prospective, randomized, multicentric study. Collaborative Group on PROM	OBJECTIVE: To assess whether antibiotic administration changes the rate of materno-fetal infectious morbidity in premature rupture of membranes occurring later than 35 weeks of gestation. METHODS: A prospective, randomized and multicentric study in the Perinatology Units of eleven hospitals in Spain. Women were randomized to either antibiotic administration or control group. All were induced, if labor had not started spontaneously after 12 hours of ruptured membranes. Main outcome measures were maternal infection (chorioamnionitis and endometritis) and neonatal infectious morbidity (neonatal sepsis, meningitis and bronchopneumonia). RESULTS: Seven hundred and thirty-three patients were enrolled in the study, 371 in the antibiotics group and 362 in the control group. The incidence of chorioamnionitis and puerperal endometritis were reduced but the differences are statistically nonsignificant. However, the incidence of neonatal sepsis was significantly lower in newborns to mothers who had received antibiotics, 1 vs. 7 cases (Fisher's exact test, p<0.007). CONCLUSION: The study strongly suggests that prophylactic use of antibiotics in premature rupture of membranes occurring at 36 or more weeks of gestation reduces the risk of neonatal sepsis and probably maternal endometritis.	V. Cararach, F. Botet, J. Sentis, R. Almirall and E. Pérez-Picañol	Acta obstetricia et gynecologica Scandinavica
115	Evaluation of the roche AMPLICOR enterovirus PCR assay in the diagnosis of enteroviral central nervous system infections	BACKGROUND: Enteroviruses cause a substantial number of cases of aseptic meningitis annually in the USA. While culture has been useful in the detection of patients with viral meningitis it is time-consuming and lacks sensitivity. Detection of viral nucleic acid in patient specimens has been demonstrated to improve enteroviral detection. OBJECTIVES: A research use only commercial amplification assay, the Roche AMPLICOR EV test, was compared to culture for the diagnosis of enteroviral meningoencephalitis. STUDY DESIGN: Four-hundred and sixty-five consecutive CSF samples sent prospectively for suspicion of enteroviral infection were evaluated by PCR and shell-vial culture. Clinical information and CSF analysis were used to resolve PCR positive, culture negative samples. Sensitivity and specificity were calculated using resolved data. RESULTS: There were 138 samples which met the definition of a true positive. Of these culture detected 77 (sensitivity 55.8%) and PCR detected 136 (sensitivity 98.6%). PCR missed two culture positive samples. Upon repeat testing, these CSF samples were found to contain inhibitors. CONCLUSIONS: The Roche AMPLICOR EV-PCR test was statistically more sensitive than culture (P<0.001) in the detection of enteroviruses in CSF in patients suspected of having enteroviral meningitis. This assay also has the advantage of a rapid turnaround time of 5-6 h compared to 3-5 days for culture.	K. C. Carroll, B. Taggart, J. Robison, C. Byington and D. Hillyard	Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
55	Sequelae from meningococcal meningitis in children: a critical analysis of dexamethasone therapy	OBJECTIVE: To evaluate the effectiveness of dexamethasone as an adjunctive therapy to antibiotics in children with meningococcal meningitis. METHOD: A total of 81 children diagnosed with meningococcal meningitis hospitalized in sequence were studied at the University Hospital of São Paulo University, with the objective of evaluating the presence of sequelae in four different groups of patients, following the administration of dexamethasone: Group I - 25 patients who received the first dose at least 10 minutes before the introduction of the antibiotic therapy; Group II - 19 patients who received the corticosteroid concomitantly; Group III - 14 patients for which the dexamethasone was administered after beginning the antibiotic scheme; Group IV - 23 patients that did not receive dexamethasone. The groups were evaluated for homogeneity through the prognostic indexes and clinical and laboratory characteristics, based on the records obtained at hospitalization. RESULTS: Some degree of sequelae occurred in 16 (26.22%) of the survivors and 23 patients (28.39%) coursed with sequelae or died. The mean period of neurological attendance was 36.97 months and neurological alterations were detected in 16.17% of the patients. No significant difference was found between the four groups. There was also no statistical difference in the comparison of the neurological sequelae in the children from group IV with the children of groups I and II or even with groups I, II and III analyzed as a whole. The presence of hearing loss occurred in 11.11% of the patients, again there was no significant difference between the four groups. Psychological evaluation was performed using the WPSSI and WISC tests. A mild mental disability was detected in one patient from group I and another in group III. The overall analysis of the sequelae (neurological, auditory and intellectual level) also did not demonstrate any significant difference between the four groups. Comparing the children from groups I and II together and also groups I, II and III as a whole with the children in group IV also failed to detect a significant difference arising from the use or nonuse of the corticosteroid. CONCLUSION: Dexamethasone was not proven to be effective in decreasing the number of sequelae among patients with meningococcal meningitis.	E. B. Casella, S. Cypel, A. A. Osmo, Y. Okay, B. H. Lefèvre, I. Lichtig and M. J. Marques-Dias	Arquivos de neuro-psiquiatria
673	Auditory brainstem responses in high risk and normal newborns	We studied the auditory brainstem responses of 50 high risk neonates from NICU and compared with those of 25 normal neonates in order to determine the percentage of significant auditory impairment in NICU and correlated it to various risk factors. Infants with the risk factors of low birth weight, hyperbilirubinemia, asphyxia, septicemia and meningitis were included in the study group. All the 150 ears were tested at 4 intensities 30 dB, 46 dB, 60 dB and 75 dB. The study recorded prolongation of latency of wave V and I-V Interwave interval in the study group with a statistically significant difference denoting an impaired condition. Incidence of significant auditory impairment was 18%. On follow up at 6 months incidence of persistent auditory abnormality was 4%. On the basis of this study it is suggested that all high risk neonates should undergo screening for hearing impairment.	S. Chadha and A. S. Bais	Indian journal of pediatrics
64	Single-dose ceftriaxone pharmacokinetics in pediatric patients with central nervous system infections	Ceftriaxone has greater in vitro and in vivo efficacy against many common bacteria than other third-generation cephalosporins. Single-dose ceftriaxone pharmacokinetics were studied in 17 patients, aged 0.6 to 52 months, with infections of the central nervous system. Patients received a randomized dose of 50 or 75 mg/kg ceftriaxone intravenously over 5 minutes on the second to fifth day of illness. Serial blood samples were collected over 24 hours in all patients, and cerebrospinal fluid (CSF) was obtained 1 to 4.5 hours after injection. Ceftriaxone mean peak plasma concentrations, determined by high-power liquid chromatography, were 267 and 184 microgram/ml for the 75 and 50 mg/kg dosage groups, respectively. The harmonic mean elimination half-life was 4.2 hours, and the mean percent drug penetrance into CSF was 4.8 +/- 3.5%. Of CSF studies evaluated, the glucose concentration was correlated most closely (inversely) with CSF penetration of ceftriaxone. Individual CSF concentrations of ceftriaxone exceeded the minimal inhibitory concentrations of the respective bacteria causing infection by 480 to 5,600 times. Ceftriaxone may be useful in the treatment of serious pediatric infections, including meningitis.	E. G. Chadwick, R. Yogev, S. T. Shulman, R. E. Weinfeld and I. H. Patel	The Journal of pediatrics
444	Carcinoma meningitis secondary to non-small cell lung cancer: combined modality therapy	BACKGROUND: Leptomeningeal metastases (LM) are increasingly diagnosed as anticancer therapies become more effective and result in prolonged patient survival. OBJECTIVE: To evaluate survival, cause of death, and treatment-related toxic effects in patients undergoing combined modality therapy for LM of non-small cell lung cancer. PATIENTS AND METHODS: Thirty-two patients (age range, 48-73 years; median, 57 years) with LM attributable to metastatic non-small cell lung cancer were treated prospectively. Neurologic presentation included headache (11 patients), cranial neuropathies (9), ataxia (5), cauda equina syndrome (3), myelopathy (3), meningismus (2), radiculopathy (2), and confusion (1). All patients underwent radiographic evaluation to determine the extent of central nervous system disease followed by radiotherapy (16 patients) and sequential and intraventricular chemotherapy (methotrexate in 32 patients; cytarabine in 16; and thiotepa in 6). Twelve patients received concurrent systemic chemotherapy. RESULTS: Central nervous system imaging demonstrated interrupted cerebrospinal fluid flow (13 patients), parenchymal brain metastases (9), subarachnoid nodules (8), hydrocephalus (5), and epidural spinal cord compression (2). Cytological responses were seen in 17 patients to first-line chemotherapy, 8 to second-line chemotherapy, and 2 to third-line chemotherapy. Treatment-related toxic effects included 20 patients with aseptic meningitis (grade 2 in 16; grade 3 in 4) and 12 patients with grade 3 or 5 thrombocytopenia or neutropenia (4 related to intraventricular chemotherapy). Median survival was 5 months (range, 1-12 months). Nineteen patients died of progressive LM or combined LM and systemic disease progression. Patients with persistent interruption of cerebrospinal fluid flow fared worse than patients with normal cerebrospinal fluid flow (median survival, 4 vs 6 months; P<.05). CONCLUSIONS: Leptomeningeal metastases in patients with non-small cell lung cancer may be palliated with combined modality therapy; however, therapy and survival is based on the extent of central nervous system disease present at pretreatment evaluation.	M. C. Chamberlain and P. Kormanik	Archives of neurology
116	Neoplastic meningitis-related encephalopathy	BACKGROUND: A retrospective comparison evaluating survival in two well-matched cohorts of patients with cytologically positive neoplastic meningitis (NM) presenting with or without encephalopathy. METHODS: Two cohorts were studied: 20 with and 20 without of NM-related encephalopathy defined as a confusional syndrome. Cohorts were matched with respect to age, primary tumor, performance status, absence of CSF compartmentalization and absence of neuroradiographic bulky CNS disease. Primary tumor histology included the following: breast(10 patients); non-small cell lung cancer (8); non-Hodgkin's lymphoma (8); colorectal cancer (6); melanoma (4); small cell lung cancer (2); prostate cancer (2). NM at presentation revealed: encephalopathy (20 patients); spinal cord dysfunction (18); and cranial neuropathy (15). Radiotherapy was administered to 31 patients (whole brain only in 17 patients; restricted spine only in 8 patients; whole brain and restricted spine in 6 patients). All patients received intraventricular chemotherapy and 16 patients received concurrent tumor-specific systemic chemotherapy. RESULTS: Median survival was 2.5 months (range 1.5-5 months) in the cohort with NM-related encephalopathy compared to 6 months (range: 2-10 months) in the cohort without NM-related encephalopathy (p < 0.001). No treatment-related deaths were observed. All patients demonstrated progressive disease and died of either NM or systemic cancer. CONCLUSIONS: NM-related encephalopathy is a clinical variable that predicts for poor survival in patients with NM. As a consequence, patients with NM-related encephalopathy may be best served by offering supportive care.	M. C. Chamberlain, D. Tsao-Wei and S. Groshen	Journal of neuro-oncology
303	Some aspects of tuberculous meningitis in Surabaya	Eighty tuberculous meningitis patients who were seen in the neurological clinics in Surabaya between the January 1971 and January 1975 were asked to cooperate in a double blind clinical trial. One group was given isoniazid, streptomycin and p-aminosalicylic acid, the other group was given isioniazid, rifampicin, ethambutol and a protease. The outcome after the treatment with isoniazid, rifampicin and ethambutol was significantly better than that with isoniazed, streptomycin and p-aminosalicylic acid. The clinical and laboratory symptoms and signs are reviewed in detail.	B. Chandra	Proceedings of the Australian Association of Neurologists
363	A controlled trial of itraconazole as primary prophylaxis for systemic fungal infections in patients with advanced human immunodeficiency virus infection in Thailand	Cryptococcal meningitis and Penicillium marneffei infection are common serious fungal infections in patients infected with human immunodeficiency virus (HIV) in Southeast Asia. In a prospective, double-blind trial, 63 patients with HIV infection and CD4+ lymphocyte counts of <200 cells/microL were randomized to receive oral itraconazole (200 mg per day), and 66 similar patients received a matched placebo. Both groups were monitored for evidence of invasive fungal infections. Baseline characteristics and the CD4+ cell counts of the 2 groups were similar. In the intent-to-treat analysis, a systemic fungal infection developed in 1 patient (1.6%) assigned to receive itraconazole (P. marneffei) and in 11 patients (16.7%) given placebo (7 patients had cryptococcal meningitis, and 4 patients had P. marneffei infection; P=.003, by the log-rank test). The incidence of recurrent or refractory mucosal candidiasis was significantly reduced in the itraconazole group. The 2 groups did not differ with regard to adverse effects. Primary prophylaxis with oral itraconazole is well tolerated and prevents cryptococcosis and penicilliosis marneffei in patients with advanced HIV infection, especially those with CD4+ lymphocyte counts of <100 cells/microL. However, prophylaxis with itraconazole was not found to be associated with a survival advantage when it was given to patients with advanced HIV disease.	S. Chariyalertsak, K. Supparatpinyo, T. Sirisanthana and K. E. Nelson	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
227	[Acute clinical syndrome associated with OKT3 administration. Prevention by single injection of an anti-human TNF monoclonal antibody]	This study analyzed the capacity of an anti-human tumour necrosis factor (TNF) monoclonal antibody, CB006 (murine IgG1, Celltech), to prevent the OKT3-induced acute clinical syndrome. Fourteen renal allograft recipients undergoing prophylactic OKT3 therapy were included. CB006 was administered as a single i.v. injection, 0.4 mg/kg (Group I, 7 patients) and 2 mg/kg (Group II, 7 patients), one hour prior to the first OKT3 administration. Nineteen consecutive patients that were part of a randomized multicenter trial constituted the historical control group. In all patients CB006 was perfectly well tolerated and significantly decreased the frequency of the common OKT3-associated acute symptoms. None of the CB006 pretreated patients showed severe life threatening symptoms (hypotension, respiratory distress or neurotoxicity), observed in 10 per cent of historical controls. At variance with controls, in CB006 treated patients gastrointestinal symptoms (vomiting, diarrhea) and pyrexia (body temperature greater than or equal to 39 degrees C) appeared in low frequency, were mild and short lasting, never promoting major prostration of the patients due to electrolytes and fluid loss. Importantly, the presence in some patients of these mild symptoms, correlated with detectable bioactive TNF in the circulation thus reflecting incomplete blockade by CB006 of OKT3-induced TNF. CB006 pharmacokinetics data further stressed the need for adequate dosage adaptation. CB006 did not affect the biological or clinical effectiveness of OKT3. None of the patients showed evidence of anti-CB006 xeno-sensitization.	B. Charpentier, C. Hiesse, C. Ferran, O. Lantz, D. Fries, J. F. Bach and L. Chatenoud	Presse médicale (Paris, France : 1983)
287	Moxalactam therapy of Haemophilus influenzae type b meningitis in children	Thirty-four children with Haemophilus influenzae type b meningitis were given prospectively either moxalactam (200 mg/kg/day) or ampicillin (400 mg/kg/day) plus chloramphenicol (75 mg/kg/day). One patient in each group died. The mean duration of fever, clinical response, sequential cerebrospinal fluid findings, and incidence of neurologic sequelae were similar between groups. Moxalactam cerebrospinal fluid bioactivity was significantly greater than that of ampicillin or chloramphenicol throughout therapy. Neutropenia, liver enzyme abnormalities, and diarrhea were not significantly different. In eight of 11 patients given moxalactam (versus one of 14 controls) there was complete elimination of gram-negative aerobic flora in the stools by day 10 (P = 0.002); however, none acquired Clostridium difficile. Moxalactam in effective therapy for H. influenzae type b meningitis.	S. A. Chartrand, M. I. Marks, R. K. Scribner, J. T. Johnston and D. F. Frederick	The Journal of pediatrics
623	Efficacy and safety study of fixed-dose combination of ceftriaxone-vancomycin injection in patients with various infections	Pathogens can infect almost all tissues and cause serious infections. Objective was to evaluate efficacy and safety of fixed-dose combination of Ceftriaxone-Vancomycin in patients with various infections. Patients (n=305) suffering from different bacterial infections (serious respiratory tract disease, bronchitis, gastrointestinal tract infections, urinary tract infection, cellulites and meningitis) were enrolled. Patients were randomized into two groups depending on severity of illness. Group A (n=106) and Group B (n=199) patients were given intravenous dose of fixed-dose combination 1.5 g B.D. and 3.0 g B.D. respectively for 3-10 days. Hemoglobin, total leukocyte count, erythrocyte sedimentation rate, urea, creatinine levels serum glutamyl oxaloacetic transaminase and glutamyl pyruvic transaminase activities were recorded before and on completion of the treatment. Most of patients (70%) were cured in seven or less than seven days of the treatment. Significant decrease in total leukocyte count, erythrocyte sedimentation rate levels were observed indicating patients were cured from the infections. No significant alterations were observed in hemoglobin, serum urea, creatinine levels, glutamyl oxaloacetic transaminase and glutamyl pyruvic transaminase activities on completion of treatment. The fixed-dose combination of Ceftriaxone-Vancomycin, is found to be effective in treating various bacterial infections without any toxic effect on liver and kidney. Patients well tolerated the drug without major adverse effects.	M. Chaudhary, S. M. Shrivastava and R. Sehgal	Current drug safety
254	A multicentre, randomized, double-blind, placebo-controlled trial of primary cryptococcal meningitis prophylaxis in HIV-infected patients with severe immune deficiency	OBJECTIVES: To assess the efficacy and survival benefit of low-dose fluconazole (400 mg weekly) for primary prophylaxis for cryptococcal meningitis in patients with advanced HIV infection. METHODS: A prospective multicentre, randomized, double-blind, placebo-controlled study was carried out in HIV-infected patients with CD4 counts <100 cells/microL. RESULTS: Of 90 patients enrolled, 44 received fluconazole and 46 received placebo. The baseline characteristics were similar in the two groups. On an intent-to-treat basis, 10 cases of cryptococcal meningitis developed, three (6.8%) in the fluconazole group and seven (15.2%) in the placebo group. Patients in the placebo group were more likely to develop cryptococcal meningitis than those in the fluconazole group [hazard ratio=2.23; 95% confidence interval (CI): 0.58-8.63; P=0.245]. The survival benefit of fluconazole was greater than that of the placebo. The number of deaths per 10 000 person-days was 2.7 for the fluconazole group (2/7342) and 11.7 for the placebo group (9/7713) (rate difference=9; 95% CI: 0.4-17.5; P=0.046). Based on survival analysis, patients in the placebo group were 4.3 times more likely to die than those in the fluconazole group (95% CI: 0.9-19.8; P=0.065). CONCLUSION: Fluconazole 400 mg once weekly for primary prophylaxis for cryptococcal meningitis in Thailand should be considered in HIV-infected patients, as our study suggested a survival benefit. However, a larger study should be conducted to confirm our findings.	P. Chetchotisakd, S. Sungkanuparph, B. Thinkhamrop, P. Mootsikapun and P. Boonyaprawit	HIV medicine
26	Treatment with the interleukin-17A-blocking antibody secukinumab does not interfere with the efficacy of influenza and meningococcal vaccinations in healthy subjects: results of an open-label, parallel-group, randomized single-center study	Our objective was to evaluate the efficacy of influenza and meningococcal vaccinations in healthy subjects exposed to the anti-interleukin-17A (IL-17A) monoclonal antibody (MAb) secukinumab. We used an open-label, parallel-group, randomized single-center study of 50 healthy subjects. Subjects received a single 150-mg dose of secukinumab or no treatment, followed by vaccination with inactivated trivalent subunit influenza virus and conjugate group C meningococcal vaccine (Agrippal and Menjugate, respectively) 2 weeks later. Primary efficacy variables were responses of ?4-fold increases in antibody titer (hemagglutination inhibition [HI; for influenza virus] and serum bactericidal assay [SBA; for Neisseria meningitides]) for meningococcus and influenza (at least two out of three serotypes), both at 4 weeks postvaccination. All subjects randomized to secukinumab (n = 25) or the control (n = 25) completed the study. Antibody responses to vaccinations measured at 4 weeks were comparable in both groups, with ?4-fold increased responses following influenza virus vaccination of 20/25 (80%) for both groups and following meningococcal vaccination of 19/25 (76%) for the secukinumab group and 18/25 (72%) for the control group. Differences between groups were 0% (90% confidence intervals [CI], 19 and 19%) and 4% (90% CI, 16 and 24%) for influenza virus and meningococcal vaccines, respectively. Antibody responses were comparable between the 2 groups at different time points. Headache was the most frequently reported adverse effect. No deaths or serious adverse events were reported. Blockade of IL-17A by secukinumab does not appear to interfere with efficacy of influenza and meningococcal vaccinations, as assessed by the achievement of protective antibody levels. A protective (?4-fold) immune response to both vaccinations at 4 weeks was achieved in 80 and 76% of subjects exposed to secukinumab and the control, respectively.	A. Chioato, E. Noseda, M. Stevens, N. Gaitatzis, A. Kleinschmidt and H. Picaud	Clinical and vaccine immunology : CVI
504	Mucosal immunogenicity of meningococcal vaccines in UK adolescents and young adults		S. Choo, Q. Zhang, R. Burkinshaw, J. Everard, R. Lakshman and A. Finn	Journal of Paediatrics & Child Health
215	Primary and booster salivary antibody responses to a 7-valent pneumococcal conjugate vaccine in infants	Salivary anticapsular antibody responses to a 7-valent pneumococcal conjugate vaccine (7VPnC) were measured in healthy infants. Infants received diphtheria-tetanus-pertussis/Haemophilus influenzae type b (DTP/Hib; group 1), DTP/Hib and 7VPnC (group 2), or DTP and 7VPnC/Hib (group 3) at ages 2, 3 and 4 months. All children received 23-valent pneumococcal polysaccharide vaccine at age 13 months. Salivary IgA and IgG responses to primary immunizations were generally poor. IgA mean concentrations at age 5 months were higher in the treatment groups than in control subjects for serotype 14 only (P<.001). At age 13-14 months, there were marked increases in IgA (mean fold difference, 3.7-4.9) and IgG (mean fold difference, 4. 1-11.7) levels for serotypes 4, 9V, 14, and 19F and serotypes 4, 18C, 19F, and 23F, respectively, in the treatment groups. This contrasts with low IgA (1.2 and 1.4) and IgG (1.3 and 2.2) mean fold differences for non-7VPnC serotypes 1 and 5. The results suggest that 7VPnC primes for mucosal memory responses in infants.	S. Choo, Q. Zhang, L. Seymour, S. Akhtar and A. Finn	The Journal of infectious diseases
313	Initial treatment of cryptococcal meningitis in AIDS	The comparison of initial treatment with amphotericin B (0.7 mg/kg/d) plus rifampin (600 mg/d) with amphotericin B (0.7 mg/kg/d) alone for 2 weeks, both followed by fluconazole (400 mg/ d) for 8 weeks in the acute treatment of cryptococcal meningitis in AIDS by an open- randomized, controlled, prospective clinical trial is reported. Twenty patients were enrolled in each group. There were no significant differences between the groups in regard to a negative CSF culture for Cryptococcus neoformans in the 2nd and 10th weeks of treatment, time until normal body temperature after treatment, number of patients who died, and persistence of high CSF pressure after completion of treatment. Elevated intracranial pressure was an important factor associated with the patients who died. These results indicate that the combination of amphotericin B plus rifampin is not superior to amphotericin B alone.	V. Chotmongkol, A. Arayawichanont, K. Sawanyawisuth and Y. Thavornpitak	The Southeast Asian journal of tropical medicine and public health
300	Corticosteroid in tuberculous meningitis	We assessed the benefit of prednisolone regimen in adult-patients with tuberculous meningitis by a randomised, double-blind trial. 59 patients were treated with combined antituberculous drugs and randomised to receive oral prednisolone regimen or a placebo. There were 29 and 30 patients in the treatment and placebo groups respectively. The results revealed that prednisolone was not beneficial in patients with severe brain lesions, increased intracranial pressure and cranial nerve palsies. The role of prednisolone in patients with paraparesis, visual impairment and newly developed neurological complications during treatment needs further study.	V. Chotmongkol, S. Jitpimolmard and Y. Thavornpitak	Journal of the Medical Association of Thailand = Chotmaihet thangphaet
155	Corticosteroid treatment of eosinophilic meningitis	The role of corticosteroids in the treatment of eosinophilic meningitis has not been definitely established. Patients given a 2-week course of prednisolone (treatment group), 60 mg/day, were compared with those given placebo (control group) in a randomized, double-blind trial. Fifty-five patients were enrolled in each group. There were significant differences between the treatment and control groups, with regard to the number of patients who still had headache after 14 days (5 vs. 25, respectively; P=.00004), the median length of time until complete disappearance of headache (5 vs. 13 days, respectively; P=.00000), and the number of patients who had repeat lumbar puncture (7 vs. 22, respectively; P=.002). Serious side effects were not detected. These results indicate that a 2-week course of prednisolone was beneficial in relieving headache in patients with eosinophilic meningitis.	V. Chotmongkol, K. Sawanyawisuth and Y. Thavornpitak	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
354	Comparison of amphotericin B, flucytosine and itraconazole with amphotericin B and flucytosine in the treatment of cryptococcal meningitis in AIDS	We compared amphotericin B (0.3 mg/kg/d) plus flucytosine (150 mg/kg/d) plus itraconazole (400 mg/d) (study group) with amphotericin B plus flucytosine (control group) by an open-randomized trial. In the study group, after CSF mycological cultures disclosed nothing, itraconazole was administrated alone through six weeks of treatment. Treatment was considered successful if the patient had two consecutive negative CSF cultures by the end of the 6-week treatment period. Fifty patients were enrolled in each group. There were significant differences between the study group and the control group in the successful treatment (100% vs 90%; P = 0.03), the mean length of time until normal body temperature after treatment (5.9 +/- 3.7 days vs 8.8 +/- 5.1 days; P = 0.02) and the adverse effects. The mean length of time to the first negative CSF culture was 13.9 +/- 6.1 days in the study group and 13.3 +/- 6.5 days in the control group (P = 0.66). Relapse rate with itraconazole 200 mg/day was higher in the study group.	V. Chotmongkol, W. Sukeepaisarncharoen and Y. Thavornpitak	Journal of the Medical Association of Thailand = Chotmaihet thangphaet
671	Randomized controlled trial of 7-Day vs. 14-Day antibiotics for neonatal sepsis	There are no evidence-based guidelines available regarding the duration of antibiotics in neonatal septicemia. We compared the effectiveness of a 7-day intravenous antibiotic regimen with the standard 14-day regime in blood-culture-proven sepsis in neonates. This was a controlled, blinded, randomized trial with stratification (for birth weight). Blood-culture-positive septic babies > or =32 weeks and/or > or =1500 g were enrolled if meningitis and other deep-seated focal infections were ruled out. Parental consent was obtained. Randomization to either 7-day or 14-day therapy was done on day 7 of antibiotics if the baby had clinically remitted by day 5. Blood culture was repeated 24 h after antibiotic completion. Subjects were observed in the hospital for at least 72 h, and followed-up for 28 days by weekly visits and telephonic contacts. The primary outcome was treatment failure within 28 days defined as a positive blood culture, or clinical signs accompanied by either positive CRP or adjudicated to be a relapse by an expert committee. A total of 120 babies were eligible, 51 were excluded (no consent: 12; non-remission: 39), and 69 were randomized to receive either a 7-day course (n = 34) or a 14-day course (n = 35) of antibiotics. Baselines variables were comparable in the two groups. Primary outcome assessment could be done in 33 cases in either group. There was a trend to greater treatment failures in the 7-day group compared with 14-day group (5 vs. 1, respectively; P = 0.19). On subgroup analysis of subjects with Staphylococcus aureus infection, those who received 7-day therapy (n = 7) had significantly more treatment failure than 14-day therapy (n = 7) (four and zero, respectively; P = 0.022), whereas on sub-group analysis of babies with non-S. aureus infections, treatment failure rates were identical (3.8% in both groups). On comparing the organisms isolated in the group of subjects which was not randomized by virtue of being symptomatic (n = 39) vs. the group which was randomized (n = 69), it was found that S. aureus infections were significantly commoner in the former group (61.5 vs. 21.3%, respectively; P < 0.001). Neonates > or =32 weeks and/or > or =1500 g with S. aureus sepsis require 14 days of antibiotics. S. aureus infection is also associated with failure to achieve clinical remission by the 5th day of antibiotic therapy. Larger trials are required to confirm whether neonates with non-S. aureus sepsis, whose symptoms remit by 5 days, can be treated with 7 days of antibiotics.	G. Chowdhary, S. Dutta and A. Narang	Journal of tropical pediatrics
212	Effect of vitamin A supplementation on childhood morbidity and mortality	In a double blind design, 1520 children aged < 10 years were individually randomised in vitamin A and placebo group in slums of Chandigarh. Children > 12, 6-12 and < 6 months of age received 200,000, 100,000, 500,000 I.U. of vitamin A respectively every 4 to 6 months during 15 months trial period. The prevalence of vitamin A deficiency was significantly reduced in vitamin A compared to placebo group during the follow-up period. In vitamin A group, incidence of diarrhoea and measles was significantly reduced but incidence of acute respiratory infections was not significantly different compared to control group. Risk of death was also significantly less in vitamin A group. Therefore, promotion of vitamin A rich diet or supplementation with synthetic vitamin A at 4-6 month interval should be a priority in populations where risk of vitamin A deficiency is high.	S. Chowdhury, R. Kumar, N. K. Ganguly, L. Kumar and B. N. Walia	Indian journal of medical sciences
566	A trial of acellular pertussis vaccine in hospital workers during the Cincinnati pertussis epidemic of 1993	The safety and immunogenicity of acellular pertussis (AP) vaccine in outbreak control was determined in a randomized, double-blind, controlled trial. Participants received AP vaccine (n=102), which contained 25 microg of pertussis toxoid (PT) and 3 microg of filamentous hemagglutinin (FHA), or licensed meningococcal vaccine (MN; n=97). Local reactions (pain or tenderness, redness, swelling, and induration) and systemic reactions (fever, sleepiness or lethargy, and irritability) were similar among AP and MN vaccinees. One month after AP vaccination, the geometric mean level of IgG anti-PT was 33.1 microg/mL, with 2-fold increases in 85% of patients and 4-fold increases in 73% of patients; for IgG anti-FHA, the respective values were 34.7 microg/mL, 92%, and 63%. After 6 months of follow-up, no serological evidence of pertussis was seen among symptomatic or asymptomatic subjects. However, recent evidence of Bordetella pertussis infection before immunization was shown. Thus, AP vaccine was safe and immunogenic in adults.	C. D. Christie, K. M. Garrison, L. Kiely, R. K. Gupta, J. Heubi and C. D. Marchant	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
469	Efficacy and safety of solifenacin succinate 10 mg once daily: a multicenter, phase III, randomized, double-blind, placebo-controlled, parallel-group trial in patients with overactive bladder	Background: Solifenacin succinate is an antimuscarinic drug with reported efficacy and tolerability at a recommended starting dose of 5 mg QD in patients with overactive bladder (OAB). Objective: The objective of this trial was to investigate the efficacy, safety, and tolerability of solifenacin 10 mg QD in patients with OAB. Methods: In this multicenter, Phase III, double-blind, placebo-controlled, parallel-group trial, patients aged >=18 years with OAB were randomized at a 1:1 ratio to receive solifenacin 10 mg or placebo QD for 12 weeks. The patients were instructed to complete a micturition diary for the 3 days preceding each scheduled visit (weeks 4, 8, and 12). The primary end point was the change from baseline in the mean number of micturitions per 24 hours; secondary end points included the mean change from baseline in the number of episodes per 24 hours of urgency, incontinence, nocturnal voiding, and nocturia and the mean volume voided per micturition. Tolerability was monitored through adverse events (AEs), vital sign measurements, ECGs, laboratory assessments, and physical examination. Results: A total of 672 patients were randomized and received >=1 dose of study drug (solifenacin, n = 340; placebo, n = 332). The mean (SE) decrease from baseline to study end in the number of micturitions per 24 hours was significantly greater in the solifenacin group compared with the placebo group (-3.0 [0.2] vs -1.5 [0.2], respectively; P < 0.001). The mean decrease in the number of episodes of incontinence was significantly greater in the solifenacin group compared with the placebo group (-2.0 [0.2] vs -1.1 [0.2]; P < 0.001), as was the mean decrease in the number of episodes of urgency (-4.1 [0.2] vs -2.1 [0.2]; P < 0.001). Of the patients with >=1 incontinence episode per 24 hours at baseline, significantly more patients in the solifenacin group achieved complete continence at study end than did patients in the placebo group (119/225 [52.9%] vs 80/237 [33.8%]; P < 0.001). The change from baseline to study end in the mean volume voided per micturition increased significantly in the solifenacin group compared with the placebo group (47.2 vs 2.7 mL; P < 0.001). Most AEs were mild or moderate in intensity. The AEs that were most commonly reported in the solifenacin-treated group were anticholinergic in nature: dry mouth (91 [26.8%] vs 13 patients [3.9%] in the placebo group; P < 0.001); constipation (58 [17.1%] vs 11 [3.3%]; P < 0.001); and blurred vision (12 [3.5%] vs 4 [1.2%]; P < 0.05). Serious AEs (SAEs) were reported for 5 patients in the solifenacin group and 3 patients in the placebo group. In the solifenacin group, 2 patients experienced chest pain, 1 had cellulitis, 1 had dehydration, and 1 had colonic obstruction; only 1 SAE (colonic obstruction) was judged to be possibly related to the study drug. In the placebo group, 1 patient had chest pain, 1 had bacterial meningitis, and 1 had hemopericardium. Conclusions: This study found that solifenacin 10 mg QD for 12 weeks was associated with significantly reduced symptoms of OAB, including the frequency of micturition, and episodes of urgency and of incontinence. With solifenacin, the volume voided per micturition increased by 47.2 mL, and 53% of patients with >=1 incontinence episode per 24 hours at baseline achieved complete continence. This efficacy was accompanied by a favorable safety and tolerability profile. 2009 Excerpta Medica Inc. All rights reserved.	F. Chu, N. Smith and T. Uchida	Current Therapeutic Research - Clinical and Experimental
213	Intensive blood and plasma exchange for treatment of coagulopathy in meningococcemia	Eight pediatric patients with fulminant meningococcemia, purpura, and disseminated intravascular cogulation who by multiple prognostic scoring systems were anticipated to have a poor outcome underwent intensive plasma exchange (IPE) or whole blood exchange (WBE) in addition to standard medical therapy. IPE/WBE was initiated shortly after admission with a mixture of both fresh frozen plasma and cryoprecipitate as the replacement solution. All IPE procedures were performed using a continuous flow system and a red cell prime. The mean fibrinogen level increased from 62 to 192 mg/dl, the prothrombin time (PT) decreased from a mean of 32.4 seconds to 15.1 seconds, and the mean activated partial thromboplastin time (APTT) decreased from 89.5 seconds to 40.1 seconds following completion of the initial IPE/WBE. There was a corresponding improvement in all coagulation factor levels but only slight improvement in antithrombin III (ATIII) and protein C levels. Seven of eight patients survived (87.5%) their initial presentation with the sole early death attributed to meningitis with cerebral edema. Mean fluid balance after the procedure was +10.8 +/- 5.87 cc/kg. There were no significant bleeding or cardiovascular complications during the procedure. There was no clinical or radiographic evidence of fluid overload after the procedure. This experience demonstrates that IPE/WBE may be conducted safely in critically ill, unstable pediatric patients and is effective in rapidly improving coagulopathy without fluid overload.	K. B. Churchwell, M. L. McManus, P. Kent, J. Gorlin, D. Galacki, D. Humphreys and S. V. Kevy	Journal of clinical apheresis
230	Removing irrelevant features in neural network classification using evolutionary computations	Evolutionary artificial neural networks (EANN) are a new paradigm that refers to a special class of artificial neural networks (ANN) in which evolution is another fundamental form of adaptation in addition to learning. Evolution can be introduced at various levels of ANN. It can be used to evolve weights, architectures and learning parameters. Evolutionary computations are population-based search methods that have shown promise in many similarly complex tasks. This paper presents an application of evolutionary programming for simultaneously inducing the input structure and weights evolving for multilayer feed-forward perceptrons (MLP) with standard sigmoidal activation function.	I. Ciuca, J. A. Ware and A. Cristea	Studies in health technology and informatics
639	Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age	Vaccination of infants with conjugated Haemophilus influenzae type b (Hib) vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization). The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis) combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3). Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.	S. C. Clemens, T. Azevedo and A. Homma	Revista da Sociedade Brasileira de Medicina Tropical
533	Design of a phase III trial of cryptococcal meningitis in AIDS patients. The NIAID Mycoses Study Group (MSG) and AIDS Clinical Trials Group (ACTG) [abstract]	Sixteenth Annual Meeting of the Society for Clinical Trials. April 30 - May 3, 1995. Westin Hotel, Seattle, Washington.	G. Cloud, M. Saag, C. Horst, R. Hafner, L. Riser, S. MaWhinney and C. Thomas	Control-Clin-Trials
537	Quality-adjusted time without symptoms and toxicity (q-twist) comparison of sustained release cytarabine (depocyt) vs. methotrexate (mtx) treatment for patients (pts) with carcinomatous meningitis		B. F. Cole, M. J. Glantz, K. Jaeckle and M. Chamberlain	Proc-Annu-Meet-Am-Soc-Clin-Oncol
134	Quality-of-life-adjusted survival comparison of sustained-release cytosine arabinoside versus intrathecal methotrexate for treatment of solid tumor neoplastic meningitis	BACKGROUND: The authors compared the quality of life of patients with solid tumor neoplastic meningitis treated in a controlled trial that compared conventional intrathecal methotrexate with a depot cytosine arabinoside liposomal injection (DepoCyt). The authors evaluated the trade-off between toxicity and improved clinical outcome. METHODS: Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis was used to evaluate data collected prospectively from a randomized clinical trial that compared DepoCyt with methotrexate. Sixty-one patients with confirmed solid tumor neoplastic meningitis were randomized to receive either methotrexate or DepoCyt. RESULTS: Within the 12-month follow-up, the average patient in the DepoCyt arm (compared with the methotrexate arm) achieved 71 more days of neurologic progression-free survival and 52 more days of overall survival, but experienced slightly more days with toxicity. The DepoCyt regimen provided greater quality-adjusted survival regardless of the quality-of-life valuations placed on time with toxicity and time following disease progression (range, 44-79 days). This gain was significant (P < 0.05) for all patients except for those who placed a high relative value on time following disease progression. CONCLUSIONS: The clinical benefits of DepoCyt offset a trend toward additional toxicity among patients with sold tumor neoplastic meningitis. The magnitude of the benefit depends on how the patient values time spent in toxicity and disease progression. The results of this analysis can be used at the bedside to make evidence-based individual treatment decisions.	B. F. Cole, M. J. Glantz, K. A. Jaeckle, M. C. Chamberlain and J. I. Mackowiak	Cancer
152	Immunogenicity and immunologic memory of meningococcal C conjugate vaccine in premature infants	BACKGROUND: Protein-polysaccharide conjugate vaccines against Neisseria meningitidis serogroup C were introduced into the U.K. routine immunization schedule in 1999. This study is the first to describe both persistence of antibody and evidence for induction of immune memory using meningococcal C conjugate (MCC) vaccine in preterm infants. METHODS: Immunogenicity and induction of immunologic memory by as MCC vaccine was assessed in premature infants; 62 preterm and 60 term controls received MCC at the accelerated schedule (2, 3 and 4 months of age). A meningococcal C polysaccharide challenge was administered at 12 months of age. RESULTS: Both groups achieved similar protective titers after primary immunization that then waned significantly by 1 year of age. Postchallenge serum bactericidal activity was significantly lower in preterm infants (P = 0.03); 73% of preterm versus 88% of term controls achieved a 4-fold rise in serum bactericidal activity (P = 0.07). CONCLUSIONS: MCC vaccine is immunogenic and primes for immunologic memory in preterm infants. The decreased memory responses in these preterm infants in conjunction with waning clinical efficacy data for all U.K. infants suggest a role for a routine booster dose of vaccine in all infants receiving MCC, especially those born preterm.	C. L. Collins, J. U. Ruggeberg, G. Balfour, H. Tighe, M. Archer, J. Bowen-Morris, L. Diggle, R. Borrow, P. Balmer, J. P. Buttery, E. R. Moxon, A. J. Pollard and P. T. Heath	The Pediatric infectious disease journal
407	Development and phase 1 clinical testing of a conjugate vaccine against meningococcus A and C	A conjugate vaccine against meningococcus A and C was prepared using the non-toxic mutant of diphtheria toxin CRM 197 as a carrier protein. Capsular polysaccharides of Neisseria meningitidis group A and C were hydrolysed and the resulting oligosaccharides were then coupled to CRM 197 in order to obtain conjugates with a carbohydrate content of 25-30%. The final vaccine that contained 11 micrograms of each oligosaccharide and 88 micrograms of CRM 197 was used to immunize mice and rabbits. After the preclinical studies which showed that the vaccine was safe and immunogenic in animal models, a pilot phase 1 clinical trial, blind versus placebo, was performed on adult volunteers. The difference between the incidence of adverse reactions associated with vaccine and placebo administration was not statistically significant. All the volunteers who received the vaccine had a significant increase in antibodies to group A and C meningococcal capsular polysaccharides after the first dose.	P. Costantino, S. Viti, A. Podda, M. A. Velmonte, L. Nencioni and R. Rappuoli	Vaccine
325	Raised intracranial pressure, the syndrome of inappropriate antidiuretic hormone secretion, and arginine vasopressin in tuberculous meningitis	Intracranial pressure (ICP) monitored shortly after admission over a period of 1 h in 31 children with tuberculous meningitis (TBM) was significantly higher (median 22.5 mmHg, range 8.4-50.9 mmHg) in 19 children with laboratory evidence of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) than in 12 children without such evidence (median 16.2 mmHg, range 5.8-42.5 mmHg; P = 0.027). Neither plasma nor cerebrospinal fluid arginine vasopressin (AVP) was related to ICP (r = 0.33 and 0.13 respectively). Mean arterial pressure (MAP) was measured in 23 children and a moderate correlation was found with plasma AVP (r = 0.62; P = 0.0019). In TBM, plasma AVP may be secreted as a response to raised ICP in an effort to raise MAP and maintain cerebral perfusion pressure. In this setting excess fluid may be inappropriately retained, leading to hyponatremia and hypo-osmolemia.	M. F. Cotton, P. R. Donald, J. F. Schoeman, L. E. Zyl, C. Aalbers and C. J. Lombard	Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
661	Single dose oral dexamethasone versus multi-dose prednisolone in the treatment of acute exacerbations of asthma in children who attend the emergency department: study protocol for a randomized controlled trial	BACKGROUND: Asthma is a major cause of pediatric morbidity and mortality. In acute exacerbations of asthma, corticosteroids reduce relapses, subsequent hospital admission and the need for ß?-agonist therapy. Prednisolone is relatively short-acting with a half-life of 12 to 36 hours, thereby requiring daily dosing. Prolonged treatment course, vomiting and a bitter taste may reduce patient compliance with prednisolone. Dexamethasone is a long-acting corticosteroid with a half-life of 36 to 72 hours. It is used frequently in children with croup and bacterial meningitis, and is well absorbed orally. The purpose of this trial is to examine whether a single dose of oral dexamethasone (0.3 mg/kg) is clinically non-inferior to prednisolone (1 mg/kg/day for three days) in the treatment of exacerbations of asthma in children who attend the Emergency Department. METHODS/DESIGN: This is a randomized, non-inferiority, open-label clinical trial. After informed consent with or without assent, patients will be randomized to either oral dexamethasone 0.3 mg/kg stat or prednisolone 1 mg/kg/day for three days. The primary outcome measure is the comparison between the Pediatric Respiratory Assessment Measure (PRAM) across both groups on Day 4. The PRAM score, a validated, responsive and reliable tool to determine asthma severity in children aged 2 to 16?years, will be performed by a clinician blinded to treatment allocation. Secondary outcomes include relapse, hospital admission and requirement for further steroid therapy. Data will be analyzed on an intention-to-treat and a per protocol basis. With a sample size of 232 subjects (105 in each group with an estimated 10% loss to follow-up), we will be able to reject the null hypothesis - that the population means of the experimental and control groups are equal with a probability (power) of 0.9. The Type I error probability associated with this test (of the null hypothesis) is 0.05. DISCUSSION: This clinical trial may provide evidence that a shorter steroid course using dexamethasone can be used in the treatment of acute pediatric asthma, thus eliminating the issue of compliance to treatment. REGISTRATION: ISRCTN26944158 and EudraCT Number 2010-022001-18.	J. Cronin, U. Kennedy, S. McCoy, S. N. An Fhailí, G. Crispino-O'Connell, J. Hayden, A. Wakai, S. Walsh and R. O'Sullivan	Trials
217	Incidence and characteristics of facial nerve stimulation in children with cochlear implants	OBJECTIVES: Electrical stimulation from a cochlear implant can spread beyond the auditory nerve. The aims of this study were to accurately measure facial nerve stimulation in pediatric implant users and to determine the characteristics and incidence of this unwanted activity. Part A consisted of a prospective study of a randomized sample of 44 pediatric implant users. Part B consisted of a retrospective analysis of 121 children with previously recorded electrically evoked auditory brainstem responses (EABR). STUDY DESIGN AND METHODS: Responses were evoked by 3 electrodes along the implant array in three groups of children: 1) postmeningitic, 2) abnormal cochlea, and 3) neither. Intraoperative measures were obtained under anesthesia; all other recordings were completed in awake children. RESULTS: Intraoperative recordings revealed large nonauditory responses in a number of channels, including the midline EABR. Under paralysis, these responses disappeared, and clear EABRs were recorded. Similarly, prospective postoperative electromyographic (EMG) responses from the facial nerve were found in more than 59% (26 of 44) of experienced implant users (Nucleus 24): 31% of postmeningitic children (4 of 13), 80% of those with abnormal cochlea (8 of 10), and 66% of those with neither (14 of 21). Retrospective analysis of previously recorded postoperative EABRs demonstrated facial nerve stimulation in 35% (42 of 121). In most cases, facial nerve stimulation occurred when levels were perceptually loud but comfortable. CONCLUSIONS: 1) Facial nerve potentials can be recorded using EMG in a large proportion of cochlear implant users at high levels of stimulation. 2) The EABR can be obscured in the presence of facial nerve stimulation and care should be taken to distinguish it from the EMG response, particularly when auditory brainstem activity is in question. 3) Use of surface EMG provides an additional objective measure to ensure the safe and comfortable use of cochlear implants.	S. L. Cushing, B. C. Papsin and K. A. Gordon	The Laryngoscope
572	Effect of a conjugate pneumococcal vaccine on the occurrence of respiratory infections and antibiotic use in day-care center attendees	BACKGROUND: Incidence and severity of respiratory infections are increased in day-care center attendees. Streptococcus pneumoniae is an important contributor to these infections. OBJECTIVE: To examine whether the use of a pneumococcal conjugate vaccine could reduce the occurrence of respiratory infections and the ensuing antibiotic drug use in the day care. METHOD: In this double blind, randomized, controlled study performed in 8 day-care centers located in Beer-Sheva, Israel, 264 toddlers ages 12 to 35 months at enrollment were randomized to receive either a 9-valent conjugate pneumococcal vaccine (conjugated to CRM197) or a control vaccine [conjugate meningococcus C vaccine (conjugated to CRM197)] and were followed for an average of 22 months. The main outcome measures were respiratory morbidity and antibiotic use. RESULTS: An overall reduction of 7% in child months with > or = 1 reported illness episodes was observed among vaccinees (P = 0.008), and 85% of all episodes were related to the respiratory tract. Reductions of 15, 16 and 17% were observed in upper respiratory infections, lower respiratory problems and otitis media, respectively. An overall reduction of 17% in antibiotic days was observed [10% for upper respiratory infections, 20% for otitis and 47% for lower respiratory problems (P < or = 0.005 for each entity)]. The reduction in episodes and antibiotic use was greater for those <36 months of age than for the older children. CONCLUSION: The reduction of respiratory problems, including those not traditionally considered of pneumococcal origin and the ensuing lowered antibiotic use in day-care center attendees by pneumococcal conjugate vaccination suggest a broader benefit from the vaccine than preventing invasive disease only.	R. Dagan, M. Sikuler-Cohen, O. Zamir, J. Janco, N. Givon-Lavi and D. Fraser	The Pediatric infectious disease journal
461	Cefotaxime use in pediatric infections. [Review] [19 refs]	Cefotaxime has been used extensively in many pediatric centers in the United States for the past 10 or more years. Its main usage has been for the treatment of various serious bacterial infections in pediatric patients, primarily meningitis and sepsis. It has also been used to treat intraabdominal, urinary tract, soft tissue, bone, and joint infections. Although there has been a marked reduction in the incidence of invasive Haemophilus influenzae type b infections following the introduction of effective vaccines, cefotaxime remains very useful against the other common pathogens causing serious infections in pediatric patients. The increasing number of pneumococci resistant to penicillin and third-generation cephalosporins has created a new challenge for the management of serious pneumococcal infections. In many institutions, cephalosporins in general have been overused and abused, resulting in the emergence of resistant organisms and an increasing burden on resources. The judicious use of cefotaxime and other cephalosporins should be emphasized. [References: 19]	A. S. Dajani	Diagnostic Microbiology & Infectious Disease
528	Ceftriaxone compared with doxycycline for the treatment of acute disseminated Lyme disease	BACKGROUND: Localized Lyme disease, manifested by erythema migrans, is usually treated with oral doxycycline or amoxicillin. Whether acute disseminated Borrelia burgdorferi infection should be treated differently from localized infection is unknown. METHODS: We conducted a prospective, open-label, randomized, multicenter study comparing parenteral ceftriaxone (2 g once daily for 14 days) with oral doxycycline (100 mg twice daily for 21 days) in patients with acute disseminated B. burgdorferi infection but without meningitis. The erythema migrans skin lesion was required for study entry, and disseminated disease had to be indicated by either multiple erythema migrans lesions or objective evidence of organ involvement. RESULTS: Of 140 patients enrolled, 133 had multiple erythema migrans lesions. Both treatments were highly effective. Rates of clinical cure at the last evaluation were similar among the patients treated with ceftriaxone (85 percent) and those treated with doxycycline (88 percent); treatment was considered to have failed in only one patient in each group. Among patients whose infections were cured, 18 of 67 patients in the ceftriaxone group (27 percent) reported one or more residual symptoms at the last follow-up visit, as did 10 of 71 patients in the doxycycline group (14 percent, P > or = 0.05). Mild arthralgia was the most common persistent symptom. Both regimens were well tolerated; only four patients (6 percent) in each group withdrew because of adverse events. CONCLUSIONS: In patients with acute disseminated Lyme disease but without meningitis, oral doxycycline and parenterally administered ceftriaxone were equally effective in preventing the late manifestations of disease.	R. J. Dattwyler, B. J. Luft, M. J. Kunkel, M. F. Finkel, G. P. Wormser, T. J. Rush, E. Grunwaldt, W. A. Agger, M. Franklin, D. Oswald, L. Cockey and D. Maladorno	The New England journal of medicine
51	Mucosal immunity in healthy adults after parenteral vaccination with outer-membrane vesicles from Neisseria meningitidis serogroup B	BACKGROUND: Nasopharyngeal carriage of meningococcus or related species leads to protective immunity in adolescence or early adulthood. This natural immunity is associated with mucosal and systemic T cell memory. Whether parenteral Neisseria meningitidis serogroup B (MenB) vaccination influences natural mucosal immunity is unknown. OBJECTIVES: To determine whether parenteral MenB vaccination affects mucosal immunity in young adults and whether this immunity differs from that induced in the blood. METHODS: Otherwise healthy volunteers were immunized with MenB outer membrane vesicle vaccine before and after routine tonsillectomy. Mucosal and systemic immunity were assessed in 9 vaccinees and 12 unvaccinated control subjects by measuring mononuclear cell proliferation, cytokine production, Th1/Th2 surface marker expression, and antibody to MenB antigens. RESULTS: Parenteral vaccination induced a marked increase in systemic T cell immunity against MenB and a Th1 bias. In contrast, although mucosal T cell proliferation in response to MenB neither increased nor decreased following vaccination, mononuclear cell interferon gamma, interleukin (IL)-5, and IL-10 production increased, and the Th1/Th2 profile lost its Th1 bias. CONCLUSIONS: Parenteral MenB vaccination selectively reprograms preexisting naturally acquired mucosal immunity. As new-generation protein-based MenB vaccine candidates undergo evaluation, the impact of these vaccines on mucosal immunity in both adults and children will need to be addressed.	V. Davenport, E. Groves, R. E. Horton, C. G. Hobbs, T. Guthrie, J. Findlow, R. Borrow, L. M. Naess, P. Oster, R. S. Heyderman and N. A. Williams	The Journal of infectious diseases
308	Combination antifungal therapy for cryptococcal meningitis	BACKGROUND: Combination antifungal therapy (amphotericin B deoxycholate and flucytosine) is the recommended treatment for cryptococcal meningitis but has not been shown to reduce mortality, as compared with amphotericin B alone. We performed a randomized, controlled trial to determine whether combining flucytosine or high-dose fluconazole with high-dose amphotericin B improved survival at 14 and 70 days. METHODS: We conducted a randomized, three-group, open-label trial of induction therapy for cryptococcal meningitis in patients with human immunodeficiency virus infection. All patients received amphotericin B at a dose of 1 mg per kilogram of body weight per day; patients in group 1 were treated for 4 weeks, and those in groups 2 and 3 for 2 weeks. Patients in group 2 concurrently received flucytosine at a dose of 100 mg per kilogram per day for 2 weeks, and those in group 3 concurrently received fluconazole at a dose of 400 mg twice daily for 2 weeks. RESULTS: A total of 299 patients were enrolled. Fewer deaths occurred by days 14 and 70 among patients receiving amphotericin B and flucytosine than among those receiving amphotericin B alone (15 vs. 25 deaths by day 14; hazard ratio, 0.57; 95% confidence interval [CI], 0.30 to 1.08; unadjusted P=0.08; and 30 vs. 44 deaths by day 70; hazard ratio, 0.61; 95% CI, 0.39 to 0.97; unadjusted P=0.04). Combination therapy with fluconazole had no significant effect on survival, as compared with monotherapy (hazard ratio for death by 14 days, 0.78; 95% CI, 0.44 to 1.41; P=0.42; hazard ratio for death by 70 days, 0.71; 95% CI, 0.45 to 1.11; P=0.13). Amphotericin B plus flucytosine was associated with significantly increased rates of yeast clearance from cerebrospinal fluid (-0.42 log10 colony-forming units [CFU] per milliliter per day vs. -0.31 and -0.32 log10 CFU per milliliter per day in groups 1 and 3, respectively; P<0.001 for both comparisons). Rates of adverse events were similar in all groups, although neutropenia was more frequent in patients receiving a combination therapy. CONCLUSIONS: Amphotericin B plus flucytosine, as compared with amphotericin B alone, is associated with improved survival among patients with cryptococcal meningitis. A survival benefit of amphotericin B plus fluconazole was not found. (Funded by the Wellcome Trust and the British Infection Society; Controlled-Trials.com number, ISRCTN95123928.).	J. N. Day, T. T. Chau, M. Wolbers, P. P. Mai, N. T. Dung, N. H. Mai, N. H. Phu, H. D. Nghia, N. D. Phong, C. Q. Thai, H. Thai le, L. V. Chuong, D. X. Sinh, V. A. Duong, T. N. Hoang, P. T. Diep, J. I. Campbell, T. P. Sieu, S. G. Baker, N. V. Chau, T. T. Hien, D. G. Lalloo and J. J. Farrar	The New England journal of medicine
221	The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine: a randomized, controlled non-inferiority study	Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18-55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ? 1:32 in initially seronegative; ? 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ? 98.0% of subjects had rSBA titers ? 1:128. Grade 3 solicited AEs were reported in ? 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.   This study is registered at clinicaltrials.gov NCT00453986.	G. Dbaibo, N. Macalalad, M. R. Aplasca-De Los Reyes, E. Dimaano, V. Bianco, Y. Baine and J. Miller	Human vaccines & immunotherapeutics
270	Efficacy of rifampin in treatment of meningococcal carriers		W. B. Deal and E. Sanders	The New England journal of medicine
361	Therapeutic trial of cephalexin in meningococcal carriers		W. B. Deal and E. Sanders	Antimicrobial agents and chemotherapy
204	Role of prophylactic antibiotics in open and basilar fractures of the skull: a randomized study	The aim of this study was to investigate the controversial issue of the use of prophylactic antibiotics in open and basilar fractures of the skull. A series of 157 patients were randomized to receive no antibiotics (group A = 46 patients) or ceftriaxone for 3 days (group B = 50 patients), or the combination ampicillin/sulphadiazine for 3 days (group C = 61 patients). The incidence of meningitis was similar in both the antibiotic and non-antibiotic groups. However, the overall incidence of infectious complications in the non-antibiotic group was significantly higher than in the antibiotic group (8.7 per cent vs 0.9 per cent, P < 0.05). There was no significant difference between the ceftriaxone group and the ampicillin/sulphadiazine group. The results of the study suggest that antibiotic prophylaxis has a role in the management of open and basilar fractures.	D. Demetriades, D. Charalambides, M. Lakhoo and D. Pantanowitz	Injury
399	Randomized, placebo-controlled trial of HA-1A, a human monoclonal antibody to endotoxin, in children with meningococcal septic shock	Meningococcal septic shock has a rapid onset and characteristic skin hemorrhages that allow bedside diagnosis. Initial plasma endotoxin levels are high and correlate closely with clinical outcome. In a double-blind, randomized, placebo-controlled trial (planned, n = 270; actual, n = 269), we compared the effectiveness of HA-1A (6 mg/kg of body weight iv; maximum, 100 mg), a human monoclonal antibody to endotoxin, and placebo in reducing the 28-day all-cause mortality rate among children with a presumptive clinical diagnosis of meningococcal septic shock. Treatment groups were well balanced for baseline characteristics and prespecified prognostic variables. In this trial no significant benefit of HA-1A could be demonstrated. The 28-day mortality rates in the intention-to-treat analysis were as follows: placebo, 28%; HA-1A, 18%; reduction in mortality, 33% (P =.11, per Fisher's exact test, two-tailed; odds ratio = 0.59; 95% confidence interval for the difference, 0.31-1.05). All patients tolerated HA-1A well, and no antibodies to HA-1A were detected. Number of References 27. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	B. Derkx, J. Wittes, R. McCloskey, P. Brandtzaeg, H. H. F. Derkx, R. Groot, F. Leclerc, M. Levin, A. P. J. Thomson, R. Cunnion, K. K. G. Lan, C. M. Hamilton, L. Lewis, W. Rodriguez, J. Wittes, J. Palensky, M. Levin, S. Nadel, I. Maconchie, R. DeGroot, A. Hazelzet, E. Voort, B. Derkx, R. Bijlmer, J. Hoek, A. P. J. Thomson, E. A. Riordan, P. Baines, J. Sills, J. Ratcliff, C. A. Hart, F. Leclerc, V. Flurin, C. Fourier, W. Tarlow, D. Floret, P. Frappat, F. R. Tario, J. I. Berenque, G. Vos, C. Simeoni, J. M. Sanchez, G. Krim, A. Menger, P. Rudd, P. Brandtzaeg, J. C. Mercier, C. C. Macias, P. Lagier, J. C. Roze, J. Camboulives, G. Teyssier and G. Huault	Clinical Infectious Diseases
511	The European multicenter HA-1A (anti-endotoxin) trial in meningococcal septic shock [Abstract]		H. H. F. Derkx, J. Wittes and R. V. McCloskey	Tijdschrift voor Kindergeneeskunde
658	Sumatriptan-naproxen and butalbital: a double-blind, placebo-controlled crossover study	OBJECTIVES: The primary objective was to compare the efficacy of a sumatriptan and naproxen combination medication (SumaRT/Nap-85mg sumatriptan and 500mg naproxen sodium), a butalbital-containing combination medication (BCM-50mg butalbital, 325mg acetaminophen, 40mg caffeine), and placebo when used to treat moderate to severe migraine headache pain in subjects who used BCMs in the past. BACKGROUND: Despite the lack of Food and Drug Administration approval and the absence of placebo-controlled trials to demonstrate efficacy, butalbital-containing medications are among the most commonly prescribed acute migraine treatments in the United States. Butalbital-containing medications are associated with serious and undesirable side effects, and have been linked to the chronification of migraine and development of medication-overuse headaches. This study compares the relative efficacy, safety, and tolerability of a fixed dose SumaRT/Nap versus a BCM and placebo. METHODS: Enrolled subjects were required to have treated at least 1 migraine with a butalbital medication in the past. Enrolled subjects treated 3 moderate to severe migraines using each of the 3 study treatments once in a randomized sequence. The primary endpoint compared SumaRT/Nap versus BCM for sustained pain freedom at 2-24 hours without the use of any rescue medication. This study combines data from 2 identical outpatient, randomized, multicenter, double-blind, double-dummy, 3 attack crossover studies in adult migraineurs (International Classification of Headache Disorders, 2nd edition). RESULTS: A total of 442 subjects treated at least 1 attack with study medication. The majority of the treated subjects were female (88%) with a mean age 43 years, who reported that their migraines had a severe impact on their lives (78% with Headache Impact Test-6 of >59). At screening, 88% of subjects reported current butalbital use; 68% had used butalbital for more than 6 weeks; and 82% reported satisfaction with butalbital. Across treatment groups, 28-29% of subjects took study medication within 15 minutes of migraine onset, 34-37% of subjects took study medication >15 minutes to 2 hours after onset, and 32-36% of subjects took study medication more than 2 hours after onset. This study did not detect a difference at the nominal 0.05 level in percent sustained pain-free between SumaRT/Nap (8%), BCM (6%), and placebo (3%). SumaRT/Nap was superior to BCM for pain free at 2, 4, 6, 8, 24, 48 hours (P?.044); pain relief (mild or no pain) at 2, 4, 6, 8, 24, 48 hours (P?.01); sustained pain relief 2-24 hours (P<.001); migraine free (pain free with no nausea, photophobia, or phonophobia) at 4, 6, 8, 24, 48 hours (P?.046); and complete symptom free (migraine free with no neck/sinus pain) at 4, 6, 8, 48 hours (P?.031). Adverse event incidence was similar for all treatments (10%, 12%, and 9% for placebo, SumaRT/Nap, and BCM, respectively). Nausea was the most frequent adverse event (2%, 2%, and <1% for placebo, SumaRT/Nap, and BCM, respectively). Five serious adverse events were reported by 3 subjects: viral meningitis and colon neoplasm (placebo); chest pain and hypertension 17 days postdose (SumaRT/Nap); and breast cancer (BCM). Investigators judged no serious adverse events related to study medication. CONCLUSIONS: This study primarily included subjects whose migraines significantly impacted their lives. Before the study, these subjects used butalbital-containing medications as part of their current migraine treatment regimen and were satisfied with it, suggesting they were butalbital responders who had found a workable treatment strategy for themselves. When treated with SumaRT/Nap versus BCM in this study, however, a significant proportion of subjects reported better treatment outcomes for themselves for both migraine pain and associated symptoms. Use of SumaRT/Nap was also associated with less rescue medication use and a longer time before use of rescue medication compared with both BCM and placebo.	F. Derosier, F. Sheftell, S. Silberstein, R. Cady, G. Ruoff, A. Krishen and M. Peykamian	Headache
296	Enteroviral meningitis: natural history and outcome of pleconaril therapy	Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (P = 0.009). For a headache score of > 5 alone, treated patients resolved headache significantly more rapidly (P = 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.	R. A. Desmond, N. A. Accortt, L. Talley, S. A. Villano, S. J. Soong and R. J. Whitley	Antimicrobial agents and chemotherapy
614	The effects of oral pentoxifylline on the cytokine release syndrome during inductive OKT3	The cytokine release syndrome (CRS) accompanying OKT3 therapy is a major cause of posttransplant morbidity. The pathogenesis of this syndrome has been attributed to the synthesis of tumor necrosis factor, interleukin 2 (IL-2), interleukin 6 (IL-6), and gamma-interferon in response on T lymphocyte stimulation by OKT3. The hemorrheologic agent pentoxifylline (PTX) inhibits the synthesis of TNF alpha in vitro in response to a variety of stimuli, including OKT3. We performed a randomized, double-blinded trial of PTX during OKT3 induction in recipients of cadaveric renal allografts. Patients received either PTX 800 mg or placebo 2 hr before the initial dose of OKT3 and every 8 hr thereafter during the first 3 posttransplant days. Serum TNF alpha and IL-6 concentrations were measured pre-OKT3 and at 2 and 6 hr post-OKT3 on the first 3 posttransplant days. Despite the achievement of apparently adequate plasma levels of PTX and its active metabolites, no difference was observed in the incidence or severity of clinical manifestations of CRS. Serious manifestations of CRS--including acute pulmonary edema, encephalopathy, and aseptic meningitis--were not seen in either group. Serum TNF alpha and IL-6 concentrations were similar in PTX and control patients throughout the course of the study. Plasma levels of PTX and its active metabolites did not correlate with serum TNF alpha levels, serum IL-6 levels, or the incidence and severity of clinical manifestations of CRS.	G. A. DeVault, D. E. Kohan, E. W. Nelson and J. M. Holman	Transplantation
264	Rifampin. Levels in serum and saliva and effect on the meningococcal carrier state		L. F. Devine, D. P. Johnson, C. R. Hagerman, W. E. Pierce, S. L. Rhode and R. O. Peckinpaugh	JAMA : the journal of the American Medical Association
278	The effect of coumermycin A on the meningococcal carrier state		L. F. Devine, D. P. Johnson, C. R. Hagerman, W. E. Pierce, S. L. Rhode and R. O. Peckinpaugh	The American journal of the medical sciences
530	Esophageal sphinctepic functions in patients of tuberculous meningitis (tbm) [abstract no:159]		R. Dewan, R. Nehru, P. Mehta, S. Kumar, S. Zachariah, S. Gulati, R. Anand and K. Kumar	Journal of the Association of Physicians of India
324	Predominance of Vgamma9/Vdelta2 T lymphocytes in the cerebrospinal fluid of children with tuberculous meningitis: reversal after chemotherapy	BACKGROUND: We analyzed the gammadelta T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children. MATERIALS AND METHODS: Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vgamma9/Vdelta2 T cells assessed by FACS analysis. Vgamma9/Vdelta2 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and IL-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. Vdelta2(D)Jdelta junctional sequence length was assessed by PCR. RESULTS: The repertoire of gammadelta T cells from the CSF of TBM patients was characterized by the predominance of Vgamma9/Vdelta2 T lymphocytes, which accounted for >80% of gammadelta T cells. Vgamma9/Vdelta2 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-gamma and TNF-alpha. The in vitro expansion of Vgamma9/Vdelta2 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and similarly, the proportion of ex vivo unstimulated Vgamma9/Vdelta2 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. Vdelta2 CDR3 TCR analysis showed that the remaining Vdelta2 cells in the CSF of TBM patients were still polyclonal. CONCLUSIONS: These findings are consistent with an involvement of Vgamma9/Vdelta2 T cells in TBM. http://link. springer-ny.com/link/service/journals/00020/bibs/5n5p301. html	F. Dieli, G. Sireci, C. Sano, E. Champagne, J. J. Fourniè and J. I. Salerno	Molecular medicine (Cambridge, Mass.)
15	A randomized, multicenter, open-label clinical trial to assess the immunogenicity of a meningococcal C vaccine booster dose administered to children aged 14 to 18 months	BACKGROUND: A booster meningococcal C (MenC) vaccine dose is recommended after the first year of life. The objective of this study was to assess its immunogenicity and factors that modify the immunoresponse. METHODS: An open label study in which 389 children 14 to 18 months of age, previously primed with 3 doses of a MenC vaccine conjugated with CRM197 (MenC-CRM) or with 2 doses of a MenC vaccine conjugated with tetanus toxoid (MenC-TT), were randomized to be boosted with either of these vaccines and a DTaP-IPV-Hib vaccine at the same time. Immunogenicity against MenC and Haemophilus influenzae type b was assessed before and 1 month after the booster dose. RESULTS: Before the second year booster, 44.9% of the studied children had MenC bactericidal (SBA) seroprotection rate of > or =1:8, with no differences related to the vaccine used for priming, whereas the anti Hib antibody concentration was higher in children primed with the MenC-TT (0.59; 95% CI: 0.49-0.71 vs. 0.39; 95% CI: 0.32-0.48).One month after the MenC vaccine booster 99.5% of the children had SBA > or =1:128. Children primed with MenC-TT reached higher SBA titers: 6520 (95% CI: 5359-7932) than those primed with MenC-CRM: 1903 (95% CI: 1600-2262). Children primed with MenC-CRM had SBA titers of 2061 (95% CI: 1599-2627) when boosted with MenC-TT and 1746 (95% CI: 1378-2213) when boosted with MenC-CRM. Children primed with MenC-TT had SBA titers of 6786 (95% CI: 5023-9167) and 6278 (95% CI: 4841-8144) when boosted with MenC-TT or MenC-CRM. There was no difference in the PRP antibody concentration after boosting. CONCLUSIONS: A booster MenC dose induces high SBA and anti Hib response with over 99% of children seroprotected. Children primed with a MenC-TT vaccine reached SBA titers 3.5 times higher no matter which vaccine was used for boosting.	J. Díez-Domingo, M. V. Cantarino, J. M. Torrentí, M. I. Sansano, A. J. Rosich, A. H. Merino, A. G. Miguel, J. B. González and M. D. Marcos	The Pediatric infectious disease journal
455	Effect of needle size on immunogenicity and reactogenicity of vaccines in infants: randomised controlled trial	OBJECTIVES: To assess the immunogenicity of vaccines for infants and to investigate whether the incidence of reactogenicity is reduced after each immunisation dose using needles of varying lengths and gauges. DESIGN: Randomised controlled trial. SETTING: 18 general practices within two UK primary care trusts. PARTICIPANTS: 696 healthy infants vaccinated at 2, 3, and 4 months of age, with follow-up to 5 months of age. INTERVENTIONS: Combined diphtheria, tetanus, whole cell pertussis, and Haemophilus influenzae type b vaccine and a serogroup C meningococcal glycoconjugate vaccine administered using either a wide, long needle (23 gauge/0.6 mm diameter, 25 mm), a narrow, short needle (25 gauge/0.5 mm diameter, 16 mm), or a narrow, long needle (25 gauge, 25 mm). MAIN OUTCOME MEASURES: Local and general reactions recorded by parents for three days after each dose; and diphtheria, tetanus, and H influenzae type b antibody concentrations and functional antibody against serogroup C Neisseria meningitidis 28-42 days after the third dose. RESULTS: Local reactions to diphtheria, tetanus, whole cell pertussis, H influenzae type b vaccinations decreased significantly with wide, long needles compared with narrow, short needles. At all three doses one less infant experienced local reactions at days 1, 2, or 3 for every six to eight vaccinated. Significantly fewer infants vaccinated with the long needle experienced severe local reactions. Non-inferiority of the immune response was shown using a wide, long needle rather than a narrow, short needle for serogroup C meningococcal glycoconjugate vaccine and for diphtheria but not for H influenzae type b or tetanus, although no evidence was found of a decrease. Little difference was found between needles of the same length but different gauges in local reaction or immune response. CONCLUSIONS: Long (25 mm) needles for infant immunisations can significantly reduce vaccine reactogenicity at each dose while achieving comparable immunogenicity to that of short (16 mm) needles. Trial registration Current Controlled Trials ISRCTN62032215 [controlled-trials.com].	L. Diggle, J. J. Deeks and A. J. Pollard	BMJ (Clinical research ed.)
670	Oxacillin prophylaxis in cerebrospinal fluid shunt procedures: results of a randomized open study in 60 hydrocephalic patients	A 27-month open randomized trial (October 1981-January 1984) was carried out to study the prophylactic efficacy of antibiotics in 60 hydrocephalic patients being shunted for the first time. The treatment group received oxacillin at a dosage of 200 mg/kg/day by six bolus intravenous injections, beginning with anesthetic induction and continuing for 24 hours after the operations. The minimum postoperative observation was 6 months. Six patients in the control group developed cerebrospinal fluid infections (20%) as compared with only a single patient in the oxacillin group (3.3%); this difference was statistically significant (p less than 0.05). Time of development of cerebrospinal fluid infection was brief (86% at 6 weeks), and as usual staphylococci were the pathogens most frequently implicated. This study would appear to confirm the choice of oxacillin for prevention of meningitis. Nevertheless, the frequency of methicillin-resistant staphylococci, which account for 20% of nosocomial staphylococcal infections, constitutes a limiting factor for such prevention.	M. Djindjian, M. J. Fevrier, G. Otterbein and J. C. Soussy	Surgical neurology
464	FDA report: eculizumab (Soliris) for the treatment of patients with paroxysmal nocturnal hemoglobinuria	On March 16, 2007, eculizumab (Soliris; Alexion Pharmaceuticals, Inc. Cheshire, CT), a humanized monoclonal antibody that binds to the human C5 complement protein, received accelerated approval by the U.S. Food and Drug Administration for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Eculizumab was studied in a randomized, double-blind, placebo-controlled clinical trial in 87 RBC transfusion-dependent adult PNH patients and in a supportive single-arm study in 96 patients. The eculizumab dose was 600 mg as a 35-minute i.v. infusion administered weekly for the first 4 weeks followed by 900 mg (week 5) then 900 mg every 14 days thereafter. Hemoglobin stabilized in 21 of 43 (48.8%) eculizumab-treated patients, compared with none of 44 placebo-treated patients. Eculizumab-treated patients required significantly fewer RBC transfusions than placebo-treated patients (median, 0 versus 10 units). There was also a significant reduction in the serum lactate dehydrogenase area under the curve with eculizumab compared with placebo treatment. Results of the phase II supportive study were similar to those of the phase III study. The safety database included 196 adult patients with PNH. Significant findings included the development of human anti-human antibody responses in three patients and serious meningococcal infections in three patients. Patients should undergo meningococcal vaccination at least 2 weeks prior to receiving the first eculizumab treatment and have revaccination according to current medical guidelines. Patients must be monitored and evaluated immediately for early signs of meningococcal infections and treated with antibiotics as indicated.	A. Dmytrijuk, K. Robie-Suh, M. H. Cohen, D. Rieves, K. Weiss and R. Pazdur	The oncologist
580	[Application of cluster randomization method on typhoid Vi vaccine trails]	OBJECTIVE: To describe the design and application of cluster randomized controlled method on typhoid Vi vaccine trial, and to assess the effect of implementation.METHODS: Simple size calculation of cluster-randomized trial was used to determine the sample size of the two groups and a vaccination campaign was conducted. The study group was given typhoid Vi vaccine and the control group was given meningococcal A vaccine.RESULTS: According to sample size calculation, a total sample of 96,121 participants was required and the study areas were divided into 108 clusters. In practice, 53 study clusters with 44,054 participants and 54 control clusters with 48,422 participants were stratified and matched according to size, location (urban or rural), characteristics (school, department, factory, demography) were randomized respectively. Confounding factors of two groups including age, sex, resident area, income, level of education were compared. It was found that the ratio of all confounding factors between the two groups were comparable and balanced.CONCLUSION: Confounding factors can be better controlled between study group and the control group by applying cluster-randomized method on vaccine trail which enabled the intervention to be more scientifically evaluated; The implementation of cluster randomization trial was simple and easy to be accepted.	B. Q. Dong, J. Yang, Z. Z. Tang, H. H. Yang, J. Zeng, J. Zhang, M. L. Wang, G. C. Liang, G. A. Si, C. Y. Li, D. B. Liang, H. Z. Liao, R. L. Ochiai, A. Mohammad, C. J. Acosta and J. Clemens	Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
266	[Evaluation on the safety of a group A + C meningococcal polysaccharide vaccine]	OBJECTIVE: To evaluate the safety of a group A + C meningococcal polysaccharide vaccine as part of a phase IV clinical trial.METHODS: The study area was divided into 108 clusters according to the principle of cluster randomization, stratified and paired sampling methods. 54 out of 108 clusters served as observation groups were administered A + C vaccine, while the rest 54 groups were administered Vi polysaccharide vaccine. An adverse event surveillance system was established to monitor the adverse events following the vaccination campaign. Identical form and methods were used for data collection to investigate the adverse events following the vaccination of both A+ C vaccine and Vi vaccine.RESULTS: 34,543 people were vaccinated, including 18,167 of whom received A + C vaccine, while the other 16,376 received Vi vaccine. The rates of immediate injection reaction and unsolicited non-serious adverse events from A + C vaccine group were 0.44% and 0.38% while of Vi vaccine group were 0.79% and 0.73% respectively. At the solicited adverse event survey on 3-day-post-vaccination, 1239 vaccinees were followed-up including 771 received A + C vaccine and 468 received Vi vaccine. The local injection reaction rate of A + C vaccine group on the 1st day was significantly higher (X2 = 13.98, P = 0.0002) than that of Vi vaccine group. Neither the local injection reaction rate nor the system reaction rate between both groups was significantly different on 2nd and 3rd day, post vaccination. It was not statistically different when comparing fever onset rate between those who received vaccine and those who did not, in each vaccine group. There were no serious adverse events observed.CONCLUSION: Results showed that the side effects of A + C vaccine and the Vi vaccine were mild and safe for vaccination campaigns targeting on populations at different age.	B. Q. Dong, Q. Ye, X. L. Cui, J. Yang, J. Gong, M. Yang, H. Z. Liao, S. L. Wei, J. Zhang, X. H. Wu, G. A. Si, H. H. Yang, A. Tsuzuki, J. Park, M. Ali, L. R. Ochiai and J. D. Clemens	Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
636	IX 207-887 in rheumatoid arthritis. A double-blind placebo-controlled study	OBJECTIVE: To determine the efficacy and the safety of IX 207-887 treatment in rheumatoid arthritis. The IX compound [10-methoxy-4H-benzo(4,5)cyclohepta-(1,2-b)thiophene-4-yliden acetic acid] is effective in several animal models of rheumatoid arthritis and has a mechanism of action involving the inhibition of interleukin-1 release. METHODS: A double-blind, controlled trial of 16 weeks' duration comparing placebo with IX at a daily dosage of 800 mg or 1,200 mg (20 patients/group) was conducted. RESULTS: Thirteen patients withdrew from the study, 3 because of lack of efficacy (all in the placebo group) and 10 because of side effects (1 in the placebo group [skin rash] and 9 in the IX groups [skin rash in 5, intestinal disturbances in 2, hepatitis in 1, meningitis in 1]). Intent-to-treat analysis showed a statistically significant difference in the variations of clinical and laboratory parameters between the 3 groups. Between-group comparisons showed an improvement in all these variables in the IX groups versus the placebo group. According to Paulus' criteria, 2 of the 20 placebo-treated patients (10%), 9 of the 20 IX 800 mg-treated patients (45%), and 11 of the 20 IX 1,200 mg-treated patients (55%) were considered responders (P = 0.008). CONCLUSION: The findings of this study suggest that the tolerability of IX is acceptable in rheumatoid arthritis patients, and that IX is an effective slow-acting drug for use in rheumatoid arthritis.	M. Dougados, B. Combe, T. Beveridge, I. Bourdeix, A. Lallemand, B. Amor and J. Sany	Arthritis and rheumatism
432	Safety and immunogenicity testing of an intranasal group B meningococcal native outer membrane vesicle vaccine in healthy volunteers	An intranasal vaccine composed of native outer membrane vesicles (NOMV) not exposed to detergent or denaturing agents was prepared from the group B meningococcal strain 9162 SynX(-)(-:15:P1.3:P5.10,11:L3,7,9) and tested in 32 healthy adult volunteers. Four groups of 8 volunteers were vaccinated intranasally with three doses of vaccine. The vaccine was very well tolerated in all dosing groups, despite the presence of lipo-oligosaccharide in the vaccine at a level of 25% relative to protein. The antibody response as measured by ELISA in serum, saliva and nasal wash fluids was relatively low in all 4 groups, but the induced serum antibodies had strong bactericidal activity. Persistent bactericidal antibodies (> or =4-fold increase) were produced in 75% of the recipients. Some of the bactericidal antibodies were cross reactive against divergent group B strains. Most of the bactericidal antibodies appeared to be specific for PorA and L3,7,9 LOS. The vaccine also produced a local antibody response which was detected in the nasal wash fluids of volunteers. These data suggest that nasal immunization with NOMV is a safe and effective approach to induce systemic and local immunity against the group B meningococcus and deserves further study.	J. J. Drabick, B. L. Brandt, E. E. Moran, N. B. Saunders, D. R. Shoemaker and W. D. Zollinger	Vaccine
177	Evaluation of ampicillin in the treatment of acute bacterial meningitis in children		A. K. Dutta, H. Sehgal and S. C. Khandpur	Indian pediatrics
246	Irradiation, methotrexate toxicity, and the treatment of meningeal leukaemia		M. J. Duttera, W. A. Bleyer, T. C. Pomeroy, C. M. Leventhal and B. G. Leventhal	Lancet
418	Comparison between bacampicillin and amoxycillin in treating genital and extragenital infection with Neisseria gonorrhoeae and pharyngeal infection with Neisseria meningitidis	Sixty three patients presumed to have genital gonorrhoea who gave histories of extragenital sexual practices were randomly treated with amoxycillin 3 g or bacampicillin 4.8 g (equivalent to 3.5 g ampicillin) with probenecid 1 g to compare the efficacy of the drugs in treating gonorrhoea at all sites. Three patients were initially culture negative, and seven failed to return for follow up. Twenty seven of 28 patients receiving bacampicillin and all 25 receiving amoxycillin gave negative genital cultures for Neisseria gonorrhoeae five to nine days after treatment. Twenty two of 60 patients had extragenital gonorrhoea. One failed to return, but all eight who had received amoxycillin and 12 of 13 who had received bacampicillin gave negative pharyngeal and anorectal cultures after treatment. N meningitidis was isolated from the pharynx in 17 of 60 patients on initial attendance. Three of 14 were still colonised with the meningococcus after treatment. Two of 32 patients receiving amoxycillin and 12 of 31 receiving bacampicillin reported experiencing gastrointestinal side effects.	L. D. Edwards and T. Gartner	The British journal of venereal diseases
431	Prophylactic antibiotic for prevention of posttraumatic meningitis after traumatic pneumocephalus: design and rationale of a placebo-controlled randomized multicenter trial [ISRCTN71132784]	BACKGROUND: The purpose of this study is to compare the efficacy of prophylactic antibiotic for prevention of meningitis in acute traumatic pneumocephalus patients. METHODS: In this prospective, randomized controlled clinical trial, 200 selected head injury patients with traumatic pneumocephalus are randomly assigned to receive intravenous antibiotics (2 grams Ceftriaxone twice a day), oral antibiotics (Azithromycin) or placebo for at least 7 days after trauma. The patients will be followed for one month posttrauma. CONCLUSION: The authors hope that this study helps clarifying the effectiveness and indications of antibiotics in prevention of meningitis in traumatic pneumocephalus after head injury and in specific subgroup of these patients	B. Eftekhar, M. Ghodsi, A. Hadadi, M. Taghipoor, S. Z. Sigarchi, V. Rahimi-Movaghar, E. S. Kazemzadeh, B. Esmaeeli, F. Nejat, A. Yalda and E. Ketabchi	Trials [Electronic Resource].
569	Indirect effect of 7-valent pneumococcal conjugate vaccine on pneumococcal carriage in newborns in rural Gambia: a randomised controlled trial	BACKGROUND: Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies. METHODS: Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2-30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study. RESULTS: 57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26-0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87-1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50-0.92], p = 0.013 in control villages and HR 0.31 [0.19-0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06-2.06], p = 0.022) and (HR 1.52 [1.11-2.10], p = 0.010 respectively) were significantly higher. CONCLUSION: PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring. TRIAL REGISTRATION: ISRCTN Register 51695599.	U. Egere, J. Townend, A. Roca, A. Akinsanya, A. Bojang, D. Nsekpong, B. Greenwood, R. A. Adegbola and P. C. Hill	PloS one
554	Comparing time-to-event analysis methodologies in a study of the treatment of acquired immune deficiency syndrome associated cryptococcal meningitis [abstract]	29th Meeting of the Society of Clinical Trials; 2008 18-21 May; St Louis, USA.	B. Eggleston, T. Nolan, D. Wallace and P. Pappas	Clinical Trials
239	In-vitro and in-vivo studies of resistance to rifampin in meningococci		T. C. Eickhoff	The Journal of infectious diseases
225	Elevated sweat sodium associated with pulmonary oedema in meningococcal sepsis	BACKGROUND: We observed a temporary positive sweat test with sodium and chloride levels greater than 60 mmol L(-1) following meningococcal septicaemia. Objective was to investigate whether this finding is reproducible and whether this disturbance in epithelial sodium transport is related to sepsis-induced pulmonary oedema. MATERIALS AND METHODS: Twenty-four children with a diagnosis of meningococcal septicaemia and 10 controls with noninfectious critical illness admitted to the Royal Liverpool Children's Hospital were included. Sweat collection was by pilocarpine iontophoresis in the acute phase of the illness (days 1-5) and on follow up. Sodium and chloride concentrations were determined by flame photometry. RESULTS: In patients with meningococcal septicaemia, sweat sodium and chloride concentrations were significantly higher in the acute compared with the recovery phase, with a mean (SD) of 31.0 (14.6) mmol L(-1) in the acute vs. 19.6 (10.2) mmol L(-1) on recovery for sodium and 21.0 (12.1) mmol L(-1) in the acute vs. 11.8 (4.9) mmol L(-1) on recovery for chloride (P < 0.01, t-test, for sodium and chloride). Sweat sodium and chloride were significantly higher in patients with meningococcal disease compared with controls and in the acute phase in patients with septicaemia-related pulmonary oedema [mean (SD) sodium: 41.0 (15.4) mmol L(-1) and chloride: 28.8 (14.3) mmol L(-1)] compared with septic patients without [mean (SD) sodium: 24.5 (10.1) mmol L(-1) and chloride: 15.3 (7.9) mmol L(-1)] (P < 0.01 for sodium and chloride). CONCLUSIONS: This is the first study to provide in vivo evidence of reduced epithelial sodium transport in children with septicaemia and of its association with pulmonary oedema.	M. Eisenhut, D. Sidaras, P. Barton, P. Newland and K. W. Southern	European journal of clinical investigation
675	Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma	The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.	D. J. Elias, L. E. Kline, B. A. Robbins, H. C. Johnson, K. Pekny, M. Benz, J. A. Robb, L. E. Walker, M. Kosty and R. O. Dillman	American journal of respiratory and critical care medicine
338	Penetration of pyrazinamide into the cerebrospinal fluid in tuberculous meningitis		G. A. Ellard, M. J. Humphries, M. Gabriel and R. Teoh	British medical journal (Clinical research ed.)
147	Antibiotic concentrations in liquor compared to the minimal inhibitory concentrations of isolates in paediatric bacterial meningitis. The Finnish Study Group	The susceptibilities of 171 bacteria which caused meningitis in 200 children were tested for their susceptibility as minimal inhibitory concentrations (MICs) for the antibiotics used in therapy. These antibiotics were chloramphenicol, ampicillin, cefotaxime and ceftriaxone. The MICs were compared to the minimal concentrations of the drugs seen in the cerebrospinal fluid (CSF) samples. The minimal bacteriostatic capacity (lowest concentration in CSF/MIC) of both cephalosporins was superior to that of chloramphenicol and ampicillin. The correlation of the finding with the speed of liquor sterilization in the treatment groups is discussed.	J. K. Ellmén, O. V. Renkonen, M. A. Anttila and H. O. Peltola	Chemotherapy
60	Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis	BACKGROUND: Identification of new therapeutic targets remains an imperative goal to improve the morbidity and mortality associated with severe sepsis and septic shock. Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, has recently emerged as a critical mediator of innate immunity and experimental sepsis, and it is an attractive new target for the treatment of sepsis. METHODS: Circulating concentrations of MIF were measured in 2 clinical trial cohorts of 145 pediatric and adult patients who had severe sepsis or septic shock caused predominantly by infection with Neisseria meningitidis or other gram-negative bacteria, to study the kinetics of MIF during sepsis, to analyze the interplay between MIF and other mediators of sepsis or stress hormones (adrenocorticotropic hormone and cortisol), and to determine whether MIF is associated with patient outcome. RESULTS: Circulating concentrations of MIF were markedly elevated in 96% of children and adults who had severe sepsis or septic shock, and they remained elevated for several days. MIF levels were correlated with sepsis severity scores, presence of shock, disseminated intravascular coagulation, urine output, blood pH, and lactate and cytokine levels. High levels of MIF were associated with a rapidly fatal outcome. Moreover, in meningococcal sepsis, concentrations of MIF were positively correlated with adrenocorticotropic hormone levels and negatively correlated with cortisol levels and the cortisol:adrenocorticotropic hormone ratio, suggesting an inappropriate adrenal response to sepsis. CONCLUSIONS: MIF is markedly and persistently up-regulated in children and adults with gram-negative sepsis and is associated with parameters of disease severity, with dysregulated pituitary-adrenal function in meningococcal sepsis, and with early death.	M. Emonts, F. C. Sweep, N. Grebenchtchikov, A. Geurts-Moespot, M. Knaup, A. L. Chanson, V. Erard, P. Renner, P. W. Hermans, J. A. Hazelzet and T. Calandra	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
92	[Prospective comparative study on 50 patients between microsurgical sublabial transsphenoidal approach and endoscopic endonasal transsphenoidal approach]	OBJECTIVE: Compare the standard transsphenoidal sublabial microscopic approach with the endoscopic transsphenoidal approach concerning the tumoral invasiveness and resection, complications of the approaches and time of post operative hospitalisation.MATERIAL AND METHODS: We realized a prospective, non randomised study with 50 patients. They were operated between 2002 and 2006. All the patients had sellar lesions with different grades of invasiveness of the cavernous sinus as classified by Knosp. The variables included in our study were tumoral invasiveness and operative resection (total, subtotal and partial), optic nerve lesion, postoperative panhypopituitarism, CSF fistula, cranial nerves deficits, epistaxis, meningitis, diabetes insipidus and carotid artery lesion. Our series included 27 males and 23 females ranging from 19 to 80 years old (48 mean). In 23 patients we used the standard sublabial microscopic approach (two patients were excluded) and for 25 patients we used the endoscopic approach. The mean follow up was of 12 months.RESULTS: In our experience the endoscopic technique presents a higher percentage of total resection comparing to the sublabial microscopic approach (60% versus 34.8%) and higher percentage of subtotal resections (32% versus 26%) with a statistical significant difference (p=0.033). The time of hospitalisation was significant shorter for the endoscopic approach group (p=0.001), diminishing by half of the time (3 days) of the microscopic approach group. Concerning the tumoral invasiveness and complications we did not appreciate any significant dissimilarity. We appreciated that a higher grade of invasiveness augments by 3.59 the risk of an unsuccessful surgery.DISCUSSION AND CONCLUSION: In our experience the endoscopic technique may favour a better tumoral resection and shorter time of hospitalisation. We did not appreciate differences concerning the complications.	J. Enseñat, J. L. Quesada, J. Aparicio, C. Pàmies, X. Barber, T. Topczewski and E. Ferrer	Neurocirugía (Asturias, Spain)
446	Mortality from tuberculous meningitis reduced by steroid therapy	In this study of 99 tuberculous meningitis patients from Cali, Colombia, treatment with steroids (in conjunction with antituberculous drugs) was shown to be more effective in reducing mortality than treatment with antibacterial drugs alone. Results further suggest that low dosages of steroids (1 mg/kg of prednisone daily for r 30 days) are equally effective in treating the disease as high dosages (10 mg/kg of prednisone at the start of treatment, gradually reduced over a 30-day period). These results are band 4(-43 and -kk mg/100 ml) demonstrated cerebral release. Arterial blood hyperammonemia can be detoxified safely in the brain as long as the levels do not exceed approximately 300 mug/100 ml. Beyond that level lactic acidosis is observed, particularly in cerebral venous drainage. Arterial blood hyperammonemia was also related to the extent of alveolar hyperventilation. These findings are very similar to those seen in experimental hyperammonemia and support the concept that neurotoxicity in children with Reye's syndrome is at least partly due to impaired oxidative metabolism secondary to hyperammonemia.	J. A. Escobar, M. A. Belsey, A. Duenas and P. Medina	Pediatrics
173	Efficacy of a pneumococcal conjugate vaccine against acute otitis media	BACKGROUND: Ear infections are a common cause of illness during the first two years of life. New conjugate vaccines may be able to prevent a substantial portion of cases of acute otitis media caused by Streptococcus pneumoniae. METHODS: We enrolled 1662 infants in a randomized, double-blind efficacy trial of a heptavalent pneumococcal polysaccharide conjugate vaccine in which the carrier protein is the nontoxic diphtheria-toxin analogue CRM197. The children received either the study vaccine or a hepatitis B vaccine as a control at 2, 4, 6, and 12 months of age. The clinical diagnosis of acute otitis media was based on predefined criteria, and the bacteriologic diagnosis was based on a culture of middle-ear fluid obtained by myringotomy. RESULTS: Of the children who were enrolled, 95.1 percent completed the trial. With the pneumococcal vaccine, there were more local reactions than with the hepatitis B vaccine but fewer than with the combined whole-cell diphtheria-tetanus-pertussis and Haemophilus influenzae type b vaccine that was administered simultaneously. There were 2596 episodes of acute otitis media during the follow-up period between 6.5 and 24 months of age. The vaccine reduced the number of episodes of acute otitis media from any cause by 6 percent (95 percent confidence interval, -4 to 16 percent [the negative number indicates a possible increase in the number of episodes]), culture-confirmed pneumococcal episodes by 34 percent (95 percent confidence interval, 21 to 45 percent), and the number of episodes due to the serotypes contained in the vaccine by 57 percent (95 percent confidence interval, 44 to 67 percent). The number of episodes attributed to serotypes that are cross-reactive with those in the vaccine was reduced by 51 percent, whereas the number of episodes due to all other serotypes increased by 33 percent. CONCLUSIONS: The heptavalent pneumococcal polysaccharide-CRM197 conjugate vaccine is safe and efficacious in the prevention of acute otitis media caused by the serotypes included in the vaccine.	J. Eskola, T. Kilpi, A. Palmu, J. Jokinen, J. Haapakoski, E. Herva, A. Takala, H. Käyhty, P. Karma, R. Kohberger, G. Siber and P. H. Mäkelä	The New England journal of medicine
327	Comparison of bedside inoculation of culture media with conventional cerebrospinal fluid culture method in patients with bacterial meningitis	BACKGROUND: The yield of bacterial cultures from cerebrospinal fluid (CSF) at Kenyatta National Hospital (KNH) is very low. Bedside inoculation of culture media with CSF may improve yields. OBJECTIVE: To compare the culture yield of CSF inoculated onto culture medium at the bedside to that of CSF inoculated onto culture medium in the microbiology laboratory. DESIGN: Cross-sectional comparative study. SETTING: Accident and Emergency Department and medical wards at Kenyatta National Hospital. SUBJECTS: Cerebrospinal fluid from patients at KNH with a clinical diagnosis of acute meningitis. RESULTS: Two hundred and twenty CSF specimens were obtained during a four month period. S. pneumaniae was isolated from 24 CSF samples and H. influenzae from one. Bacterial cultures were positive in 25 (11.4%, 95% CI 7.0-15.6%) samples inoculated at the bedside and 23 (10.5%, 95% CI 6.5-14.5%) samples inoculated at the laboratory. Bacteria were isolated 5 hours earlier in samples inoculated at the bedside (95% CI 4.34-6.86 hrs, p < 0.05). Four per cent of S. pneumaniae isolates were resistant to crystalline penicillin. CONCLUSION: There was no significant difference in culture yield after bedside inoculation of culture media with CSF compared to traditional CSF culture method. Bedside inoculation of culture media with CSF resulted in faster time to positive culture.	A. O. Etyang, E. O. Amayo, S. M. Bhatt, I. A. Wamola and M. C. Maritim	East African medical journal
366	Discontinuing penicillin prophylaxis in children with sickle cell anemia. Prophylactic Penicillin Study II	OBJECTIVE: To evaluate the consequences of discontinuing penicillin prophylaxis at 5 years of age in children with sickle cell anemia who had received prophylactic penicillin for much of their lives. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Eighteen teaching hospitals throughout the United States. PATIENTS: Children with sickle cell anemia (hemoglobin SS or hemoglobin S beta 0-thalassemia) who had received prophylactic penicillin therapy for at least 2 years immediately before their fifth birthday and had received the 23-valent pneumococcal vaccine between 2 and 3 years of age and again at the time of randomization. Of 599 potential candidates, 400 were randomly selected and followed for an average of 3.2 years. INTERVENTIONS: After randomization, patients received the study medication twice daily--either penicillin V potassium, 250 mg, or an identical placebo tablet. Patients were either seen in the clinic or contacted every 3 months thereafter for an interval history and dispensing of the study drug. A physical examination was scheduled every 6 months. MAIN OUTCOME MEASURES: The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo. RESULTS: Six children had a systemic infection caused by S. pneumoniae, four in the placebo group (2.0%; 95% confidence interval 0.5%, 5.0%) and two in the continued penicillin prophylaxis group (1.0%; 95% confidence interval 0.1%, 3.6%) with a relative risk of 0.5 (95% confidence interval 0.1, 2.7). All invasive isolates were either serotype 6(A or B) or serotype 23F. Four of the isolates were penicillin susceptible, and two (one from each treatment group) were penicillin and multiply antibiotic resistant. Adverse effects of the study drug were reported for three patients (nausea, vomiting, or both), one of whom was in the placebo group. CONCLUSION: Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age. Parents must be aggressively counseled to seek medical attention for all febrile events in children with sickle cell anemia.	J. M. Falletta, G. M. Woods, J. I. Verter, G. R. Buchanan, C. H. Pegelow, R. V. Iyer, S. T. Miller, C. T. Holbrook, T. R. Kinney and E. Vichinsky	The Journal of pediatrics
33	Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine	Individuals with properdin, C3 or late complement component deficiency (LCCD) frequently develop meningococcal disease. Vaccination of these persons has been recommended, although reports on efficacy are scarce and not conclusive. We immunized 53 complement-deficient persons, of whom 19 had properdin deficiency, seven a C3 deficiency syndrome and 27 had LCCD with the tetravalent (ACYW) meningococcal capsular polysaccharide vaccine. Serological studies were performed in 43 of them. As controls 25 non-complement-deficient relatives of the complement-deficient vaccinees and 21 healthy non-related controls were vaccinated. Post-vaccination, complement-deficient individuals and controls developed a significant immunoglobulin-specific antibody response to capsular polysaccharides group A, C, Y, W135, but a great individual variation was noticed. Also, the proportion of vaccinees of the various vaccinated groups with a significant increase in bactericidal titre (assayed with heterologous complement) was similar. Opsonization of meningococci A and W135 with sera of the 20 LCCD individuals yielded in 11 (55%) and eight (40%) sera a significant increase of phagocytic activity after vaccination, respectively. Despite vaccination, four complement-deficient patients experienced six episodes of meningococcal disease in the 6 years post-vaccination. Four episodes were due to serogroup B, not included in the vaccine. Despite good response to serogroup Y upon vaccination, disease due to serogroup Y occurred in two C8beta-deficient patients, 3.5 and 5 years post-vaccination. These results support the recommendation to vaccinate complement-deficient individuals and to revaccinate them every 3 years.	C. A. Fijen, E. J. Kuijper, M. Drogari-Apiranthitou, Y. Leeuwen, M. R. Daha and J. Dankert	Clinical and experimental immunology
6	Investigation of different group A immunoassays following one dose of meningococcal group A conjugate vaccine or A/C polysaccharide vaccine in adults	A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a > or = 4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group.	H. Findlow, B. D. Plikaytis, A. Aase, M. C. Bash, H. Chadha, C. Elie, G. Laher, J. Martinez, T. Herstad, E. Newton, S. Viviani, C. Papaspyridis, P. Kulkarni, M. Wilding, M. P. Preziosi, E. Marchetti, M. Hassan-King, F. M. Force, G. Carlone and R. Borrow	Clinical and vaccine immunology : CVI
7	Meningococcal group C and w135 immunological hyporesponsiveness in african toddlers	A phase II clinical study was conducted in African toddlers (aged 12 to 23 months), with subjects receiving either investigational meningococcal group A conjugate (PsA-TT), meningococcal ACWY polysaccharide (PsACWY), or Haemophilus influenzae type b (Hib-TT) vaccine. Ten months following vaccination, the 3 study groups were further randomized to receive a dose of PsA-TT, a 1/5 dose of PsACWY, or a dose of Hib-TT vaccine. Group A serum bactericidal antibody (SBA) results have been reported previously, with PsA-TT demonstrating superior immunogenicity versus PsACWY vaccine. Immunogenicity for serogroups W135 and C was assessed by SBA assay to investigate the impact of multiple doses in this age group. Blood samples were taken prior to vaccination, 28 days and 40 weeks post-primary vaccination, and 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY. Subjects who had previously received a full dose of PsACWY had W135 SBA geometric mean titers (GMTs) of 26.1 and 4.4 at 7 and 28 days post-booster vaccination with a 1/5 PsACWY dose, respectively, whereas the W135 SBA GMTs of naïve subjects at these time points following vaccination with a 1/5 dose of PsACWY were 861.1 and 14.6, respectively. Similar differences were observed for serogroup C, with SBA GMTs of 99 and 5.9 at 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY, respectively, for naïve subjects, compared to 4.1 and 3.2 for previously vaccinated subjects. Immunologic hyporesponsiveness for groups C and W135 was observed following a full dose of PsACWY vaccine at 12 to 23 months of age and a 1/5 dose of PsACWY 10 months later compared to the case for PsACWY-naïve subjects receiving a 1/5 dose of PsACWY vaccine.	H. Findlow, S. Sow, R. Borrow, M. Tapia, F. C. Haidara, A. K. Akinsola, O. T. Idoko, F. Diallo, R. Adegbola, Y. Tang, V. Parulekar, H. Chadha, L. Mabey, D. Holme, K. Townsend, J. Chaumont, F. M. Laforce, P. S. Kulkarni, E. Marchetti, S. Viviani, M. Hassan-King and M. P. Preziosi	Clinical and vaccine immunology : CVI
179	Ampicillin in the treatment of bacterial meningitis		P. C. Fleming, J. D. Murray, M. W. Fujiwara, J. S. Prichard and G. A. McNaughton	Antimicrobial agents and chemotherapy
252	Evaluation of combining upper respiratory tract swab samples with cerebrospinal fluid examination for the diagnosis of enteroviral meningitis in children	In a prospective comparative study, the use of combined analysis of upper respiratory tract swab samples and cerebrospinal fluid (CSF) samples was assessed to improve the detection rate of enteroviral meningitis in children. An enterovirus was detected in 32% of patients with aseptic meningitis when testing CSF samples alone compared with 71.5% when combining CSF and respiratory tract findings. An enterovirus was detected in 17% of respiratory tract samples in an age- and sex-matched control group without meningitis. Thus, combining the examination of upper respiratory tract with CSF findings may improve the detection rate of enteroviral meningitis. Upper respiratory tract samples should be included in the diagnosis scheme to differentiate benign enteroviral meningitis from other life-threatening infections of the central nervous system.	S. Foray, F. Pailloud, D. Thouvenot, D. Floret, M. Aymard and B. Lina	Journal of medical virology
143	Antibody response of adults to an aluminum hydroxide-adsorbed Neisseria meningitidis serotype 2b protein-group B polysaccharide vaccine	A group B Neisseria meningitidis serotype protein vaccine was studied clinically in adults. The vaccine comprised lipopolysaccharide-depleted outer membrane vesicles from a serotype 2b strain, 3006-M2, noncovalently complexed with group B meningococcal polysaccharide. Volunteers received 25 micrograms each of protein and polysaccharide administered intramuscularly either in 0.9% NaCl or adsorbed onto aluminum hydroxide on weeks 0 and 6. Most individuals experienced mild local reactions, but there were no systemic reactions. Both vaccine formulations stimulated antibodies to the outer membrane proteins of serotypes 2a:P1.2 and 2b:P1.2, but higher levels were achieved with the aluminum hydroxide-adsorbed vaccine after two immunizations. Vaccine-induced antibodies were primarily IgG and were bactericidal for both a serotype 2a and a serotype 2b strain. Induction of bactericidal antibodies has been shown to be a major predictor of protection against meningococcal disease.	C. E. Frasch, J. M. Zahradnik, L. Y. Wang, L. F. Mocca and C. M. Tsai	The Journal of infectious diseases
345	Evaluation of intrathecal therapy with streptomycin and hydrocortisone in tuberculous meningitis		I. Freiman and J. Geefhuysen	The Journal of pediatrics
476	Efficacy and Tolerability of Liposomal Amphotericin B (Ambisome) in the Treatment of Visceral Leishmaniasis in Brazil	Thirty-two patients were enrolled in an open-label, dose/schedule ranging clinical trial to evaluate the efficacy and tolerability ofliposomal amphotericin B (Ambisome) in the treatment of visceral leishmaniasis. All patients received a dose of 2mg/kg daily for the first 4 days, followed by a single repeat dose of 2mg/kg at day 10 in 4 patients (total dose 10mg/kg); repeat doses on days 5, 6, and 10 in 13 patients (total dose 14mg/kg); or daily doses were continued on days 5 through 10 in 15 patients (total dose 20mg/kg). Patients had a mean age of 9 years, ranging between 3 and 26 years. Their mean weight was 25.9kg, ranging between 9.5kg and 75kg. All patients had splenomegaly, 31/32 had hepatomegaly, and 20 patients tested had leishmania documented on splenic aspirate. Six of the 32 patients were treated after relapse following antimony therapy. The duration of illness prior to therapy was a mean of 2 months, ranging between 2 weeks and 23 months. During and after treatment, there were significant reductions in liver and spleen sizes, and significant increases in body weight, hemoglobin levels and white blood cell counts. All patients showed initial cure at the 1 month follow-up. Seven patients relapsed between 2 and 6 months after the start of treatment. There was no dose relationship to the occurrence of relapse. The relapse rate in children 5 years of age or less was 7/15 (47%). Associated causes of relapse were refractory disease (i.e., previous relapses) in 2, severe malnutrition in 1, and concurrent disease (meningococcal meningitis) in 1. In the other 2 cases, no associated event was observed except young age (ages 3 and 5 years). One relapsed patient was treated successfully with 14 days of lipid amphotericin B, and the others were cured by use of antimony for 20 to 30 days. There were no dose related adverse events. The most common event was fever which occurred in 13/32 patients (41%); 3/4 patients in the 10mg dose group, 7/13 in the 14mg dose group, and 3/15 in the 20mg dose group. Three patients had cardiac arrhythmia, one also with myocarditis diagnosed 2 weeks after therapy was discontinued. One patient developed hepatitis after dose 3 and the drug was discontinued. We concluded that liposomal amphotericin B is effective in a daily dose of 2mg/kg given for 5-10 doses as an initial cure, but that relapse occurs in young children, particularly those with documented treatment resistant disease or concurrent malnutrition or infection. Patients should be carefully monitored for these risk factors before and during the months alter therapy, and for the occurrence of arrhythmia, cardio-pulmonary effects or hepatotoxicity. This treatment provides an important advance over previously used antimony therapy and appears to be more effective and well-tolerated than non-lipid amphotericin B.	M. Freire, F. Badaro, M. E. Avelar, K. Luz, M. S. Nakatani, R. Teixeira, E. Martins Netto and R. Badaro	Braz J Infect Dis
249	Dexamethasone and long-term survival in bacterial meningitis	BACKGROUND: Data on the long-term effect of dexamethasone on survival in bacterial meningitis are lacking. METHODS: A long-term follow-up study of the European Dexamethasone in Adulthood Bacterial Meningitis Study was performed. In this double-blind, randomized clinical trial, 301 patients were randomly assigned to receive adjunctive dexamethasone (n = 157) or placebo (n = 144) between June 1993 and December 2001. We obtained survival data of patients using the Dutch Municipal Population Register. RESULTS: Death had occurred in 32 of 301 included patients (11%) at the primary outcome measurement 8 weeks after randomization. Follow-up was obtained for 228 of 246 evaluable patients (93%), with median follow-up of 13 years. Overall, 31 of 144 patients (22%) in the dexamethasone group died and 44 of 134 patients (33%) in the placebo group died (log-rank p = 0.029). After the primary end point of the study at 8 weeks, 20 patients in the dexamethasone group died and 23 patients in the placebo group died (log-rank p = 0.27), with age being the sole predictor of death (p < 0.001). CONCLUSIONS: In adults with community-acquired bacterial meningitis, the survival benefit from adjunctive dexamethasone therapy is obtained in the acute phase of the disease and remains for years. CLASSIFICATION OF EVIDENCE: This study of a population of Dutch patients shows Class III evidence that dexamethasone provides an extended survival benefit in patients treated for bacterial meningitis, and this survival benefit extends as long as 20 years.	D. Fritz, M. C. Brouwer and D. Beek	Neurology
73	Meningococcal strains isolated from teenage patients during the serogroup B vaccination trial in Norway: serotyping, serosubtyping, immunotyping and clonal analysis		L. O. Frøholm, D. A. Caugant, E. Holten, E. A. Høiby, E. Rosenqvist and E. Wedege	NIPH annals
620	[Pharmacokinetic and clinical studies with L-627 (biapenem) in the pediatric field. Pediatric study group of L-627]	To conduct pharmacokinetic and clinical studies on newly developed L-627 (biapenem) against various infections in pediatrics, a study group was organized and a joint research by 15 institutions and their related hospitals was undertaken. Informed consents of subjects were obtained prior to the study. The obtained results are as follows. 1. Plasma concentrations and urinary excretion Pharmacokinetics of L-627 in children was studied in 29 subjects using 30 minutes intravenous drip infusion of 6 mg/kg and 12 mg/kg. Maximum plasma levels of L-627 was observed at the completion of drip infusion and were 25.1 micrograms/ml with administration of 6 mg/kg and 39.2 micrograms/ml with administration of 12 mg/kg on average. Dose dependency was noted in Cmax and AUC with these doses. Maximum blood levels in all of the 5 participated sucklings under the age of one year were similar to the average. As for urinary excretion, L-627 was excreted 66.0% with administration of 5 mg/kg and 62.3% with 12 mg/kg. 2. Cerebrospinal fluid concentrations Cerebrospinal fluid concentrations ranged from 0.76 to 8.54 micrograms/ml in 30-240 minutes after the completion of drip infusion with dose of 20-40 mg/kg in 9 subjects with purulent meningitis, when they were measured within 3 days after the initiation of the treatment with L-627. 3. Clinical results Thirty-three cases of exclusion and drop-out were deducted from a total of 330 cases, hence 297 cases were evaluated as the subjects in the study for analysis of clinical effects. As for clinical effects in group A where pathogenic bacteria were detected, 166 out of 173 were rated as effective or above, hence the efficacy rate of 96.0% was obtained. In group B where pathogenic bacteria were not detected, 114 out of 124 cases were rated as effective or above, thus the efficacy rate was 91.9%, which is similar to that of the group A. The overall efficacy rate was 94.3% in the entire 297 cases. The rates of "excellent" responses out of the cases rated as effective or above were 62.7% (104/166) in the group A and 55.3% (63/114) in the group B, thus the rate was markedly high in the former group. Efficacy rate for each pathogenic strain was also high, and that in subjects infected by a single pathogenic strain was 96.7% (145/150) and that in subjects infected by two or more pathogenic strains was 91.3% (21/23).(ABSTRACT TRUNCATED AT 400 WORDS)	R. Fujii, K. Fujita, M. Yoshikawa, K. Murono, S. Maruyama, H. Sakata, F. Inyaku, S. Takahashi, T. Saino and S. Chiba	The Japanese journal of antibiotics
611	[Pharmacokinetics and clinical evaluation of ceftriaxone in neonates]	A parenteral cephem antibiotic ceftriaxone (CTRX) was studied for its pharmacokinetic features and clinical efficacy and safety in various infections in neonates including premature infants at 11 institutions associated with Japan Perinatal Infection Research Group. The following results obtained are summarized as follows. 1. Following single intravenous bolus injections with 10 and 20 mg/kg of CTRX, serum levels of the drug at 30 minutes post-dose 36-42 micrograms/ml and 46-76 micrograms/ml, respectively, and those at 12 hours post-dose were 10-14 micrograms/ml and 13-21 micrograms/ml, respectively, in a total of 105 neonates. Serum levels detected were on very gentle descending curves. 2. Half-lives (T 1/2) of the drug in serum were significantly prolonged in 0-3 day age groups of both mature and premature infants: it was especially long in premature infants with age of 0-3 days; i.e., 17.1 hours. There was no difference in T 1/2 between the 4-7 day and 8-28 day age groups. 3. Urinary excretion rates were 20-30% in the first 6 hours post-dose and 30-40% in 12 hours post-dose, in 80 neonates examined. 4. Clinical efficacy: Clinical efficacies were evaluated in 112 of 168 enrolled excluding infants with 90 days of age or older, who were treated for prophylaxis and unevaluable cases. The safety was evaluated in 161 of the 168. (1) Demographic background of the 112 cases: The 112 cases were composed of 89 neonates with ages of 28 days or younger, 21 premature infants, 57 males and 55 females. The drug was given to 102 of the cases by intravenous bolus injection, with 81 cases administered twice a day and 97 cases receiving 10-50 mg/kg a day. (2) Efficacy rate in the 112 cases: In 60 cases for whom causative pathogens were identified the efficacy rate was 90.0% in total (excellent: 31/60; good: 23/60); efficacy rates of 87.5% were obtained in 8 cases with purulent meningitis and 90.9% in 11 with septicemia. In 52 with causative pathogen not identified, the efficacy rate was 96.2% in total (excellent: 21/52; good: 29/52). (3) Adverse reaction: Adverse reactions were noted in 14 of the 161 cases where the safety was evaluated (8.7%). These reactions included diarrhea in 11, vomiting in 2 and exanthema in 1. Abnormalities in laboratory test values were observed in 25 of the 152 cases (16.4%). They included eosinophilia in 14, elevated GOT in 4 and thrombocytosis in 3 etc.(ABSTRACT TRUNCATED AT 250 WORDS)	R. Fujii, S. Hashira, H. Sakata, F. Inyaku, K. Fujita, S. Maruyama, H. Yoshioka, S. Nakazawa, H. Satoh and A. Narita	The Japanese journal of antibiotics
525	[Pharmacokinetic and clinical studies with meropenem in the pediatric field. Pediatric Study Group of Meropenem]	Pharmacokinetic and clinical evaluations in pediatrics were made on meropenem (SM-7338, MEPM), a new parenteral dehydropeptidase-1 stable carbapenem used without any inhibitors, at 33 medical institutions. The results are summarized as follows. 1. Pharmacokinetic studies. MEPM at a dose of 10, 20, or 40 mg/kg was administered to 53 children by 30-minute drip infusion. Peak plasma concentrations (Cmax's) and plasma half-lives (T1/2's) of these doses were 28.5, 47.2 and 130.0 micrograms/ml, and 0.80, 0.93 and 0.94 hours, respectively. A clear dose response was observed in Cmax's and T1/2 values were quite similar to those observed in adults. In the first 6 hours after administration, 54.4 to 68.1% of the administered drug was recovered in urine. The cerebrospinal fluid (CSF) levels of MEPM in patients with purulent meningitis were 0.13 microgram/ml at a dose of 6 mg/kg, and 0.64 to 4.22 micrograms/ml at a dose of 29 to 44 mg/kg within day 4 of onset. The penetration rate of MEPM showed an intermediate value among those for other cephalosporin antibiotics. 2. Clinical study. Clinical efficacies of MEPM were evaluated in 389 cases. The most common doses used were 10 to 20 mg/kg/once, 2 to 3 times a day. The maximum dose was 173 mg/kg/day q.i.d. MEPM gave "excellent" or "good" responses in 242 (97.6%) out of 248 cases in which causative organisms were documented and in 134 (95.0%) out of 141 cases in which causative organisms were not identified. Clinical efficacy rates were 100% in 11 patients with purulent meningitis, 85.7% in 7 with septicemia, 98.8% in 173 with pneumonia, and 100% in 65 with UTI. Bacteriologically, 260 strains (96.7%) out of 269 strains were eradicated by MEPM treatment. Eradication rates were 89.2% for Staphylococcus aureus (37 strains) and 100% for Streptococcus pneumoniae (35 strains). The overall eradication rate for Gram-positive bacteria was 94.6%. Among Gram-negative bacteria, 98.3% out of 172 strains were eradicated. The eradication rate of Haemophilus influenzae (73 strains) was 98.6% and Pseudomonas aeruginosa (11 strains) was 90.9%, and all of Branhamella catarrhalis (15 strains), Escherichia coli (42 strains), and Klebsiella pneumoniae (6 strains) were eradicated. Out of 84 cases for which previous antibiotic therapies of 3 days or longer were not successful, MEPM gave "excellent" or "good" responses in 77 cases (91.7%) and excellent bacteriological responses (95.7%).(ABSTRACT TRUNCATED AT 400 WORDS)	R. Fujii, H. Yoshioka, K. Fujita, S. Maruyama, H. Sakata, F. Inyaku, S. Chiba, H. Tsutsumi, Y. Wagatsuma and N. Fukushima	The Japanese journal of antibiotics
99	Intra-operative antibiotic prophylaxis in neurosurgery. A prospective, randomized, controlled study on cefotiam	In this prospective, randomized and controlled study the effect of cefotiam for the prevention of wound infections following trepanations was investigated. The main interest was centered on the rate of post-operative bone flap infections requiring operative revision. Administration of cefotiam was randomized for patients undergoing major craniotomies. The antibiotic was administered intravenously in a single dose of 2 g with induction of anaesthesia. Only clean or clean contaminated cases were included. Excluded were contaminated cases, operations with a transnasal-transsphenoidal approach, shunt-operations and patients with any other preoperative infection or antibiotic therapy. Outpatients were excluded due to difficulties in obtaining sufficient clinical information. From originally 918 consecutive patients operated on 711 fulfilled the entry criteria. With regard to age, sex, diagnosis and the site of te trepanation, control patients (n = 355) and cefotiam treated patients (n = 356) were shown to be comparable. In the various subgroups formed for different primary diagnoses, concomitant steroidal therapy and concomitant severe internal medical diseases cefotiam treated patients and controls were comparable as well. A highly significant difference for bone flap infection could be shown with 0.3% in the cefotiam group versus 5.1% in the control group (p less than 0.001). The overall rate of post-operative deep wound infections including meningitis and abscesses was also significantly (p less than 0.005) different with 3.1% in the cefotiam versus 9.0% in the control group. Thus it was concluded that a single dose of cefotiam significantly reduces post-operative deep wound infection.	T. Gaillard and J. M. Gilsbach	Acta neurochirurgica
590	Caudal neuroplasty plus Botulinum toxin A injection in piriformis muscle in failed back surgery syndrome	Objective: Decompressive neuroplasty is used for management of pain in cases of failed back surgery syndrome (FBSS). The aim of this study is to compare between sacral neuroplasty alone and with piriformis botox injection regarding pain relief, quality of life, patient satisfaction and side effects. Methods: Forty patients with FBSS associated with radiculopathy were randomly allocated into two groups: group A(20 patients) done caudal neuroplasty only and group B(20 patients) done caudal neuroplasty plus piriformis muscle injection with botulinum toxin A 100 units. VAS, patient satisfaction, performance scale and side effects were recorded at baseline, 3rd day, 1, 2, 3 and 4 months after injection. Results: significant decrease in VAS in group B compared to group A at 1,2,3 and 4 months(P<0.05). Patient satisfaction increased significantly in group B more than group A at 2, 3 and 4 months. No statistical significant differences in patient performance scale between the two groups. No significant side effects were recorded in both groups. Conclusion: caudal neuroplasty plus botulinum toxin A injection in piriformis muscles is effective and safe in management of pain in failed back surgery syndrome.	G. Gamal, S. ElSheikh, N. Gouda, W. Gamal and G. A. El-Awady	Egyptian Journal of Anaesthesia
597	Amdinocillin pharmacokinetics. Simultaneous administration with cephalothin and cerebrospinal fluid penetration	In the treatment of serious infections, combinations of beta-lactam antibiotics are being utilized in order to avoid aminoglycoside toxicity and to achieve antibacterial synergy. The pharmacokinetics disposition of amdinocillin and cephalothin was determined, when administered alone or in combination to healthy volunteers, as well as the penetration of amdinocillin into human cerebrospinal fluid. Six subjects received, on separate occasions, single intravenous doses of amdinocillin 10 mg/kg, cephalothin 15 mg/kg, or a combination of the two in the same doses. The elimination half-lives of amdinocillin and cephalothin are increased when these drugs are given simultaneously, compared with when they are administered alone. However, no significant differences were observed. When they were given in combination, no significant changes in plasma clearance, renal clearance, or steady-state volume of distribution were found. Eight patients undergoing lumbar puncture for various neurologic disorders without inflamed meninges received a single dose of 10 mg/kg amdinocillin intravenously. One to two hours later, simultaneous plasma and cerebrospinal fluid samples were obtained. The concentration of amdinocillin in the cerebrospinal fluid ranged from approximately 1 to 10 percent of concomitant plasma concentrations. Thus, amdinocillin penetrates in the cerebrospinal fluid in marginal amounts in the absence of meningeal inflammation. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. G. Gambertoglio, S. L. Barriere, E. T. Lin and J. E. Conte Jr	American Journal of Medicine
244	Evaluation of CSF-adenosine deaminase activity in tubercular meningitis	Sixty patients of inflammatory brain disease were diagnosed and classified according to clinico-investigational criteria by Ahuja et al into tuberculous meningitis group (36 patients) and non-tuberculous meningitis group (24 patients). Tuberculous meningitis (TBM) patients were classified as probable (9 patients) and possible (27 patients) TBM. Non-TBM group comprised of pyogenic meningitis (8.3%), viral encephalitis (23.3%), cerebral malaria (5%) and enteric encephalopathy (3.3%). Cerebrospinal fluid-adenosine deaminase (CSF-ADA) activities were measured in both TBM and non-TBM groups. Mean CSF-ADA levels in TBM patients was 9.61 +/- 4.10 IU/L and was significantly elevated as compared to viral encephalitis and enteric encephalopathy cases; but difference was insignificant in comparison to pyogenic meningitis (7.92 +/- 0.95 IU/L) and cerebral malaria. Using 8 IU/L as cut off value for diagnosis of TBM a sensitivity of 44% and specificity of 75% was observed.	I. S. Gambhir, M. Mehta, D. S. Singh and H. D. Khanna	The Journal of the Association of Physicians of India
25	Dexamethasone in adults with bacterial meningitis	BACKGROUND: Mortality and morbidity rates are high among adults with acute bacterial meningitis, especially those with pneumococcal meningitis. In studies of bacterial meningitis in animals, adjuvant treatment with corticosteroids has beneficial effects. METHODS: We conducted a prospective, randomized, double-blind, multicenter trial of adjuvant treatment with dexamethasone, as compared with placebo, in adults with acute bacterial meningitis. Dexamethasone (10 mg) or placebo was administered 15 to 20 minutes before or with the first dose of antibiotic and was given every 6 hours for four days. The primary outcome measure was the score on the Glasgow Outcome Scale at eight weeks (a score of 5, indicating a favorable outcome, vs. a score of 1 to 4, indicating an unfavorable outcome). A subgroup analysis according to the causative organism was performed. Analyses were performed on an intention-to-treat basis. RESULTS: A total of 301 patients were randomly assigned to a treatment group: 157 to the dexamethasone group and 144 to the placebo group. The base-line characteristics of the two groups were similar. Treatment with dexamethasone was associated with a reduction in the risk of an unfavorable outcome (relative risk, 0.59; 95 percent confidence interval, 0.37 to 0.94; P=0.03). Treatment with dexamethasone was also associated with a reduction in mortality (relative risk of death, 0.48; 95 percent confidence interval, 0.24 to 0.96; P=0.04). Among the patients with pneumococcal meningitis, there were unfavorable outcomes in 26 percent of the dexamethasone group, as compared with 52 percent of the placebo group (relative risk, 0.50; 95 percent confidence interval, 0.30 to 0.83; P=0.006). Gastrointestinal bleeding occurred in two patients in the dexamethasone group and in five patients in the placebo group. CONCLUSIONS: Early treatment with dexamethasone improves the outcome in adults with acute bacterial meningitis and does not increase the risk of gastrointestinal bleeding.	J. Gans and D. Beek	The New England journal of medicine
546	Dexamethason gunstig bij volwassenen met acute bacteriële meningitis; een gerandomiseerd placebogecontroleerd onderzoek		J. Gans and D. Beek	Nederlands Tijdschrift voor Geneeskunde
304	Itraconazole compared with amphotericin B plus flucytosine in AIDS patients with cryptococcal meningitis	OBJECTIVE: We conducted a comparison of itraconazole versus amphotericin B plus flucytosine in the initial treatment of cryptococcal meningitis in patients with AIDS and established the efficacy of itraconazole as maintenance treatment. DESIGN: The trial was a prospective, randomized, and non-blinded study. SETTING: The study was performed at an academic centre for AIDS, Amsterdam, The Netherlands. PATIENTS, PARTICIPANTS: Twenty-eight HIV-1-seropositive men with a presumptive diagnosis of cryptococcal meningitis, randomized between 5 February 1987 and 1 January 1990, were included for analysis. INTERVENTIONS: Oral itraconazole (200 mg twice daily), versus amphotericin B (0.3 mg/kg daily) intravenously plus oral flucytosine (150 mg/kg daily) was administered for 6 weeks followed by maintenance therapy with oral itraconazole (200 mg daily) to all patients. MAIN OUTCOME MEASURES: Outcome measures were a complete or partial response, recrudescence and relapse. RESULTS: A complete response was observed in five out of the 12 patients who completed 6 weeks of initial treatment with itraconazole versus all 10 patients who completed treatment with amphotericin B plus flucytosine (P = 0.009). A partial response was observed in seven out of the 14 patients assigned to itraconazole. During maintenance therapy, recrudescence (n = 6) or relapse (n = 1) occurred in seven out of the 12 patients initially assigned to itraconazole, whereas two relapses occurred among nine patients initially treated with amphotericin B plus flucytosine (P = 0.22); recurrence of clinical symptoms was significantly related to a positive cerebrospinal fluid culture at 6 weeks (P = 0.003). CONCLUSION: Itraconazole is less effective compared with amphotericin B plus flucytosine in achieving a complete response in initial therapy in AIDS patients with cryptococcal meningitis.	J. Gans, P. Portegies, G. Tiessens, J. K. Eeftinck Schattenkerk, C. J. Boxtel, R. J. Ketel and J. Stam	AIDS (London, England)
536	Corticosteroids (dexamethasone versus intravenous methylprednisolone) in patients with tuberculous meningitis: a pilot study		R. K. Garg and H. S. Malhotra	Journal of the Neurological Sciences
81	Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults	This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.	R. Gasparini, M. Conversano, G. Bona, G. Gabutti, A. Anemona, P. M. Dull and F. Ceddia	Clinical and vaccine immunology : CVI
632	Sickle cell anaemia trial	The major cause of death in sickle cell anaemia is from infection, especially infection caused by Streptococcus pneumoniae. Meningitis, pneumonia and septicaemia caused by this organism are the primary types of infection leading to death. Children under three years of age are at highest risk. We have known for over twenty years that approximately 30 per cent of the infants born with sickle cell anaemia will become infected in the first three years of life and one-third can be expected to die from the infection. These data were the reason that we conducted the Prophylactic Penicillin Study (PROPS), a trial to investigate the effectiveness of oral prophylactic penicillin in preventing severe infection due to S. pneumoniae. This investigation was a very efficient, cost effective study because of its timeliness and its conduct within the framework of an ongoing study. Moreover, the question being answered was simple and focused with up-to-date data that permitted accurate estimates of sample size and incidence.	M. H. Gaston and J. Verter	Statistics in medicine
269	Dexamethasone and bacterial meningitis. A meta-analysis of randomized controlled trials	A meta-analysis of 5 randomized, controlled trials using dexamethasone as adjunctive therapy in the treatment of bacterial meningitis in children was done to assess the efficacy in reducing sequelae. A 6th study including both children and adults was analyzed separately. Results of the 5 pediatric studies indicated no significant difference in case-fatality rate between the placebo and dexamethasone groups. Significantly more neurologic sequelae were found in the placebo group during the period from discharge from hospital to 6 weeks after discharge (relative risk [RR] = 1.99, 95% confidence interval [CI] 1.13 to 3.53) and during the period beginning 6 months after discharge (RR = 3.90, 95% CI 1.72 to 8.85). The incidence of neurologic sequelae from 6 weeks to 6 months after discharge, though less with dexamethasone administration, did not reach statistical significance. The frequency of bilateral hearing loss was significantly greater in the placebo group (RR = 4.12, 95% CI 1.74 to 9.79), but unilateral loss was not statistically different in the two groups. Dexamethasone administration in addition to antimicrobial therapy appears to be effective in reducing neurologic sequelae and bilateral hearing loss associated with bacterial meningitis in children.	B. J. Geiman and A. L. Smith	The Western journal of medicine
490	Evaluation of corticosteroids in treatment of tuberculous meningitis		S. Ghosh, R. Seshardri and K. C. Jain	Archives of Disease in Childhood
315	Levels of serum immunoglobulin G, CSF IgG and IgG index in acute bacterial meningitis	This study characterised the levels of serum immunoglobulin G (IgG), cerebrospinal fluid IgG (CSF IgG) and IgG index as an aid to the diagnosis and prognosis of acute bacterial meningitis (ABM). A total of 28 patients with proven ABM at admission (age range: one month to 10 years; 17 males, 11 females) (group A) and 17 age- and sex-matched control children (group B) were studied. Levels were also compared between patients with neurological morbidity (n = 4; group C) and without neurological morbidity (n = 24; group D) who were subsets of group A. In addition, patients were divided randomly into two groups based on the treatment received (i.e. ceftriaxone together with dexamethasone [n = 11; group A1] and ceftriaxone only [n = 9; group A2] to assess the effect of dexamethasone. The results (mean +/- SEM) demonstrated intrathecal synthesis of IgG in ABM (group A vs group B: CSF IgG (mg/L): 92.64 +/- 23.54 vs 2.12 +/- 1.08, P < 0.002; IgG index: 0.959 +/- 0.481 vs 0.029 +/- 0.006, P < 0.001) which showed good diagnostic significance. In the patients with permanent neurological morbidity (group C) vs healthy survivors (group D), the CSF IgG and IgG index showed good prognostic significance (group C vs group D: CSF IgG (mg/L): 10.75 +/- 9.75 vs 106.24 +/- 29.37, P < 0.01; IgG index: 0.046 +/- 0.039 vs 1.132 +/- 0.568, P < 0.05). Dexamethasone lowered CSF-IgG and IgG-index levels, but the effect was not statistically significant (group A1 vs group A2: P > 0.1).	A. S. Giasuddin, N. M. Shembesh, S. M. el-Bargathy, I. M. Kashbur and B. N. Rao	British journal of biomedical science
282	Dexamethasone therapy for bacterial meningitis in adults: a double blind placebo control study	Routine use of steroids in the treatment of bacterial meningitis remains controversial. A prospective placebo controlled double blind study of dexamethasone was carried out in 40 patients (age>10 years) of acute bacterial meningitis. The patients were randomly assigned to receive either placebo (n=20) or dexamethasone (n=20) in addition to injection ceftriaxone 100 mg/kg/day (maximum 4 gm/day) for 14 days. Dexamethasone sodium phosphate was given in dose of 0.6 mg/kg/day in 4 divided doses, for first 4 days of therapy. First dose of dexamethasone was given 15 minutes prior to first dose of ceftriaxone. Baseline demographics, clinical and laboratory features of the two groups were similar. Clinical improvement of signs of meningeal irritation was rapid in dexamethasone group than in the placebo group, but no significant difference was observed regarding resolution of fever, headache and vomiting. Secondary fever (mean+/-SD 15.00), gastrointestinal tract bleeding (mean+/-SD 15.00) and psychiatric manifestations (mean+/-SD 10.00) were more common in dexamethasone group. Neurological complications and hearing loss were more common and severe in placebo group as compared to the dexamethasone group (p<0.05). It is concluded that dexamethasone may be beneficial in some aspects of bacterial meningitis, in adults. A study with a larger number of cases in each group is recommended.	D. Gijwani, M. R. Kumhar, V. B. Singh, V. S. Chadda, P. K. Soni, K. C. Nayak and B. K. Gupta	Neurology India
129	Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial	BACKGROUND: AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS: Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION: Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.	S. Gilman, M. Koller, R. S. Black, L. Jenkins, S. G. Griffith, N. C. Fox, L. Eisner, L. Kirby, M. B. Rovira, F. Forette and J. M. Orgogozo	Neurology
3	Intramuscular ceftriaxone versus ampicillin-chloramphenicol in childhood bacterial meningitis	70 children aged 4 months-12 years, with bacteriologically proven bacterial meningitis were treated with either intramuscular (IM) ceftriaxone (CFT) 100 mg/kg given once daily, or with combined IM ampicillin 160 mg/kg/day and IM chloramphenicol 100 mg/kg/day (AMC) given every 6 h. There were 35 children in each of the treatment groups. The children in both groups were comparable with regard to age, sex, duration of illness, and state of consciousness. 29 children in the CFT group and 26 in the AMC group recovered without any permanent complications or sequelae. Of the 15 children who died 10 (3 in the CFT and 7 in the AMC group) were in deep coma when treatment was started. Intramuscular CFT given once daily proved effective and much easier to administer than our standard hospital therapy with combined AMC given every 6 h IM.	N. I. Girgis, A. H. Abu el Ella, Z. Farid, R. L. Haberberger, F. S. Galal and J. N. Woody	Scandinavian journal of infectious diseases
265	Dexamethasone adjunctive treatment for tuberculous meningitis	During a 5-year period, 280 of 2010 patients admitted to the meningitis ward of a referral hospital in Cairo, Egypt, were clinically diagnosed as having tuberculous meningitis and were treated with either antituberculous chemotherapy and dexamethasone or antituberculous chemotherapy alone. Fatality rates and neurologic sequelae were compared for the 2 treatment groups in the 160 patients who had cerebrospinal fluid cultures positive for Mycobacterium tuberculosis. The overall mortality rate of 51% reflects the delay in receiving appropriate therapy (79% with symptoms for more than 2 weeks) and the severity of illness on admission (56% in coma, 39% drowsy). The fatality rate was significantly lower in the group receiving dexamethasone (43% vs. 59%, P less than 0.05), particularly in the drowsy patients (15% vs. 40% P less than 0.04), and in patients surviving long enough to receive at least 10 days of treatment (14% vs. 33%, P less than 0.02). Development of neurologic complications after initiation of therapy (4 vs. 10) and permanent sequelae (6 vs. 13) were significantly lower in the dexamethasone-treated group (P less than 0.02).	N. I. Girgis, Z. Farid, M. E. Kilpatrick, Y. Sultan and I. A. Mikhail	The Pediatric infectious disease journal
316	Rifampicin in the treatment of tuberculous meningitis	Seventy-one patients diagnosed to have tuberculous meningitis were treated with isoniazid, streptomycin plus either rifampicin (36 patients or ethambutol (35 patients). Results of therapy were identical in both treatment-groups (approximately 50 per cent mortality). Rifampicin appears to be as effective as ethambutol in the treatment of this infection.	N. I. Girgis, M. W. Yassin, L. W. Laughlin, D. C. Edman, Z. Farid and R. H. Watten	The Journal of tropical medicine and hygiene
5	Ampicillin compared with penicillin and chloramphenicol combined in the treatment of bacterial meningitis		N. I. Girgis, M. W. Yassin, W. R. Sanborn, R. E. Burdick, H. A. el-Ela, D. C. Kent, K. Sorensen and I. M. Nabil	The Journal of tropical medicine and hygiene
312	The value of ethambutol in the treatment of tuberculous meningitis	This is a prospective treatment study of 86 patients with tuberculous meningitis admitted to the Abbassia Fever Hospital Cairo, Egypt. The causative organism was cultured from the cerebro spinal fluidin 47 patients, was identified by Zeihl Nelson stain in five and in the remaining 34 patients the diagnosis was based on the clinical course and changes in the CSF chemistry and cell count. The data indicate that ethambutol can be used as a companion drug to INH and streptomycin in the treatment of the disease and that the mortality is directly dependent on the state of consciousness upon initiation of therapy.	N. I. Girgis, M. W. Yassin, J. E. Sippel, K. Sorensen, A. Hassan, W. F. Miner, Z. Farid and A. Abu el Ella	The Journal of tropical medicine and hygiene
105	Intramuscular compared with intravenous ampicillin in the treatment of meningococcal meningitis		N. I. Girgis, W. Yassin, J. E. Sippel and Z. Farid	Scandinavian journal of infectious diseases
553	Interaction between route of intra-CSF chemotherapy administration and efficacy of therapy in patients wtih neoplastic meningitis	42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta,GA, 2-6 June, 2006	M. J. Glantz, M. C. Chamberlain, T. Batchelor, W. Eric, F. Cavalli and W. R. Shapiro	Journal of Clinical Oncology: ASCO annual meeting proceedings
154	Route of intracerebrospinal fluid chemotherapy administration and efficacy of therapy in neoplastic meningitis	BACKGROUND: A study was undertaken to determine whether route (intraventricular vs intralumbar) of intracerebrospinal fluid (intra-CSF) drug administration influences progression-free survival in the treatment of patients with neoplastic meningitis, which occurs in 1% to 5% of patients with known cancer. Currently available treatment options result in modest responses, which is in part a reflection of obstacles to drug delivery into the leptomeningeal space. METHODS: One hundred patients with clinically and cytologically or radiographically documented neoplastic meningitis because of solid cancers received intra-CSF liposomal cytarabine or methotrexate as specified in a randomized phase 4 trial. The 2 treatment arms were well balanced for demographic and tumor-related characteristics of known prognostic importance, including age, performance status, tumor type, extent of systemic and other central nervous system (CNS) disease, prior CNS therapy, and concurrent systemic chemotherapy. RESULTS: One hundred patients were randomized and treated (52 with sustained-release cytarabine, and 48 with methotrexate). Progression-free survival (the primary study endpoint) was identical between the sustained-release cytarabine and methotrexate treatment arms for all 100 patients (35 vs 37.5 days, P = .79). When progression-free survival was examined as a function of route of chemotherapy administration (lumbar vs ventricular), there was no difference for patients treated with sustained-release cytarabine (29 vs 43 days, P = .35). For patients treated with methotrexate, however, there was a statistically significant difference favoring patients receiving intraventricular therapy (19 vs 43 days, P = .048). CONCLUSIONS: Site of intra-CSF chemotherapy drug administration is clinically relevant with short half-life drugs such as methotrexate.	M. J. Glantz, A. Horn, R. Fisher and M. C. Chamberlain	Cancer
429	A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors	Standard treatment for neoplastic meningitis requires frequent intrathecal (IT) injections of chemotherapy and is only modestly effective. DepoCyt is a sustained-release formulation of cytarabine that maintains cytotoxic concentrations of the drug in the cerebrospinal fluid (CSF) for more than 14 days after a single 50-mg injection. We conducted a randomized, controlled trial of DepoCyt versus methotrexate in patients with solid tumor neoplastic meningitis. Sixty-one patients with histologically proven cancer and positive CSF cytologies were randomized to receive IT DepoCyt (31 patients) or IT methotrexate (30 patients). Patients received up to six 50-mg doses of DepoCyt or up to sixteen 10-mg doses of methotrexate over 3 months. Treatment arms were well balanced with respect to demographic and disease-related characteristics. Responses occurred in 26% of DepoCyt-treated and 20% of methotrexate-treated patients (P = 0.76). Median survival was 105 days in the DepoCyt arm and 78 days in the methotrexate arm (log-rank P = 0.15). The DepoCyt group experienced a greater median time to neurological progression (58 versus 30 days; log-rank P = 0.007) and longer neoplastic meningitis-specific survival (log-rank P = 0.074; median meningitis-specific survival, 343 versus 98 days). Factors predictive of longer progression-free survival included absence of visible central nervous system disease on neuroimaging studies (P<0.001), longer pretreatment duration of CSF disease (P<0.001), history of intraparenchymal tumor (P<0.001), and treatment with DepoCyt (P = 0.002). The frequency and grade of adverse events were comparable between treatment arms. In patients with solid tumor neoplastic meningitis, DepoCyt produced a response rate comparable to that of methotrexate and significantly increased the time to neurological progression while offering the benefit of a less demanding dose schedule.	M. J. Glantz, K. A. Jaeckle, M. C. Chamberlain, S. Phuphanich, L. Recht, L. J. Swinnen, B. Maria, S. LaFollette, G. B. Schumann, B. F. Cole and S. B. Howell	Clinical cancer research : an official journal of the American Association for Cancer Research
326	Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis	PURPOSE: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days. PATIENTS AND METHODS: Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle. RESULTS: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trend in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P >.05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P =.041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease. CONCLUSION: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.	M. J. Glantz, S. LaFollette, K. A. Jaeckle, W. Shapiro, L. Swinnen, J. R. Rozental, S. Phuphanich, L. R. Rogers, J. C. Gutheil, T. Batchelor, D. Lyter, M. Chamberlain, B. L. Maria, C. Schiffer, R. Bashir, D. Thomas, W. Cowens and S. B. Howell	Journal of clinical oncology : official journal of the American Society of Clinical Oncology
127	[Ribonuclease therapy for tick-borne encephalitis]		B. M. Glukhov, A. P. Ierusalimski and R. I. Salganik	Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952)
586	Post-lumbar puncture headache: The relation between experimental suprathreshold pain sensitivity and a quasi-experimental clinical pain syndrome	The relation between general experimental pain sensitivity and the clinical expression of post-lumbar puncture syndrome (PLPS) was examined in a prospective double-blind study of patients who underwent a lumbar puncture with a 20-gauge spinal needle. In 44 neurology patients randomized pain was induced on the middle phalanges of fingers II-IV of both hands using a tension device on the day before lumbar puncture. Pain intensity was measured using the category sub-dividing procedure. The correspondence between experimental pain stimuli and induced pain intensities could be described by a logarithmic function. PLPS symptoms were documented in a multi-dimensional quantitative fashion using various scales. Pronounced position-dependent headache occurred in 31% of the patients. There proved to be very significant effects of experimental pain sensitivity on intensity and duration of position-dependent headaches, as well as on vegetative symptoms of PLPS (P less than or equal to 0.01). The results provide an explanation for the varying interindividual manifestation of PLPS symptoms, in addition to factors already identified such as the size of needle used in individual patients. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	H. Gobel and S. Schenkl	Pain
628	Is the BCG test of diagnostic value in tuberculosis? [see comments]	SETTING: In developing countries including Turkey, tuberculosis is still a major problem. Rapid diagnosis and early medical intervention are the two most important considerations in preventing the spread of the disease. OBJECTIVE: This study was carried out to determine the diagnostic value of BCG test in childhood tuberculosis and compare it with tuberculin test in this regard. DESIGN: 50 patients and 20 healthy children without any evidence of previous BCG vaccination and aged 80 days-15 years were simultaneously tested with purified protein derivative (PPD) and BCG vaccine. RESULTS: In pulmonary tuberculosis BCG test was positive in 100% of cases and the PPD test in 44.5%. Similarly, BCG test was positive in 100% of military tuberculosis and tuberculous meningitis cases but PPD test was negative in all of them. Out of 22 patients with malnutrition 18 (82%) had positive BCG test and 4 had positive PPD test. BCG test showed uniformly high positivity in all grades of malnutrition. CONCLUSION: BCG is more reliable and sensitive than the tuberculin test in the diagnosis of tuberculosis. It is still valuable in the diagnosis of tuberculosis especially in developing countries where the disease is still a major public health problem and where sophisticated methods such as rapid culture with BACTEC and demonstration of bacilli with DNA probes are not widely available.	A. Gocmen, N. Kiper, U. Ertan, O. Kalayci and U. Ozcelik	Tuber Lung Dis
447	Persistent urinary antigen excretion in infants vaccinated with Haemophilus influenzae type b capsular polysaccharide conjugated with outer membrane protein from Neisseria meningitidis	Testing for urinary excretion of capsular polysaccharide antigen was carried out in 40 four-month-old Navajo infants who had received injections of a Haemophilus influenzae type b Neisseria meningitidis outer membrane protein conjugate vaccine (PedvaxHIB; Merck, Sharp and Dohme Research Laboratories) as part of an ongoing efficacy trial of the vaccine. Urine from 12 placebo recipients was also analyzed. Urine samples were collected on the day of injection (the first voided urine following the injection) and 3, 7, 10, 14, 21 and 30 days later. All vaccine recipients had at least 1 positive specimen. Vaccine recipients excreted antigen for a median period of 14 days after injection. On the first day 54% of vaccinees excreted antigen. Antigen was excreted by 89% of vaccinees on Day 3, 79% on Day 7, 82% on Day 10, 64% on Day 14, 56% on Day 21 and 41% on Day 30. Urine from placebo recipients tested positive in 12% on Day 1, 18% on Day 3, none on Day 7, 14% on Day 10, 11% on Day 14, 10% on Day 21 and none on Day 30. The rate of positive test results was significantly higher among vaccine recipients than among controls. Physicians should not rely on urinary antigen detection tests for predicting the presence of invasive disease caused by H. influenzae type b in infants for at least 30 days after injections with this conjugate vaccine, and possibly longer.	J. G. Goepp, M. Hohenboken, J. Almeido-Hill and M. Santosham	The Pediatric infectious disease journal
110	Immunogenicity of a reduced schedule of pneumococcal conjugate vaccine in healthy infants and correlates of protection for serotype 6B in the United Kingdom	BACKGROUND: Pneumococcal conjugate vaccine (PCV) was introduced in the United Kingdom immunization schedule in September 2006. This study was conducted to establish the immunogenicity of licensed PCV (Prevenar) at a reduced, 2 priming dose schedule (2+1) and to evaluate functional responses in the context of vaccine effectiveness. METHODS: Infants were randomized to receive PCV at 2 and 3 months or 2 and 4 months of age. Boosters were administered at the same time as Haemophilus influenzae type B/meningococcal C conjugate and Measles, Mumps and Rubella or with Measles, Mumps and Rubella alone (www.ClinicalTrials.gov NCT00197808). RESULTS: PCV at 2/3 months of age was poorly immunogenic and recruitment to this arm was terminated. PCV at 2/4 months of age resulted in lower than expected responses to serotypes 6B and 23F. Functional analysis of serotype 6B by OPA revealed that an enzyme-linked immunosorbent assay cutoff of 0.2 microg/mL was a better predictor of OPA positivity than a cut off of 0.35 microg/mL. PCV booster responses were excellent and no interference from concomitant vaccines was noted. CONCLUSIONS: An interval of at least 8 weeks is required when starting PCV vaccination at 2 months of age although not all serotypes are equally immunogenic. Correlates of protection derived from enzyme-linked immunosorbent assay values may not be equally appropriate for all serotypes as illustrated by results for 6B in this study.	D. Goldblatt, J. Southern, L. Ashton, N. Andrews, S. Woodgate, P. Burbidge, P. Waight and E. Miller	The Pediatric infectious disease journal
21	Cefotaxime and ceftriaxone cerebrospinal fluid levels during treatment of bacterial meningitis in children	Cefotaxime (CTX) and ceftriaxone (CRO) were compared for cerebrospinal fluid (CSF) penetration and antimicrobial efficacy in cases of bacterial meningitis in children. This was a comparative study of CRO (100mg/kg once daily) and CTX (50 mg/kg 6 hourly) in the treatment of children with bacterial meningitis. The aetiological agents included Streptococcus pneumoniae (SPn), Haemophilus influenzae type b (Hib) and Neisseria meningitidis (NMen). Minimum inhibitory concentrations (MICs) were measured. In 33 patients from whom a second CSF specimen was obtained, CSF was cultured and assayed for antibiotic concentration. Median MICs of CTX and CRO for SPn, Hib and NMen were 0.01 and 0.01 microg/mL, 0.004 and 0.002 microg/mL and 0.008 and 0.004 microg/mL, respectively. All 33 repeat lumbar puncture specimens were sterile. The lowest CSF level recorded (0.45 microg/mL for CTX) was 45 times the MIC (0.01 microg/mL). The highest levels (24-35 microg/mL for CRO) were up to 8750 times the MIC of the patient's causative organism. A wide range of CSF levels for both antibiotics was observed. Levels varied with post-dose interval and duration of illness. On the basis of these findings, clinicians should be reassured that repeat lumbar puncture is not recommended for the causative organisms in this study (i.e., for Hib, NMen and penicillin/cefotaxime/ceftriaxone fully-susceptible SPn).	P. N. Goldwater	International journal of antimicrobial agents
583	Treatment of urinary infection with cotrimoxazole (trimethoprim sulphamethoxazole)	The therapeutic efficiency of co trimoxazole used in the treatment of urinary infection was evaluated by comparing it with ampicillin and sulphadimidine. 40 patients entered the trial. The sole criterion of infection was a bacterial count exceeding 10sup 5 bacteria per ml of urine in 2 consecutive specimens. Allocation to treatment group was at random. The duration of chemotherapy was 7 days. The cure rate effected by co trimoxazole and ampicillin was comparable and superior to sulphadimidine. No toxic effects were reported in the trial. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	N. C. Gong, S. K. Thavaraja, K. E. Chan and K. H. Chai	Medical Journal of Malaysia
76	Immunogenicity and tolerability of recombinant serogroup B meningococcal vaccine administered with or without routine infant vaccinations according to different immunization schedules: a randomized controlled trial	CONTEXT: In the absence of an effective vaccine, serogroup B Neisseria meningitidis (MenB) remains a major cause of invasive disease in early childhood in developed countries. OBJECTIVE: To determine the immunogenicity and reactogenicity of a multicomponent MenB vaccine (4CMenB) and routine infant vaccines when given either concomitantly or separately. DESIGN, SETTING, AND PARTICIPANTS: Phase 2b, multicenter, open-label, parallel-group, randomized controlled study of 1885 infants enrolled at age 2 months from August 2008 to July 2010 in Europe. INTERVENTION: Participants were randomized 2:2:1:1 to receive (1) 4CMenB at 2, 4, and 6 months with routine vaccines (7-valent pneumococcal and combined diphtheria, tetanus, acellular pertussis, inactivated polio, hepatitis B, Haemophilus influenzae type b vaccines); (2) 4CMenB at 2, 4, and 6 months and routine vaccines at 3, 5, and 7 months; (3) 4CMenB with routine vaccines at 2, 3, and 4 months; or (4) routine vaccines alone at 2, 3, and 4 months. MAIN OUTCOME MEASURES: Percentage of participants with human complement serum bactericidal activity (hSBA) titer of 1:5 or greater against 3 MenB strains specific for vaccine antigens (NZ98/254, 44/76-SL, and 5/99). RESULTS: After three 4CMenB vaccinations, 99% or more of infants developed hSBA titers of 1:5 or greater against strains 44/76-SL and 5/99. For NZ98/254, this proportion was 79% (95% CI, 75.2%-82.4%) for vaccination at 2, 4, and 6 months with routine vaccines, 86.1% (95% CI, 82.9%-89.0%) for vaccination at 2, 4, and 6 months without routine vaccines, and 81.7% (95% CI, 76.6%-86.2%) for vaccination at 2, 3, and 4 months with routine vaccines. Responses to routine vaccines given with 4CMenB were noninferior to routine vaccines alone for all antigens, except for the responses to pertactin and serotype 6B pneumococcal polysaccharide. Fever was seen following 26% (158/602) to 41% (247/607) of 4CMenB doses when administered alone, compared with 23% (69/304) to 36% (109/306) after routine vaccines given alone and 51% (306/605) to 61% (380/624) after 4CMenB and routine vaccines administered together. CONCLUSION: A 4CMenB vaccine is immunogenic against reference strains when administered with routine vaccines at 2, 4, and 6 or at 2, 3, and 4 months of age, producing minimal interference with the response to routine infant vaccinations. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00721396.	N. Gossger, M. D. Snape, L. M. Yu, A. Finn, G. Bona, S. Esposito, N. Principi, J. Diez-Domingo, E. Sokal, B. Becker, D. Kieninger, R. Prymula, P. Dull, E. Ypma, D. Toneatto, A. Kimura and A. J. Pollard	JAMA : the journal of the American Medical Association
400	Toward a rational therapeutic strategy for arachnoiditis. A possible role for d-penicillamine	Twenty-six patients (13 men and 13 women), ranging in age from 38 to 75 years, with surgical and/or radiculographic evidence of chronic adhesive spinal arachnoiditis (CASA) were admitted to a randomly allocated, double-blind, 6-month crossover trial of d-penicillamine (500 mg/day) versus matching placebo. Assessments using subjective and objective criteria at 3-month intervals demonstrated no statistically significant effect with either d-penicillamine or placebo or between them. Thirteen of the 17 patients completing the trial expressed no clear preference. One patient preferred placebo. The remaining three patients who expressed strong preference for d-penicillamine (supported by objective data) subsequently maintained improvement on long-term therapy for up to 5 years. It is concluded that there may be a small subgroup of patients with CASA who might benefit from d-penicillamine therapy.	R. Grahame, B. Clark, M. Watson and C. Polkey	Spine
43	Protective activity of group C anticapsular antibodies elicited in two-year-olds by an investigational quadrivalent Neisseria meningitidis-diphtheria toxoid conjugate vaccine	BACKGROUND: Quadrivalent capsular group A, C, Y and W-135 meningococcal conjugate (MC-4) vaccines are under development OBJECTIVE: Predict efficacy of an investigational MC-4 vaccine in 2-year-old children for prevention of group C disease. DESIGN: Measurement of group C antibody concentrations, avidity and bactericidal and passive protective activity in sera from 2-year-olds given 1 dose of MC-4 vaccine (N = 30) and 3-year-olds (N = 30) and adults (N = 26) given 1 dose of meningococcal polysaccharide (MPS-4) vaccine. RESULTS: One month after vaccination, the geometric mean anticapsular antibody concentration of children given MC-4 vaccine (3.1 microg/ml) was lower than that of control children (5.1 microg/ml; P < 0.04) or adults immunized with MPS-4 vaccine (22.9 microg/ml; P < 0.001). However, the percent of sera with protective bactericidal titers of >/=1/4 was higher in children given MC-4 vaccine (50%, versus 17% in children given MPS-4 vaccine; P < 0.02) and was not significantly different from that of immunized adults (65%). In children, the mean antibody avidity at 1 month was higher in the MC-4 group (22 nM versus 16 nM in the MPS-4 group; P = 0.002), and at 6 months increased in the MC-4 group (28 nM; P < 0.001), but not in the MPS-4 vaccine group (17 nM). Higher avidity antibody gave greater passive protection in the infant rat bacteremia model than did lower avidity antibody (P < 0.03). CONCLUSIONS: Although MPS-4 vaccine elicited higher group C serum antibody concentrations in 3-year-olds than did MC-4 vaccine in 2-year-olds, the higher antibody avidity after MC-4 vaccine resulted in higher bactericidal and passive protective activity.	D. M. Granoff and S. L. Harris	The Pediatric infectious disease journal
575	Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation. The Collaborative Vaccine Study Group	Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically. To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM). Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappa II-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having lambda VII variable regions. HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001). The respective values for HibId-2 were 47, 18, and 10% (P = 0.001). Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies. In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile. These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines.	D. M. Granoff, P. G. Shackelford, S. J. Holmes and A. H. Lucas	The Journal of clinical investigation
494	Concerns regarding a randomized study of the timing of antiretroviral therapy in Zimbabweans with AIDS and acute cryptococcal meningitis		P. M. Grant, J. A. Aberg and A. R. Zolopa	Clinical infectious diseases
281	Diagnosis and management of increased intracranial pressure in patients with AIDS and cryptococcal meningitis. The NIAID Mycoses Study Group and AIDS Cooperative Treatment Groups	This study was undertaken to characterize the laboratory and clinical course of patients with AIDS and cryptococcal meningitis who had normal or elevated cerebrospinal fluid (CSF) pressure. Data were obtained retrospectively from a randomized multicenter quasifactorial phase III study comparing amphotericin B with or without flucytosine in primary treatment of cryptococcal meningitis. CSF pressure was measured before treatment and at 2 weeks. Repeated lumbar punctures were done to drain CSF and to reduce pressure. Patients with the highest baseline opening pressures (> or = 250 mm H2O) were distinguished by higher titers of cryptococcal capsular polysaccharide antigen in CSF; more frequently positive India ink smears of CSF; and more frequent headache, meningismus, papilledema, hearing loss, and pathological reflexes. After receiving antifungal therapy, those patients whose CSF pressure was reduced by >10 mm or did not change had more frequent clinical response at 2 weeks than did those whose pressure increased >10 mm (P<.001). Patients with pretreatment opening pressure <250 mm H2O had increased short-term survival compared with those with higher pressure. We recommend that opening pressures >/=250 mm H2O be treated with large-volume CSF drainage.	J. R. Graybill, J. Sobel, M. Saag, C. Horst, W. Powderly, G. Cloud, L. Riser, R. Hamill and W. Dismukes	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
128	Intensive versus conventional insulin therapy in critically ill neurologic patients	BACKGROUND: Previous studies of glycemic control in non-neurologic ICU patients have shown conflicting results. The purpose was to investigate whether intensive insulin therapy (IIT) to keep blood glucose levels from 80 to 110 mg/dl or conventional treatment to keep levels less than 151 mg/dl was associated with a reduction of mortality and improved functional outcome in critically ill neurologic patients.METHODS: Within 24 h of ICU admission, mechanically ventilated adult neurologic patients were enrolled after written informed consent and randomized to intensive or conventional control of blood glucose levels with insulin. Primary outcome measure was death within 3 months. Secondary outcome measures included 90-day modified Rankin scale (mRS) score, ICU, and hospital LOS.RESULTS: 81 patients were enrolled. The proportion of deaths was higher among IIT patients but this was not statistically significant (36 vs. 25%, P = 0.34). When good versus poor outcome at 3 months was dichotomized to mRS score 0-2 versus 3-6, respectively, there was no difference in outcome between the two groups (76.2 vs. 75% had a poor 3-month outcome, P = 1.0). There was also no difference in ICU or hospital LOS. Hypoglycemia (<60 mg/dl) and severe hypoglycemia (<40 mg/dl) were more common in the intensive arm (48 vs. 11%, P = 0.0006; and 4 vs. 0%, P = 0.5, respectively).CONCLUSION: There was no benefit to IIT in this small critically ill neurologic population. This is the first glycemic control study to specifically examine both critically ill stroke and traumatic brain injury (TBI) patients and functional outcome. Given these results, IIT cannot be recommended over conventional control.	D. M. Green, K. H. O'Phelan, S. L. Bassin, C. W. Chang, T. S. Stern and S. M. Asai	Neurocritical care
53	CNS infection, CSF matrix metalloproteinase concentrations, and clinical/laboratory features		J. A. Green, T. Thi Hong Chau, J. J. Farrar, J. S. Friedland and G. E. Thwaites	Neurology
337	Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis	BACKGROUND: Adjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations were studied in a subset of HIV uninfected adults (n = 37) with TBM recruited to a randomized, placebo-controlled trial of adjuvant dexamethasone. Analysis followed a pre-defined plan. Dexamethasone significantly reduced CSF MMP-9 concentrations in early follow up samples (median 5 days (range 3-8) of treatment), but had no significant influence on other MMPs/TIMPs. Additionally CSF MMP-9 concentration was strongly correlated to concomitant CSF neutrophil count. CONCLUSIONS/SIGNIFICANCE: Dexamethasone decreased CSF MMP-9 concentrations early in treatment and this may represent one mechanism by which corticosteroids improve outcome in TBM. The strong correlation between CSF MMP-9 and neutrophil count suggests that polymorphonuclear leukocytes may play a central role in the early pathogenesis of TBM.	J. A. Green, C. T. Tran, J. J. Farrar, M. T. Nguyen, P. H. Nguyen, S. X. Dinh, N. D. Ho, C. V. Ly, H. T. Tran, J. S. Friedland and G. E. Thwaites	PloS one
393	Prevention of secondary cases of meningococcal disease in household contacts by vaccination	Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.	B. M. Greenwood, M. Hassan-King and H. C. Whittle	Br Med J
374	Control of meningococcal infection in the African meningitis belt by selective vaccination	During an outbreak of group-A meningococcal meningitis, information was collected on the distribution of cases of this infection in an area in northern Nigeria. More than 1 case was recorded in all but 3 of 23 affected villages. Members of 9 villages, with a population of about 10 000, in which there had been 2 cases of meningococcal disease were vaccinated with 50 microgram of group-A and group-C meningococcal polysaccharide vaccine. There were subsequently 10 cases of meningococcal disease in these villages but only 2 of these patients had been vaccinated. In contrast there were 38 cases of meningococcal disease in 7 control villages with a similar population. Until we have more information on the duration of immunity after meningococcal vaccination, selective vaccination may be a more cost-effective means of controlling meningococcal disease in the African meningitis belt than routine mass immunisation.	B. M. Greenwood and S. S. Wali	Lancet
435	Safety and immunogenicity of group Y and group W135 meningococcal capsular polysaccharide vaccines in adults	Serogroup Y and W135 Neisseria meningitidis capsular polysaccharide vaccines were tested as monovalent and divalent preparations in groups of 10 adult human volunteers at a dose of 50 (monovalent) or 100 micrograms (divalent) injected subcutaneously. Reactogenicity was low for the group Y vaccine and the group Y-W135 combined vaccine; 3 of 10 volunteers developed systemic reactions after group W135 vaccination. All three vaccines induced significant homologous and heterologous binding and bactericidal antibody. Except for group W135 bactericidal antibody, homologous responses exceeded heterologous responses, and divalent and monovalent vaccines induced equivalent homologous responses. Homologous bactericidal antibody responses were maintained for 4 weeks in 85% of group W135 vaccinates and in 100% of group Y vaccinates. Bactericidal antibody was induced in 11 of 11 group Y and 12 of 15 group W135 volunteers without preexisting respective bactericidal activities, regardless of which vaccine they received. For all three vaccines, antibody levels declined only slightly over 6 months. Prevaccination antibody levels positively affected postvaccination binding antibody levels, but not bactericidal levels.	J. M. Griffiss, B. L. Brandt, P. L. Altieri, G. B. Pier and S. L. Berman	Infection and immunity
436	Human immune response to various doses of group Y and W135 meningococcal polysaccharide vaccines	A divalent vaccine containing equal weights of Neisseria meningitidis group Y and group W135 capsular polysaccharides was inoculated subcutaneously into groups of 32 military recruit volunteers at doses of 10, 25, 50, and 100 micrograms in 10-microliter/microgram volumes. At 4 weeks, the two higher doses induced significantly greater binding antibody responses than did the two lower doses. Differences in response were not found between the two higher doses or between the two lower doses. An additional 32 volunteers received a dose of 25 micrograms in a 20-microliter/microgram volume. Binding antibody response to this vaccine did not differ from the response to doses of 10 and 25 microgram in 10-microliter/microgram volumes. In contrast, bactericidal antibody responses did not differ among doses. Bactericidal antibody was induced in 100% of individuals with low (greater than 4 log2) preexisting serum bactericidal activity, regardless of dose. Bactericidal antibody nonresponse was restricted to individuals with high preexisting serum bactericidal titers. The discrepant dose response between binding and bactericidal antibody resulted from the induction of nonlytic antibody by the higher doses. We conclude that there are no advantages to doses in excess of 5 micrograms of these two chemically similar polysaccharides for the target population of young adult military recruits.	J. M. Griffiss, B. L. Brandt and D. D. Broud	Infection and immunity
643	Comparative trial of immunoprophylaxis with RATG versus OKT3	A randomized trial of rabbit antithymocyte globulin (polyclonal) versus OKT3 monoclonal antibody prophylaxis was carried out in 82 heart transplant recipients, who, in addition, received baseline immunosuppression with cyclosporine, azathioprine, and prednisone. One-year actuarial survival was comparable between groups (95% to 98%), but the likelihood of histologic rejection within the first 30 days of transplant was more than seven times greater in OKT3 patients (0.58/patient vs 0.08/patient). Patients receiving OKT3 were more likely to have repeated episodes of rejection, and the mean time to rejection for patients receiving OKT3 was shorter (33 days) than for patients receiving rabbit antithymocyte globulin (67 days). At 120 days, while 52% of patients receiving rabbit antithymocyte globulin were free of rejection, versus 37% of the OKT3 patients, the difference was not significant. There was no difference in the incidence of major or minor bacterial or viral infection between groups, but significant hemodynamic side effects were seen after the first dose of OKT3, and aseptic meningitis developed in two OKT3 patients.	B. P. Griffith, R. L. Kormos, J. M. Armitage, J. S. Dummer and R. L. Hardesty	The Journal of heart transplantation
160	Randomized prospective comparison of intraventricular methotrexate and thiotepa in patients with previously untreated neoplastic meningitis. Eastern Cooperative Oncology Group	PURPOSE: This prospective randomized cooperative group study was conducted in patients with neoplastic meningitis treated with intrathecal methotrexate or thiotepa to assess response rates and survival, prognostic factors, and the toxicity of these regimens. PATIENTS AND METHODS: Fifty-nine adults with nonleukemic malignancies, performance status of 0 to 3, and positive CSF cytologies were assigned to receive intrathecal methotrexate (10 mg) or thiotepa (10 mg) twice weekly. Radiation, was administered to mass lesions and/or symptomatic sites and appropriate systemic therapy was given concomitantly. RESULTS: Fifty-two patients were assessable. Most were female (79%), nonambulatory (77%), had been pretreated with radiation (52%) and chemotherapy (77%), and had evidence of systemic disease (65%). Most primary cancers were of the breast (48%), lung (23%), or lymphatics (19%). Treatment arms were well balanced, except that more patients randomized to methotrexate had breast cancer (61% v 33%) and were without evidence of systemic cancer (21% v 4%). No patient had important neurologic improvement with therapy, and 75% deteriorated neurologically within 8 weeks of initiating therapy. Survival ranged from 4 days to 110.5+ weeks. Median survival for patients receiving methotrexate was 15.9 weeks and 14.1 weeks for patients treated with thiotepa. Factors predictive of shorter survival included progressive systemic disease (P = .0005), poor performance status (P = .03), and significant cranial nerve palsies (P = .02). Although serious toxicities were similar, mucositis (P = .04) and neurologic complications (P = .008) were more common in patients who received methotrexate. CONCLUSION: The efficacy and overall toxicities of intraventricular methotrexate and thiotepa seem similar and neither reverses fixed neurologic deficits. Early diagnosis and treatment and new therapeutic approaches are needed to improve the outcome for patients with neoplastic meningitis.	S. A. Grossman, D. M. Finkelstein, J. C. Ruckdeschel, D. L. Trump, T. Moynihan and D. S. Ettinger	Journal of clinical oncology : official journal of the American Society of Clinical Oncology
573	Early atopic disease and early childhood immunization--is there a link?	BACKGROUND: There are frequent concerns about early immunizations among the parents of children at heightened risk for atopy. The study assessed the effect of vaccine immunization before the first birthday on eczema severity and allergic sensitization in the second year of life. METHODS: A total of 2184 infants, aged 1-2 years, with established atopic dermatitis and a family history of allergy, from 97 study centres in 10 European countries, South Africa and Australia were included. Exposure to vaccines (diphtheria, tetanus, pertussis, polio, Haemophilus influenzae Type B, hepatitis B, mumps, measles, rubella, varicella, BCG, meningococci and pneumococci) and immunization dates were recorded from immunization cards. Immunoglobulin E (IgE) was determined by RAST and eczema severity was assessed by scoring atopic dermatitis (SCORAD). RESULTS: Immunization against any target was not associated with an increased risk of allergic sensitization to food or inhalant allergens. Varicella immunization (only 0.7% immunized) was inversely associated with total IgE > 30 kU/l (OR 0.27; 95% CI 0.08-0.87) and eczema severity (OR 0.34; 95% CI 0.12-0.93). Pertussis immunization (only 1.7% nonimmunized) was inversely associated with eczema severity (OR 0.30; 95% CI 0.10-0.89). Cumulative received vaccine doses were inversely associated with eczema severity (P = 0.0107). The immunization coverage of infants before and after the onset of atopic dermatitis was similar. CONCLUSION: In children at heightened risk for atopy, common childhood immunization in the first year is not associated with an increased risk of more severe eczema or allergic sensitization. Parents of atopic children should be encouraged to fully immunize their children.	C. Grüber, J. Warner, D. Hill and V. Bauchau	Allergy
691	[Effectiveness and safety of intraventricular fibrinolysis in secondary intraventricular hemorrhages (a prospective, randomized study)]	BACKGROUND AND PURPOSE: Intraventricular clot secondary to brain hemorrhage has still one of the worst prognosis among all stroke subtypes, regardless of conservative therapy or surgical interventions. The rapid clot resolution with thrombolytic agents could improve the outcome by restoring the impaired cerebrospinal fluid circulation, for this reason, the authors examined the safety and efficacy of Urokinase therapy in a randomized, controlled study.METHODS: They enrolled 27 patients with severe intraventricular hemorrhage between 1998 and 2002. All patients had supratentorial intracerebral hemorrhage caused by hypertension, with IVH, moreover clinically worsening course due to the obstructive hydrocephalus confirmed by CT. Eleven persons were treated with ventriculostomy alone and 16 received adjunctive intraventricular urokinase. The authors examined the early, 30-day and 1-year mortality, furthermore the neurological (Scandinavian Stroke Scale) and functional outcome (Barthel Scale). The mean age was 60 +/- 9.5. The initial Scandinavian Stroke Scale was 7.51 +/- 8.64, Glasgow Coma Scale was 6.85 +/- 2.52, intracerebral hemorrhage volume was 22.44 +/- 18.14 ml.RESULTS: The 1 year survival rate was significant higher in the urokinase treated group (p = 0.014), This tendency in the mortality (31.3% vs. 54.5%) and in the neurological/functional condition (SSS, p = 0.078/Barthel, p = 0.119) at 30th day have been also documented. No hemorrhagic complications due to urokinase were observed. Two meningitis (7.4%) and two intraparenchymal hemorrhages (7.4%) related to drain insertion were detected (p = 0.009). The probability of pulmonary infection was roughly two times higher in the group without clot lysis (RR = 1.870; 95% CI: 1.004-3.482).CONCLUSIONS: In the authors experience, urokinase treatment reveals to be safe in the intraventricular clot lysis. This therapy allows earlier mobilization and rehabilitation, and decreases the number of infections, which are favorable to the long-term survival rate.	I. Gubucz, I. Kakuk, O. Major, N. Szegedi, P. Barsi, G. Pánczél, D. Varga, C. Ovary, Z. May, G. Ricsói, J. Kenéz, G. Szilágyi and Z. Nagy	Orvosi hetilap
82	Immunogenicity of fractional doses of tetravalent a/c/y/w135 meningococcal polysaccharide vaccine: results from a randomized non-inferiority controlled trial in Uganda	BACKGROUND: Neisseria meningitidis serogroup A is the main causative pathogen of meningitis epidemics in sub-Saharan Africa. In recent years, serogroup W135 has also been the cause of epidemics. Mass vaccination campaigns with polysaccharide vaccines are key elements in controlling these epidemics. Facing global vaccine shortage, we explored the use of fractional doses of a licensed A/C/Y/W135 polysaccharide meningococcal vaccine.METHODS AND FINDINGS: We conducted a randomized, non-inferiority trial in 750 healthy volunteers 2-19 years old in Mbarara, Uganda, to compare the immune response of the full dose of the vaccine versus fractional doses (1/5 or 1/10). Safety and tolerability data were collected for all subjects during the 4 weeks following the injection. Pre- and post-vaccination sera were analyzed by measuring serum bactericidal activity (SBA) with baby rabbit complement. A responder was defined as a subject with a > or =4-fold increase in SBA against a target strain from each serogroup and SBA titer > or =128. For serogroup W135, 94% and 97% of the vaccinees in the 1/5- and 1/10-dose arms, respectively, were responders, versus 94% in the full-dose arm; for serogroup A, 92% and 88% were responders, respectively, versus 95%. Non-inferiority was demonstrated between the full dose and both fractional doses in SBA seroresponse against serogroups W135 and Y, in total population analysis. Non-inferiority was shown between the full and 1/5 doses for serogroup A in the population non-immune prior to vaccination. Non-inferiority was not shown for any of the fractionate doses for serogroup C. Safety and tolerability data were favourable, as observed in other studies.CONCLUSIONS: While the advent of conjugate A vaccine is anticipated to largely contribute to control serogroup A outbreaks in Africa, the scale-up of its production will not cover the entire "Meningitis Belt" target population for at least the next 3 to 5 years. In view of the current shortage of meningococcal vaccines for Africa, the use of 1/5 fractional doses should be considered as an alternative in mass vaccination campaigns.TRIAL REGISTRATION: ClinicalTrials.gov NCT00271479.	P. J. Guerin, L. M. Naess, C. Fogg, E. Rosenqvist, L. Pinoges, F. Bajunirwe, C. Nabasumba, R. Borrow, L. O. Frøholm, S. Ghabri, V. Batwala, R. Twesigye, I. S. Aaberge, J. A. Røttingen, P. Piola and D. A. Caugant	PLoS neglected tropical diseases
245	HHH regime for arteritis secondary to TB meningitis: a prospective randomized study	BACKGROUND: Tuberculous meningitis (TBM) is a fairly common, debilitating disease and is often complicated by arteritis resulting in brain infarction. Few treatment regimes specifically address this condition. Hypervolemia-hypertension-hemodilution (HHH) regime is known to be effective for treatment of vasospasm complicating subarachnoid hemorrhage. We studied the efficacy of HHH regime in patients with TBM with arteritis using a prospective, randomized study design. PATIENTS AND METHODS: Patients diagnosed to have TB meningitis by clinical, CSF, and imaging findings were evaluated for arteritis, which was recognized by presence of focal neurologic deficits with or without corresponding focal hypodensities on brain CT scan. Patients with deficits of < 96 h were randomized to HHH or conservative treatment. All patents received four-first-line anti-TB drugs and Inj.dexamethasone. HHH therapy was administered over 3-9 days. Neurologic status and modified Rankin score were noted serially and at discharge. RESULTS: Seven patients received HHH and 5, conservative treatment. All had hemiparesis with power 0-3/5. Median GCS was worse in HHH group (11 vs. 13). In the HHH group, 6/7 improved in motor power, and 5/7 in sensorium. In the control group, 3/5 improved in motor power and 3/5 in sensorium. Four patients died in each group. CONCLUSION: HHH therapy is safe and may be beneficial in the management of patients with infective arteritis secondary to TBM. Further study in a larger group with improved monitoring of cerebral circulation is indicated.	A. R. Gujjar, S. G. Srikanth and G. S. Umamaheshwara Rao	Neurocritical care
101	Effect of rifampin and minocycline on meningococcal carrier rates		R. B. Guttler, G. W. Counts, C. K. Avent and H. N. Beaty	The Journal of infectious diseases
44	Combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C (HibMenC) or serogroup C and Y-tetanus toxoid conjugate (and HibMenCY) vaccines are well-tolerated and immunogenic when administered according to the 2,3,4 months schedule with a fourth dose at 12-18 months of age	Combined HibMenCY and HibMenC conjugate vaccines may facilitate inclusion of vaccination against MenC and MenY into routine vaccination schedules, without additional injections. Immunogenicity and reactogenicity of vaccination with three different formulations of a novel HibMenCY-conjugate vaccine, or a HibMenC-conjugate vaccine was assessed. Infants were randomized to receive either Hib(2.5 µg)-MenC(5 µg)-MenY(5 µg)-TT, Hib(5 µg)-MenC(10 µg)-MenY(10 µg)-TT, Hib(5 µg)-MenC(5 µg)-MenY(5 µg)-TT or Hib(5 µg)-MenC(5 µg)-TT vaccines co-administered with DTPa-HBV-IPV at 2-3-4 months of age. Controls received licensed conjugate MenC-CRM197 vaccine co-administered with DTPa-HBV-IPV/Hib. A fourth dose was administered to a subset of children at age 12-18 months. Anti-PRP concentrations and meningococcal bactericidal (rSBA-MenC/Y) titres were measured prior to and one month post third and fourth vaccination dose. Solicited local, general symptoms and unsolicited adverse events were recorded for 7 and 30 days after each vaccination, respectively. Post dose 3, all subjects had anti-PRP antibody levels ? 0.15 µg/ml and rSBA-MenC ? 1:8. 97.0%-98.6% of HibMenCY recipients had rSBA-MenY ? 1:8. Pre-dose-4, 95.6%-100% of HibMenCY and HibMenC recipients had anti-PRP ? 0.15 µg/ml and 90.7%-97.6% recipients had rSBA-MenC titres ? 1:8. In HibMenCY groups, 78.6%-86.7% had persisting rSBA-MenY ? 1:8. The post-dose-4 response was robust after all vaccines with all subjects having anti-PRP ? 1 µg/ml and 92.3%-100% rSBA-MenC ? 1:128. All HibMenCY recipients had rSBA-MenY ? 1:128. Vaccination with the novel Hib-meningococcal vaccines had a safety profile similar to control. HibMenCY and HibMenC conjugate vaccine formulations given at 2-3-4 months of age with a fourth dose in the second year of life were immunogenic and had a comparable safety profile to licensed vaccines. (study 792014 and 100381;www.clinicaltrial.govID:NCT00129116)	P. Habermehl, G. Leroux-Roels, R. Sänger, G. Mächler and D. Boutriau	Human vaccines
492	Treatment of tuberculous meningitis [letter]		B. Halikowski	British Medical Journal
39	Safety and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine after one or two doses given to infants and toddlers	With the emergence of multiple meningococcal serogroups in different geographic areas, broad vaccine protection from infancy is desirable. One hundred and seventy-five infants received either two doses of a meningococcal quadrivalent (A, C, W-135, Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM at 18 months. Bactericidal antibody titers using human complement were measured before and 1 month after each dose. Injection-site reactions were reported by 22-45% of participants following MenACWY-CRM given at 6 or 12 months. Similar proportions of subjects had injection-site reactions following two doses of MenACWY-CRM (32-41%) or one dose of MenC (26-44%). The incidence of systemic adverse events was comparable between groups. After two doses of MenACWY-CRM, the percentages of participants reporting hSBA titers >or=8 were 100% for C, W-135, and Y, and 84% for A. Serogroup C titers were more than 10-fold higher after two doses of MenACWY-CRM than after one dose of MenC or MenACWY-CRM at 12 months. Serogroup C titers were comparable following a single dose of MenACWY-CRM or MenC at 12 months. MenACWY-CRM is well tolerated and immunogenic given at 12 months, or two doses at 6 and 12 months of age.	S. A. Halperin, F. Diaz-Mitoma, P. Dull, A. Anemona and F. Ceddia	European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
389	Human opsonins to meningococci after vaccination	Two groups of volunteers were immunized with either a serogroup A plus C meningococcal polysaccharide vaccine or a combined serogroup B polysaccharide-serotype 2 protein vaccine. Serum opsonin responses were measured by chemiluminescence of polymorphonuclear leukocytes exposed to opsonized live meningococci. Two of the 6 volunteers immunized with the A plus C vaccine had an increase in serum opsonins to group A meningococci, 4 responded to group C meningococci, and none to group B meningococci. Five other volunteers who were immunized with the combined group B polysaccharide-serotype 2 protein vaccine responded with an increase in serum opsonins to group B meningococci of two different protein serotypes, as well as to a group C-serotype 2 meningococcal strain. Although no booster effect was observed after a second dose of the combined vaccine, both the polysaccharide and the protein components appear to be able to stimulate an opsonin response. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Halstensen, B. Haneberg and L. O. Froholm	Infection & Immunity
294	Comparison of 2 doses of liposomal amphotericin B and conventional amphotericin B deoxycholate for treatment of AIDS-associated acute cryptococcal meningitis: a randomized, double-blind clinical trial of efficacy and safety	BACKGROUND. It is generally acknowledged that amphotericin B is the most effective treatment for cryptococcal meningitis. However, administration of this drug is accompanied by substantial adverse effects. This double-blind study, performed before the routine availability of highly active antiretroviral therapy, was designed to compare the efficacy and safety of liposomal amphotericin B to conventional amphotericin deoxycholate in patients with acquired immunodeficiency syndrome (AIDS) and acute cryptococcal meningitis. METHODS. Patients were randomized (ratio, 1:1:1) from multiple sites in the United States and Canada to receive either amphotericin B at 0.7 mg/kg/day (n = 87), liposomal amphotericin B at 3 mg/kg/day (n = 86), or liposomal amphotericin B at 6 mg/kg/day (n = 94). RESULTS. Efficacy was similar among all 3 treatment groups. The overall incidence of infusion-related reactions was significantly lower for both the 3 mg/kg/day and 6 mg/kg/day dosages of liposomal amphotericin B, compared with conventional amphotericin B (P < .001). Significantly fewer patients who received the 3 mg/kg/day dosage of liposomal amphotericin B developed nephrotoxicity, indicated by a doubling of the serum creatinine value, compared with recipients of conventional amphotericin B (P = .004). Overall mortality at 10 weeks was 11.6%, with no significant differences among the treatment groups. CONCLUSIONS. Liposomal amphotericin B provides an equally efficacious alternative to conventional amphotericin B deoxycholate in patients with AIDS and acute cryptococcal meningitis. Liposomal amphotericin B at a dosage of 3 mg/kg/day is accompanied by significantly fewer adverse effects.	R. J. Hamill, J. D. Sobel, W. El-Sadr, P. C. Johnson, J. R. Graybill, K. Javaly and D. E. Barker	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
29	Towards a nasal vaccine against meningococcal disease, and prospects for its use as a mucosal adjuvant	A Norwegian outer membrane vesicle (OMV) vaccine against group B meningococcal disease proved to be strongly immunogenic when administered intranasally in mice. The OMV preparation, made from Neisseria meningitidis and intended for parenteral use, was therefore given without adjuvant to human volunteers (n = 12) in the form of nose drops or nasal spray. Such immunizations, which were carried out at weekly intervals during a three-week period, were able to induce systemic antibodies with bactericidal activity in more than half of the individuals. In addition, all vaccinees developed marked increases in OMV-specific IgA antibodies in nasal secretions. The potential of the OMV particles as carriers for other less immunogenic antigens were elucidated in mice with use of whole inactivated influenza virus. Even though influenza virus alone did induce some systemic and salivary antibody responses after being administered intranasally, these responses were greatly augmented when the virus was presented together with OMVs. Thus, it is possible that a nasal OMV vaccine may induce protection against invasive meningococcal disease, and also that it might be used as a vehicle for nasal vaccines against other diseases.	B. Haneberg, R. Dalseg, F. Oftung, E. Wedege, E. A. Høiby, I. L. Haugen, J. Holst, S. R. Andersen, A. Aase, L. Meyer Naess, T. E. Michaelsen, E. Namork and L. R. Haaheim	Developments in biological standardization
241	Heparin for infants and children with meningococcal septicemia. Results of a randomized therapeutic trial	Heparin has been given intravenously, as part of a prospective study, to 11 of 26 infants and children with severe meningococcal septicemia. This therapy was started as early as possible following admission to hospital, and continued for two days. The age and sex distributions were roughly similar for the two treatment groups, but the prognostic signs on admission were somewhat less favourable for the group that did not receive heparin. Two boys who received heparin and two girls who did not, died. The clinical courses of the surviving patients in the two groups were also roughly similar, except that the tendency to cutaneous necroses was slightly more prominent in those who had not received heparin. We have thus no evidence that heparin has any great influence on the final outcome of meningococcal septicemia, even when given so early that shock had not developed.	B. Haneberg, T. J. Gutteberg, P. J. Moe, B. Osterud, B. Bjorvatn and E. H. Lehmann	NIPH annals
1	Corticosteroids as adjunctive therapy for acute bacterial meningitis	Although anecdotal reports and the results of clinical trials suggest that corticosteroids may be efficacious in the treatment of acute bacterial meningitis, controlled and double-blind studies fail to support this view with the exception that corticosteroids may be of benefit for patients with pneumococcal meningitis. Corticosteroids may also be of benefit to patients with acute bacterial meningitis in the presence of life-threatening complications of increased intracranial pressure, such as coma, seizures, fluctuating blood pressure, or rapidly deteriorating mental status, but results of controlled or double-blind studies to substantiate this have not been reported. The possible advantages gained from the use of corticosteroids must be considered with regard to a significant detrimental effect in patients over 16 years of age.	G. L. Harbin and G. R. Hodges	Southern medical journal
364	A polymerase chain reaction for the diagnosis of Haemophilus influenzae type b disease in children and its evaluation during a vaccine trial	BACKGROUND: Determination of the etiology of pneumonia in young children is difficult because blood culture, the usual method of diagnosis, is positive in only a small proportion of cases. For this reason vaccine trials that include bacterial pneumonia as an endpoint must be large. OBJECTIVES: To determine whether a diagnostic test based on a polymerase chain reaction could be used as an alternative to conventional blood culture for diagnosis of invasive Haemophilus influenzae type b (Hib) infections in young children investigated during the course of a large vaccine trial. METHODS: DNA was extracted from blood culture supernatants and probed for the presence of Hib DNA with a PCR assay with primers derived from the cap gene locus of Hib. Results of the PCR assay were compared with those obtained by conventional culture techniques. RESULTS: Blood cultures were obtained from 1544 children with suspected pneumonia, meningitis or septicemia and from 31 healthy control children who were contacts of cases. Blood culture supernatants were tested for Hib DNA in the PCR test. The sensitivity and specificity of a positive PCR test in blood culture supernatant as against culture of Hib from any normally sterile site were 100 and 99%, respectively. Eleven children had positive Hib PCR tests on blood culture supernatants but were negative by culture. In one of these cases Hib was isolated from a lung aspirate and in two other patients H. influenzae strains other than Hib were obtained from the cerebrospinal fluid. Eight of these 11 children were in the control group. When the results of the PCR assay were used to determine vaccine efficacy, a value of 86% was obtained compared with a figure of 95% obtained when conventional culture techniques were used. CONCLUSIONS: An Hib PCR assay on blood culture supernatants proved to be sensitive and specific for the diagnosis of Hib disease in children. The distribution of PCR-positive, culture-negative cases between Hib-vaccinated and control groups paralleled that of culture-positive cases, suggesting that most of these children had been infected with Hib. A trial of a highly efficacious vaccine provides a novel way for evaluating new diagnostic tests for which there is no standard diagnostic test of 100% reliability.	M. Hassan-King, R. Adegbola, I. Baldeh, K. Mulholland, C. Omosigho, A. Oparaugo, S. Usen, A. Palmer, G. Schneider, O. Secka, M. Weber and B. Greenwood	The Pediatric infectious disease journal
593	Dosing and safety of cyclosporine in patients with severe brain injury: clinical article	Object. Cyclosporine neuroprotection has been reported in brain injury models but safety and dosing guidelines have not been determined in humans with severe traumatic brain injury (TBI). The purpose of this investigation was to establish the safety of cyclosporine using 4 clinically relevant dosing schemes. Methods. The authors performed a prospective, blinded, placebo-controlled, randomized, dose-escalation trial of cyclosporine administration initiated within 8 hours of TBI (Glasgow Coma Scale score range 4-8; motor score range 2-5). Four dosing cohorts (8 patients treated with cyclosporine and 2 receiving placebo treatment per cohort) received cyclosporine (1.25-5 mg/kg/day) or placebo in 2 divided doses (Cohorts I-III) or continuous infusion (Cohort IV) over 72 hours. Adverse events and outcome were monitored for 6 months. Results. Forty patients were enrolled over 3 years (cyclosporine cohorts, 24 male and 8 female patients; placebo group, 8 male patients). Systemic trough concentrations were below 250 ng/ml during intermittent doses. Higher blood concentrations were observed in Cohorts III and IV. There was no significant difference in immunological ef fects, adverse events, infection, renal dysfunction, or seizures. Mortality rate was not affected by cyclosporine ad ministration, independent of dose, compared with placebo (6 of 32 patients receiving cyclosporine and 2 of 8 receiving placebo died, p > 0.05). At 6 months, a dose-related improvement in favorable outcome was observed in cyclosporine-treated patients (p < 0.05). Conclusions. In patients with acute TBI who received cyclosporine at doses up to 5 mg/kg/day, administered intravenously, with treatment initiated within 8 hours of injury, the rate of mortality or other adverse events was not significantly different from that of the placebo group. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. Hatton, B. Rosbolt, P. Empey, R. Kryscio and B. Young	Journal of Neurosurgery
237	Complement activation in relation to capillary leakage in children with septic shock and purpura	To assess the relationship between capillary leakage and inflammatory mediators during sepsis, blood samples were taken on hospital admission, as well as 24 and 72 h later, from 52 children (median age, 3.3 years) with severe meningococcal sepsis, of whom 38 survived and 14 died. Parameters related to cytokines (interleukin 6 [IL-6] IL-8, plasma phospholipase A2, and C-reactive protein [CRP]), to neutrophil degranulation (elastase and lactoferrin), to complement activation (C3a, C3b/c, C4b/c, and C3- and C4-CRP complexes), and to complement regulation (functional and inactivated C1 inhibitor and C4BP) were determined. The degree of capillary leakage was derived from the amount of plasma infused and the severity of disease by assessing the pediatric risk of mortality (PRISM) score. Levels of IL-6, IL-8, C3b/c, C3-CRP complexes, and C4BP on admission, adjusted for the duration of skin lesions, were significantly different in survivors and nonsurvivors (C3b/c levels were on average 2.2 times higher in nonsurvivors, and C3-CRP levels were 1.9 times higher in survivors). Mortality was independently related to the levels of C3b/c and C3-CRP complexes. In agreement with this, levels of complement activation products correlated well with the PRISM score or capillary leakage. Thus, these data show that complement activation in patients with severe meningococcal sepsis is associated with a poor outcome and a more severe disease course. Further studies should reveal whether complement activation may be a target for therapeutical intervention in this disease.	J. A. Hazelzet, R. Groot, G. Mierlo, K. F. Joosten, E. Voort, A. Eerenberg, M. H. Suur, W. C. Hop and C. E. Hack	Infection and immunity
176	[Study on the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine]	OBJECTIVE: In order to evaluate the safety and immunogenicity of group A + C meningococcal polysaccharide vaccine, a controlled field trial was performed among children at 6-24 months and 5-13 years old in Longsheng county, Guangxi Zhuang Autonomous Region.METHODS: More than 600 children were selected in this trial. 428 children, aged 6-24 month-old and 5-13 year-old were involved in two experimental groups and were inoculated 100 microg of group A + C meningococcal polysaccharide vaccine. 103 children in positive control group were inoculated 50 microg of group A meningococcal polysaccharide vaccine while 94 children in negative control group were inoculated 30 microg of Typhoid Vi polysaccharide vaccine. Both systemic and local reactions were observed in each group at 6 h,24 h,48 h and 72 h after inoculation. Blood samples were collected in all children before and at 1 month after inoculation. Additionally, at least 50 blood samples were taken in each experimental group at 6 and 12 months after inoculation. Serum bactericidal antibody was tested by micro bactericidal test.RESULTS: Both systemic and local reactions were mild in two experimental groups with only 3 children (0.7%) had > or = 37. 6 degrees C fever, 4 children (0.9%) appeared mild areola but all adverse reaction disappeared within 48 hours. In 5-13 year-old experimental group, the rates for four-fold increase of bactericidal antibody were 96.59% and 92.15% to group A and group C meningococcus respectively at 1 month after inoculation, and remained 90.91% and 90.08% at 12 months after inoculation.CONCLUSION: Group A + C meningococal polysaccharide vaccine was safe and having good immunogenicity among Chinese children.	L. He, R. C. Li, Y. N. Li, Y. N. Huang, Q. Yao, Z. L. Yuan, F. X. Li, X. L. Cui, Y. Nong and M. Yang	Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi
243	Intensified treatment with high dose rifampicin and levofloxacin compared to standard treatment for adult patients with tuberculous meningitis (TBM-IT): protocol for a randomized controlled trial	BACKGROUND: Tuberculous meningitis is the most severe form of tuberculosis. Mortality for untreated tuberculous meningitis is 100%. Despite the introduction of antibiotic treatment for tuberculosis the mortality rate for tuberculous meningitis remains high; approximately 25% for HIV-negative and 67% for HIV positive patients with most deaths occurring within one month of starting therapy. The high mortality rate in tuberculous meningitis reflects the severity of the condition but also the poor antibacterial activity of current treatment regimes and relatively poor penetration of these drugs into the central nervous system. Improving the antitubercular activity in the central nervous system of current therapy may help improve outcomes. Increasing the dose of rifampicin, a key drug with known poor cerebrospinal fluid penetration may lead to higher drug levels at the site of infection and may improve survival. Of the second generation fluoroquinolones, levofloxacin may have the optimal pharmacological features including cerebrospinal fluid penetration, with a ratio of Area Under the Curve (AUC) in cerebrospinal fluid to AUC in plasma of >75% and strong bactericidal activity against Mycobacterium tuberculosis. We propose a randomized controlled trial to assess the efficacy of an intensified anti-tubercular treatment regimen in tuberculous meningitis patients, comparing current standard tuberculous meningitis treatment regimens with standard treatment intensified with high-dose rifampicin and additional levofloxacin.METHODS/DESIGN: A randomized, double blind, placebo-controlled trial with two parallel arms, comparing standard Vietnamese national guideline treatment for tuberculous meningitis with standard treatment plus an increased dose of rifampicin (to 15 mg/kg/day total) and additional levofloxacin. The study will include 750 patients (375 per treatment group) including a minimum of 350 HIV-positive patients. The calculation assumes an overall mortality of 40% vs. 30% in the two arms, respectively (corresponding to a target hazard ratio of 0.7), a power of 80% and a two-sided significance level of 5%. Randomization ratio is 1:1. The primary endpoint is overall survival, i.e. time from randomization to death during a follow-up period of 9 months. Secondary endpoints are: neurological disability at 9 months, time to new neurological event or death, time to new or recurrent AIDS-defining illness or death (in HIV-positive patients only), severe adverse events, and rate of treatment interruption for adverse events.DISCUSSION: Currently very few options are available for the treatment of TBM and the mortality rate remains unacceptably high with severe disabilities seen in many of the survivors. This trial is based on the hypothesis that current anti-mycobacterial treatment schedules for TBM are not potent enough and that outcomes will be improved by increasing the CSF penetrating power of this regimen by optimising dosage and using additional drugs with better CSF penetration.TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number ISRCTN61649292.	D. Heemskerk, J. Day, T. T. Chau, N. H. Dung, N. T. Yen, N. D. Bang, L. Merson, P. Olliaro, T. Pouplin, M. Caws, M. Wolbers and J. Farrar	Trials
434	Ceftriaxone versus conventional therapy in bacterial meningitis of childhood	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	H. Helwig, P. Tosberg, P. Peller, H. Ludwig, H. Gotze and F. Schindera	Zac Zeitschrift fur Antimikrobielle Antineoplastische Chemotherapie
485	Our experience in the treatment of purulent meningitis with ampicillin		M. Hernández and N. Rodríguez	Boletín de la Sociedad Vasco-Navarra de Pediatría
103	[A controlled trial with 2 anti-Neisseria B meningitidis vaccines and placebo in Chilean population]		P. Herrera and R. Lagos	Revista médica de Chile
130	A pharmacologic evaluation of penicillin in children with purulent meningitis	We undertook a prospective study of the pharmacokinetics of penicillin G (administered intravenously every four hours for a total of b50,000 U per kilogram per day) in the cerebrospinal fluid of children with purulent meningitis. Both the absolute mean cerebrospinal-fluid penicillin concentration (0.8, 0.7 and 0.3 microgram per milliliter) and the percentage of the simultaneous serum penicillin concentration measurable in the cerebrospinal fluid (18.4, 9.9, 4.9 per cent) declined on the first, fifth and 10th days of therapy, respectively. A mean peak cerebrospinal-fluid penicillin concentration of 0.96 micrograms per milliliter was measured at least transiently on all three study days. This pharmacokinetic pattern correlated with the return of cerebrospinal-fluid protein concentration toward normal (P less than 0.01). Penicillin G in the dosage studied is adequate therapy for most streptococcal and meningococcal meningitis in children; an increased dosage may be necessary when the minimal inhibitory concentration of penicillin to the etiologic agent is unusually high.	J. P. Hieber and J. D. Nelson	The New England journal of medicine
113	A phase II, randomized study on an investigational DTPw-HBV/Hib-MenAC conjugate vaccine administered to infants in Northern Ghana	BACKGROUND: Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. METHODS AND FINDINGS: In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres > or = 1:8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres > or = 1:8 or SBA-MenC titres > or = 1:8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 microg of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 microg of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6-28.1] of doses vs 14.1%; 95% CI [10.9-17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study. CONCLUSIONS: Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN35754083.	A. Hodgson, A. A. Forgor, D. Chandramohan, Z. Reed, F. Binka, C. Bevilacqua, D. Boutriau and B. Greenwood	PloS one
95	Tacrolimus ointment does not affect the immediate response to vaccination, the generation of immune memory, or humoral and cell-mediated immunity in children	BACKGROUND: Concern exists that the prolonged application of immunomodulators to treat atopic dermatitis may cause systemic immunosuppression. AIMS: In a 7-month, multicentre, randomised, controlled trial, we investigated the equivalence of response to vaccination against meningococcal serogroup C disease with a protein-conjugate vaccine in children (2-11 years) with moderate to severe atopic dermatitis, by applying either 0.03% tacrolimus ointment (TAC-O; n = 121[corrected]) or a hydrocortisone ointment regimen (HC-O; n = 111). METHODS: TAC-O was applied twice daily (bid) for 3 weeks, and thereafter daily until clearance. 1% hydrocortisone acetate (HA) for head/neck and 0.1% hydrocortisone butyrate ointment for trunk/limbs was applied bid for 2 weeks; thereafter HA was applied bid to all affected areas. At week 1, patients were vaccinated with protein-conjugate vaccine against meningococcal serogroup C, and challenged at month 6 with low dose meningococcal polysaccharide vaccine. The control group (44 non-atopic dermatitis children) received the primary vaccination and challenge dose. Assessments were made at baseline, weeks 1 and 5, and months 6 and 7. The primary end point was the percentage of patients with a serum bactericidal antibody (SBA) titre > or = 8 at the week 5 visit. RESULTS: The response rate (patients with SBA titre > or = 8) was 97.5% (confidence interval (CI) approximately 97.3 to 100), 99.1% (94.8 to 100) and 97.7% (93.3 to 100) in the TAC-O, HC-O and control groups, respectively. CONCLUSIONS: The immune response to vaccination against meningococcal serogroup C in children with atopic dermatitis applying either 0.03% TAC-O or HC is equivalent. Ointment application does not affect the immediate response to vaccination, generation of immune memory or humoral and cell-mediated immunity.	T. Hofman, N. Cranswick, P. Kuna, A. Boznanski, T. Latos, M. Gold, D. F. Murrell, K. Gebauer, U. Behre, E. Machura, J. Olafsson and Z. Szalai	Archives of disease in childhood
148	Short course single daily ceftriaxone monotherapy for acute bacterial meningitis in children: results of a Swiss multicenter study. Part II: Bacteriological results	The in vitro activity of ceftriaxone, ampicillin and chloramphenicol was studied at a reference laboratory against the isolates of the first 33 patients enrolled in a pediatric Swiss Multicenter Meningitis Study. The predictive value of the MIC data of 31 of the strains was further corroborated by two sets of bacterial killing curves in broth supplemented with 2 g/l of albumin. Ceftriaxone had the lowest geometric mean MIC values against all groups of isolates except for ampicillin against Streptococcus agalactiae. The bactericidal activity of ceftriaxone and that of ampicillin, alone and in combination with chloramphenicol, was compared at six times the respective MICs and at pharmacologically readily achievable concentrations in cerebrospinal fluid. The bactericidal power of ceftriaxone at six times the MIC was as good or better than that of ampicillin alone or in combination against Neisseria meningitidis and Streptococcus pneumoniae despite the very low drug concentrations of ceftriaxone compared to that of the competitors; and it was barely lower at six times the MIC and at 1 mg/l (a level that is readily surpassed in CSF at the 24 h trough level after a single daily dose of ceftriaxone of 100 mg/kg (neonates 50 mg/kg) than that of ampicillin and chloramphenicol at much higher concentrations against Haemophilus influenzae type b.	P. Hohl, E. Martin and F. H. Kayser	Infection
54	The Norwegian meningococcal serogroup B outer membrane vesicle vaccine protection trials: case tracing, meningococcal antigen detection and serological diagnosis	A survey is given of the efforts made to inform the general public, the potential vaccinees and their parents, and the health care personnel about meningococcal disease in general and the vaccination trial in particular, as a preparation for the meningococcal outer membrane vesicle serogroup B vaccine (MenB-vaccine "Folkehelsa") trials in secondary school students and military conscripts in Norway. Our case reporting system, supplementing the official notification, concerning even vaguely suspected cases in the age cohorts involved, is described. The efforts made to collect clinical material as well as laboratory and clinical data from 221 registered suspected cases are delineated. We also briefly summarize our cerebrospinal fluid antigen detection methods and diagnostic meningococcal serology work on these suspected cases. The compiled information on findings done at the admitting hospital of the possible cases and the additional diagnostic data provided at the National Institute of Public Health were put at the disposal of the independent Diagnosis Review Committee (DRC) as a basis for their diagnostic decisions before code opening for the meningococcal serogroup B outer membrane vesicle vaccine protection trial 3 June 1991.	E. A. Høiby, G. Bjune, L. O. Frøholm, J. Eng, A. Halstensen, E. Rosenqvist, E. Rønnild and E. Wedege	NIPH annals
600	Pilot study on the effectiveness of the conventional CROS, the transcranial CROS and the BAHA transcranial CROS in adults with unilateral inner ear deafness	The objective of the present pilot study is to evaluate the effectiveness of three conventional contralateral routing of sound (CROS) hearing aids in adults with unilateral inner ear deafness. The study included tertiary referral center. Ten patients with unilateral inner ear deafness and normal hearing in the contralateral ear were selected to evaluate three different methods of amplification: the CROS hearing aid, the completely in the canal hearing aid and the bone-anchored hearing aid CROS (BAHA). Each of the three hearing aids was tried in a random order for a period of 8 weeks. Audiometric performance, including speech-in-noise, directional hearing and subjective benefit were measured after each trial period, using the APHAB, SSQ and single-sided deafness questionnaire. Sound localization performance was essentially at chance level in all four conditions. Mixed results were seen on the other patient outcome measures that alternated in favor of one of the three CROS devices. After the trial, three patients chose to be fitted with the BAHA CROS and one with the conventional CROS. In conclusion, most of the patients experienced some degree of benefit with each of the three hearing aids. Preference for one of the three hearing aids was independent of the order in which they were tried. It would be worthwhile to formulate selection criteria; still, we recommend that all patients with unilateral inner ear deafness should be offered a trial with at least the BAHA CROS. The Author(s) 2009.	M. K. S. Hol, S. J. W. Kunst, A. F. M. Snik and C. Cremers	European Archives of Oto-Rhino-Laryngology
4	Combined administration of serogroup B meningococcal vaccine and conjugated serogroup C meningococcal vaccine is safe and immunogenic in college students	This study evaluated the first use of a combination of the lyophilized components of the conjugated group C vaccine Menjugate reconstituted with the liquid group B outer membrane vesicle (OMV) vaccine MeNZB. At 6-week intervals, healthy residential students received three doses of MeNZB alone or concomitantly with one dose of Menjugate (MeNZB+MenC). Short-lasting injection-site reactions of mild or moderate intensity were frequent in both groups. There were no vaccine-related serious adverse events. After three doses, the percentage of subjects with serum bactericidal assay (SBA) titres > or = 1:8 against the serogroup B strain NZ98/254 was 82% for MeNZB+MenC and 78% for MeNZB. All subjects in the MeNZB+MenC group achieved SBA titres > or = 1:8 against serogroup strain C11 and 67% in the MeNZB group. All SBA and ELISA responses of the combined vaccine were at least as good as for MeNZB alone. After vaccination, the pharyngeal carriage rate of any meningococcus in the vaccinated group had declined from 40% to 21%.	J. D. Holmes, D. Martin, C. Ramsay, E. Ypma and P. Oster	Epidemiology and infection
14	Serum bactericidal activity correlates with the vaccine efficacy of outer membrane vesicle vaccines against Neisseria meningitidis serogroup B disease	For evaluation of serum bactericidal activity (SBA) as surrogate for the efficacy of outer membrane vesicle (OMV) vaccines against Neisseria meningitidis serogroup B disease, we have reanalyzed data from a randomized double blind placebo-controlled efficacy trial involving 172000 secondary school students (aged 13-14 years) in Norway (1988-1991). A cohort of the efficacy trial consisting of 880 individuals was selected for immunogenicity studies. An efficacy of 87% was calculated for a 10-month observation period. However, after an observation period of 29 months, the estimated efficacy against group B disease induced by vaccination was 57%. The immunogenicity study showed that the SBA geometric mean titer (GMT) for the vaccinees was 2.4 before vaccination and 19.0 six weeks after the second vaccine dose. One year after vaccination the GMT was reduced to 2.8. A separate three-dose study with 304 adolescents showed that with a third dose at 10 months after the second dose (i.e. when cases of disease started to appear) a strong booster response was induced. Ten months after the second dose the SBA was reduced to near pre-immunization level. Following the third dose the SBA geometric mean titer of 2.7 increased to 62.3. One year after the third dose, the GMT was markedly higher than 6 weeks after the second dose (12.6 versus 8.8). Thus, protection after vaccination corresponds with the level of SBA. In order to reach lasting protective levels of SBA in a population, three vaccine doses are probably required. Measurements of SBA are likely to be useful for evaluating various upcoming formulations and improvements of immunization regimens for OMV vaccines.	J. Holst, B. Feiring, J. E. Fuglesang, E. A. Høiby, H. Nøkleby, I. S. Aaberge and E. Rosenqvist	Vaccine
468	Fundamental and clinical investigation of cefozopran	Cefozopran (CZOP), a new semisynthetic cephalosporin was studied, yielding the following results. 1) Pharmacokinetics: Pharmacokinetics of CZOP and ceftazidime (CAZ) were compared by i. v. d. injection in male healthy volunteers. The serum concentrations of CZOP and CAZ were 61.7 +/- 13.7 mug/ml and 62.1 +/- 9.2 mug/ml at end of infusion respectively, and the halflives beta phase were 1.776 +/- 0.150 hr for CZOP and 1.796 +/- 0.263 hr for CAZ. When probenecid was administered before CZOP dosing, serum levels and urinary excretions were slightly affected. These results suggested that main excretion route of CZOP was glomerular filtration. 2) Clinical: In four cases of respiratory tract infection, one case of meningitis, three cases of urinary tract infection and one case of prostatitis, one or two gram of CZOP daily were given for 4 to 15 days. The therapeutic results were excellent in three and good in five cases. All of isolated bacteria, three Escherichia coli, one Klebsiella pneumoniae, one Klebsiella oxyloca, one Proteus mirabilis, three Pseudomonas aeruginosa, one Haemophilus parainfluenzae, one Citrobacter freundii were eradicated. No adverse reactions were observed. In one case elevation of gamma-GTP and LAP, two cases elevation of serum-potassium and one case elevation of basophil were observed. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. Hori, K. Shiba, M. Yoshida, J. Shimada, A. Saito and O. Sakai	Chemotherapy
309	Treatment of cryptococcal meningitis associated with the acquired immunodeficiency syndrome. National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group	BACKGROUND: Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization. METHODS: In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks. RESULTS: At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P=0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization. CONCLUSIONS: For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.	C. M. Horst, M. S. Saag, G. A. Cloud, R. J. Hamill, J. R. Graybill, J. D. Sobel, P. C. Johnson, C. U. Tuazon, T. Kerkering, B. L. Moskovitz, W. G. Powderly and W. E. Dismukes	The New England journal of medicine
159	Level of transforming growth factor beta 1 is elevated in cerebrospinal fluid of children with acute bacterial meningitis	We investigated the levels of transforming growth factor beta 1 (TGF-beta 1) in cerebrospinal fluid (CSF) in children with meningitis, with a view to prognostic relevance. CSF TGF-beta 1 levels on admission were measured by a sandwich enzyme immunoassay in children with bacterial meningitis (n = 16), aseptic meningitis (n = 12), and control subjects without evidence of central nervous system (CNS) infection (n = 16). Patients were followed up for a mean duration of 13 months, and neurodevelopmental sequelae was determined for those with bacterial meningitis. On admission, CSF TGF-beta 1 levels were significantly higher in children with bacterial meningitis (mean, standard error, 32.92, 2.36 pg/ml) as opposed to those with aseptic meningitis (25.26, 1.72 pg/ml) (P = 0.0155), or control subjects (20.53, 1.05 pg/ml) (P < 0.0001). The CSF TGF-beta 1 levels in children with aseptic meningitis were higher than those in the control group, but without significance (P = 0.02). No apparent correlation existed between CSF TGF-beta 1 levels and CSF protein or cell counts in patients with bacterial meningitis. No significant difference in CSF TGF-beta 1 levels was found between patients with or without major sequelae following bacterial meningitis.	C. C. Huang, Y. C. Chang, N. H. Chow and S. T. Wang	Journal of neurology
699	Extended-release fluvastatin 80 mg shows greater efficacy, with comparable tolerability, versus immediate-release fluvastatin 40 mg for once daily treatment of primary hypercholesterolaemia	A new extended-release (XL) formulation of fluvastatin has been developed for once daily treatment of primary hypercholesterolaemia. This study was designed to determine the safety and effect of fluvastatin XL 80 mg on a range of lipid parameters compared with the immediate-release (IR) formulation of fluvastatin 40 mg. In a multicentre, double-blind study, 555 patients with primary hypercholesterolaemia (Fredrickson types IIa or IIb) were randomised to 24 weeks treatment with fluvastatin XL 80 mg or IR 40 mg, each given once daily at bedtime. The study found the least square mean reduction in LDL-C after 24 weeks treatment was 32.6% in the fluvastatin XL 80 mg group (n=312) and 23.9% in the fluvastatin IR 40 mg group (n=165), an 8.7% between-treatment difference (95% confidence interval: 6.5%, 10.9%) in favour of the XL formulation (p<0.001). A higher proportion of patients in the fluvastatin XL 80 mg group achieved [greater-than or equal to]35% reductions in low-density lipoprotein cholesterol (42.3% vs. 13.3%). High-density lipoprotein cholesterol levels were increased by 9.1% and 7.0%, respectively in the XL and IR groups; median triglyceride levels fell by 19% and 13%, respectively. Tolerability was comparable in the two groups, and there were no laboratory safety concerns. The study concluded that fluvastatin XL 80 mg once daily is safe as a starting dose and effectively lowers low-density lipoprotein cholesterol and triglyceride levels in patients with primary hypercholesterolaemia. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	D. B. Hunninghake, M. Davidson, H. R. Knapp, H. G. Schrott, S. Manfreda, J. Angelo, J. Becker, G. A. Bray, M. J. Conway, R. Detrano, M. Drehobl, C. Dujovne, M. Nunez, S. Glasser, A. C. Goldberg, R. C. Gove, J. A. Herd, P. N. Hopkins, C. S. Horn, A. K. Khachadurian, J. R. Schmidt, N. M. Lunde, F. P. Maggiacomo, J. M. Morgan, R. J. Goldstein, J. D. Norton, R. J. Noveck, K. B. Powers, W. V. Brown, S. Rosenblatt, R. Superko and J. H. Zavoral	British Journal of Cardiology
9	Induction of protective serum meningococcal bactericidal and diphtheria-neutralizing antibodies and mucosal immunoglobulin A in volunteers by nasal insufflations of the Neisseria meningitidis serogroup C polysaccharide-CRM197 conjugate vaccine mixed with chitosan	Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis serogroup C polysaccharide (MCP)-CRM197 conjugate vaccine in alum or two nasal insufflations 28 days apart of the same vaccine powder, without alum, mixed with chitosan. Nasal immunization was well tolerated, with fewer symptoms reported than after intramuscular injection. The geometric mean concentrations of MCP-specific immunoglobulin G (IgG) after one nasal immunization were 3.25 microg/ml in naïve subjects and 14.4 microg/ml in subjects previously immunized parenterally, compared with 4.30 microg/ml in naïve subjects immunized intramuscularly. The geometric mean titer of serum bactericidal antibody (SBA) rose 24-fold after two nasal immunizations in naïve subjects and was comparable to parenteral immunization (1,080 versus 1,625). All subjects achieved SBA titers associated with protection after two nasal immunizations: even those with titers of <8 at entry. A single nasal immunization boosted the SBA titer to > or =128 in 96% of previously immunized subjects, and two immunizations achieved this level in 92% of naive subjects. MCP-specific IgG levels were approximately 70% IgG2 and approximately 20% IgG1 after nasal or intramuscular immunization. Increases in CRM197-specific IgG and diphtheria toxin-neutralizing activity were observed after nasal or intramuscular immunization, with balanced IgG1/IgG2 and higher IgG4. Significant MCP-specific secretory IgA was detected in nasal wash only after nasal immunization and predominantly on the immunized side. Simple nasal insufflation of existing MCP-CRM197 conjugate vaccines in chitosan offers an inexpensive but effective needle-free prime and boost against serogroup C N. meningitidis and diphtheria.	Z. Huo, R. Sinha, E. A. McNeela, R. Borrow, R. Giemza, C. Cosgrove, P. T. Heath, K. H. Mills, R. Rappuoli, G. E. Griffin and D. J. Lewis	Infection and immunity
587	Prevention of CNS relapse in all with cranial radiation and weekly intrathecal methotrexate (IT MTX)	Although 2400 R cranial radiation and twice weekly IT MTX reduces initial central nervous system (CNS) relapse in acute lymphocytic leukemia (ALL), the optimal schedule of IT MTX is unknown. The authors evaluated 2400 R to the cranium over 2.5 to 3 wk, and 3 weekly doses of 12 mg/Msup 2 IT MTX in 45 patients with ALL who achieved a complete remission (CR). Prednisone 20 mg/Msup 2 P.O. was given the first 2 wk of CNS therapy and then tapered. Maintenance therapy was P.O. 6MP 50 mg/Msup 2/day, MTX 20 mg/Msup 2/wk and Cytoxan 200 mg/Msup 2/wk, plus pulse phases of Oncovin 1.5 mg/Msup 2 IV and prednisone 1000 mg/Msup 2 P.O. for one day q 3 mth. Twenty six remain in continuous CR (range 17 to 41 mth). Initial sites of relapse are: one CNS and 18 marrow. This contrasts with the authors' experience with identical therapy without CNS prophylaxis where 13 of 25 initial relapses were CNS. No significant neurological toxicity was noted during CNS therapy. Eight patients had transient anorexia, lethargy and somnolence 4 to 6 wk after CNS therapy. No neurological sequelae were noted. Patients were randomized to Group A: IT MTX 12 mg/Msup 2 q 3 mth and Group B: no further IT therapy. Of 27 in Group A, 1 had initial CNS relapse; none of 15 in Group B have had initial CNS relapse. It is concluded that the above regimen of CNS therapy is effective with minimal toxicity. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. Hutter, C. Holton and K. Chapman	Procamerasscancer Res
428	Candida fungemia in neonates treated with fluconazole: Report of forty cases, including eight with meningitis	Purpose of the study. To assess efficacy and safety of fluconazole, in neonates with Candida fungemia. Study design. Multicenter prospective protocol of all fungemias appearing between January 1, 1993, and December 31, 1997, in four major university hospitals. Results. Forty neonates, 28 of them with very low birth weight (<1500 g; 30.5 median gestation week), with documented Candida albicans fungemia were treated with intravenous fluconazole in a daily dosage of 6 mg/kg once daily for 6 to 48 days. Thirty- four received fluconazole as monotherapy and 6 received it in combination with amphotericin B. Thirty-two (80%) were cured; 4 of them relapsed despite at least 14 days of therapy, but they were ultimately cured without sequelae. Eight other neonates died, 4 because of fungal infection and 4 because of prematurity or hemorrhage or lung failure, with fungemia (20% overall and 10% attributable mortality). Two neonates had elevated liver enzymes during fluconazole therapy and 2 others had elevated serum creatinine during fluconazole monotherapy. In none of them did these abnormalities necessitate discontinuation of antifungal therapy. In 8 neonates fungal meningitis developed as a complication of fungemia. All but 3 fungemias were C. albicans; 3 were Candida parapsilosis. Conclusions. Fluconazole was safe and effective antifungal therapy even in complicated or Candida fungemia in neonates and in infants with very low birth weight. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. Huttova, I. Hartmanova, K. Kralinsky, J. Filka, J. Uher, J. Kurak, S. Krizan and V. Krcmery	Pediatric Infectious Disease Journal
119	Dexamethasone decreases cerebrospinal fluid soluble tumor necrosis factor receptor 1 levels in bacterial meningitis	It is known that the use of adjunctive dexamethasone in bacterial meningitis reduces audiologic and neurologic sequelae. The cerebrospinal fluid (CSF) level of soluble tumor necrosis factor 1 (sTNFR1) is an important indicator of neurologic sequelae in bacterial meningitis. We measured the CSF levels of IL-6 and sTNFR1 before administration of antibiotics (CSF1) and 1-3 days after administration of antibiotics (CSF2) in nine patients with bacterial meningitis who received dexamethasone sodium and five without dexamethasone. The CSF2 IL-6 levels of patients with/without dexamethasone were significantly lower than for CSF1 IL-6 levels (p = 0.0077, and p = 0.0431, respectively). There were no significant differences of the ratio of CSF2/CSF1 IL-6 levels between patients with dexamethasone and those without dexamethasone. CSF2 sTNFR1 levels of patients with dexamethasone were significantly lower than for CSF1 sTNFR1 levels (p = 0.0208). However, CSF2 sTNFR1 levels of patients without dexamethasone were significantly higher than for CSF1 sTNFR1 levels (p = 0.0422). The ratio of CSF2/CSF1 sTNFR1 levels of patients with dexamethasone was significantly lower than that without dexamethasone (p = 0.0063). Our present study suggests that dexamethasone inhibits increase of CSF sTNFR1 levels after antibiotics therapy in bacterial meningitis.	T. Ichiyama, T. Matsushige, M. Kajimoto, K. Tomochika, T. Matsubara and S. Furukawa	Brain & development
680	[Studies on panipenem/betamipron in the field of pediatrics]	Pharmacokinetic and clinical studies in pediatrics were performed on panipenem/betamipron (PAPM/BP), a combined drug of a carbapenem antibiotic (panipenem) and organic ion inhibitor (betamipron) at a weight ratio of 1:1. 1. Plasma levels and urinary excretion were studied when PAPM/BP, at 10 mg/10 mg/kg (4 cases) or 20 mg/20 mg/kg (5 cases), was administered using intravenous drip infusion in 30 minutes to 9 children (4-14 years old). The plasma PAPM level at the end of drip infusion was 30.75 +/- 4.98 micrograms/ml in the cases administered with 10 mg/10 mg/kg and 68.72 +/- 5.73 micrograms/ml in the cases administered with 20 mg/20 mg/kg. Drug concentrations then gradually decreased with half-lives of 1.08 +/- 0.09 hours and 0.98 +/- 0.02 hour, and reached 0.39 +/- 0.14 micrograms/ml and 0.62 +/- 0.06 micrograms/ml, respectively, after 5.5 hours. Plasma BP levels at the end of drip infusion was 18.93 +/- 3.75 micrograms/ml in the cases administered 10 mg/10 mg/kg and 37.09 +/- 2.68 micrograms/ml in the cases administered 20 mg/kg, and half-lives were 0.55 +/- 0.07 hour and 0.61 +/- 0.03 hour, respectively; the plasma BP level could not be determined in any cases after 5.5 hours. Mean urinary recovery rates of PAPM in the first 6 hours after the start of intravenous drip infusion were 33.0 +/- 6.1% in the cases administered 10 mg/10 mg/kg and 21.8 +/- 2.3% in the cases administered 20 mg/20 mg/kg and those of BP were 77.0 +/- 2.4% and 76.6 +/- 7.3%, respectively. 2. When PAPM/BP, was administered at 31.3 mg/31.3 mg/kg thought by intravenous drip infusion in 30 minutes to 1 case of purulent meningitis, PAPM levels were 0.76 micrograms/ml at the end of drip infusion but varied between 0.80 to 1.97 micrograms/ml 30 minutes after the end of drip infusion during 8 days of treatment. 3. PAPM/BP was administered to 43 cases, 47 diseases of bacterial infections in the domain of pediatrics to study its clinical efficacy, bacteriological efficacy and adverse reactions. Single doses were 5.2mg/5.2mg to 31.3 mg/31.3 mg/kg; frequencies of administration were 3 to 4 times a day, and durations of administration were 3 1/3 to 11 days; and total dosages ranged between 1.125 g/1.125 g and 11.0 g/11.0 g.(ABSTRACT TRUNCATED AT 400 WORDS)	N. Iwai, H. Nakamura, M. Miyazu, Y. Watanabe and Y. Taneda	The Japanese journal of antibiotics
56	[Levels of interleukin-6 in cerebrospinal fluid of patients with meningitis]	UNLABELLED: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates the immune response, differentiation of B cells, activation of T lymphocytes and acute phase reactions.AIM OF THE STUDY: Quantitation of interleukin-6 in cerebrospinal fluid from patients with purulent bacterial meningitis (PBM) and viral meningitis (VM) on the first day of hospitalization.PATIENTS AND METHODS: IL-6 activity was measured in cerebrospinal fluid (CSF) of 15 children with VM (predominantly 13/15 caused by mumps virus) in age ranging from 2.5 to 15 years and 13 patients with PBM (age ranging from 18 to 52 years). The control group consisted of 10 patients with meningeal syndrome and normal laboratory estimation of CSF (white cells count, concentration of glucose and protein). The IL-6 assays were performed using immunoenzymatic method, ELISA (Amersham) technique.RESULTS: Increased levels of IL-6 were detected in the CSF of patients with bacterial meningitis and with viral meningitis. CSF IL-6 levels were 6 times greater in patients with purulent bacterial versus viral meningitis. The highest level of IL-6 was observed in a 18 years old patient with pneumococcal meningitis who died.CONCLUSION: We suggest that cytokine levels may be valuable in distinguishing patients with purulent bacterial meningitis from viral meningitis and may help in prognosis of patients with purulent meningitis.	E. Jab?onowska, J. Lisiewicz, J. Kuydowicz and Z. Pojda	Neurologia i neurochirurgia polska
323	A phase II randomized controlled trial adding oral flucytosine to high-dose fluconazole, with short-course amphotericin B, for cryptococcal meningitis	BACKGROUND: Cryptococcal meningitis in Africa is associated with up to 70% mortality at 3 months and 500?000 deaths annually. We examined strategies to improve on fluconazole (FLU) monotherapy: addition of flucytosine (5-FC) and/or addition of short-course amphotericin B (AmB). METHODS: In step 1, previously reported, patients were randomized to receive FLU 1200?mg per day with or without 5-FC 100?mg/kg per day for 14 days. In step 2, 43 patients were similarly randomized, with addition of AmB 1?mg/kg per day for 7 days to both arms. After 2 weeks, patients received FLU monotherapy and were followed to 10 weeks. The primary endpoint was rate of clearance of infection (early fungicidal activity, EFA). Secondary endpoints related to safety and mortality. RESULTS: Forty patients (25% with Glasgow Coma Scale <15) were analyzed. EFA for the triple combination arm was greater than that for AmB-FLU: -0.50?±?0.15 log CFU/day vs. -0.38?±?0.19 log colony forming units per day (P=0.03); and greater than that for step 1 with FLU-5-FC (-0.28?±?0.17) or FLU alone (-0.11?±?0.09). Combined analysis across steps revealed that addition of 5-FC and AmB had significant, independent additive effects on EFA, with trends toward fewer early deaths with addition of 5-FC (4/41 vs. 11/39, P?=?0.05) and fewer deaths overall with addition of AmB (13/39 vs. 20/40, P?=?0.1). CONCLUSION: Addition of 5-FC and short-course AmB to high-dose FLU significantly enhanced EFA and may be associated with favorable trends in survival. Both these strategies should be tested in a larger phase III study.	A. T. Jackson, J. C. Nussbaum, J. Phulusa, D. Namarika, M. Chikasema, C. Kanyemba, J. N. Jarvis, S. Jaffar, M. C. Hosseinipour, C. Horst and T. S. Harrison	AIDS (London, England)
564	Safety of varying dosages of 7-valent pneumococcal protein conjugate vaccine in seniors previously vaccinated with 23-valent pneumococcal polysaccharide vaccine	In a phase I/II dose escalation study, varying volumes (0.1 ml, 0.5 ml, 1.0 ml and 2.0 ml) of 7-valent pneumococcal conjugate vaccine (PCV) (Prevnar or 0.5 ml of 23-valent pneumococcal polysaccharide vaccine (PPV) were administered to 220 adults 70 through 79 years of age previously vaccinated with 0.5 ml PPV at age 65 years or above and at least 5 years previously. Fever was uncommon and did not vary by study group. The rate of local reactions increased with higher volumes of PCV and the rate following 2.0 ml of PCV was comparable to that following 0.5 ml PPV.	L. A. Jackson, K. M. Neuzil, C. G. Whitney, P. Starkovich, M. Dunstan, O. Yu, J. C. Nelson, D. R. Feikin, D. K. Shay, J. Baggs, B. Carste, M. H. Nahm and G. Carlone	Vaccine
171	Cefotaxime and desacetylcefotaxime in neonates and children: a review of microbiologic, pharmacokinetic, and clinical experience	Over the past 5 yr, we have conducted two clinical and two pharmacokinetic investigations of cefotaxime (CTX) and desacetylcefotaxime (dCTX) in neonates, infants, and children. A total of 50 children with culture-proven bacterial meningitis were randomized to receive either 200 mg/kg/day of CTX (n = 23, mean age 24.4 mo) or standard doses of ampicillin (AMP) and chloramphenicol succinate (CAPS; n = 27, mean age 16.6 mo). Results were similar between the CTX and Amp/CAPS groups for clinical/microbiological cures (100% versus 96%, respectively) and for survival without sequelae (78% vs. 77%, respectively). All bacterial isolates were sensitive to CTX, and the comparison of the MIC/MBC values for CTX to the CSF bactericidal titers suggested antimicrobial activity for dCTX. In a second clinical trial, 20 infants (1 wk-3 mo) were treated with 200 mg/kg/day of CTX for Gram-negative enteric bacillary meningitis. Cultures of CSF obtained 24 hr after the initiation of treatment were sterile in all subjects. Survival and complication rates of 95% and 21%, respectively, were observed. This compared favorably to previously published experiences with alternate treatment regimens for Gram-negative meningitis in the newborn. In both meningitis studies, the safety profile for CTX was excellent.(ABSTRACT TRUNCATED AT 250 WORDS)	R. F. Jacobs and G. L. Kearns	Diagnostic microbiology and infectious disease
433	Intensive short course chemotherapy for tuberculous meningitis	This nonrandomized, open clinical investigation of tuberculous meningitis evaluated 53 children with Stage I (n = 8), Stage II (n = 29) and Stage III (n = 16) disease. The overall mortality was 20.8% (11 of 53) with a rate of sequelae of 35.7% (15 of 42) in survivors reflecting the advanced stages of children at diagnosis. Various combinations of standard antituberculous drugs including isoniazid, rifampin, pyrazinamide, streptomycin and ethambutol were given. Three treatment durations used during various time periods were evaluated: 12, 9 and 6 months with only the 6-month regimen receiving pyrazinamide (PZA). This prospective evaluation demonstrated that: (1) severe disease at presentation is highly associated with early mortality (P less than 0.05), regardless of drug regimen; and (2) intensive short course chemotherapy (6 months) with PZA, regardless of stage of disease at presentation, is more efficacious than longer course therapy (9 or 12 months) without PZA in preventing total negative outcomes and sequelae (P less than 0.05). This study demonstrates that a 6-month regimen containing PZA can be used in treating children with tuberculous meningitis.	R. F. Jacobs, P. Sunakorn, T. Chotpitayasunonah, S. Pope and K. Kelleher	Pediatr Infect Dis J
602	Application of the study of prognostic factors to the treatment of childhood (<20 years old) acute lymphoblastic leukemia. Protocol 08 LA 74	405 children with acute lymphoblastic leukemia were classified according to age, initial leucocyte count, lymph nodes, liver and spleen size, into three prognostic classes. Protocol 08 LA 74 which applied included: 1) initial randomization between Prednisone, Vincristine, Daunorubicin or the same plus Cyclophosphamide for induction and reinductions; 2) dose adjustments to prognostic factors, increased doses being given to increased risk patients; 3) comparison between intrathecal Methotrexate and intrathecal Methotrexate plus Ara-C in addition to skull irradiation for CNS prophylaxis; 4) L-Asparaginase consolidation for all patients; 5) maintenance by 6-Mercaptopurine and Methotrexate in all patients and reinductions. The most striking conclusions to date are the improvement for increased risk patients, the frequency of primary testicular relapses contrasting with the low rate of meningitis, the prognostic implication of sex, the influence on remission duration of the number of courses necessary to achieve complete remission and the importance of using the Cox method to improve the identification of prognostic groups. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. Jacquillat, M. Weil and M. F. Auclerc	Bull-Cancer-(Paris)
654	Application of the study of prognostic factors to the treatment of childhood (less than 20 years old) acute lymphoblastic leukemia	405 children with acute lymphoblastic leukemia were stratified according to age, initial leucocytes count, lymph nodes, liver and spleen size, into three prognostic classes I, II, III. Protocol 08 LA 74 which they were applied included: 1)initial randomization between Prednisone, Vincristine, Daunorubicin or the same plus Cyclophosphamide for induction and reinductions; 2)doses adjustments to prognostic factors, increased doses being given to increased risk patients; 3)comparison between intrathecal Methotrexate and intrathecal Methotrexate plus Ara-C in addition to skull irradiation for CNS prophylaxis; 4)L-Asparaginase consolidation for all patients; 5)maintenance by 6-Mercaptopurine and Methotrexate in all patients and reinductions. The most striking conclusions to date are the improvement for increased risk patients, the frequency of primary testicular relapses contrasting with the low rate of meningitis, the prognostic implication of sex, the influence on remission duration of the number of courses necessary to achieve complete remission, the importance of using Cox Method to improve the identification of prognostic groups.	C. Jacquillat, M. Weil, M. F. Auclerc, G. Schaison, C. Chastang, J. L. Harousseau, F. Bauters, D. Olive, C. Griscelli, M. Bonnet, J. P. Lamagnere and J. Bernard	Bulletin du cancer
289	Liposomal amphotericin B (Fungisome) for the treatment of cryptococcal meningitis in HIV/AIDS patients in India: a multicentric, randomized controlled trial	BACKGROUND: There is need to investigate the use of liposomal amphotericin B in cryptococcal meningitis in India.AIMS: To compare the efficacy, safety, duration of treatment and cost of two doses of liposomal amphotericin B (Amp B) (Fungisome) in cryptococcal meningitis in HIV/AIDS patients.SETTINGS AND DESIGN: Prospective, randomized, multicenter study in tertiary care hospitals across India.MATERIALS AND METHODS: Adult patients with culture-proven cryptococcal meningitis with HIV/AIDS were randomized to receive either 1 (Group A) or 3 mg/kg/day of Fungisome (Group B). Clinical efficacy and tolerability, laboratory evaluations and mycological response were assessed daily, twice weekly and weekly respectively. The patients were assessed at four and eight-week follow-up.STATISTICS: We calculated average and standard deviation for the various parameters.RESULTS: The time to show clinical response was 13.66 days (1 mg) and 9.55 days (3 mg). In Group B (n=6 complete response), 50% patients responded within one week by microbial conversion, 83% in two weeks and 100% in three weeks. Patients with 1 mg dose (n=4 complete response), none showed microbial conversion within one week, 75% responded in two weeks, whereas one patient took four weeks. The average duration of treatment was 36.5+/-14.4 and 26.5+/-5.89 (S.D.) days in 1 and 3 mg/kg/day respectively. Drug was tolerated with little renal, hepatic or hematological toxicity. The cost was found to be 3.81 lacs and 1.74 lacs with 3mg/kg/day and 1mg/kg/day respectively.CONCLUSION: Higher dose showed better efficacy and quicker microbial conversion of Cerebrospinal fluid (CSF) (cerebrospinal fluid) than 1 mg/kg/day. It shortened the duration of treatment in days by 27% while drug cost almost doubled (Clinical trial registration number: ISRCTN 52812742).	M. P. Jadhav, A. Bamba, V. M. Shinde, N. Gogtay, N. A. Kshirsagar, L. S. Bichile, D. Mathai, A. Sharma, S. Varma and R. Digumarathi	Journal of postgraduate medicine
420	Liposomal amphotericin b (fungisome tm) for the treatment of cryptococcal meningitis in hiv/aids patients in india: A multicentric, randomized controlled trial	Background : There is need to investigate the use of liposomal amphotericin B in cryptococcal meningitis in India. Aims : To compare the efficacy, safety, duration of treatment and cost of two doses of liposomal amphotericin B (Amp B) (Fungisome TM ) in cryptococcal meningitis in HIV/AIDS patients. Settings and Design : Prospective, randomized, multicenter study in tertiary care hospitals across India. Materials and Methods : Adult patients with culture-proven cryptococcal meningitis with HIV/AIDS were randomized to receive either 1 (Group A) or 3 mg/kg/day of Fungisome (Group B). Clinical efficacy and tolerability, laboratory evaluations and mycological response were assessed daily, twice weekly and weekly respectively. The patients were assessed at four and eight-week follow-up. Statistics : We calculated average and standard deviation for the various parameters. Results : The time to show clinical response was 13.66 days (1 mg) and 9.55 days (3 mg). In Group B (n=6 complete response), 50% patients responded within one week by microbial conversion, 83% in two weeks and 100% in three weeks. Patients with 1 mg dose (n=4 complete response), none showed microbial conversion within one week, 75% responded in two weeks, whereas one patient took four weeks. The average duration of treatment was 36.5Â±14.4 and 26.5Â±5.89 (S.D.) days in 1 and 3 mg/kg/day respectively. Drug was tolerated with little renal, hepatic or hematological toxicity. The cost was found to be 3.81 lacs and 1.74 lacs with 3mg/kg/day and 1mg/kg/day respectively. Conclusion : Higher dose showed better efficacy and quicker microbial conversion of Cerebrospinal fluid (CSF) (cerebrospinal fluid) than 1 mg/kg/day. It shortened the duration of treatment in days by 27% while drug cost almost doubled (Clinical trial registration number: ISRTCN 52812742)	M. P. Jadhav, A. Bamba, V. M. Shinde, N. Gogtay, N. A. Kshirsagar, L. S. Bichile, D. Mathai, A. Sharma, S. Varma and R. Digumarathi	Journal of Postgraduate Medicine
473	Treatment of carcinomatous meningitis (CM) and lymphomatous meningitis (LM) with intra-CSF cytarabine sustained-release liposome injection (DepoCyt?) vs methotrexate (MTX) and ara-C		K. Jaeckle, M. Glantz, M. Chamberlain, S. Phuphanich, L. Swinnen, T. Campbell, B. Maria and S. LaFollette	Blood
502	Studies to clarify the central side effects, particularly the affection of the optic nerve, due to INH- and streptomycin therapy for tuberculous meningitis		G. Janssen, W. Böke and S. Eicken	Klinische Wochenschrift
279	Adjunctive interferon-? immunotherapy for the treatment of HIV-associated cryptococcal meningitis: a randomized controlled trial	BACKGROUND: Interferon-gamma (IFN?) is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis remains high, and novel treatment strategies are needed. We performed a randomized controlled trial to determine whether addition of IFN? to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated cryptococcal meningitis. METHODS: Patients were randomized to amphotericin B 1?mg/kg per day and 5FC 100?mg/kg per day for 2 weeks (standard therapy), standard therapy and IFN?1b 100??g days 1 and 3 (IFN? two doses), or standard therapy and IFN?1b 100??g days 1, 3, 5, 8, 10 and 12 (IFN? six doses). Primary outcome was rate of clearance of cryptococcus from the cerebrospinal fluid (CSF) (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival. RESULTS: Rate of fungal clearance was significantly faster in IFN? containing groups than with standard treatment. Mean EFA [log colony forming unit (CFU)/ml per day] was -0.49 with standard treatment, -0.64 with IFN? two doses, and -0.64 with IFN? six doses. Difference in EFA was -0.15 [confidence interval (95% CI) -0.02 to -0.27, P=0.02] between standard treatment and IFN? two doses, and -0.15 (95% CI -0.05 to -0.26, P=0.006) between standard treatment and IFN? six doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated. CONCLUSION: Addition of short-course IFN? to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFN? are as effective as six doses.	J. N. Jarvis, G. Meintjes, K. Rebe, G. N. Williams, T. Bicanic, A. Williams, C. Schutz, L. G. Bekker, R. Wood and T. S. Harrison	AIDS (London, England)
387	Non-traumatic adhesive arachnoiditis as a cause of spinal cord syndromes. Investigation of 507 patients	Spinal cord syndromes with a mainly syringomyelic pattern of sensory diorders, radiculopathies, mixed paresis of varying degree (without any history of trauma), have been found in 507 out of 1305 new patients referred to out Clinic from January 1976 till 31 October 1977. In 105 randomised and unselected cases with these syndromes, myelographies have disclosed findings compatible with an adhesive spinal and/or cisternal arachnoiditis. A prospective study of the syndromes for evidence of infectious aetiology has been performed, in which tuberculosis, syphilis and other infections appear to be causative agents. A randomised therapeutic trial on a limited number of cases has been evaluated, as well as the results of specific therapy in a larger number of cases. Results of treatment have not been satisfactory. Operations were performed on only five patients and in no case was an autopsy obtained. Spinal cord syndromes due to non-traumatic adhesive arachnoiditis are discussed. The possible pathogenetic mechanisms the predominantly syringomyelic sensory deficits in those syndromes are briefly mentioned.	F. Jenik, R. Tekle-Haimanot and B. H. Hamory	Paraplegia
27	Bacterial meningitis; a review of 356 cases with special reference to corticosteroid and antiserum treatment		K. Jensen, L. Ranek and N. Rosdahl	Scandinavian journal of infectious diseases
507	Broad vaccine coverage predicted for a bivalent recombinant factor H binding protein based vaccine to prevent serogroup B meningococcal disease		H. Q. Jiang, S. K. Hoiseth, S. L. Harris, L. K. McNeil, D. Zhu, C. Tan, A. A. Scott, K. Alexander, K. Mason, L. Miller, I. DaSilva, M. Mack, X. J. Zhao, M. W. Pride, L. Andrew, E. Murphy, M. Hagen, R. French, A. Arora, T. R. Jones, K. U. Jansen, G. W. Zlotnick and A. S. Anderson	Vaccine
380	Prevention of antibiotic-associated diarrhea in infants by probiotics	Probiotics administration has been claimed to prevent antibiotic-associated diarrhea. The investigators thus conducted a double blind, placebo controlled study of providing probiotics to infants and children with severe bacterial infections and receiving broad spechum antibiotics. The results of the study showed that the group receiving probiotics had fewer diarrheal episodes (37.5%) than the control group (80%), although the numbers were too small for statistical analysis. In conclusion, probiotics administration to patients receiving high doses of broad spectrum antibiotics may prevent the occurrence of antibiotic-associated diarrhea. A further study with a larger number is required.	P. Jirapinyo, N. Densupsoontorn, N. Thamonsiri and R. Wongarn	Journal of the Medical Association of Thailand = Chotmaihet thangphaet
166	Albendazole therapy for eosinophilic meningitis caused by Angiostrongylus cantonensis	Eosinophilic meningitis in humans is commonly caused by the nematode Angiostrongylus cantonensis. A severe headache is the most common presenting symptom. A prospective, randomized, double-blind, placebo, controlled study was conducted to determine if albendazole was efficacious in relieving such headaches. Seventy-one patients (36 and 35 in the treatment and control groups) were enrolled in the study. Five patients (two and three in the treatment and control groups) were excluded from the study because of being lost to follow-up, and the clinical data were incomplete. Therefore, 34 and 32 patients in the treatment and control groups were studied, respectively. Albendazole was administered at 15 mg/kg/day or identical placebo for 2 weeks. The number of patients with persistent headaches after 2 weeks was 7 and 13 in the albendazole and placebo groups (p = 0.08), respectively. The mean duration of a headache was 8.9 and 16.2 days in the albendazole and placebo groups, respectively (p = 0.05). No serious drug events were observed. A 2-week course of albendazole appeared to reduce the duration of headache in eosinophilic meningitis.	S. Jitpimolmard, K. Sawanyawisuth, N. Morakote, A. Vejjajiva, M. Puntumetakul, K. Sanchaisuriya, W. Tassaneeyakul, W. Tassaneeyakul and N. Korwanich	Parasitology research
311	Amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients	We determined the safety and efficacy of deoxycholate-amphotericin B (d-AmB) mixed with Intralipid (IL) as the initial treatment of AIDS-associated cryptococcal meningitis in a phase II, multicentre, non-comparative open study, assessing two dosages of ILd-AmB: 1 mg/kg (group A, n = 9) and 1.5 mg/kg (group B, n = 6). Patients were treated daily for 2 weeks, then three times weekly for 4 weeks. The ILd-AmB dosage was decreased due to toxicity in three patients in each group. Serum creatinine increased significantly on day 14 in group A and on day 7 in group B. Nephrotoxicity, (serum creatinine level > 165 mumol/L) was noted in two and five patients in groups A and B, respectively. Nine adverse haematological events were noted (seven cases of anaemia requiring transfusion, and two cases of neutropenia < 750/mm). Two patients had an increase in serum alkaline phosphatase. In each cohort, 15% of the infusions were associated with fever and/or chills. Successful outcome was obtained in half of the patients. We conclude that, in AIDS patients with cryptococcosis, tolerance to ILd-AmB was acceptable when the daily dosage did not exceed 1 mg/kg, but the higher 1.5 mg/kg daily dosage was associated with an unacceptable rate of nephrotoxicity. Neither of these relatively high daily dosages of ILd-AmB achieved an improved rate of successful outcomes compared with lower daily dosages of conventional d-AmB in glucose.	V. Joly, C. Geoffray, J. Reynes, C. Goujard, D. Méchali, C. Maslo, F. Raffi and P. Yeni	The Journal of antimicrobial chemotherapy
90	Meningitis and meningococcal septicaemia		R. Jones, F. Finlay, V. Crouch and S. Anderson	Archives of disease in childhood
348	Dexamethasone for the treatment of tuberculous meningitis in adolescents and adults		B. Jubelt	Current neurology and neuroscience reports
599	A phase I/II trial of high-dose erythropoietin in extremely low birth weight infants: pharmacokinetics and safety	OBJECTIVES. High-dose recombinant erythropoietin is neuroprotective in animal models of neonatal brain injury. Extremely low birth weight infants are at high risk for brain injury and neurodevelopmental problems and might benefit from recombinant erythropoietin. We designed a phase I/II trial to test the safety and determine the pharmacokinetics of high-dose recombinant erythropoietin in extremely low birth weight infants. METHODS. In a prospective, dose-escalation, open-label trial, we compared 30 infants who were treated with high-dose recombinant erythropoietin with 30 concurrent control subjects. Eligible infants were <24 hours old, < or =1000 g birth weight, and < or =28 6/7 weeks of gestation and had an umbilical artery catheter in place. Each infant received 3 intravenous doses of 500, 1000, or 2500 U/kg at 24-hour intervals beginning on day 1 of age. Blood samples were collected at scheduled intervals to determine recombinant erythropoietin pharmacokinetics. Safety parameters were also evaluated. In the concurrent control group, only clinical data were collected. RESULTS. Mean erythropoietin concentrations 30 minutes after recombinant erythropoietin infusion were 5973 +/- 266, 12 291 +/- 403, and 34 197 +/- 1641 mU/mL after 500, 1000, or 2500 U/kg, respectively. High-dose recombinant erythropoietin followed nonlinear pharmacokinetics as a result of decreasing clearance from the lowest dosage (17.3 mL/hour per kg for 500 U/kg) to the highest dosage (8.2 mL/hour per kg for 2500 U/kg). Steady state was achieved within 24 to 48 hours. Both 1000 and 2500 U/kg recombinant erythropoietin produced peak serum erythropoietin concentrations that were comparable to neuroprotective concentrations that previously were seen in experimental animals. No excess adverse events occurred in the recombinant erythropoietin-treated infants compared with control infants. CONCLUSIONS. Early high-dose recombinant erythropoietin is well tolerated by extremely low birth weight infants, causing no excess morbidity or mortality. Recombinant erythropoietin dosages of 1000 and 2500 U/kg achieved neuroprotective serum levels. Copyright copyright 2008 by the American Academy of Pediatrics. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. E. Juul, R. J. McPherson, L. A. Bauer, K. J. Ledbetter, C. A. Gleason and D. E. Mayock	Pediatrics
136	Erythropoietin in the cerebrospinal fluid of neonates who sustained CNS injury	We previously reported that erythropoietin (Epo) is present in human cerebrospinal fluid (CSF). It is not known whether CSF Epo concentrations change under conditions of CNS injury or, if so, whether this change reflects loss of blood-brain barrier integrity or increased CNS Epo synthesis. We hypothesized that CSF Epo increases in conditions of neural injury including hypoxia, meningitis, and intraventricular hemorrhage (IVH) and that CSF Epo concentrations are independent of plasma Epo concentrations. To test these hypotheses, Epo concentrations were measured in 122 paired CSF and blood samples obtained from neonates and children categorized as follows: 16, asphyxia; 31, meningitis; 11, IVH; 41, controls. Twelve infants treated with recombinant Epo (rEpo) and 11 additional samples from children with miscellaneous neurologic problems were also evaluated. CSF and plasma Epo concentrations were significantly higher in asphyxiated infants than in controls (225.0+/-155.0 versus 4.5+/-0.5 mU/mL; mean +/- SEM, p < 0.05, respectively, in CSF; 1806.7+/-1254 versus 5.2+/-0.5, p < 0.05 in plasma). Neonates with IVH had higher CSF Epo concentrations than controls (p < 0.01) but did not have higher plasma Epo concentrations than controls. Patients with meningitis did not have elevated CSF or plasma Epo concentrations. There was no correlation between CSF and plasma Epo concentrations in infants treated with rEpo. We conclude that Epo is selectively increased in the CSF by hypoxia, less so by IVH, and not at all by meningitis. rEpo treatment does not elevate CSF Epo. These findings suggest that rEpo does not cross the blood-brain barrier and that hypoxia induces increased CNS synthesis of Epo.	S. E. Juul, S. A. Stallings and R. D. Christensen	Pediatric research
555	Effect of methyl prednisolone on sensory motor functions in tuberculous meningitis		J. Kalita and U. K. Misra	Neurology India
347	Humoral and cell mediated immune responses in patient with tuberculous meningitis	A study was carried out to find out the humoral and cell mediated immunity levels in patients with TBM and healthy controls. For humoral immunity, the amounts of immunoglobulins--IgG, IgM and IgA were quantitated by SRID method. For cell mediated immunity, percentages of total T cells, Th cells and Ts cells and the ratio of Th:Ts cells was studied. Hypergammaglobulinemia of all three immunoglobulins was observed together with a decrease in the total T cells and Th cells, and a lower Th:Ts cell ratio indicating a deficiency or a defect in the immune system of patients infected with TBM.	H. A. Kamat, M. Williamson and G. V. Koppikar	Indian journal of medical sciences
616	Endoscopic treatment of hydrocephalus in children: a controlled study using newly developed Yamadori-type ventriculoscopes	Although cerebrospinal fluid (CSF) shunting is the most common neurosurgical treatment for hydrocephalus, the long-term results have still been unsatisfactory because of a wide variety of shunt complications. We have recently developed flexible ventriculoscopes (Yamadori-type) which have excellent image quality, maneuverability, and capabilities for endoscopic operation. Here we report the efficacy of the new treatment in 88 children with hydrocephalus who initially underwent either ventriculoscopic operation or shunting surgery. The primary outcome measures were the rate of shunt independency and/or shunt complications with a follow-up of 2 years in each group. We performed endoscopic third ventriculostomy in cases of aqueductal stenosis, cyst fenestration, and choroid plexus coagulation in limited cases of communicating hydrocephalus. Overall, thirty-three (75%) of the 44 children initially treated endoscopically did not require ventriculoperitoneal (VP) shunts. The endoscopic procedures were repeated in the remaining 11 children (25%) mostly less than 1-year-old who ultimately required endoscope-guided VP shunting. Even in such patients, there was virtually no need for shunt revisions and no major complications such as slit-like ventricle, meningitis, and intraventricular hemorrhage. These results were statistically highly significant (p < 0.0001) compared to a control group of 44 patients treated initially by VP shunting. Our data demonstrate that therapeutic ventriculoscopy is safe and clinically effective as the first-line treatment of hydrocephalus in children.	S. Kamikawa, A. Inui, N. Kobayashi, K. Kuwamura, M. Kasuga, T. Yamadori and N. Tamaki	Minimally invasive neurosurgery : MIN
594	Phase I study of the immunogenicity and safety of conjugated Hemophilus influenzae type b vaccines in the elderly	In infants, vaccines consisting of a carrier protein conjugated to the bacterial capsular polysaccharide (PRP) are far more protective against Hemophilus influenzae type b (Hib) disease than unconjugated PRP. To determine the tolerability and immunogenicity of Hib conjugate vaccines in the elderly, we vaccinated 30 volunteers, aged 69-84 years, with either PRP conjugated to an outer membrane protein complex (PRP-OMP), or PRP oligomers conjugated to CRM197, a nontoxic, mutant diphtheria toxin (HbOC). Prior to vaccination, 40% of subjects had serum anti-PRP antibody levels < 1.0 microgram ml-1. Four weeks following vaccination, all subjects had concentrations > 1.0 microgram ml-1, a level generally considered to be protective. The post-vaccination geometric mean concentrations were 35.5 and 50.1 micrograms ml-1 for the PRP-OMP and HbOC groups, respectively (0.05 < P < 0.10). Subjects in the HbOC group, but not the PRP-OMP group, showed, on average, ten fold increases in IgG antibody to diphtheria toxoid after conjugate vaccination. Side-effects of vaccination were mild except in one subject given HbOC, who developed extensive erythema and swelling of the injected arm.	E. Kantor, J. S. Luxenberg, A. H. Lucas and D. M. Granoff	Vaccine
235	Spinal epidermoid tumors: novel approach to aseptic meningitis	Intraoperative hydrocortisone irrigation of the cerebrospinal fluid pathways may reduce symptoms attributed to aseptic meningitis, which often follow the resection of epidermoid spinal tumors. Here, 20 patients undergoing surgical resection of epidermoid tumors were randomly assigned to two groups: Group I received intraoperative hydrocortisone irrigation, whereas Group II served as a control. No patient receiving hydrocortisone experienced fevers or meningismus, but nontreated patients experienced fevers (100%) and meningismus (78%). Nausea and vomiting were reduced (9%) in the treated versus untreated groups (22% vs. 11%, respectively), whereas none in the treated group noted dizziness, vertigo, or diabetes insipidus. As steroid irrigation significantly decreased the perioperative morbidity of epidermoid tumor resection, indications for intravenous steroids may become more limited, thereby reducing cost.	J. R. Kapoor, R. Kapoor, C. Buzea and M. R. Gropper	Journal of spinal disorders & techniques
273	Brainstem auditory evoked response (BAER) in childhood bacterial meningitis	Brainstem auditory responses were recorded in 50 children of bacterial meningitis and age matched 50 normal children. Abnormal BAER was found in 32 (64%) patients of bacterial meningitis. These abnormalities included prolonged latency (56.2%); unilateral absent response (25%); bilateral absent response (25%) and prolonged interwave interval (25%). Follow-up could be done in 23 patients of 46 survivors. All the patients with prolonged latency either became normal or improved. In majority of the patients having absent response, the abnormality persisted. Abnormal BAER was significantly associated with age < 2 years (p < 0.02), Modified GCS Score < or = 8 (p < 0.001), Seizures (p < 0.02), raised Intracranial Pressure (ICP) (p < 0.02) and CSF sugar < 20 mg% (p < 0.05).	R. K. Kapoor, R. Kumar, P. K. Misra, B. Sharma, R. Shukla and S. Dwivedee	Indian journal of pediatrics
108	Brainstem auditory evoked response in tuberculous meningitis	Brainstem auditory evoked response (BAER) abnormalities in tuberculous meningitis (TBM) were determined in 50 cases of tuberculous meningitis (36 male and 14 female) and 50 normal healthy children. Fifty six per cent cases had abnormal BAER findings. The commonest BAER abnormality observed in 32% was a combination of prolonged latency and prolonged interval while unilateral and bilateral absent response was observed in 4% cases. Prolonged latency was observed in 16% patients. Seizure activities, modified glasgow coma scale (GCS), raised intracranial pressure (ICP) and TBM stage III were significantly correlated with abnormal BAER, while age, sex, duration of illness, depressed sensorium, neurological deficit and CSF findings did not have a significant correlation with abnormal BAER. Follow up could be done in ten patients only. All the three patients with only prolonged latency had a normal BAER on follow up, two out of four patients with prolonged latency and prolonged interval had normalization of BAER while in three patients, initial as well as follow up BAER was normal. The present study shows that BAER abnormalities are observed in more than fifty per cent of the patients of tuberculous meningitis.	R. K. Kapoor, A. Makharia, R. Shukla, P. K. Misra and B. Sharma	Indian journal of pediatrics
346	Corticosteroids in tuberculous meningitis		B. Karak and R. K. Garg	Indian pediatrics
68	Differential diagnosis of tuberculous meningitis from partially-treated pyogenic meningitis by cell ELISA	BACKGROUND: Tuberculous meningitis (TBM) is a major global health problem, and it is sometimes difficult to perform a differential diagnosis of this disease from other diseases, particularly partially-treated pyogenic meningitis (PTPM). In an earlier study, we demonstrated the presence of a 30-kD protein antigen in cerebrospinal fluid (CSF) of TBM patients. We have also shown that lymphocytes from CSF of TBM patients respond differently to this antigen than do those from PTPM patients. The purpose of this study was to develop an assay that can discriminate between TBM and PTPM. METHODS: We developed a cell enzyme-linked immunosorbant assay (Cell ELISA) to quantitatively measure production of antibodies against the 30-kD protein in B cells from CSF of TBM and PTPM patients. RESULTS: The cell ELISA yielded 92% (11/12) sensitivity and 92% (11/12) specificity for the differential diagnosis of TBM from PTPM. CONCLUSION: When induced with the 30-kD protein antigen, B cells derived from CSF of TBM patients respond to IgG production within 24 h while those derived from PTPM patients do not respond.	R. S. Kashyap, R. P. Kainthla, R. M. Satpute, N. P. Agarwal, N. H. Chandak, H. J. Purohit, G. M. Taori and H. F. Daginawala	BMC neurology
141	Immunogenicity and safety testing of a group B intranasal meningococcal native outer membrane vesicle vaccine	The presently licensed meningococcal vaccine is a tetravalent capsular polysaccharide vaccine that induces immunity to serogroups A, C, Y, and W-135 but not to group B, which causes nearly half of the meningitis cases in the United States. The purpose of this study was to evaluate the safety and immunogenicity of an intranasal native outer membrane vesicle (NOMV) vaccine prepared from a capsule negative strain of group B of Neisseria meningitidis. In this study all volunteers received the same dose of vaccine, but we evaluated two different immunization schedules and the oropharyngeal and intranasal routes of vaccine delivery, assessed nasal cytology for cellular infiltration, and measured antibody-secreting cells (enzyme-linked immunospot assay [ELISPOT]) as an early marker for systemic immune response. Additionally, both intranasal and serum vaccine-specific antibodies were measured as well as serum bactericidal activity. Four groups with a total of 42 subjects were immunized on days 0, 28, and 56. Group 3 received an additional dose on day 7. Group 2 subjects were immunized both intranasally and oropharyngeally. Group 4 received a different lot of vaccine. All groups received approximately 1,200 microg of vaccine per subject. Patients were evaluated for side effects. The vaccine was well tolerated without evidence of inflammation on nasal cytology. The group receiving the extra vaccine dose showed the maximum increase in bactericidal activity. Thirty of 42 subjects demonstrated an increase in meningococcus-specific intranasal immunoglobulin A (IgA) titers, while 23 of 42 demonstrated an increase in specific IgG titers. The group receiving vaccine intranasally and oropharyngeally showed the highest rise in intranasal titers for both IgA and IgG. Groups 1, 3, and 4 showed a significant increase in antibody-secreting cells on ELISPOT. Eighteen of 42 volunteers demonstrated a fourfold or greater rise in bactericidal titers, with 81% showing an increase over baseline. We have demonstrated the immunogenicity and safety of a group B lipopolysaccharide-containing, intranasal, NOMV vaccine.	R. K. Katial, B. L. Brandt, E. E. Moran, S. Marks, V. Agnello and W. D. Zollinger	Infection and immunity
406	Efficacy of a single dose of ciprofloxacin vs. rifampicin in eradicating the nasopharyngeal carriage of Neisseria meningitidis	A prospective study was performed to test efficacy of a single dose of 750 mg oral ciprofloxacine in comparison with 600 mg rifampicin twice daily for 2 days in eradicating Neisseria meningitidis from healthy nasopharyngeal carriers. Nasopharyngeal samples were obtained for culture before and 1 and 2 weeks after therapy. We found 54 (18%) of 300 healthy adult volunteers to be carriers of N. meningitidis. Of these, 51 were considered suitable candidates for evaluating the efficacy and safety of the drugs. One week after therapy, the eradication rates for ciprofloxacine and rifampicin were 92% and 96%, respectively; at 2 weeks, they were the same. The difference in the eradication rates of the two drugs was evaluated using the Chi-square test, and this was not statistically significant. No clinically important side-effects were associated with either drugs. A single dose of ciprofloxacine provides an effective and safe alternative to rifampicin in eradicating meningococcal carriage. [References: 11]. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Kaya, M. A. Tasyaran, S. Celebi and S. Yilmaz	Turkish Journal of Medical Sciences
140	Pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine is immunogenic in infants and children	Sixty-two infants and 31 toddlers were vaccinated with the tetravalent pneumococcal conjugate vaccine PncOMPC consisting of the capsular polysaccharide of pneumococcal types 6B, 14, 19F, and 23F conjugated to the outer membrane protein complex of Neisseria meningitidis. Infants were vaccinated at 2, 4, and 6 months (group A) or at 4, 6, and 14 months (group B); toddlers were vaccinated at 24 or at 24 and 26 months of age. The IgG responses to the four pneumococcal polysaccharide types were measured by EIA. In infants, types 14 and 19F induced a significant response after the first dose and types 6B and 23F after the second dose. A clearcut booster response was seen to the booster dose given at 14 months, indicating immunologic priming by the primary series at 2-6 months of age. The responses of the toddlers to one or two doses of the vaccine were very similar to the responses in infants.	H. Käyhty, H. Ahman, P. R. Rönnberg, R. Tillikainen and J. Eskola	The Journal of infectious diseases
153	Persistence of antibodies to the Salmonella typhi Vi capsular polysaccharide vaccine in South African school children ten years after immunization	Between 10 and 11 years after children were vaccinated with Vi capsular polysaccharide of Salmonella typhi or meningococcal A + C control vaccine in a double blind randomized trial, we traced 83 subjects, aged 16-20 years. A blood sample was taken for determination of Vi antibody titres in both groups by radioimmunoassay. TO and TH titres were also done to assess if the participants had had recent exposure to typhoid fever. Fifty-eight percent of subjects in both groups had protective levels of Vi antibody against Salmonella typhi (a titre greater than 1 microgram ml-1). There was no significant difference in the levels of Vi antibodies in the cases versus the controls (p = 0.5). Two of the children who had received meningococcal A + C vaccine had recently had typhoid fever. Our data show that adolescents in typhoid endemic areas have high levels of Vi antibodies regardless of previous vaccination status, suggesting that Vi antibodies are acquired in adolescence by a large percentage of the population in this area. Moreover, Vi vaccination has led to ongoing antibody production in greater than 50% of Vi vaccinated children in an endemic area for a period of 10 years. Ongoing antigenic exposure may have contributed to these antibody levels.	K. H. Keddy, K. P. Klugman, C. F. Hansford, C. Blondeau and N. N. Bouveret le Cam	Vaccine
515	A phase 1 study of a meningococcal native outer membrane vesicle vaccine made from a group B strain with deleted lpxL1 and synX, over-expressed factor H binding protein, two PorAs and stabilized OpcA expression		P. B. Keiser, S. Biggs-Cicatelli, E. E. Moran, D. H. Schmiel, V. B. Pinto, R. E. Burden, L. B. Miller, J. E. Moon, R. A. Bowden, J. F. Cummings and W. D. Zollinger	Vaccine
388	A phase 1 study of a group B meningococcal native outer membrane vesicle vaccine made from a strain with deleted lpxL2 and synX and stable expression of opcA	This phase 1 clinical trial assessed the safety and immunogenicity of a native outer membrane vesicle (NOMV) vaccine prepared from a lpxL2(-) synX(-) mutant of strain 44/76 with opcA expression stabilized. Thirty-four volunteers were assigned to one of the three dose groups (25 mcg, 25 mcg with aluminum hydroxide adjuvant, and 50 mcg) to receive three intramuscular injections at 0, 6 and 24 weeks. Specific local and systemic adverse events (AEs) were solicited by diary and at visits on days 1, 2, 7 and 14 after each vaccination and at the end of the study at 30 weeks. Blood chemistries, complete blood count, and coagulation studies were measured on each vaccination day and again two days later. Blood for antibody measurements and bactericidal assays were drawn 0, 14, and 42 days after each vaccination. The proportion of volunteers who developed a fourfold or greater increase in serum bactericidal activity (SBA) to the wild-type parent of the vaccine strain with high opcA expression at 6 weeks after the third dose was 12/26 (0.46, 95% confidence interval 0.27-0.65). Antibody levels to OpcA were significantly higher in vaccine responders than in non-responders (p= 0.008), and there was a trend for higher antibody levels to the lipooligosaccharide (LOS) (p= 0.059). Bactericidal depletion assays on sera from volunteers with high-titer responses also indicate a major contribution of anti-OpcA and anti-LOS antibodies to the bactericidal response. These results suggest that genetically modified NOMV vaccines can induce protection against group B meningococcus. 2010.	P. B. Keiser, B. T. Gibbs, T. S. Coster, E. E. Moran, M. B. Stoddard, J. E. Labrie, D. H. Schmiel, V. Pinto, P. Chen and W. D. Zollinger	Vaccine
531	Plasma fibrinogen levels after vaccination with a native outer membrane vesicle vaccine for Neisseria meningitidis		P. B. Keiser, L. B. Miller, S. Biggs-Cicatelli and W. D. Zollinger	Vaccine
149	CRM197-conjugated serogroup C meningococcal capsular polysaccharide, but not the native polysaccharide, induces persistent antigen-specific memory B cells	Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia in children. Vaccines containing the purified polysaccharide capsule from the organism, a T cell-independent antigen, have been available for decades but do not appear to provide protection in infancy or immunologic memory as measured by antibody responses. By contrast, T cell-dependent serogroup C protein-polysaccharide conjugate vaccines protect against serogroup C meningococcal disease from infancy onward and prime for immunologic memory. We compared the magnitude and kinetics of plasma cell and memory B-cell responses to a meningococcal plain polysaccharide vaccine and a serogroup C glycoconjugate vaccine in adolescents previously primed with the conjugate vaccine. Plasma cell kinetics were similar for both vaccines, though the magnitude of the response was greater for the glycoconjugate. In contrast to the glycoconjugate vaccine, the plain polysaccharide vaccine did not induce a persistent immunoglobulin G (IgG) memory B-cell response. This is the first study to directly show that serogroup C meningococcal glycoconjugate vaccines induce persistent production of memory B cells and that plain polysaccharide vaccines do not, supporting the use of the conjugate vaccine for sustained population protection. Detection of peripheral blood memory B-cell responses after vaccination may be a useful signature of successful induction of immunologic memory during novel vaccine evaluation.	D. F. Kelly, M. D. Snape, E. A. Clutterbuck, E. A. Cutterbuck, S. Green, C. Snowden, L. Diggle, L. M. Yu, A. Borkowski, E. R. Moxon and A. J. Pollard	Blood
368	The place of BCG vaccine in the management of infants born of tuberculous mothers		E. L. Kendig	The New England journal of medicine
201	[Evaluation of tumor necrosis factor and C-reactive protein level determination in cerebrospinal fluid of meningitis and encephalitis]	The evaluation of TNF-alpha and CRP in cerebrospinal fluid (CSF) concentrations determining in the differential diagnosis of infectious meningitis was shown. The highest concentrations of these parameters were detected in the group of patients with bacterial meningitis. The findings correlated with the severity of clinical course of bacterial meningitis and with the routine determined laboratory data of CSF. Usefulness of examination CSF for TNF-alpha and CRP in differential diagnosis of meningitis was underlined, especially in cases, where routine parameters of CSF are not conclusive.	L. Kepa and B. Adamek	Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
209	Persistence of immunity following a booster dose of Haemophilus influenzae type B-Meningococcal serogroup C glycoconjugate vaccine: follow-up of a randomized controlled trial	BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) wane after early infant immunization.METHODS: Children previously immunized in a randomized controlled trial at ages 2, 3, and 4 months with DTPa-IPV-Hib and MenC-CRM197 (MenC-CRM group) or DTPa-IPV and Hib-MenC-TT (Hib-MenC-TT group) had blood samples drawn at 1 and 2 years following a booster dose of Hib-MenC-TT at 12 to 15 months of age. A blood sample was also drawn at the year 2 follow-up from a separately recruited age-matched control group who had not received a booster.RESULTS: In 271 children at year 1, mean 14.6 months (range: 12-18 months) following the Hib-MenC-TT booster, MenC bactericidal titers above the protective threshold (rSBA ? 1:8) was demonstrated in 89.0% of the Hib-MenC-TT group and 69.5% of MenC-CRM participants. Antipolyribosylribitol phosphate Ig ? 1.0 ?g/mL (Hib correlate for long-term protection) was seen in 94.9% and 82.5%, respectively.In 379 participants (including 72 control children) at year 2 (age: 39-43 months, 25-31 months post Hib-MenC-TT) persistence of MenC antibodies was demonstrated in 67.1% of the Hib-MenC-TT group and 40.5% of the MenC-CRM group, compared with 44.1% of control group participants. Antipolyribosylribitol phosphate Ig ? 1.0 ?g/mL was seen in 89.0%, 74.7%, and 38.9%, respectively.CONCLUSIONS: A toddler Hib-MenC-TT booster helps sustain immunity against Hib to 3½ years of age. Persistence of MenC antibody is similar in children primed with MenC-CRM197 in infancy who receive a booster Hib-MenC-TT, to those who receive no booster. Persistence of MenC antibody is better when primed and boosted with Hib-MenC-TT.	A. Khatami, M. D. Snape, T. John, S. Westcar, C. Klinger, L. Rollinson, D. Boutriau, N. Mesaros, J. Wysocki, A. Galaj, L. M. Yu and A. J. Pollard	The Pediatric infectious disease journal
532	Role of intrathecal hydrocortisone in tuberculous meningitis in children		S. P. Khatua	Br Med J
121	Safety and efficacy of combined meningococcal and typhoid vaccine		S. H. Khoo, J. Clair Roberts and B. K. Mandal	BMJ (Clinical research ed.)
598	Patterns of neuropsychological deficits in children with medulloblastoma according to craniospatial irradiation doses	This study aimed to analyse the relationship between supratentorial irradiation dose and the intellectual outcome in 36 children (aged between 5 and 15 years) treated for medulloblastoma. The supratentorial radiation dose was reduced to 25 Gy in 23 children and given at the standard dose, 35 Gy, in 13 other children. Neuropsychological evaluation was performed at a mean of 4.3 years (SD 4.7 years) after radiotherapy. The supratentorial radiation dose was the principal risk factor associated with impaired intellectual outcome. Verbal fluency, immediate word list recall, block design, and fine motricity of the dominant hand were significantly lower in children irradiated at the standard doses than in those irradiated at reduced doses. These findings suggest that the dose of radiotherapy applied to the brain strongly influences later verbal and non-verbal skills in children with medulloblastoma. This should be taken into account in treatment planning and in rehabilitation programs. Number of References 30. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	V. Kieffer-Renaux, C. Bulteau, J. Grill, C. Kalifa, D. Viguier and I. Jambaque	Developmental Medicine & Child Neurology
688	Immunogenicity and safety of LBVH0101, a new Haemophilus influenzae type b tetanus toxoid conjugate vaccine, compared with Hiberix? in Korean infants and children: a randomized trial	BACKGROUND: The World Health Organization (WHO) recommends that all countries adopt Haemophilus influenzae type b (Hib) vaccine into routine child immunization programs to protect children from the significant burden of life-threatening pneumonia and meningitis. METHODS: In this blind, comparative, randomized, phase-III Korean multicenter study, we assessed immunogenicity and safety following primary vaccination of a new H. influenzae type b tetanus toxoid conjugate vaccine, LBVH0101 (LG Life Sciences, Ltd., Seoul, Korea) compared with Hiberix? (GSK, Rixensart, Belgium) in Korean children at 2, 4 and 6 months of age followed by a booster vaccination at 12-15 months. Serum anti-PRP IgG concentration and bactericidal activity were determined. Local/systemic symptoms were assessed after vaccination. Serious adverse events were recorded throughout the study. RESULTS: A total of 185 infants were included in immunogenicity evaluations. After the second and third doses of LBVH0101, 90.32% and 100% of infants achieved an antibody level ?1 ?g/mL, respectively, compared with 78.26% and 96.74% of those who received Hiberix?. After the second vaccination, the geometric mean concentration (GMC) of LBVH0101 recipients was 7.34 ?g/mL and was higher than that of Hiberix? recipients (3.55 ?g/mL). After the third vaccination, the GMCs were 14.59 ?g/mL and 12.15 ?g/mL in the LBVH0101 and Hiberix? recipients, respectively. The booster dose produced higher antibody concentrations: 30.25 ?g/mL and 71.64 ?g/mL for LBVH0101 and Hiberix? recipients, respectively. Bactericidal capacity and antibody potency of anti-PRP IgG induced by LBVH0101 was 35.05 and 116.27 after the second and third vaccinations, respectively, compared with 53.76 and 79.64 for Hiberix?. Anti-PRP IgG seroprotection rate and GMC were similar post-primary immunization between the groups; both showed functional maturation and similar booster responses. LBVH0101 had comparable safety results as the control vaccine, Hiberix?, as most of the solicited adverse events and unsolicited adverse events upon LBVH0101 administration were mild in severity. No serious vaccination-related adverse reactions were observed. CONCLUSIONS: LBVH0101 showed a good immunogenicity and safety profile in infants and children. The two-dose infant-priming schedule with a booster dose may suffice for Hib immunization in Korean infants (Clinical trial registration numbers: NCT01019772 and NCT01251133).	K. H. Kim, Y. K. Kim, N. H. Kim, S. H. Chang, J. Lee, E. A. Park, S. E. Park, B. W. Eun, H. Lee and H. J. Lee	Vaccine
524	Immunogenicity and safety of two different Haemophilus influenzae type b conjugate vaccines in Korean infants	The incidence of invasive diseases, including meningitis caused by Haemophilus influenzae type b (Hib) was markedly decreased after routine immunization of Hib vaccine through diverse schedules in many countries. The purpose of this study was to evaluate the immunogenicity and safety of Hib conjugate vaccines in Korean children before the implementation of a national immunization program against Hib in Korea. A multicenter controlled trial was performed on two different Hib vaccines in Korean children. A total of 319 infants were enrolled: 199 infants were immunized with the Hib polysaccharide conjugated to the tetanus toxoid (PRP-T) and 120 infants with the Hib polysaccharide conjugated to the outer-membrane protein of Neisseria meningitides (PRP-OMP). Immunogenicity was evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay. Both vaccines showed good immunologic responses after primary immunization. After 2 doses of PRP-T or PRP-OMP, 78.9% and 91.7% of infants achieved an antibody level of >or=1.0 microg/mL, respectively. Both vaccines were safe and well-tolerated. No serious adverse events were observed. Thus, Hib conjugate vaccines appear to be safe and show good immunogenicity in Korean infants. These results will be important reference data for the implementation of Hib vaccine in the national immunization program of Korea.	K. H. Kim, H. Lee, E. H. Chung, J. H. Kang, J. H. Kim, J. S. Kim, H. J. Lee, S. H. Oh, E. A. Park and S. E. Park	Journal of Korean medical science
595	Comparative immune responses to Haemophilus influenzae type b polysaccharide and a polysaccharide-protein conjugate vaccine		K. S. Kim, V. K. Wong, R. Adler and E. A. Steinberg	Pediatrics
644	A multicenter, randomized, double-blind, placebo-controlled trial of high-dose intravenous immunoglobulin for oral corticosteroid-dependent asthma	To determine the efficacy of high doses of intravenous gammaglobulin (IVIG) for the treatment of severe, steroid-dependent asthma in patients between 6 and 68 years of age, a randomized, double-blind, placebo-controlled multicenter clinical trial was conducted in private and university hospitals in the United States. Patients were randomized to one of three treatment arms: 2 g IVIG/kg/month (16 patients); 1 g IVIG/kg/month (9 patients); or 2 g iv albumin (placebo)/kg/month (15 patients). The treatment consisted of seven monthly infusions followed by a posttreatment observation period. The primary outcome measurement was mean daily prednisone-equivalent dose requirements, determined during the observation month preceding initiation of treatment and compared to the month preceding the seventh infusion. Secondary clinical endpoints measured were pulmonary function, frequency of emergency room visits or hospitalizations, and number of days absent from school or work. When adjusted for body weight, the mean dose requirements fell by 33, 39, and 33% in the placebo, IVIG (1 g/kg), and IVIG (2 g/kg) treatment arms, respectively. The differences between therapies were not statistically different (P = 0.9728). The mean percentage-of-predicted FEV1 fell in all three treatment groups during the treatment period but there was no significant difference between treatment groups (P = 0.8291). There was also no significant difference in the percentage of subjects requiring emergency room visits or hospitalizations or missing days of work/school, among the three treatment groups. The trial was terminated prematurely after interim analysis determined the adverse experience rate was different between the three groups. Three patients, all randomized to the 2-g/kg IVIG dose group, were hospitalized with symptoms consistent with aseptic meningitis. In summary, in this randomized, double-blind, placebo-controlled multicenter study, high doses of IVIG did not demonstrate a clinically or statistically significant advantage over placebo (albumin) infusions for the treatment of corticosteroid-dependent asthma. Subgroup analysis failed to identify markers predicting responsiveness. High-dose IVIG can also be associated with a significant incidence of serious adverse events.	J. L. Kishiyama, D. Valacer, C. Cunningham-Rundles, K. Sperber, G. W. Richmond, S. Abramson, M. Glovsky, R. Stiehm, J. Stocks, L. Rosenberg, R. S. Shames, B. Corn, W. T. Shearer, B. Bacot, M. DiMaio, S. Tonetta and D. C. Adelman	Clinical immunology (Orlando, Fla.)
297	Neurologic manifestations of the cryopyrin-associated periodic syndrome	BACKGROUND: The cryopyrin-associated periodic syndrome (CAPS) is a rare but treatable hereditary autoinflammatory condition. Without treatment, one third of patients develop amyloidosis with consequent renal failure and death. CAPS encompasses 3 conditions: familial cold autoinflammatory syndrome, Muckle-Wells syndrome, and chronic infantile, neurologic, cutaneous, and articular syndrome. Neurologic complications are common in children with the chronic infantile, neurologic, cutaneous, and articular phenotype, but there are no previous published reports of neurologic features in adults with milder phenotypes.METHODS: In this case series, we report in detail an adult case of CAPS and summarize the neurologic features seen in 12 other adults with genetically proven CAPS. These patients participated in a recent randomized study of canakinumab in CAPS and we used pretreatment data collected in this study.RESULTS: Twelve of the 13 patients (92%) had headache, of whom 10 (77%) had features of migraine. Seven patients (54%) had sensorineural deafness. Nine patients (69%) reported myalgia. Six patients (46%) had papilledema and a further 2 (15%) had optic disc pallor. MRI brain scan was normal in all patients.CONCLUSION: CAPS is a rare but treatable condition that may be encountered by neurologists in adult clinical practice since it can present with headache, myalgia, papilledema, sensorineural deafness, and aseptic meningitis. Unrecognized and untreated, it can lead to significant morbidity and mortality from renal failure. Treatment with anti-interleukin-1 therapy leads to complete resolution of symptoms and should also prevent progression to amyloidosis and subsequent renal failure.	J. L. Kitley, H. J. Lachmann, A. Pinto and L. Ginsberg	Neurology
672	Comparative clinical study of tobramycin and gentamicin	Gentamicin and tobramycin have been compared in vitro and as single-drug therapy in patients with a serious infection caused by gram-negative rods. In vitro, a slight advantage of tobramycin over gentamicin has been found against Pseudomonas aeruginosa. Cross-resistance between gentamicin and tobramycin has been observed for gentamicin-resistant strains of P. aeruginosa and Providence but was not always present. The clinical effectiveness of gentamicin and tobramycin was similar: 14 (45.1%) out of the 31 patients in each series responded favorably. The clinical results were much better in urinary tract infections (66% of favorable responses) than in wound infections, pulmonary infections, septicemia, and meningitis (26% of favorable responses). The frequency of adverse reactions encountered in the present series was similar for both drugs.	J. Klastersky, C. Hensgens, A. Henri and D. Daneau	Antimicrobial agents and chemotherapy
150	Antimicrobial prophylaxis in patients with rhinorrhea or otorrhea: a double-blind study	A controlled double-blind study was performed on patients with injury to the head and face which had caused rhinorrhea or otorrhea. The patients were treated, at the time of the admission to the hospital, with penicillin (20 mega-units daily) or a placebo. A total of 52 patients was studied, 26 in each treatment group. Meningitis developed in one patient in the placebo group. Staphylococcus epidermidis (sensitive to penicillin) was the causative pathogen in this patient who also had a retained intraventricular foreign body. The frequency of extra-neurological infections and of asymptomatic pulmonary bacterial colonization was similar in both groups, but frequency of asymptomatic bacteriuria was higher in the placebo-treated patients.	J. Klastersky, M. Sadeghi and J. Brihaye	Surgical neurology
350	Serum bactericidal activity and isotype distribution of antibodies in toddlers and schoolchildren after vaccination with RIVM hexavalent PorA vesicle vaccine	A clinical phase II trial with the RIVM hexavalent OMV vaccine containing six different PorAs was carried out in toddlers (2-3 years) and schoolchildren (7-8 years) in The Netherlands. Children were vaccinated three times (0, 2, 8 months). Sera after two and three vaccinations were analysed for serum bactericidal activity (SBA) and isotype distribution in whole cell enzyme linked immunosorbent assay (ELISA). The SBA after vaccination against the six PorAs was significantly different. We investigated whether the age specific and PorA specific differences in SBA titers correlated with differences in PorA specific IgG isotype distribution. The SBA titers were higher in toddlers compared with schoolchildren. After vaccination, IgG1 antibodies dominated the response followed by IgG3 antibodies. IgG2 levels were low, whereas IgG4 was not detected. Irrespective of PorA, IgG total and isotype specific titers after two and three vaccinations were significantly higher in toddlers than in schoolchildren. A weak correlation was found between IgG total or IgG1 and SBA. Although the immunogenicity of the six PorAs is very different, the isotype distribution was similar for all six tested PorAs. We conclude that the RIVM hexavalent PorA vesicle vaccine induces bactericidal antibodies mainly of the IgG1 and IgG3 isotypes that are considered to be most important for protection against disease. The isotype distribution of the response is not age-dependent.	E. Kleijn, L. Eijndhoven, C. Vermont, B. Kuipers, H. Dijken, H. Rümke, R. Groot, L. Alphen and G. Dobbelsteen	Vaccine
408	Immunogenicity and safety of a hexavalent meningococcal outer-membrane-vesicle vaccine in children of 2-3 and 7-8 years of age	To study the reactogenicity and immunogenicity of a hexavalent meningococcal outer-membrane-vesicle vaccine (OMV), two different dosages of this vaccine (7.5 and 15 microg of individual PorA proteins) consisting of vesicles expressing class 1 outer-membrane proteins (OMPs) of subtypes P1.7,16; P1.5,2; P1.19,15 and P1.5(c), 10; P1.12,13; P1.7(h),4 were administered to a group of 7-8 year (n=165) and a group of 2-3 year old children (n=172). Control groups of children with similar ages were vaccinated against hepatitis B. All participants received three injections. Pre- and postimmunisation sera were tested for bactericidal antibodies against six isogenic meningococcal vaccine strains expressing different PorA proteins. Antibody titres against OMP of the two different vesicles (PL16215 and PL10124) were measured by ELISA. The meningococcal hexavalent OMV vaccine was well tolerated. No statistically significant differences were seen between the high and low dose of hexavalent meningococcal OMV vaccine. The percentage of children showing a fourfold increase of bactericidal antibody titres against the specific serosubtype varied in toddlers from 28 to 98% and in older children from 16 to 100%. Both ELISA antibody titres and bactericidal activity showed the highest level in the youngest age-group.	E. D. Kleijn, R. Groot, J. Labadie, A. B. Lafeber, G. Dobbelsteen, L. Alphen, H. Dijken, B. Kuipers, G. W. Omme, M. Wala, R. Juttmann and H. C. Rümke	Vaccine
259	Immunogenicity and safety of monovalent p1.7(h),4 meningococcal outer membrane vesicle vaccine in toddlers: comparison of two vaccination schedules and two vaccine formulations	The safety and immunogenicity of two PorA-based meningococcal outer membrane vesicle (OMV) vaccines against the P1.4 serosubtype adsorbed with AlPO(4) or Al(OH)(3) were studied in 134 toddlers. Vaccinations were given three times with an interval of 3-6 weeks or twice with an interval of 6-10 weeks. A vaccination was repeated after 20-40 weeks. Pre- and post-immunization sera were tested for bactericidal activity against an isogenic strain expressing P1.7(h), 4 PorA. Both meningococcal OMV vaccines were well tolerated. The percentage of children with a fourfold increase in bactericidal activity was 96% (AlPO(4)-adjuvated vaccine/2+1 schedule), 100% (AlPO(4)-adjuvated vaccine/3+1 schedule), 93% (Al(OH)(3)-adjuvated vaccine/2+1 schedule) and 97% (Al(OH)(3)-adjuvated vaccine/3+1 schedule). Adsorption with AlPO(4) makes the OMV vaccine more immunogenic than adsorption with Al(OH)(3). Bactericidal activity was highest after the 3+1 schedule, although the response shortly after the primary series was higher in the two-dose priming group.	E. D. Kleijn, R. Groot, A. B. Lafeber, J. Labadie, K. C. Limpt, J. Visser, G. A. Berbers, L. Alphen and H. C. Rümke	Vaccine
93	Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants	BACKGROUND: In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. METHODS: In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. RESULTS: Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. CONCLUSIONS: A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.	N. P. Klein, K. S. Reisinger, W. Johnston, T. Odrljin, C. J. Gill, L. Bedell and P. Dull	The Pediatric infectious disease journal
98	Immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine administered concomitantly with measles, mumps, rubella, varicella vaccine in healthy toddlers	BACKGROUND: Invasive meningococcal disease can have devastating outcomes, especially in high-risk groups such as infants. As infants are recommended to receive multiple vaccines during a single office visit, this phase 3 study assessed the safety and immune response to MenACWY-CRM at alternative visits in older infants and concomitant use with measles, mumps, rubella, varicella vaccine (MMRV) at 12 months of age. METHODS: Two age groups were concurrently enrolled: 7- to 9-month-old infants who received 2 doses of MenACWY-CRM at 7-9 and 12 months and were randomized 1:1 to receive MenACWY-CRM with or without MMRV at 12 months, and 12-month-old infants who received MMRV only at 12 months. Using predefined non-inferiority criteria, immune responses to the antigens in MMRV were compared between those who did and did not receive MenACWY-CRM; immune responses to MenACWY-CRM as measured by the percentage of subjects with human serum bactericidal activity (hSBA) titers ? 8, were compared between those who did and did not receive concomitant MMRV. Adequacy of the immune response to 2 doses of MenACWY-CRM administered at 7-9 and 12 months was also assessed. Local and systemic reactions, adverse events resulting in withdrawal or requiring medical attention and serious adverse events were monitored. RESULTS: Concomitant administration of MMRV with MenACWY-CRM did not affect the immune response to either vaccine. The 2-dose series of MenACWY-CRM induced adequate immune response to all 4 serogroups. No increased reactogenicity was observed with MenACWY-CRM+MMRV compared with MMRV alone, and there were no study-related serious adverse events. CONCLUSIONS: Concomitant administration of MenACWY-CRM with MMRV vaccinations at 12 months was well-tolerated, without safety concerns. Robust immune responses to all components of both vaccines were produced and all criteria for non-inferiority were met, supporting the use of a 2-dose regimen of MenACWY-CRM in this age group.	N. P. Klein, J. Shepard, L. Bedell, T. Odrljin and P. Dull	Vaccine
481	Pivotal Safety and Immunogenicity of an Investigational Quadrivalent Meningococcal Vaccine (MenACWY-CRM; Menveo®) in Infants in the United States		N. P. G. C. J. B. L. K. A. D. P. M. Klein	Pediatric Academic Societies Annual Meeting
565	Protective activity of Vi capsular polysaccharide vaccine against typhoid fever	The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination.	K. P. Klugman, I. T. Gilbertson, H. J. Koornhof, J. B. Robbins, R. Schneerson, D. Schulz, M. Cadoz and J. Armand	Lancet
206	Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children	The present extension study, conducted in children originally vaccinated at 12-14 mo or 3-5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development. Exploratory comparisons showed that (1) All children and ? 92.3% of the toddlers maintained serum bactericidal (rSBA) titers ? 1:8 at 15 mo post MenACWY-TT vaccination; statistically significantly higher rSBA geometric mean titers (GMTs) were observed compared with control vaccines. (2) At one month after polysaccharide challenge, all toddlers primed with MenACWY-TT or with the monovalent serogroup C conjugate vaccine had rSBA titers ? 1:8 and ? 1:128 for serogroup C and similar rSBA-GMTs; rSBA-GMTs for serogroups A, W-135 and Y were statistically significantly higher in toddlers primed with MenACWY-TT compared with the control vaccine. Thus, a single dose of MenACWY-TT induced persisting antibodies in toddlers and children and immune memory in toddlers. This study has been registered at www.clinicaltrials.gov NCT00126984.	M. Knuf, Y. Baine, V. Bianco, D. Boutriau and J. M. Miller	Human vaccines & immunotherapeutics
62	A dose-range study assessing immunogenicity and safety of one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate (MenACWY-TT) vaccine administered in the second year of life and in young children	Meningococcal disease incidence is highest in young children, yet a tetravalent conjugate vaccine is currently not available for this age group. This study evaluated a single dose of four different ACWY-TT conjugate vaccine formulations in 240 toddlers (12-14 months) and 268 children (3-5 years) compared to licensed age-appropriate control vaccines. In toddlers, rSBA-MenC GMTs for the selected formulation were statistically higher than after monovalent-MenC-conjugate vaccine. In children, rSBA-GMTs against each serogroup were statistically higher than after tetravalent polysaccharide vaccine. The safety profile was comparable to licensed controls. The new ACWY-TT conjugate vaccine promises high seroprotection levels against meningococcal disease from 1 year of age.	M. Knuf, D. Kieninger-Baum, P. Habermehl, P. Muttonen, H. Maurer, P. Vink, J. Poolman and D. Boutriau	Vaccine
45	An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix? hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children	Tetravalent meningococcal serogroups ACWY conjugate vaccines will provide an advantage to those at most risk of invasive meningococcal disease; namely young children. Co-administration of ACWY-TT with DTaP-HBV-IPV/Hib was assessed in a randomized trial in 793 children aged 12-23 months. Pre-specified criteria for non-inferiority of immunogenicity following co-administration versus separate ACWY-TT and DTaP-HBV-IPV/Hib administration were reached. One month post-vaccination, ? 97.3% of ACWY-TT vaccinees had rSBA titres ? 1:8 (all serogroups). Seroprotection/seropositivity rates against DTaP-HBV-IPV/Hib antigens were ? 98.2%. The safety profile of co-administration was similar to that of DTaP-HBV-IPV/Hib alone. ACWY-TT and DTaP-HBV-IPV/Hib co-administration during the second year would facilitate introduction of ACWY-TT into routine toddler vaccination schedules.	M. Knuf, A. Pantazi-Chatzikonstantinou, U. Pfletschinger, I. Tichmann-Schumann, H. Maurer, L. Maurer, T. Fischbach, H. Zinke, H. Pankow-Culot, V. Papaevangelou, V. Bianco, M. Wielen and J. M. Miller	Vaccine
512	An investigational tetravalent meningococcal serogroups A, C, W-135 and Y-tetanus toxoid conjugate vaccine co-administered with Infanrix hexa is immunogenic, with an acceptable safety profile in 12-23-month-old children		M. Knuf, A. Pantazi-Chatzikonstantinou, U. Pfletschinger, I. Tichmann-Schumann, H. Maurer, L. Maurer, T. Fischbach, H. Zinke, H. Pankow-Culot, V. Papaevangelou, V. Bianco, M. Wielen and J. M. Miller	Vaccine
625	[Concentrations of tumor necrosis factor alpha and interleukin-1 beta in cerebrospinal fluid in the course of tick-borne encephalitis]	CSF concentrations of TNF-alpha and Il-1 beta were detected in patients with TBE. The cytokines were detected by immunometric assay by MEDGENIX kit. CSF Concentrations of TNF-alpha and IL-1 beta in patients with TBE were significantly higher than in control group before as well as after treatment and normalization of CSF parameters. These concentrations were lower comparing to one obtained in group of bacterial meningitis. There was no correlation between concentration of cytokines and other CSF parameters (cytosis, protein, glucose concentration). Concentrations of analysed cytokines did not change significantly before and after treatment. Detection of CSF concentrations of TNF-alpha and Il-1 beta in patients with tick-borne encephalitis can be used to evaluate efficacy of treatment and retreat of infection.	M. Kondrusik, T. Hermanowska-Szpakowicz and E. Jaroszewicz	Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
484	[On the therapy of suppurating meningitis]		W. Konzert	Wiener Klinische Wochenschrift
255	Prediction of academic and behavioural limitations in school-age survivors of bacterial meningitis	AIM: To develop a prediction rule to identify postmeningitic children at high risk of academic and behavioural limitations. METHODS: 182 children (mean age 10 y; range 5-14) were selected from a cohort of 674 school-age survivors of bacterial meningitis. These children had neither meningitis with "complex onset", nor prior cognitive or behavioural problems, nor severe disease sequelae. On average, 7 y after the meningitis, they were evaluated using an "Academic Achievement Test", and their parents filled in the "Child Behaviour Checklist". By reviewing the medical records, potential risk factors for academic and/or behavioural limitations were collected. Independent predictors were identified using multivariate logistic regression analysis, leading to the formulation of a prediction rule. RESULTS: The cumulative incidence of academic and/or behavioural limitations among children who survived bacterial meningitis without severe disease sequelae was 32%. The prediction rule was based on nine independent risk factors: gender, birthweight, educational level of the father, S. pneumoniae, cerebrospinal fluid leukocyte count, delay between admission and start of antibiotics, dexamethasone use, seizures treated with anticonvulsive therapy, and prolonged fever. When 10 was taken as a cut-off point for the risk score computed using this rule, 76% of the children with limitations could be identified, while 38% of the children in the cohort were selected as at risk for these limitations. CONCLUSION: With a prediction rule based on nine risk factors, postmeningitic children at high risk of developing academic and/or behavioural limitations could be identified. Additional research is required to further validate this prediction rule. In the future, a careful follow-up of high risk children may enhance early detection and treatment of these limitations.	I. Koomen, D. E. Grobbee, J. J. Roord, A. Jennekens-Schinkel, H. D. Lei, M. A. Kraak and A. M. Furth	Acta paediatrica (Oslo, Norway : 1992)
161	[Procalcitonin in diagnosis of purulent and aseptic meningitis in children]	UNLABELLED: Procalcitonin (PCT) is a new indicator of the systemic response to severe infections. To evaluate clinical usefulness of serum procalcitonin measurements in the differential diagnosis of purulent versus aseptic meningitis in children was the aim of the study. Fifteen children (aged 1 month-14 years) with purulent meningitis and 12 children (aged 6 months-12 years) with aseptic meningitis were included into the study. Serum PCT concentration was measured on admission by immunoluminometric assay. Thirty healthy controls (aged 3 months-14 years) were also enrolled into the study. Serum PCT concentration was above 0.5 ng/ml in 14 out of 15 children with purulent meningitis (range 0.0-95.2 ng/ml; arrhythmetic mean--28.2 ng/ml). In all children with aseptic meningitis (range 0.0-0.3 ng/ml; mean--0.1 ng/ml) as well as in healthy controls (range 0.0-0.3 ng/ml; mean--0.1 ng/ml) serum PCT was below 0.5 ng/ml. CONCLUSION: Elevated serum PCT concentration in child with meningitis suggests bacterial aetiology.	B. Korczowski, A. Bijo and A. Rybak	Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
192	Optimal perioperative immunosuppression in cardiac transplantation using rabbit antithymocyte globulin	A randomized trial of RATG (polyclonal) vs. OKT3 (monoclonal) antibody prophylaxis was carried out in 82 cardiac transplant recipients who, in addition, received baseline immunosuppression with cyclosporine, azathioprine and prednisone. One-year actuarial survival was comparable between groups (95% and 98%). The incidence of moderate or severe rejection within the first 30 days of transplant was over 7 times greater in patients receiving OKT3 vs. those receiving RATG. Patients receiving OKT3 were more likely to have repeated episodes of rejection and the mean time to rejection for patients receiving OKT3 was shorter (33 days) than for RATG patients (67 days). At 120 days, 52% of RATG patients were free of rejection while only 37% of the OKT3 patients were rejection-free. There was no difference in the incidence of major or minor bacterial or viral infection between groups. Patients receiving OKT3 showed a less-prolonged depression of the CD3 and CD4 T cell subsets than did those receiving RATG. Significant hemodynamic side-effects were seen after the first dose of OKT3 and there was a 5% incidence of aseptic meningitis associated with its use.	R. L. Kormos, J. M. Armitage, J. S. Dummer, Y. Miyamoto, B. P. Griffith and R. L. Hardesty	Transplantation
222	The relationship between plasminogen activator inhibitor-1 and proinflammatory and counterinflammatory mediators in children with meningococcal septic shock	Proinflammatory cytokines (tumor necrosis factor [TNF]-alpha and interleukin [IL]-6 and -8), counterinflammatory compounds (IL-10 and soluble TNF receptors p55 and p75 [sTNFR-55 and -75]), and hemostatic parameters were determined in 38 patients with meningococcal septic shock. Eleven patients (29%) died. Serum levels of pro- and counterinflammatory compounds and plasma levels of plasminogen activator inhibitor (PAI)-1 were significantly higher in nonsurvivors. The interval between appearance of petechiae and blood sampling was shorter in nonsurvivors than in survivors (3.6 +/- 2.4 vs. 6.1 +/- 3.3 h; P = 0.4). This interval correlated strongly with the levels of TNF-alpha, IL-6, -8, and -10, sTNFR-55 and -75, and PAI-1. However, with the exception of PAI-1, differences between concentrations of these mediators disappeared after adjustment for the interval. PAI-1 levels correlated with TNF-alpha concentrations (r = .75; P < .001) and were 1.9 (P = .01) times higher in nonsurvivors at a similar TNF-alpha concentration. Thus, an increased PAI-1 response to TNF-alpha may be associated with fatality, probably because of polymorphism of the PAI-1 gene.	R. F. Kornelisse, J. A. Hazelzet, H. F. Savelkoul, W. C. Hop, M. H. Suur, A. N. Borsboom, I. M. Risseeuw-Appel, E. Voort and R. Groot	The Journal of infectious diseases
322	The role of nitric oxide in bacterial meningitis in children	To investigate the role of nitric oxide (NO) in bacterial meningitis, concentrations in serum, cerebrospinal fluid (CSF), or both of the precursor (L-arginine) and degradation products of NO (nitrate, nitrite) and tumor necrosis factor (TNF)-alpha were measured in 35 patients and 30 controls. CSF nitrate levels were significantly elevated, mainly due to increased blood-brain barrier permeability, and are therefore not a good parameter for gauging endogenous NO production in the CSF compartment. CSF NO/nitrite levels were significantly elevated in patients. NO/nitrite levels decreased over time (26%/6 h; P < .001). CSF levels of NO/nitrite correlated with those of TNF-alpha (r = .55; P = .001) and glucose (r = -.43; P = .02). CSF levels of L-arginine were lower in patients than in controls (P < .001). Dexamethasone did not exert a significant effect on NO metabolism. In conclusion, enhanced NO production may contribute to anaerobic glycolysis and neurologic damage in bacterial meningitis.	R. F. Kornelisse, K. Hoekman, J. J. Visser, W. C. Hop, J. G. Huijmans, P. J. Straaten, A. J. Heijden, R. N. Sukhai, H. J. Neijens and R. Groot	The Journal of infectious diseases
466	[Enzyme linked immunosorbent assay for characterization of affinity and epitope specificity of antibodies to a polysaccharide antigen]	The use of the Langmuir equation for processing ELISA data (the sandwich variant) helped to ascribe a physical sense to the parameters of the optimization of the antigen-antibody titration curve: the maximum response that characterizes complete binding corresponds to the saturation of all epitopes of the antigen, and the concentration at which half of the maximum response is attained corresponds to the dissociation constant of the immune complex, i.e., to the average affinity of the antibodies. The algorithm was tested for systems in which antibodies against IgE and IgD were sorbed on a support, and the antigen bound was determined by the antibodies conjugated with peroxidase. A good fit of the experimental and theoretical curves and reasonable values for the affinity constants were found. In another system, the binding of specific IgG, IgM, and IgA antibodies with the polysaccharide from Neisseria meningitidis serotype A was studied during vaccine testing. The structural simplicity of the antigen molecule made it possible to suggest the presence of two main epitopes and to reveal the dynamics of formation of the antibodies to them.	L. V. Kozlov, T. N. Batalova, T. V. Faddeeva and R. L. Panurina	Bioorganicheskaia khimiia
487	Influenza virus infection and the risk of serious bacterial infections in young febrile infants	OBJECTIVE: We aimed to determine the risk of SBIs in febrile infants with influenza virus infections and compare this risk with that of febrile infants without influenza infections. PATIENTS AND METHODS: We conducted a multicenter, prospective, cross-sectional study during 3 consecutive influenza seasons. All febrile infants <or=60 days of age evaluated at any of 5 participating pediatric EDs between October and March of 1998 through 2001 were eligible. We determined influenza virus status by rapid antigen detection. We evaluated infants with blood, urine, cerebrospinal fluid, and stool cultures. Urinary tract infection (UTI) was defined by single-pathogen growth of either >or=5 x 10(4) colony-forming units per mL or >or=10(4) colony-forming units per mL in association with a positive urinalysis. Bacteremia, bacterial meningitis, and bacterial enteritis were defined by growth of a known bacterial pathogen. SBI was defined as any of the 4 above-mentioned bacterial infections. RESULTS: During the 3-year study period, 1091 infants were enrolled. A total of 844 (77.4%) infants were tested for the influenza virus, of whom 123 (14.3%) tested positive. SBI status was determined in 809 (95.9%) of the 844 infants. Overall, 95 (11.7%) of the 809 infants tested for influenza virus had an SBI. Infants with influenza infections had a significantly lower prevalence of SBI (2.5%) and UTI (2.4%) when compared with infants who tested negative for the influenza virus. Although there were no cases of bacteremia, meningitis, or enteritis in the influenza-positive group, the differences between the 2 groups for these individual infections were not statistically significant. CONCLUSIONS: Febrile infants <or=60 days of age with influenza infections are at significantly lower risk of SBIs than febrile infants who are influenza-negative. Nevertheless, the rate of UTI remains appreciable in febrile, influenza-positive infants	W. I. Krief, D. A. Levine, S. L. Platt, C. G. Macias, P. S. Dayan, J. J. Zorc, N. Feffermann and N. Kuppermann	Pediatrics
214	A randomized, double-blind trial of pneumococcal vaccination in adult allogeneic stem cell transplant donors and recipients	BACKGROUND: Adult allogeneic hematopoietic stem cell transplant (HSCT) recipients are at high risk of invasive pneumococcal disease but have suboptimal responses to the recommended pneumococcal polysaccharide vaccine (PPV23). Pneumococcal conjugate vaccine (PCV7) may improve immunogenicity in this population, and a donor vaccination strategy may benefit patients undergoing HSCT. METHODS: Sixty-four pairs of donors and recipients scheduled to undergo HSCT were randomized to receive either PPV23 or PCV7. Vaccinations were administered to donors before transplantation and to recipients at 6 months after transplantation. Serotype-specific antipneumococcal titers were measured in donors at the time of harvest and in recipients before transplantation and 6 and 12 months after transplantation. RESULTS: Overall, immunogenicity was poor with both strategies. However, at 6 months, response to at least 1 serotype was seen in 0 (0%) of 19 and 8 (38.6%) of 21 evaluable recipients whose donors had received PPV23 and PCV7, respectively (P=.003). At 12 months, response was seen in 10 (55.6%) of 18 and 20 (90.9%) of 22 HSCT recipients who had received PPV23 and PCV7, respectively (P=.02). Multivariate logistic regression revealed that, at 12 months after transplantation, the type of vaccine given was the only significant factor affecting response, with an odds ratio of 8.85 (95% confidence interval, 1.62-47.6; P=.012) favoring PCV7. CONCLUSION: A donor and recipient paired vaccination strategy with PCV7 demonstrated safety and greater immunogenicity than did a similar strategy with PPV23.	D. Kumar, M. H. Chen, B. Welsh, D. Siegal, I. Cobos, H. A. Messner, J. Lipton and A. Humar	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
284	Randomized controlled trial of dexamethasone in tuberculous meningitis	SETTING: The patients admitted to the Neurology ward of the All India Institute of Medical Sciences Hospital. OBJECTIVE: To assess the role of dexamethasone as an adjunct to antimicrobial therapy in the treatment of tuberculous meningitis. DESIGN: A randomised controlled trial of 47 patients was conducted over a 13-month period. 41 patients completed the trial. Patients were stratified into mild, moderate and severe groups and randomly allocated to steroid and non-steroid groups. All patients received a standardized antituberculosis drug regime. The end point was 3 months, or death if earlier. The evaluation at the end point included survival, resolution of symptoms, sequelae and activities of daily living. Results were analysed using the Wilcoxon rank sum test. RESULTS: The patients in the dexamethasone group fared better. 75% of this group had mild sequelae as opposed to 62% of the control group. Amongst the survivors, those who received dexamethasone sensorium improved earlier, and there was greater improvement in mental function and daily activities. The difference, however, did not reach statistical significance. CONCLUSIONS: Dexamethasone appears useful as an adjunct in the treatment of tuberculous meningitis especially in patients who have severe disease. The results need confirmation by a larger trial.	S. Kumarvelu, K. Prasad, A. Khosla, M. Behari and G. K. Ahuja	Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
489	The psychological impact of pediatric bacterial meningitis on the family		M. J. Kupst, J. L. Schulman, A. T. Davis and C. C. Richardson	Pediatric infectious disease
465	Immunologic priming by one dose of Haemophilus influenzae type b conjugate vaccine in infancy	Immunogenicity of one dose of Haemophilus influenzae type b (Hib) conjugate vaccine in infancy and its ability to induce immunologic memory was studied in infants immunized at 4 and 14 months with either PRP-OMP (Hib polysaccharide conjugated with Neisseria meningitidis group B outer membrane protein complex) or PRP-T (Hib polysaccharide-tetanus toxoid conjugate) and compared with three doses of the same vaccines at 4, 6, and 14 months. Each group received diphtheriatetanus-pertusis vaccine at 3, 4, and 5 months of age. At 7 months of age, both vaccines were immunogenic after one dose, even though higher antibody concentrations were achieved after two doses. A booster dose given at 14 months resulted in a high antibody concentration and a strongly IgG-dominated isotype distribution, speaking for a secondary-type response in all groups, including those who had received only one dose in infancy. Subsequent persistence of antibodies suggestive of full protection for up to 36 months was similar in all groups.	S. Kurikka, H. Käyhty, L. Saarinen, P. R. Rönnberg, J. Eskola and P. H. Mäkelä	The Journal of infectious diseases
667	Cerebrospinal fluid drainage and pressure monitoring after acute human spinal cord injury	26th Annual National Neurotrauma Society Symposium July 27 to 30, 2008 Orlando, FL Abstract number P156 BACKGROUND: Ischemia is a major component of the acute pathophysiology of spinal cord injury (SCI). Maintaining adequate cord perfusion is widely accepted as critical in the acute management of SCI. Draining CSF to lower the intrathecal pressure and improve cord perfusion pressure is routinely done during thoracoabdominal aortic aneurysm repairs to reduce the risk of ischemic paralysis. Here, we evaluate the practice of CSF drainage in patients with acute traumatic SCI. METHODS: 20 patients within 48 hours of sustaining an SCI (ASIA A, B, or C) were prospectively randomized to receive CSF drainage or no drainage. All patients had a lumbar intrathecal catheter inserted and left in place for 72 hours. In patients randomized to drainage, the drain was opened post-operatively to allow free drainage (to a limit of 10 mm Hg). Intrathecal pressure was recorded intra- and postoperatively RESULTS: No patient suffered a headache, meningitis, or neurologic deterioration. The CSF pressure upon drain insertion was 13.1 _ 1.3 mm Hg (mean _ SEM), and after surgical decompression, unexpectedly rose to 22.1 _ 1.4 mm Hg. Postoperatively, the average CSF pressure and peak recorded CSF pressure was 17.3 _ 1.7 mm Hg and 25.7 _ 2.6 mm Hg in those drained, and 18.8 _ 1.3 mm Hg and 29.8 _ 2.2 mm Hg in those not drained (NS). Average cord perfusion pressure was 65.7 _ 2.0 vs 68.6 _ 3.5 in drained vs not drained patients (p _ 0.10, NS). CONCLUSIONS: Our protocol for CSF drainage was not effective at significantly lowering intrathecal pressure. Protocol parameters were likely responsible for the limited effectiveness. Interestingly, the CSF pressure appears to increase after decompression, and further increases in the acute post-operative period. The routine and accepted practice of increasing the blood pressure to keep the spinal cord perfusion pressure adequate assumes that the intrathecal pressure remains constant. We show here that the intrathecal pressure is not constant, and in fact increases after spinal decompression and in the acute post-operative period. This has important implications on the monitoring and management of blood pressure.	B. Kwon, L. Belanger, D. Chan, A. Bernardo, G. Slobogean, M. Boyd, S. Paquette, H. Umedaly, M. Giffin, J. Street, C. Fisher, A. Curt and M. Dvorak	Journal of Neurotrauma
665	Intrathecal pressure monitoring and cerebrospinal fluid drainage in acute spinal cord injury: a prospective randomized trial	OBJECT: Ischemia is an important factor in the pathophysiology of secondary damage after traumatic spinal cord injury (SCI) and, in the setting of thoracoabdominal aortic aneurysm repair, can be the primary cause of paralysis. Lowering the intrathecal pressure (ITP) by draining CSF is routinely done in thoracoabdominal aortic aneurysm surgery but has not been evaluated in the setting of acute traumatic SCI. Additionally, while much attention is directed toward maintaining an adequate mean arterial blood pressure (MABP) in the acute postinjury phase, little is known about what is happening to the ITP during this period when spinal cord perfusion pressure (MABP - ITP) is important. The objectives of this study were to: 1) evaluate the safety and feasibility of draining CSF to lower ITP after acute traumatic SCI; 2) evaluate changes in ITP before and after surgical decompression; and 3) measure neurological recovery in relation to the drainage of CSF. METHODS: Twenty-two patients seen within 48 hours of injury were prospectively randomized to a drainage or no-drainage treatment group. In all cases a lumbar intrathecal catheter was inserted for 72 hours. Acute complications of headache/nausea/vomiting, meningitis, or neurological deterioration were carefully monitored. Acute Spinal Cord Injury motor scores were documented at baseline and at 6 months postinjury. RESULTS: On insertion of the catheter, mean ITP was 13.8 +/- 1.3 mm Hg (+/- SD), and it increased to a mean peak of 21.7 +/- 1.5 mm Hg intraoperatively. The difference between the starting ITP on catheter insertion and the observed peak intrathecal pressure after decompression was, on average, an increase of 7.9 +/- 1.6 mm Hg (p < 0.0001, paired t-test). During the postoperative period, the peak recorded ITP in the patients randomized to the no-drainage group was 30.6 +/- 2.3 mm Hg, which was significantly higher than the peak intraoperative ITP (p = 0.0098). During the same period, the peak recorded ITP in patients randomized to receive drainage was 28.1 +/- 2.8 mm Hg, which was not statistically higher than the peak intraoperative ITP (p = 0.15). CONCLUSIONS: The insertion of lumbar intrathecal catheters and the drainage of CSF were not associated with significant adverse events, although the cohort was small and only a limited amount of CSF was drained. Intraoperative decompression of the spinal cord results in an increase in the ITP measured caudal to the injury site. Increases in intrathecal pressure are additionally observed in the postoperative period. These increases in intrathecal pressure result in reduced spinal cord perfusion that will otherwise go undetected when measuring only the MABP. Characteristic changes in the observed intrathecal pressure waveform occur after surgical decompression, reflecting the restoration of CSF flow across the SCI site. As such, the waveform pattern may be used intraoperatively to determine if adequate decompression of the thecal sac has been accomplished.	B. K. Kwon, A. Curt, L. M. Belanger, A. Bernardo, D. Chan, J. A. Markez, S. Gorelik, G. P. Slobogean, H. Umedaly, M. Giffin, M. A. Nikolakis, J. Street, M. C. Boyd, S. Paquette, C. G. Fisher and M. F. Dvorak	Journal of neurosurgery. Spine
558	Treatment of carinomatous meningitis with intra-csf cytarabin lipid particle injection vs. methotrexate	No.230	S. LaFollett, M. Glantz and K. jaeckle	Breast Cancer Research & Treatment
253	Epilepsy after central nervous system infection: clinical characteristics and outcome after epilepsy surgery	Fifty-six (5.8%) patients with partial epilepsy secondary to central nervous system (CNS) infection (meningitis = 20 and encephalitis = 36) were identified from 963 patients studied with prolonged video-EEG monitoring. Twenty-seven (48.2%) patients had unilateral mesial temporal lobe epilepsy (UMTLE), 9 (16.1%) had bilateral mesial temporal lobe epilepsy (BMTLE), and 20 (35.7%) had neocortical epilepsy (NE). Younger age at infection and prolonged latency between the time of infection and development of epilepsy were predictive factors for UMTLE. Predictors for BMTLE were late age of infection and short latency between infection and epilepsy development. Development of NE was associated with short latency between infection and epilepsy, and younger age at infection. When outcome after temporal lobectomy was compared between the UMTLE group and a control group with UMTLE without history of CNS infection, no statistically significant differences were found. Central nervous system infection may lead to epilepsy, which in many cases, is generated by a single portion of the brain. In such cases, epilepsy surgery should be considered, as in patients without history of CNS infection.	M. E. Lancman and H. H. Morris	Epilepsy research
689	Safety and immunogenicity of a Proteosome -trivalent inactivated influenza vaccine, given nasally to healthy adults	We studied the safety and immunogenicity of a nasally administered vaccine comprising three monovalent inactivated influenza antigens (A/New Caledonia/20/99 (H1N1), A/Panama/2007/99 (H3N2), and B/Guangdong/120/2000) non-covalently associated with outer membrane proteins of Neisseria meningitidis (Proteosome) in normal, healthy adults. In a randomized, double-blind trial participants (n = 78) were allocated to placebo or a single nasal dose of vaccine containing 15, 30, or 45 microg of each of the three HA antigens, or two nasal doses containing 30 microg of each HA, separated by 2 weeks. The vaccine was generally well tolerated in all doses tested, and in a one or two-dose schedule. A shallow vaccine reactogenicity dose-response was seen. The most common local reaction was nasal congestion, which occurred in up to 48.3% of vaccine recipients in days 0-6 after vaccine but was mild and self-limiting; this reaction was not significantly more common among active vaccine recipients than placebo recipients. Mild to moderate headache was the most commonly reported systemic reactogenicity complaint in all treatment groups, and was the only solicited complaint to increase significantly in frequency after a second active dose. No severe systemic reactions occurred. A positive and statistically significant antibody response was observed, in serum and in nasal secretions, to increasing dose for all three antigens. Serum HAI titre responses and nasal secretory IgA immune responses were elicited against all three antigens. Further testing of this nasal influenza vaccine is warranted to determine its safety and immunogenicity in these populations and its efficacy in the prevention of clinical illness.	J. M. Langley, S. A. Halperin, S. McNeil, B. Smith, T. Jones, D. Burt, C. P. Mallett, G. H. Lowell and L. Fries	Vaccine
570	A pilot study to quantify parental anxiety associated with enrollment of an infant or toddler in a phase III vaccine trial	We sought to measure the anxiety felt by parents at the time of entry into a randomized controlled vaccine trial, and to determine if anxiety level was associated with parental demographic variables or past experience. The children were 2-month-old infants entering a randomized controlled clinical trial (RCT) of a diphtheria-tetanus toxoid-acellular pertussis vaccine adsorbed with Haemophilus influenzae B conjugate, or toddlers enrolling in a RCT of a Meningococcal C conjugate vaccine. Nurses interviewed parents to collect demographic data and parents self-administered the Spielberger Self-evaluation Questionnaire (State Anxiety STAI-Y-I) [Manual for the State-Trait Anxiety Inventory (Form Y) (Self-evaluation Questionnaire), Consulting Psychologists Press Inc., Palo Alto, 1983], a validated instrument measuring the temporary condition of "state anxiety." A regression tree (CART) (S-Plus) was used to identify factors associated with higher anxiety scores. Parents of 97 children enrolled. Anxiety scores ranged from 22.75 (lower anxiety) to 36.43 (higher anxiety). The regression tree identified a structured tree with six branches. The highest anxiety scores occurred in fathers with education less then grade 8, mothers with education less than high school, birth order of the child less then the third, previous serious illness in the family, or lack of experience with research. In a group of parents agreeing to enroll their infant or toddler in a vaccine study, certain attributes and experiences were associated with higher anxiety at the time of immunization in the context of a RCT. These factors should be considered by vaccine researchers in the recruitment process of clinical trials.	J. M. Langley, S. A. Halperin and B. Smith	Vaccine
560	Dexamethasone as adjunctive therapy in adult patients with probable tuberculosis meningitis stage II and III: an open randomized controlled trial		D. V. Lardizabal and A. A. Roxas Jr	The Philippine Journal of Neurology
684	Polymorphonuclear leukocyte transfusion for the treatment of sepsis in the newborn infant	A therapeutic trial of transfusions with polymorphonuclear leukocyte concentrates was performed in newborn infants with bacterial sepsis proven by blood culture. With each transfusion, 20 ml/kg of a preparation obtained by continuous flow filtration leukapheresis, and containing 0.5 to 1 x 10(9) WBC, with less than 6% lymphocytes, was administered. Twenty newborn infants with sepsis received from 2 to 15 PMN transfusions. Results were compared with findings in 18 newborn infants with sepsis admitted during the trial period, and not treated because of unavailability of the PMN preparation (Group B). Infants with fulminant illness were excluded from both groups. Groups A and B were similar with respect to clinical characteristics and to etiology (in the majority cases a highly antibiotic-resistant Klebsiella). The mortality rate was significantly lower in Group A than in Group B in the whole series (10% vs 72%, P < 0.001), and also in the subgroups with birth weight equal or below 1,500 gm (10% vs 91%, P < 0.001). Major complications and associated conditions (i.e., necrotizing enterocolitis, meningitis, pneumonia, peritonitis, osteoarthritis, disseminated intravascular coagulation) were observed in 12 patients of Group B, and in only three infants of Group A. Untoward effects attributable to PMN transfusions were never observed. PMN transfusion was a highly effective therapeutic tool in our population of infected newborn infants.	F. Laurenti, R. Ferro, G. Isacchi, A. Panero, P. G. Savignoni, F. Malagnino, D. Palermo, F. Mandelli and G. Bucci	Journal of Pediatrics
126	Delayed cerebrospinal fluid sterilization and adverse outcome of bacterial meningitis in infants and children	To determine the clinical importance of CSF cultures that are persistently positive for pathogens in patients treated for meningitis with the new cephalosporins, the records of 301 infants and children with bacterial meningitis enrolled prospectively in four clinical efficacy trials of cefuroxime or ceftriaxone therapy were reviewed. CSF culture results were positive for 20 patients and they were sterile at 18 to 36 hours after start of therapy for 281 patients. Seizures, subdural effusions, and hemiparesis were found significantly more often during hospitalization in those with delayed sterilization of CSF. Children with persistently positive cultures had a significantly higher incidence of neurologic abnormalities at the time of hospital discharge (45% v 19%) and at follow-up (41% v 13%) and of moderate to profound hearing impairment (35% v 15%) than did those with prompt sterilization of CSF. Repeat CSF examination is a useful prognostic indicator in infants and young children with bacterial meningitis.	M. H. Lebel and G. H. McCracken	Pediatrics
419	Liposomal amphotericin B (AmBisome) compared with amphotericin and both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis	Objective: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. Design and methods: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. Results: Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare lime to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. Conclusions: A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Leenders, P. Reiss, P. Portegies, K. Clezy, W. C. J. Hop, J. Hoy, J. C. C. Borleffs, T. Allworth, R. H. Kauffmann, P. Jones, F. P. Kroon, H. A. Verbrugh and M. S. De	Aids
307	Liposomal amphotericin B (AmBisome) compared with amphotericin B both followed by oral fluconazole in the treatment of AIDS-associated cryptococcal meningitis	OBJECTIVE: Amphotericin B deoxycholate initial therapy and fluconazole maintenance therapy is the treatment of choice for AIDS-associated cryptococcal meningitis. However, the administration of amphotericin B is associated with considerable toxicity. A potential strategy for reducing the toxicity and increasing the therapeutic index of amphotericin B is the use of lipid formulations of this drug. DESIGN AND METHODS: HIV-infected patients with cryptococcal meningitis were randomized to treatment with either liposomal amphotericin B (AmBisome) 4 mg/kg daily or standard amphotericin B 0.7 mg/kg daily for 3 weeks, each followed by fluconazole 400 mg daily for 7 weeks. During the first 3 weeks, clinical efficacy was assessed daily. Mycological response was primarily evaluated by cerebrospinal fluid (CSF) cultures at days 7, 14, 21 and 70. RESULTS: Of the 28 evaluable patients, 15 were assigned to receive AmBisome and 13 to receive amphotericin B. Baseline characteristics were comparable. The time to and the rate of clinical response were the same in both arms. AmBisome therapy resulted in a CSF culture conversion within 7 days in six out of 15 patients versus one out of 12 amphotericin B-treated patients (P = 0.09), within 14 days in 10 out of 15 AmBisome patients versus one out of nine amphotericin B patients (P = 0.01), and within 21 days in 11 out of 15 AmBisome patients versus three out of eight amphotericin B patients (P = 0.19). When Kaplan-Meier estimates were used to compare time to CSF culture conversion, AmBisome was more effective (P < 0.05; median time between 7 and 14 days for AmBisome versus > 21 days for amphotericin B). AmBisome was significantly less nephrotoxic. CONCLUSIONS: A 3-week course of 4 mg/kg AmBisome resulted in a significantly earlier CSF culture conversion than 0.7 mg/kg amphotericin B, had equal clinical efficacy and was significantly less nephrotoxic when used for the treatment of primary episodes of AIDS-associated cryptococcal meningitis.	A. C. Leenders, P. Reiss, P. Portegies, K. Clezy, W. C. Hop, J. Hoy, J. C. Borleffs, T. Allworth, R. H. Kauffmann, P. Jones, F. P. Kroon, H. A. Verbrugh and S. Marie	AIDS (London, England)
386	Immunization against serogroup B meningococci. Opsonin response in vaccinees as measured by chemiluminescence	One hundred and thirteen healthy volunteers were immunized twice (six weeks apart) with four different doses (12.5, 25, 50 and 100 mug, measured as protein content) of an outer membrane vesicle vaccine from a serogroup B meningococcal strain (44/76, B:15:P1.16) complexed to serogroup C meningococcal polysaccharide and/or Al(OH)3 i.e. 12 different vaccines. Serum opsonic activity against the serogroup B strain was measured using a chemiluminescence method. A significant rise in serum opsonic activity was demonstrated in 84 volunteers (74%) six weeks after the first injection and in 97 (86%) six weeks after the second. All vaccinees with low preimmunization values (< 25 mVs) experienced a significant increase in opsonic activity. A dose-related response was most evident for the vaccines containing adjuvant, and these vaccines were associated with a maximum response six weeks after the second injection, while the vaccines without Al(GH)3 induced a peak response six weeks after the first injection. The postimmunization opsonic activity was similar to that found in convalescent sera, indicating that the vaccines may protect against serogroup B meningococcal disease. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. K. Lehmann, A. Halstensen, A. Naess, S. E. Vollset, H. Sjursen and G. Bjune	Apmis
629	Improvement after cerebrospinal fluid drainage is related to levels of N-acetyl-aspartate in idiopathic normal pressure hydrocephalus	OBJECTIVE: This study uses proton magnetic resonance spectroscopy to investigate whether or not idiopathic normal pressure hydrocephalus is associated with neuronal dysfunction or ischemia in the brain. We evaluate whether or not proton magnetic resonance spectroscopy is useful for predicting improvement after long-term external lumbar drainage (ELD) of cerebrospinal fluid. METHODS: Eighteen patients (mean age, 73 yr; six women) and 10 matching controls participated. Participants were characterized by clinical features, cognitive and motor function tests, and cerebrospinal fluid hydrodynamics (patients only). Signals from N-acetyl-aspartate (NAA), choline, lactate, and creatine (Cr) (reference) were sampled once in controls and twice in patients (before and after a 3-day ELD of approximately 135 mL/24 h) by proton magnetic resonance spectroscopy (1.5 T) from a 7.2-mL volume in the frontal white matter. Improvement was defined by video recordings of the patients' gait. RESULTS: Sixteen patients finished the ELD (one patient had meningitis, and one patient had catheter insertion failure) with a mean drain volume of 395 mL. NAA/Cr ratios were lower in patients than in controls (1.60 versus 1.84, P = 0.02), but no difference was found for choline/Cr ratios. No lactate signals were detected. Fifty percent of patients improved after ELD. They had higher NAA/Cr ratios than nonimproved patients (1.70 versus 1.51, P = 0.01), but no differences were found in choline/Cr ratios or drain volume. CONCLUSION: NAA/Cr ratios were decreased in patients with idiopathic normal pressure hydrocephalus, which is consistent with neuronal dysfunction in the frontal white matter. Improved patients had NAA/Cr ratios close to normal, indicating that enough functional neurons are a prerequisite for the cerebrospinal fluid drainage to have an effect.	N. Lenfeldt, J. Hauksson, R. Birgander, A. Eklund and J. Malm	Neurosurgery
585	Acute respiratory and neurotropic viral diseases and isoprinosine. <ORIGINAL> VIROSI ACUTE RESPIRATORIE E NEUROTROPE ED ISOPRINOSINA	21 patients affected by acute respiratory virosis (9 rubella, 5 influenza, 4 mumps, 3 measles cases) have been treated with isoprinosine. The clinical course has been compared with a similar control group of placebo-treated patients. In some of the cases the behavior of the cellular immunity before and after the treatment was also examined. Generally a statistically significant improvement was not observed as a consequence of treatment, even if a mild attenuation of the course of the illness has been noted in most cases of each group. The 6 patients affected by viral meningoencephalitis, no clear modifications of the clinical picture were noted. However, in one fulminant case, a short improvement was obtained but this patient received contemporary levamisole and an interferon-inducer drug. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	G. C. Leoni, C. Carvelli and S. C. De	G Mal Infett Parassit
568	Comparison of active and combined passive/active immunization of Navajo children against Haemophilus influenzae type b	In a high risk Navajo population we compared the immunogenicity of a new Haemophilus influenzae type b mutant-diphtheria toxic conjugate vaccine (HbOC) with simultaneous active (HbOC) and passive immunization with bacterial polysaccharide immunoglobulin prepared from adults immunized with H. influenzae b, pneumococcal and meningococcal vaccines. Only 7 of 26 (27%) 2-month-olds had an increase in H. influenzae b capsular polysaccharide antibody after a single dose of HbOC, a proportion similar to that of saline controls (9 of 25, 36%). After a second HbOC dose at 4 months 88% had antibody concentrations of 0.15 microgram or more, and after a third dose at 6 months all had antibody levels greater than or equal to 0.15 microgram/ml. The group receiving both HbOC and bacterial polysaccharide immunoglobulin at 2 months uniformly had H. influenzae b CP antibody concentrations of greater than or equal to 0.15 microgram/ml at 4 months (P less than 0.001 relative to "HbOC alone" group) and subsequently responded similarly to second and third doses of HbOC vaccine as did also the "HbOC alone" group. We conclude that combined passive/active immunization with bacterial polysaccharide immunoglobulin and HbOC at 2 months maintains antibody at concentrations thought to be protective (greater than or equal to 0.15 microgram/ml) without interfering with the active antibody response to second and third doses of HbOC at 4 and 6 months of age.	G. W. Letson, M. Santosham, R. Reid, C. Priehs, B. Burns, A. Jahnke, S. Gahagan, L. Nienstadt, C. Johnson and D. Smith	The Pediatric infectious disease journal
695	[Efficacy and safety of inhalation premixed nitrous oxide and oxygen for the management of procedural diagnostic pain in neuropediatrics]	AIM: We studied the use of premixed nitrous oxide and oxygen in 80 patients with neurologic diseases. PATIENTS AND METHODS: Mean ages ranged 10 +/- 5 yrs. Twenty-three patients (29%) were mentally retardated among which 17 of them presented with severe epilepsy. Painful procedures consisted of: lumbar punctures (80%), intravenous access (7), gastric endoscopy (6), skin biopsy (4), gastrostomy tube management (3). High-risk children were continuously monitored using ECG, non invasive blood pressure and transcutaneous oxygen saturation. We studied acceptation of the inhalation, vital signs, satisfaction of children, parents, medical and nursing staffs; side effects were compared with a group of healthy children undergoing venous access before induction of anesthesia. RESULTS AND DISCUSSION: Acceptation increased with age. No significant changes in vital signs variables were observed. Satisfaction rate regarding the method was 88% for all children, parents, physicians and nurses. No serious undesirable event (as respiratory depression, seizure, inhalation of gastric content) occurred in these patients. The more frequent side-effects were: drowsiness during and after inhalation (35 and 9% respectively in the handicapped patients); nausea and vomiting (8%), headaches (3%), were more frequent than reported in literature but there were 25% of meningitis among our patients. CONCLUSION: Premixed nitrous oxide and oxygen was effective for reducing procedural pain and anxiety in children with neurological disorders, even in severely handicapped patients, with minor side-effects.	C. Lévêque, Y. Mikaeloff, J. Hamza and G. Ponsot	Archives de pédiatrie : organe officiel de la Sociéte française de pédiatrie
188	Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: a randomised trial. rBPI21 Meningococcal Sepsis Study Group	BACKGROUND: Endotoxin is a primary trigger of the inflammatory processes that lead to shock, multiorgan failure, and purpura fulminans in meningococcal sepsis. Bactericidal/permeability-increasing protein (BPI) is a natural protein, stored within the neutrophil granules, that binds to and neutralises the effects of endotoxin in vitro, in laboratory animals, and in humans. To establish whether a recombinant 21-kDa modified fragment of human BPI (rBPI21), containing the active antimicrobial and endotoxin-neutralising moiety, would decrease death and long-term disability from meningococcal sepsis, we did a randomised, double-blind, placebo-controlled trial of rBPI21 in children with severe meningococcal sepsis. METHODS: We enrolled children (2 weeks to 18 years of age) presenting to 22 centres in the UK and the USA with a clinical picture suggestive of meningococcal sepsis, and with evidence of severe disease. Children were randomly assigned rBPI21 (2 mg/kg over 30 min followed by 2 mg/kg over 24 h) or placebo (0.2 mg/mL human albumin solution) in addition to conventional medical therapy. Primary outcome variables were mortality, amputations, and change in paediatric overall performance category (POPC) from before illness to day 60. Analysis was by intention to treat. FINDINGS: Of 1287 patients screened, 892 were excluded, including 57 patients who died or who met criteria for imminent death before receiving the study drug. 190 patients received rBPI21, and 203 placebo. 34 (8.7%) of 393 patients died during the study: 14 (7.4%) in the rBPI21 group and 20 (9.9%) in the placebo group (odds ratio 1.31 [95% CI 0.62-2.74], p=0.48). Compared with patients randomised to placebo, fewer patients treated with rBPI21 had multiple severe amputations (six of 190 [3.2%] vs 15 of 203 [7.4%], odds ratio 2.47 [0.94-6.51], p=0.067), and more had a functional outcome similar to that before illness (as measured by the POPC scale) at day 60 (136 of 176 [77.3%] vs 126 of 190 [66.3%], p=0.019). INTERPRETATION: Because most deaths occurred in the interval between identification of patients and study drug administration, the mortality rate in the placebo group was substantially lower than predicted. The trial was therefore underpowered to detect significant differences in mortality. However, patients receiving rBPI21 had a trend towards improved outcome in all primary outcome variables. Given the excellent severity match between placebo and rBPI21 groups at study entry, the results overall indicate that rBPI21 is beneficial in decreasing complications of meningococcal disease.	M. Levin, P. A. Quint, B. Goldstein, P. Barton, J. S. Bradley, S. D. Shemie, T. Yeh, S. S. Kim, D. P. Cafaro, P. J. Scannon and B. P. Giroir	Lancet
403	Recombinant bactericidal/permeability-increasing protein (rBPI21) as adjunctive treatment for children with severe meningococcal sepsis: A randomised trial	Background: Endotoxin is a primary trigger of the inflammatory processes that lead to shock, multiorgan failure, and purpura fulminans in meningococcal sepsis. Bactericidal/permeability-increasing protein (BPI) is a natural protein, stored within the neutrophil granules, that binds to and neutralises the effects of endotoxin in vitro, in laboratory animals, and in humans. To establish whether a recombinant 21-kDa modified fragment of human BPI (rBPI21), containing the active antimicrobial and endotoxin-neutralising moiety, would decrease death and long-term disability from meningococcal sepsis, we did a randomised, double-bind, placebo-controlled trial of rBPI21 in children with severe meningococcal sepsis. Methods: We enrolled children (2 weeks to 18 years of age) presenting to 22 centres in the UK and the USA with a clinical picture suggestive of meningococcal sepsis, and with evidence of severe disease. Children were randomly assigned rBPI21 (2 mg/kg over 30 min followed by 2 mg/kg over 24 h) or placebo (0.2 mg/mL human albumin solution) in addition to conventional medical therapy. Primary outcome variables were mortality, amputations, and change in paediatric overall performance category (POPC) from before illness to day 60. Analysis was by intention to treat. Findings: Of 1287 patients screened, 892 were excluded, including 57 patients who died or who met criteria for imminent death before receiving the study drug. 190 patients received rBPI21 and 203 placebo. 34 (8.7%) of 393 patients died during the study: 14 (7.4%) in the rBPI21 group and 20 (9.9%) in the placebo group (odds ratio 1.31 [95% Cl 0.62-2.74], p=0.48). Compared with patients randomised to placebo, fewer patients treated with rBPI21 had multiple severe amputations (six of 190[3.2%] vs 15 of 203 [7.4%], odds ratio 2.47 [0.94-6.51], p=0.067), and more had a functional outcome similar to that before illness (as measured by the POPC scale) at day 60 (136 of 176 [77.3%] vs 126 of 190 [66.3%], p=0.019). Interpretation: Because most deaths occurred in the interval between identification of patients and study drug administration, the mortality rate in the placebo group was substantially lower than predicted. The trial was therefore underpowered to detect significant differences in mortality. However, patients receiving rBPI21 had a trend towards improved outcome in all primary outcome variables. Given the excellent severity match between placebo and rBPI21 groups at study entry, the results overall indicate that rBPI21 is beneficial in decreasing complications of meningococcal disease. Number of References 30. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. Levin, P. A. Quint, B. Goldstein, P. Barton, J. S. Bradley, S. D. Shemie, T. Yeh, S. S. Kim, D. P. Cafaro, P. J. Scannon, B. P. Giroir, A. P. J. Thomson, E. Carrol, J. Fellick, S. Nichani, J. Alexander, I. Murdoch, S. Hoare, D. A. Thomas, N. Klein, L. Martin, M. M. Shelton, A. Loeffler, S. Kaplan, M. J. Darowski, A. Finn, J. P. Orlowski, A. Durmowicz, R. G. Gedeit, N. Pathan, S. Faust, K. White and S. Harrison	Lancet
506	Compound dyers woad leaf mixture combined with Qiang li ning injection in treating epidemic parotitis complicated with meningitis in 31 cases		L. S. Li, H. T. Liu, W. M. Wu, G. H. Sun and D. X. Jia	Zhongguo Zhong Xi Yi Jie He Za Zhi [Chinese Journal of Integrated Traditional and Western Medicine]
112	Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar): primary dosing series in healthy Chinese infants	This was a randomized safety/immunogenicity evaluation of PCV7 primary series at 3, 4, 5 months in healthy Chinese infants. Eight hundred subjects were randomized to Group 1 (PCV7 > or =7 days before DTaP), or Group 2 (PCV7 with DTaP), or Group 3 (DTaP only). Erythema and induration/swelling were recorded at the PCV7 injection site at any individual dose in no more than 12% and 8% of subjects, respectively, and neither exceeded 2.5 cm in >1% of subjects. Fever >38.0 degrees C was observed in <13% of subjects at any individual dose. For each vaccine serotype, at least 90% of subjects (Groups 1 and 2) had IgG concentrations > or = 0.35 microg/mL after dose 3, except type 6B (Group 2) with 83.3%. PCV7 had an acceptable safety profile and was immunogenic in Chinese infants.	R. C. Li, F. X. Li, Y. P. Li, S. Y. Guo, Y. Nong, Q. Ye, K. X. Fang, S. C. Wei, Z. Wang and S. Lockhart	Vaccine
652	Central nervous system infection in patients with postirradiated nasopharyngeal carcinoma: a case-controlled study	BACKGROUND: It has been assumed that postirradiated nasopharyngeal carcinoma (NPC) patients are prone to central nervous system (CNS) infection.OBJECTIVE: The purpose of this study was to better understand this clinical entity.METHODS: From September 1989 to May 2006, we conducted a retrospective study of 18 postirradiated NPC patients with CNS infection including brain abscess, cavernous sinus thrombosis, epidural abscess, and meningitis in our institute. During the same period, 18 NPC patients without CNS infection who were matched for tumor stage, age, and gender with the study group were randomly selected from the cancer registry at our hospital and enrolled as the control group. All medical records of these patients were evaluated.RESULTS: The local tumor relapse rate, nasopharyngeal radiotherapy dose, and skull base osteoradionecrosis were all significantly higher in patients with CNS infection (p = 0.003, 0.011, and 0.001, respectively). Although the incidences of otitis media and chronic rhinosinusitis were higher in patients with CNS infection, there were no significant differences between the two groups (p = 0.469 and 0.568, respectively). The in-hospital mortality was 61.1%, and the overall mortality of CNS infection was 83.3%. There was a significant difference in overall survival rate between the two groups (p = 0.001).CONCLUSIONS: Postirradiated NPC patients with skull base osteoradionecrosis are prone to have CNS infection. CNS infection is an adverse prognostic factor in postirradiated NPC patients.	K. L. Liang, R. S. Jiang, J. C. Lin, Y. J. Chiu, J. Y. Shiao, M. C. Su and C. H. Hsin	American journal of rhinology & allergy
674	Once-weekly fluconazole (450 mg) for 4, 6, or 9 months of treatment for distal subungual onychomycosis of the toenail	BACKGROUND: Fluconazole is a bis-triazole antifungal agent approved for the treatment of oropharyngeal, esophageal, and vaginal candidiasis, serious systemic candidal infections, and cryptococcal meningitis. OBJECTIVE: The purpose of this study was to evaluate three different durations of once-weekly fluconazole for the treatment of onychomycosis of the toenail caused by dermatophytes. METHODS: In a multicenter, randomized, double-blind, parallel, placebo-controlled trial, 384 patients with distal subungual onychomycosis of the toenail received fluconazole, 450 mg once weekly, or placebo for 4, 6, or 9 months. For inclusion, patients were required to have mycologically confirmed distal subungual onychomycosis of the toenail with a large toenail at least 25% clinically affected but having at least 2 mm of healthy nail between the nail fold and the proximal onychomycotic border. Efficacy was assessed by clinical and mycologic (microscopic and microbiologic) measures at screening, at every treatment visit starting at month 3, and at months 2, 4, and 6 after therapy. Observed or volunteered adverse events were recorded and classified at all visits. RESULTS: At the end of treatment, very significantly superior clinical and mycologic results were achieved in all fluconazole groups compared with placebo (p=0.0001). This superiority was largely maintained over 6 months of follow-up. The clinical and mycologic responses of the 9-month treatment duration were significantly superior to the 4- and 6-month durations. Similar percentages of patients in the fluconazole and placebo groups reported adverse experiences for all three durations of the study. CONCLUSION: Results of this study support the efficacy and safety of fluconazole in the treatment of distal subungual onychomycosis of the toenail.	M. R. Ling, L. J. Swinyer, M. T. Jarratt, L. Falo, E. W. Monroe, M. Tharp, J. Kalivas, G. D. Weinstein, R. G. Asarch, L. Drake, A. G. Martin, J. J. Leyden, J. Cook, D. M. Pariser, R. Pariser, B. H. Thiers, M. G. Lebwohl, D. Babel, D. M. Stewart, W. H. Eaglstein, V. Falanga, H. I. Katz, W. F. Bergfeld, J. M. Hanifin and M. R. Young	Journal of the American Academy of Dermatology
218	Strain characteristics of Streptococcus pneumoniae carriage and invasive disease isolates during a cluster-randomized clinical trial of the 7-valent pneumococcal conjugate vaccine	Widespread use of 7-valent pneumococcal conjugate vaccine (PCV7) has led to significant reductions in disease while changing pneumococcal population dynamics via herd immunity and serotype replacement. We performed multilocus sequence typing (MLST) on 590 pneumococcal isolates obtained during the American Indian clinical trial of PCV7, in which communities were randomized for eligible children to receive either PCV7 or a meningococcal conjugate vaccine (MCV). Sequence types (STs) were analyzed to determine the impact of the vaccine on pneumococcal population structure and to assess the possible impact of pneumococcal genetic background on vaccine effects. One hundred forty-three STs were obtained, the most frequent being ST199, the only one that included vaccine serotypes (VTs), non-vaccine-associated nonvaccine serotypes (NVA/NVTs), and vaccine-associated serotypes (VATs). Serotype replacement observed in the PCV communities was due to a diverse population of STs, most of which also existed in the MCV communities. Possible capsular switching to create novel ST associations with NVA/NVTs was detected only once. Reductions in VTs and changes in VATs in PCV communities did not show evidence of variation by ST, after accounting for lower vaccine effectiveness against serotype 19F. These observations suggest the hypothesis that the vaccine acts as a "serotype filter": its effect on a particular strain can be predicted on the basis of the serotype of the strain, with little effect of genetic background (as assessed by MLST) over and above capsule. If sustained, such patterns provide some cause for optimism that rapid evolution of PCV escape strains with drug resistance or high virulence is unlikely.	M. Lipsitch, K. O'Neill, D. Cordy, B. Bugalter, K. Trzcinski, C. M. Thompson, R. Goldstein, S. Pelton, H. Huot, V. Bouchet, R. Reid, M. Santosham and K. L. O'Brien	The Journal of infectious diseases
521	Short-term safety of live attenuated Japanese encephalitis vaccine (SA14-14-2): results of a randomized trial with 26,239 subjects	The short-term safety of an effective and inexpensive new live attenuated Japanese encephalitis vaccine (SA14-14-2) was studied in a randomized trial, using block randomization. Of 26,239 children who were enrolled, half received the vaccine and half served as controls. Subjects were prospectively followed for 30 days for severe adverse events, such as encephalitis, meningitis, and "all-cause" hospitalization. No cases of encephalitis or meningitis occurred in either group. The upper 95% confidence limit for adverse events not occurring among subjects receiving their first dose was 4.1/10,000. Risk ratios and 95% confidence intervals for other adverse events were 0.70 (0.43-1.15) for all-cause hospitalization, 0.91 (0.37-2.22) for seizure, and 0.79 (0.56-1.11) for fever lasting > or = 3 days. These data attest to the short-term safety of the SA14-14-2 virus strain and the hamster kidney cell substrate.	Z. L. Liu, S. Hennessy, B. L. Strom, T. F. Tsai, C. M. Wan, S. C. Tang, C. F. Xiang, W. B. Bilker, X. P. Pan, Y. J. Yao, Z. W. Xu and S. B. Halstead	The Journal of infectious diseases
582	Isosorbide in the medical treatment of infantile hydrocephalus		J. Lorber	J Neurosurg
634	[Procalcitonin in pediatric emergencies: comparison with C-reactive protein, interleukin-6 and interferon alpha in the differentiation between bacterial and viral infections]	OBJECTIVE: Procalcitonin concentration increases in bacterial infections but remains low in viral infections and inflammatory diseases. The change is rapid and the molecule is stable making it a potentially useful marker for distinguishing between bacterial and viral infections. PATIENTS AND METHODS: Procalcitonin (PCT) was determined with an immunoluminometric assay on plasma collected at admission in 436 infants and children hospitalized for bacterial or viral infection. It was compared with C reactive protein, interleukin-6 and interferon-alpha measured on the same sample. RESULTS: PCT was 41.3 +/- 77.4 micrograms/l in children with septicemia or bacterial meningitis (n = 53), 0.39 +/- 0.57 microgram/l in children with viral infection (n = 274) and 3.9 +/- 5.9 micrograms/l in children with a localized bacterial infection who had a negative blood culture (n = 109). PCT was > 1 microgram/l in 126 children with a localized or systemic bacterial infection (sensitivity 78%). PCT was < 1 microgram/l in 258 children with a viral infection (specificity 94%). For differenciation between viral and bacterial infections, CRP value > or = 20 mg/l, IL-6 > 100 pg/ml and interferon-alpha > 0 Ul/ml have 85, 48 and 76% sensitivity and 73, 85 and 92% specificity respectively. CONCLUSIONS: In this study, a PCT value of 1 microgram/l or greater had better specificity, sensitivity and predictive value than CRP, IL-6 and interferon-alpha in children for distinguishing between viral and bacterial infections. PCT may be useful in pediatric emergency room for making decision about antibiotic treatments.	M. Lorrot, F. Moulin, J. Coste, S. Ravilly, S. Guérin, P. Lebon, C. Lacombe, J. Raymond, C. Bohuon and D. Gendrel	Presse médicale (Paris, France : 1983)
305	Comparison of the early fungicidal activity of high-dose fluconazole, voriconazole, and flucytosine as second-line drugs given in combination with amphotericin B for the treatment of HIV-associated cryptococcal meningitis	BACKGROUND: HIV-associated cryptococcal meningitis is associated with an estimated 600 000 deaths worldwide per year. Current standard initial therapy consists of amphotericin B (AmB) plus flucytosine (5-FC), but 5-FC remains largely unavailable in Asia and Africa. Alternative, more widely available, and/or more effective antifungal combination treatment regimens are urgently needed. METHODS: Eighty HIV-seropositive, antiretroviral naive patients presenting with cryptococcal meningitis were randomized to 4 treatment arms of 2 weeks duration: group 1, AmB (0.7-1 mg/kg) and 5-FC (25 mg/kg 4 times daily); group 2, AmB (0.7-1 mg/kg) and fluconazole (800 mg daily); group 3, AmB (0.7-1 mg/kg) and fluconazole (600 mg twice daily); and group 4, AmB (0.7-1 mg/kg) and voriconazole (300 mg twice daily). The primary end point was the rate of clearance of infection from the cerebrospinal fluid (CSF) or early fungicidal activity (EFA), as determined by results of serial, quantitative CSF cryptococcal cultures. RESULTS: There were no statistically significant differences in the rate of clearance of cryptococcal colony-forming units (CFU) in CSF samples among the 4 treatment groups; the mean (±standard deviation) EFA for treatment groups 1, 2, 3, and 4 were -0.41 ± 0.22 log CFU/mL CSF/day, -0.38 ± 0.18 log CFU/mL CSF/day, -0.41 ± 0.35 log CFU/mL CSF/day, and -0.44 ± 0.20 log CFU/mL CSF/day, respectively. Overall mortality was 12% (9 of 78 patients died) at 2 weeks and 29% (22 of 75 patients died) at 10 weeks, with no statistically significant differences among groups. There were few laboratory abnormalities related to the second agents given; in particular, there were no statistically significant (?grade 3) increases in alanine transaminase level or decreases in neutrophil count. CONCLUSIONS: There was no statistically significant difference in EFA between AmB in combination with fluconazole and AmB plus 5-FC for the treatment of HIV-associated cryptococcal meningitis. AmB plus fluconazole (800-1200 mg/day) represents an immediately implementable alternative to AmB plus 5-FC. AmB plus voriconazole is an effective alternative combination in patients not receiving interacting medications.	A. Loyse, D. Wilson, G. Meintjes, J. N. Jarvis, T. Bicanic, L. Bishop, K. Rebe, A. Williams, S. Jaffar, L. G. Bekker, R. Wood and T. S. Harrison	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
479	Meningococcal conjugate vaccination among adolescents aged 13-17 years, United States, 2007		P. J. Lu, N. Jain and A. C. Cohn	Vaccine
61	Immunogenicity and safety of 1 vs 2 doses of quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus	OBJECTIVE: To compare the immunogenicity of 1 vs 2 doses of meningococcal polysaccharide conjugate vaccine (MCV4) in youth infected with human immunodeficiency virus (HIV). STUDY DESIGN: P1065 was a phase I/II immunogenicity and safety trial of MCV4 in 324 youth infected with HIV performed at 27 sites of the International Maternal Pediatric Adolescent AIDS Clinical Trials Group network in the US. At entry subjects received 1 dose of MCV4. At 24 weeks, those with screening cluster of differentiation 4 (CD4)% ? 15 were randomized to receive a second dose or not, and all with screening CD4% <15 received a second dose. Immunogenicity was evaluated as the proportion of subjects with a ? 4-fold rise from entry in serum bactericidal antibody against each meningococcal serogroup (SG) at weeks 28 and 72. Logistic regression models adjusting for HIV disease severity were used to evaluate the effect of 1 vs 2 MCV4 doses among those with screening CD4% ? 15. RESULTS: Subjects randomized to receive 2 vs 1 MCV4 dose had significantly higher response rates to all SGs at week 28 and to all except Neisseria meningitidis SG Y at week 72, with adjusted ORs of 2.5-5.6. In 31 subjects with screening CD4% <15 who received 2 MCV4 doses, response rates ranged from 22%-55% at week 28 and 6%-28% at week 72. CONCLUSION: In youth infected with HIV with a CD4% ? 15, a second dose of MCV4 given 6 months after the initial dose significantly improves response rates at 28 and 72 weeks. Subjects with CD4% <15 at entry had lower response rates despite 2 doses of MCV4.	J. Lujan-Zilbermann, M. G. Warshaw, P. L. Williams, S. A. Spector, M. D. Decker, M. J. Abzug, B. Heckman, A. Manzella, B. Kabat, P. Jean-Philippe, S. Nachman and G. K. Siberry	The Journal of pediatrics
356	Renal effects of amphotericin B lipid complex	A study was conducted to compare the renal effects of amphotericin B lipid complex (ABLC), a lipid formulation of the widely used antifungal medication, with conventional amphotericin B (AmB) in the treatment of serious fungal infections, including invasive candidiasis, cryptococcal meningitis, and aspergillosis. The clinical experience of ABLC includes two types of open-label studies: randomized comparative (ABLC 5 mg/kg/d compared with AmB 0.6 to 1 mg/kg) and emergency use. In the comparative studies, changes in serum creatinine were evaluated three ways: doubling of the baseline value, an increase from < or = 1.5 mg/dL at baseline to > or = 1.5 mg/dL, and an increase from < or = 1.5 mg/dL at baseline to > or = 2.0 mg/dL. More patients in the AmB group reached these end points than in the ABLC group (P < or = 0.007), and the time needed to reach each of these end points was significantly shorter for the AmB group (P < or = 0.02). Increased serum creatinine was reported as an adverse event more frequently by patients receiving AmB than by patients receiving ABLC. In the emergency use study, a steady and statistically significant decrease in serum creatinine was observed among patients who started ABLC treatment with serum creatinine greater than 2.5 mg/dL due to prior AmB treatment. ABLC offers the physician a valuable, less-nephrotoxic alternative to AmB for the treatment of patients with severe, invasive fungal infections.	R. G. Luke and J. A. Boyle	American journal of kidney diseases : the official journal of the National Kidney Foundation
17	Five days of antibacterial therapy for bacterial meningitis in children?	We evaluated the effectiveness of 5-day antibacterial therapy for bacterial meningitis in children. The study group included 26 children from 2 months to 15 years of age, admitted with microbiologically confirmed bacterial meningitis in 1990-1993 and treated for 5 days. A historical comparison group of 49 patients treated for 8 to 15 days was used. Penicillin monotherapy (300 mg/kg body weight) was used for meningococcal and pneumococcal meningitis and ampicillin (300 mg/kg body weight) for Haemophilus influenzae b meningitis. On day 5 of therapy the activity of aspartate aminotransferase (AST), lactic dehydrogenase (LDH), creatine phosphokinase (CPK) and gamma-glutamyl-transpeptidase (gamma GT) in the CSF was determined by photocolorimetric assay and the concentration of creatine kinase BB (CK-BB) by ELISA. IL-6 was analysed using EIA technique and a cerebral ultrasound was performed at the time of the termination of the antibacterial therapy. The mean follow-up time was 1.3 years for children in the study group and 3.2 in the control group. The time of hospitalisation was shorter in children treated for 5 days (p < 0.005). Complete clinical recovery was 81% in the study group and 66% in the comparison group at the time of the termination of antibacterial therapy. No relapses occurred. The activity of AST, CPK, LDH, and gamma GT in the CSF had returned to normal by the 5th day of therapy, but almost a 7-fold higher concentration of CK-BB was registered. The concentration of IL-6 in the CSF decreased with the therapy from 1,800 pg/ml to 685 pg/ml but still remained high.(ABSTRACT TRUNCATED AT 250 WORDS)	I. Lutsar, A. Gontmacher, M. Närska, V. Rüütel, M. Topman, P. Ilves, T. Siirde and A. Beilmann	Infection
11	[Study on immunogenicity of group A and group C meningococcal conjugate vaccine with coupling group B meningococcal outer membrane protein]	OBJECTIVE: To evaluate the Immunogenicity of Group A and Group C Meningococcal conjugate Vaccine with coupling Group B Meningococcal Outer Membrane Protein (Men B-OMP).METHODS: 458 healthy children aged 3-5 months, 6-23 months, 2-6 years and 7-24 years were given the Groups A and C conjugate Vaccine with MenB-OMP or other vaccine as control group to measure the pre-and post-vaccination Men A and C and B by Serum Bactericidal Assay (SBA) in the double-blind randomized controlled trial.RESULTS: 97.65%-100% were 4 times or greater increase in SBA titer for the healthy children given the Groups A and C conjugate Vaccine with MenB-OMP, The geometric mean titer of SBA were 1:194-1:420, which significantly higber than controls.CONCLUSION: The Group A and C conjugate Vaccine with MenB-OMP was safe and well immunogenic.	F. B. Ma, H. Tao and H. J. Wang	Zhongguo yi miao he mian yi
75	Single injection treatment of meningococcal meningitis. 1. Long-acting penicillin	A single injection of a long-acting preparation of penicillin (Triplopen) was compared with a five-day course of crystalline and procaine penicillin in the treatment of meningococcal meningitis. The clinical response of patients treated with Triplopen was very similar to that of patients treated with crystalline penicillin and much more convenient to administer. However, four patients treated with Triplopen had a positive CSF culture 48 or 72 hours after their injection. One injection of Triplopen cannot, therefore, be recommended as an entirely safe form of treatment for meningococcal meningitis unless patients can be carefully followed.	J. T. Macfarlane, F. I. Anjorin, P. G. Cleland, M. Hassan-King, S. Tor-Agbidye, S. S. Wali, W. R. Weir, H. C. Whittle, H. N. Yahaya and B. M. Greenwood	Transactions of the Royal Society of Tropical Medicine and Hygiene
355	Failure of heparin to alter the outcome of pneumococcal meningitis		J. T. MacFarlane, P. G. Cleland, E. D. Attai and B. M. Greenwood	British medical journal
293	Polymerase chain reaction in the diagnosis of tuberculous meningitis. Preliminary report	In this preliminary report the results of PCR for detection of DNA sequences (65 KDa antigen) of Mycobacterium tuberculosis in CSF samples from 20 patients are registered. In 10 patients there were clinical and laboratory findings suggesting the diagnosis of tuberculous meningitis (test group). In the other 10 patients, clinical and laboratory findings suggested meningitis or meningo-encephalitis from other etiologies (control group). In 7 patients from the test group antigenic DNA sequences of Mycobacterium tuberculosis were found in CSF by PCR; positive results were not registered in the control group.	L. R. Machado, J. A. Livramento, S. P. Bydlowski, I. Bendit, L. M. Bravo and A. Spina-França	Arquivos de neuro-psiquiatria
520	Immunological memory 5 years after meningococcal C conjugate vaccination [abstract]	Fifth Conference of the Federation of Infection Societies, 25-27 November 1998, Manchester, UK.	J. M. MacLennan, J. J. Deeks, S. Obaro, D. Williams, G. M. Carlone, E. R. Moxon and B. M. Greenwood	J-Infect
454	Ceftriaxone vs cefotaxime for treatment of Haemophilus influenzae meningitis (I)	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	L. Madson and C. Grose	Pediatrics
331	Early versus delayed initiation of antiretroviral therapy for concurrent HIV infection and cryptococcal meningitis in sub-saharan Africa	BACKGROUND. Cryptococcal meningitis (CM) remains a leading cause of acquired immunodeficiency syndrome-related death in sub-Saharan Africa. The timing of the initiation of antiretroviral therapy (ART) for human immunodeficiency virus (HIV)-associated CM remains uncertain. The study aimed to determine the optimal timing for initiation of ART in HIV-positive individuals with CM. METHODS. A prospective, open-label, randomized clinical trial was conducted at a tertiary teaching hospital in Zimbabwe. Participants were aged > or = 18 years, were ART naive, had received a first CM diagnosis, and were randomized to receive early ART (within 72 h after CM diagnosis) or delayed ART (after 10 weeks of treatment with fluconazole alone). Participants received 800 mg of fluconazole per day. The ART regimen used was stavudine, lamivudine, and nevirapine given twice daily. The duration of follow-up was up to 3 years. The primary end point was all-cause mortality. RESULTS. Fifty-four participants were enrolled in the study (28 in the early ART arm and 26 in the delayed ART arm). The median CD4 cell count at enrollment was 37 cells/mm(3) (interquartile range, 17-69 cells/mm(3)). The 3-year mortality rate differed significantly between the early and delayed ART groups (88% vs 54%; P < .006); the overall 3-year mortality rate was 73%. The median durations of survival were 28 days and 637 days in the early and delayed ART groups, respectively (P = .031, by log-rank test). The risk of mortality was almost 3 times as great in the early ART group versus the delayed ART group (adjusted hazard ratio, 2.85; 95% confidence interval, 1.1-7.23). The study was terminated early by the data safety monitoring committee. CONCLUSIONS. In resource-limited settings where CM management may be suboptimal, when compared with a delay of 10 weeks after a CM diagnosis, early initiation of ART results in increased mortality. Trial registration. ClinicalTrials.gov identifier: NCT00830856.	A. T. Makadzange, C. E. Ndhlovu, K. Takarinda, M. Reid, M. Kurangwa, P. Gona and J. G. Hakim	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
579	Isotype concentrations of human antibodies to Haemophilus influenzae type b polysaccharide (Hib) in young adults immunized with the polysaccharide as such or conjugated to a protein (diphtheria toxoid)	Antibody responses of young adults to Haemophilus influenzae type b polysaccharide (Hib) or its protein conjugate were studied with special attention to the isotype composition of the antibodies. Three conclusions of interest can be made: 1) Immunoglobulin G (IgG) antibodies in polysaccharide-immunized volunteers displayed the subclass pattern previously found in antibodies to meningococcal type A polysaccharide. IgG1 was the predominant subclass in IgG antibodies of some individuals, IgG2 in others. Still others had the two subclasses in varying but more even proportions. 2) The conjugate vaccine induced a geometric mean response 2 to 3 times higher and an IgG response 4 times higher to Hib than the polysaccharide vaccine. 3) Anti-Hib antibodies induced by the conjugate vaccine still had essentially the same IgG subclass composition as anti-Hib antibodies induced by the polysaccharide. This composition was strikingly different from the composition of the anti-diphtheria toxoid response induced by the same conjugate vaccine. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	O. Makela, P. Mattila and N. Rautonen	Journal of Immunology
268	Corticosteroids (dexamethasone versus intravenous methylprednisolone) in patients with tuberculous meningitis	As inflammatory changes play an important role in the neuropathogenesis of the disease, adjunctive corticosteroid treatment may be of benefit in tuberculous meningitis. In an open-label study in India, 97 patients with such meningitis were randomized into a control group, a dexamethasone group (with the drug given intravenously once a day for 4 weeks, and then orally, once daily, for another 4 weeks) and a methylprednisolone group (with the drug given intravenously once a day for 5 days). All the patients also received standard anti-tuberculosis drugs. The primary outcome measure was death or severe disability 6 months after the randomization, with a modified Rankin scale used to assess each patient's level of disability. The other outcome measures investigated were deterioration in vision, focal neurological deficits and new-onset seizures. Six patients (one of those given dexamethasone, three of those given methylprednisolone and two of those in the control group) were lost to follow-up. Although each corticosteroid was associated with a reduction in death or disability, this reduction did not reach statistical significance in either the dexamethasone group (relative risk of death=0.6, with a 95% confidence interval of 0.29-1.2; P>0.05) or the methylprednisolone group (relative risk of death=0.7, with a 95% confidence interval of 0.4-1.4; P>0.05), probably because of the small sample sizes. Among the patients who died within 10 months of randomization, the mean time to death (post-randomization) was 8.8 months in the dexamethasone group, 8.2 months in the methylprednisolone group, and 7.1 months in the control group (P>0.05). The prevalence of impaired vision, among all the patients evaluated, decreased from 41.8% at baseline to 29.9% (among the survivors) 6 months later. Adverse events were similar and equally reported in the two corticosteroid groups. Larger trials are still needed to determine if dexamethasone and/or methylprednisolone are useful in the treatment of tuberculous meningitis, at least in India.	H. S. Malhotra, R. K. Garg, M. K. Singh, A. Agarwal and R. Verma	Annals of tropical medicine and parasitology
23	Immunogenicity and safety of CRM??? conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants	Streptococcus pneumoniae and Neisseria meningitidis cause invasive disease in children aged <2 years. While individual conjugate vaccines are available to protect this age group against these pathogens, availability of a vaccine combining these antigens into a single injection is desirable. This study randomized 467 healthy infants to receive 4 doses of combination 9-valent pneumococcal and meningococcal serogroup C conjugate vaccine (9vPnC-MnCC) or 9-valent pneumococcal conjugate vaccine (9vPnC). Percentages of subjects achieving immunoglobulin G (IgG) antibody concentrations ?0.35?g/mL and geometric mean IgG concentrations for each pneumococcal serotype in the 9vPnC-MnCC group were noninferior compared to the 9vPnC group. Both vaccines were well-tolerated.	E. Mallet, E. Brachet, P. Fernsten, F. Laudat, A. Razmpour and W. C. Gruber	Vaccine
517	Immunogenicity and safety of CRM(197) conjugated 9-valent pneumococcal and meningococcal C combination vaccine in healthy infants		E. Mallet, E. Brachet, P. Fernsten, F. Laudat, A. Razmpour and W. C. Gruber	Vaccine
111	[Placebo-controlled EEG-double blind study with the further purified TBE-vaccine (author's transl)]	In a placebo-controlled double blind study at random with 72 healthy persons the effect of an active TBE-vaccination (purified TBE vaccine) on EEG was investigated. 49 out of 72 examined persons could be examined twice, before and 3 to 5 days after vaccination respectively. The EEG was registered according to the international 10-20 electrode system in bipolar, unipolar and source derivations, using a 16 channel Elema-Schoenander electroencephalograph. The registration was made at rest, with hyperventilation and photo-stimulation. The EEG was registered on a tape-recorder and, using a computer, an automatic analysis (Fourier-Analysis) of the CZ-O2 derivations was performed, in order to get more exact results and a quantification of the basic-rhythmus. The visual evaluation and automatic analysis showed no significant changes of the EEG after TBE vaccination. There results were statistically determined by T-Tests and by discriminance analysis.	B. Mamoli, K. Pateisky, A. Steinringer and H. Steinringer	EEG-EMG Zeitschrift für Elektroenzephalographie, Elektromyographie und verwandte Gebiete
257	Fulminant meningococcemia. Heparin therapy and survival rate		S. G. Manios, F. Kanakoudi and E. Maniati	Scandinavian journal of infectious diseases
409	Peroperative prednisolone fails to improve the clinical outcome following surgery for prolapsed lumbar intervertebral disc. A randomized controlled trial	Ninety three patients undergoing their first conventional hemilaminectomy for lumbar disc protusion were randomized to a double blind clinical trial. Half of the patients were treated immediately following surgery with prednisolone; 50 mg per day for fourteen days and then 25 mg per day for another 14 days. The other patients were treated for the same time period with placebo tablets. Assessments using subjective and objective outcome criteria at 26 weeks, 52 weeks and 156 weeks of follow-up, demonstrated no statistically significant differences between the randomized groups. It is concluded that systemic prednisolone administration in the pre- and postoperative period does not in this study improve the clinical outcome after first time lumbar discectomy.	C. Manniche, B. Lauritsen and H. Vinterberg	Scandinavian journal of rheumatology
310	Monitoring and impact of fluconazole serum and cerebrospinal fluid concentration in HIV-associated cryptococcal meningitis-infected patients	OBJECTIVES: The aim of the present study was to assess fluconazole pharmacokinetic measures in serum and cerebrospinal fluid (CSF); and the correlation of these measures with clinical outcomes of invasive fungal infections. METHODS: A randomized trial was conducted in HIV-infected patients receiving three different regimens of fluconazole plus amphotericin B (AmB) for the treatment of cryptococcal meningitis. Regimens included fluconazole 400 mg/day+AmB (AmB+Fluc400) or fluconazole 800 mg/day+AmB (AmB+Fluc800) (14 days followed by fluconazole alone at the randomized dose for 56 days); or AmB alone for 14 days followed by fluconazole 400 mg/day for 56 days. Serum (at 24 h after dosing) and CSF samples were taken at baseline and days 14 and 70 (serum only) for fluconazole measurement, using gas-liquid chromatography. RESULTS: Sixty-four treated patients had fluconazole measurements: 11 in the AmB group, 12 in the AmB+Fluc400 group and 41 in the AmB+Fluc800 group. Day 14 serum concentration geometric means were 24.7 mg/L for AmB+Fluc400 and 37.0 mg/L for AmB+Fluc800. Correspondingly, CSF concentration geometric means were 25.1 mg/L and 32.7 mg/L. Day 14 Serum and CSF concentrations were highly correlated with AmB+Fluc800 (P<0.001, r=0.873) and AmB+Fluc400 (P=0.005, r=0.943). Increased serum area under the curve (AUC) appears to be associated with decreased mortality at day 70 (P=0.061, odds ratio=2.19) as well as with increased study composite endpoint success at days 42 and 70 (P=0.081, odds ratio=2.25 and 0.058, 2.89, respectively). CONCLUSION: High fluconazole dosage (800 mg/day) for the treatment of HIV-associated cryptococcal meningitis was associated with high serum and CSF fluconazole concentration. Overall, high serum and CSF concentration appear to be associated with increased survival and primary composite endpoint success.	W. Manosuthi, P. Chetchotisakd, T. L. Nolen, D. Wallace, S. Sungkanuparph, T. Anekthananon, K. Supparatpinyo, P. G. Pappas, R. A. Larsen, S. G. Filler and D. Andes	HIV medicine
624	Markers for bacterial infection in children with fever without source	OBJECTIVES: To compare the diagnostic properties of procalcitonin (PCT), C reactive protein (CRP), total white blood cells count (WBC), absolute neutrophil count (ANC) and clinical evaluation to detect serious bacterial infection (SBI) in children with fever without source.DESIGN: Prospective cohort study.SETTING: Paediatric emergency department of a tertiary care hospital.PARTICIPANTS: Children aged 1-36 months with fever and no identified source of infection.INTERVENTION: Complete blood count, blood culture, urine analysis and culture. PCT and CRP were also measured and SBI probability evaluated clinically with a visual analogue scale before disclosing tests results. Outcome measure Area under the curves (AUC) of the receiver operating characteristic curves.RESULTS: Among the 328 children included in the study, 54 (16%) were diagnosed with an SBI: 48 urinary tract infections, 4 pneumonias, 1 meningitis and 1 bacteraemia. The AUC were similar for PCT (0.82; 95% CI 0.77 to 0.86), CRP (0.88; 95% CI 0.84 to 0.91), WBC (0.81; 95% CI 0.76 to 0.85) and ANC (0.80; 95% CI 0.75 to 0.84). The only statistically significant difference was between CRP and ANC (? AUC 0.08; 95% CI 0.01 to 0.16). It is important to note that all the surrogate markers were statistically superior to the clinical evaluation that had an AUC of only 0.59 (95% CI 0.54 to 0.65).CONCLUSION: The study data demonstrate that CRP, PCT, WBC and ANC had almost similar diagnostic properties and were superior to clinical evaluation in predicting SBI in children aged 1 month to 3 years.	S. Manzano, B. Bailey, A. Gervaix, J. Cousineau, E. Delvin and J. B. Girodias	Archives of disease in childhood
662	Impact of procalcitonin on the management of children aged 1 to 36 months presenting with fever without source: a randomized controlled trial	OBJECTIVE: The aim of the study was to evaluate the impact of procalcitonin (PCT) measurement on antibiotic use in children with fever without source.METHOD: Children aged 1 to 36 months presenting to a pediatric emergency department (ED) with fever and no identified source of infection were eligible to be included in a randomized controlled trial. Patients were randomly assigned to 1 of 2 groups as follows: PCT+ (result revealed to the attending physician) and PCT- (result not revealed). Patients from both groups also had complete blood count, blood culture, urine analysis, and culture performed. Chest radiography or lumbar puncture could be performed if required.RESULTS: Of the 384 children enrolled and equally randomized into the PCT+ and PCT- groups, 62 (16%) were diagnosed with a serious bacterial infection (urinary tract infection, pneumonia, occult bacteremia, or bacterial meningitis) by primary ED investigation. Ten were also found to be neutropenic (<500 x 10(6)/L). Of the remaining undiagnosed patients, 14 (9%) of 158 received antibiotics in the PCT+ group vs 16 (10%) of 154 in the PCT- group (Delta -2%; 95% confidence interval [CI], -8 to 5). A strategy to treat all patients with PCT of 0.5 ng/mL or greater with prophylactic antibiotic in this group of patients would have resulted in an increase in antibiotic use by 24% (95% CI, 15-33).CONCLUSION: Semiquantitative PCT measurement had no impact on antibiotic use in children aged 1 to 36 months who presented with fever without source. However, a strategy to use prophylactic antibiotics in all patients with abnormal PCT results would have resulted in an increase use of antibiotics.	S. Manzano, B. Bailey, J. B. Girodias, A. Galetto-Lacour, J. Cousineau and E. Delvin	The American journal of emergency medicine
38	Randomized trial to assess immunogenicity and safety of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in infants	BACKGROUND: Study assessed the immunogenicity and safety of an investigational Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) in infants. METHODS: In a single-blinded, controlled study, 609 infants were randomized 1:1 to receive primary vaccination (2, 4, and 6 months) with either HibMenCY-TT or monovalent Haemophilus influenzae type b tetanus toxoid conjugate vaccine (Hib-TT), co-administered with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine and 7-valent pneumococcal conjugate vaccine. A second control group of 3- to 5-year-old children received a single dose of licensed meningococcal ACWY polysaccharide vaccine (MPSV4). Immunogenicity was measured before and 1 month after dose 3/MPSV4 using human (hSBA) and rabbit complement bactericidal assays (rSBA) and enzyme-linked immunosorbent assay assays for IgG antibodies to MenC and MenY polysaccharides. Anti-polyribosylribitol phosphate antibody concentrations were measured 1 month after the third dose. Safety was also assessed. RESULTS: One month after primary vaccination statistically significantly more HibMenCY-TT than Hib-TT vaccines had anti-PRP antibody concentrations > or =1.0 microg/mL (93.5% vs. 85.8%). The percentage of HibMenCY-TT recipients with hSBA titers > or =1:8 (MenC: 95.9%, MenY: 89.4%) was statistically significantly higher than for MPSV4 recipients (MenC: 30.2%, MenY: 47.5%). The percentage of subjects reporting any severe (grade 3) symptom within 4 days of each vaccination was: 11.5% (HibMenCY-TT) and 24.8% (Hib-TT) (group difference, 13.27%, 95% CI: [7.22;19.29], P < 0.001). CONCLUSION: The investigational HibMenCY-TT vaccine was well tolerated and immunogenic in infants, induced Hib immune responses that were comparable to licensed Hib-TT vaccine, and induced high levels of bactericidal antibodies against N. meningitidis serogroups C and Y.	C. D. Marchant, J. M. Miller, G. S. Marshall, M. Blatter, E. Aris, L. R. Friedland and D. Boutriau	The Pediatric infectious disease journal
193	Clinical algorithms teach pediatric decisionmaking more effectively than prose	Despite the rapidly increasing volume of medical literature, little attention has been paid to the appropriate printed format for teaching clinical content. This study attempted to determine whether a clinical algorithm (CA) or prose is more effective for teaching clinical decisionmaking. Clerkship students, preclerkship students, and pediatric house officers in five medical centers in the USA and Israel were presented with clinical algorithms and prose describing management of fever in a child under 2 years of age, and management of meningitis in children. Knowledge of decisionmaking was measured before and after learning, using audio-taped clinical problems and learning time as measured. It was concluded that CAs are more effective and more efficient than prose for teaching clinical decisionmaking. When writing about clinical decisionmaking, the use of CAs should always be considered, especially if a series of interdependent decisions is being described.	C. Z. Margolis, C. D. Cook, N. Barak, A. Adler and A. Geertsma	Medical care
608	A trial of vidarabine for cytomegalovirus infection in renal transplant patients	Vidarabine was evaluated in renal transplant patients as a potential therapeutic agent in cytomegalovirus (CMV) infection. Four patients received vidarabine on an open protocol, then ten additional patients were enrolled in a double-blind protocol. Among the nine patients who received vidarabine, no notable clinical improvement occurred in either the vidarabine- or placebo-treated groups. Thus, vidarabine showed no therapeutic effect in the treatment of CMV infections at the dosages used. Four patients showed dramatic CNS deterioration within several days of the onset of vidarabine therapy. Tremors and myoclonus were common, and one patient had unusual brain pathologic changes with widespread neuronal chromatolysis. The pathologic findings in the brain in the other three patients were complex and included intracerebral hemorrhage, Fabry's disease, coccidioidomycosis meningitis, and cerebral vascular occlusion. Thus, there was no conclusive proof that vidarabine contributed to the sudden neurologic deterioration of these patients.	S. C. Marker, R. J. Howard, K. E. Groth, A. R. Mastri, R. L. Simmons and H. H. Balfour	Archives of internal medicine
559	Dexamethasone for tuberculous meningitis		T. K. Marras	N Engl J Med
30	Co-administration of a novel Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine does not interfere with the immune response to antigens contained in infant vaccines routinely used in the United States	An investigational combined Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY-TT) has been developed to protect infants from invasive disease caused by Hib and these meningococcal serogroups without adding injections to the immunization schedule. Incorporation of this novel vaccine into the US vaccination schedule will require demonstration of a lack of immunologic interference with other routine pediatric vaccines. This study assessed the immune response to 7-valent pneumococcal conjugate vaccine (PCV7) and combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus vaccine (DTaP-HepB-IPV) when separately co-administered with HibMenCY-TT as compared to a US-licensed H. influenzae type b tetanus toxoid conjugate vaccine (Hib-TT) at 2, 4, 6 (N=606) and 12-15 months of age (N=366). HibMenCY-TT was non-inferior to Hib-TT in terms of antibody responses to all Streptococcus pneumoniae serotypes contained in PCV7 and the diphtheria, tetanus, pertussis, hepatitis B and poliovirus antigens contained in DTaP-HepB-IPV one month after the third vaccine dose, and the anti-tetanus geometric mean antibody concentration (GMC) was significantly higher in the HibMenCY-TT group than in the Hib-TT group. In an exploratory analysis, no significant differences in the proportion of subjects with anti-pneumococcal antibody concentrations ?0.2 µg/ml or anti-pneumococcal GMC were seen between the two groups after the fourth vaccine dose. A schedule of HibMenCY-TT given concomitantly with PCV7 and DTaP-HepB-IPV would be expected to protect infants against all of the targeted diseases.	G. S. Marshall, C. D. Marchant, M. Blatter, L. R. Friedland, E. Aris and J. M. Miller	Human vaccines
610	Use of beclomethasone dipropionate as rescue treatment for children with mild persistent asthma (TREXA): a randomised, double-blind, placebo-controlled trial	BACKGROUND: Daily inhaled corticosteroids are an effective treatment for mild persistent asthma, but some children have exacerbations even with good day-to-day control, and many discontinue treatment after becoming asymptomatic. We assessed the effectiveness of an inhaled corticosteroid (beclomethasone dipropionate) used as rescue treatment.METHODS: In this 44-week, randomised, double-blind, placebo-controlled trial we enrolled children and adolescents with mild persistent asthma aged 5-18 years from five clinical centres in the USA. A computer-generated randomisation sequence, stratified by clinical centre and age group, was used to randomly assign participants to one of four treatment groups: twice daily beclomethasone with beclomethasone plus albuterol as rescue (combined group); twice daily beclomethasone with placebo plus albuterol as rescue (daily beclomethasone group); twice daily placebo with beclomethasone plus albuterol as rescue (rescue beclomethasone group); and twice daily placebo with placebo plus albuterol as rescue (placebo group). Twice daily beclomethasone treatment was one puff of beclomethasone (40 ?g per puff) or placebo given in the morning and evening. Rescue beclomethasone treatment was two puffs of beclomethasone or placebo for each two puffs of albuterol (180 ?g) needed for symptom relief. The primary outcome was time to first exacerbation that required oral corticosteroids. A secondary outcome measured linear growth. Analysis was by intention to treat. This study is registered with clinicaltrials.gov, number NCT00394329.RESULTS: 843 children and adolescents were enrolled into this trial, of whom 288 were assigned to one of four treatment groups; combined (n=71), daily beclomethasone (n=72), rescue beclomethasone (n=71), and placebo (n=74)-555 individuals were excluded during the run-in, according to predefined criteria. Compared with the placebo group (49%, 95% CI 37-61), the frequency of exacerbations was lower in the daily (28%, 18-40, p=0·03), combined (31%, 21-43, p=0·07), and rescue (35%, 24-47, p=0·07) groups. Frequency of treatment failure was 23% (95% CI 14-43) in the placebo group, compared with 5·6% (1·6-14) in the combined (p=0·012), 2·8% (0-10) in the daily (p=0·009), and 8·5% (2-15) in the rescue (p=0·024) groups. Compared with the placebo group, linear growth was 1·1 cm (SD 0·3) less in the combined and daily arms (p<0·0001), but not the rescue group (p=0·26). Only two individuals had severe adverse events; one in the daily beclomethasone group had viral meningitis and one in the combined group had bronchitis.INTERPRETATION: Children with mild persistent asthma should not be treated with rescue albuterol alone and the most effective treatment to prevent exacerbations is daily inhaled corticosteroids. Inhaled corticosteroids as rescue medication with albuterol might be an effective step-down strategy for children with well controlled, mild asthma because it is more effective at reducing exacerbations than is use of rescue albuterol alone. Use of daily inhaled corticosteroid treatment and related side-effects such as growth impairment can therefore be avoided.FUNDING: National Heart, Lung and Blood Institute.	F. D. Martinez, V. M. Chinchilli, W. J. Morgan, S. J. Boehmer, R. F. Lemanske, D. T. Mauger, R. C. Strunk, S. J. Szefler, R. S. Zeiger, L. B. Bacharier, E. Bade, R. A. Covar, N. J. Friedman, T. W. Guilbert, H. Heidarian-Raissy, H. W. Kelly, J. Malka-Rais, M. H. Mellon, C. A. Sorkness and L. Taussig	Lancet
482	Recombinant human activated protein C in the treatment of children with meningococcal purpura fulminans		F. Martinon-Torres, J. M. Iglesias Meleiro, M. Fernandez Sanmartin, A. Rodriquez Nunez and J. M. Martinon Sanchez	Anales de Pediatria (Barcelona, Spain)
186	Gentamicin in the treatment of meningitis		A. W. Mathies, A. Lavetter, J. M. Leedom, D. Ivler and P. F. Wehrle	The Journal of infectious diseases
319	Combination therapy with fluconazole and flucytosine for cryptococcal meningitis in Ugandan patients with AIDS	We performed a randomized trial in which combination therapy with fluconazole and short-term flucytosine was compared with fluconazole monotherapy in 58 patients with AIDS-associated cryptococcal meningitis (CM). Thirty of these patients were randomized to receive combination therapy with fluconazole, 200 mg once a day for 2 months, and flucytosine, 150 mg/(kg.d) for the first 2 weeks, and 28 were randomized to receive monotherapy with fluconazole at the same dose for 2 months. Patients in both groups who survived for 2 months received fluconazole as maintenance therapy at a dose of 200 mg three times per week for 4 months. The combination therapy prevented death within 2 weeks and significantly increased the survival rate among these patients (32%) at 6 months over that among patients receiving monotherapy (12%) (P = .022). The combination therapy also resulted in a significant decrease in the severity of headache after 1 month of treatment, compared with monotherapy (P = .005). No serious adverse reactions were observed in patients receiving either regimen. These data indicate that treatment with fluconazole and short-term flucytosine is a cost-effective and safe regimen that improves the quality of life for patients with AIDS-associated CM in developing countries where human immunodeficiency virus is endemic.	H. Mayanja-Kizza, K. Oishi, S. Mitarai, H. Yamashita, K. Nalongo, K. Watanabe, T. Izumi, n. Ococi-Jungala, K. Augustine, R. Mugerwa, T. Nagatake and K. Matsumoto	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
619	Primary prevention with cotrimoxazole for HIV-1-infected adults: results of the pilot study in Dakar, Senegal	OBJECTIVES: To assess the efficacy and tolerance of chemoprophylaxis with cotrimoxazole compared with placebo among HIV-1-infected adults. DESIGN: Randomized, double-blind, placebo-controlled clinical trial in the urban community of Dakar, Senegal. METHODS: Eligibility criteria were age greater than 15 years, HIV-1 or HIV-1 and HIV-2 dual seropositivity, CD4 cell count lower than 400 copies/mm3, no progressive infection, no previous history of intolerance to sulphonamide, lack of severe anemia or neutropenia, and renal or hepatic failure. Written informed consent was obtained. Recruited patients received 80 mg of trimethoprim and 400 mg of sulphamethoxazole daily or a matching placebo. The main outcomes were survival and the occurrence of clinical events defined as Pneumocystis carinii pneumonia, cerebral toxoplasmosis, bacterial pneumonia, infectious enteritis, bacterial meningitis, urinary tract infection, bacterial otitis and sinusitis, and pyomyositis. RESULTS: Between September 1996 and March 1998, 297 patients were screened, and 100 were randomized in the study. Demographic, clinical, and biological characteristics of the two groups were similar as was the mean length of follow-up (7.7 months for the cotrimoxazole group vs. 8.0 months for the placebo group). There was no significant difference between the two groups in survival (hazard ratio = 0.84; 95% confidence interval [CI]: 0.36-1.94) in the probability of severe event occurrence, defined as death or hospital admission (hazard ratio = 1.10; 95% CI: 0.57-2.13), or in the probability of clinical event occurrence (hazard ratio = 1.19; 95% CI: 0.55-2.59). Adjustment for initial CD4 cell count did not change these results. A low dose of cotrimoxazole was tolerated well clinically as well as biologically; only one treatment interruption occurred as the result of a moderate cutaneous eruption (grade 2). CONCLUSION: Our study does not show a beneficial effect of chemoprophylaxis with low-dose cotrimoxazole on survival or occurrence of opportunistic or nonopportunistic infections for HIV-1-infected patients in Dakar, Senegal.	M. Maynart, L. Lièvre, P. S. Sow, S. Kony, N. F. Gueye, E. Bassène, A. Metro, I. Ndoye, D. S. Ba, J. P. Coulaud and D. Costagliola	Journal of acquired immune deficiency syndromes (1999)
622	Electrographic seizures in neonates correlate with poor neurodevelopmental outcome	OBJECTIVE: To quantify the number, duration, and intensity of electrographic seizures (ESz) in neonates and to compare the outcome of neonates with ESz with those who were at risk but did not have ESz recorded. METHODS: The EEG and outcome data were reviewed from 68 infants who met at-risk criteria for neonatal seizures and underwent prolonged continuous EEG monitoring. Forty infants had ESz. The control group contained 28 infants monitored for at least 18 hours and found not to have ESz. Outcomes for both groups were evaluated using hospital and follow-up clinic records and a standardized telephone interview. RESULTS: The etiology of ESz included asphyxia (n = 23), stroke (n = 7), and other (n = 10, intraparenchymal, subdural, and subarachnoid bleeding; meningitis; sepsis; hyponatremia; and unknown). The cumulative recorded ESz duration was 8 minutes to 30 hours. Forty-three percent of infants with ESz spent 38 minutes to 32 hours in electrographic status. Despite doses of 40 mg/kg of phenobarbital and 20 mg/kg of phenytoin, 30% of infants continued to have ESz. Ten infants with ESz and one without died from causes related to neurologic instability. The occurrence of ESz was correlated with microcephaly (p = 0.04), severe cerebral palsy (CP) (p = 0.03), and failure to thrive (p = 0. 03). In the subgroup of infants with asphyxia, those with ESz were more likely to die of neurologic causes (p = 0.02) and have microcephaly (p = 0.05) or severe CP (p = 0.04). Additionally, those with the greatest number of ESz were more likely to have these severe outcomes. CONCLUSION: The authors' data indicate an association between the amount of electrographic seizure activity and subsequent mortality and morbidity in at-risk infants in general and in infants with perinatal asphyxia. Only with more effective treatment of neonatal electrographic seizures can their potential contribution to poor neurodevelopmental outcome, independent of degree of insult, be ascertained.	M. C. McBride, N. Laroia and R. Guillet	Neurology
46	Intraventricular gentamicin therapy in gram-negative bacillary meningitis of infancy. Report of the Second Neonatal Meningitis Cooperative Study Group	In a multicentre controlled trial in the U.S.A. and Latin America 52 infants with meningitis and ventriculitis were randomly assigned to receive either systemic ampicillin and gentamicin or intraventricular gentamicin plus systemic antimicrobial agents. The aetiological agents most often encountered were Escherichia coli in the U.S. infants and Salmonella spp. in Latin American infants. Infants receiving systemic antibiotics plus intraventricular gentamicin had a significantly higher mortality rate (42.9%) than those who received systemic therapy only (12.5%). Duration of positive CSF cultures and morbidity rates were not significantly different in the two treatment groups. The concentrations of gentamicin in ventricular and lumbar CSF 1--6 h after an intraventricular dose of 2.5 mg gentamicin were 10--130 microgram/ml and 8--85 microgram/ml, respectively. The study was terminated early because of the higher mortality rate in the intraventricular-therapy group. Intraventricular gentamicin should not be used as routine treatment for neonatal meningitis caused by gram-negative enteric bacilli.	G. H. McCracken, S. G. Mize and N. Threlkeld	Lancet
145	Moxalactam therapy for neonatal meningitis due to gram-negative enteric bacilli. A prospective controlled evaluation	Moxalactam and ampicillin sodium therapy were compared with amikacin sulfate and ampicillin therapy for meningitis due to gram-negative enteric bacilli in 63 infants enrolled in the Third Neonatal Meningitis Cooperative Study. The population characteristics and causative organisms were comparable for the two treatment groups. Cultures of CSF were positive for approximately three days in both study groups. Case-fatality rates were 23% and 15% for moxalactam-treated infants and ampicillin- and amikacin-treated infants, respectively. Developmental or neurological abnormalities were found in about 40% of survivors, and the rates were comparable for both treatment groups. Computed tomograms in 44 infants were interpreted as normal in 13 (30%); hydrocephalus, abscesses, and low-density areas were the most frequent abnormalities. We conclude that moxalactam is a suitable alternative for treatment of meningitis due to gram-negative enteric bacilli.	G. H. McCracken, N. Threlkeld, S. Mize, C. J. Baker, S. L. Kaplan, I. Faingezicht, W. E. Feldman and U. Schaad	JAMA : the journal of the American Medical Association
459	Management of opportunistic infections in AIDS	Opportunistic infections (OI) in AIDS patients are an important source of morbidity and mortality. Major clinical research efforts are utilizing the large numbers of patients with these previously rare and exotic infections to rapidly improve treatment and prevention. A group of infectious disease specialists at four major California medical schools (California Collaborative Treatment Group) have made major contributions to the management of OI, especially those involving nervous system infections. We have established 1) the role of corticosteroids as adjunctive therapy for pneumocystis pneumonia (PCP), 2) the value of quantitative cultures of Mycobacterium avium complex (MAC) in assessing drugs and of oral treatment regimens for reducing symptoms or MAC bacteremia, 3) proven the value of fluconazole as treatment (with flucytosine) and prophylaxis (alone) for cryptococcal meningitis, and 4) performed the first randomized study of treatment of toxoplasmic encephalitis confirming the value of clindamycin and pyrimethamine as an alternative to sulfadiazine and pyrimethamine. We are beginning studies of primary prophylaxis of MAC with azithromycin, rifabutin, or the combination, of serious fungal infections wiht fluconazole, and of cytomegalovirus with ganciclovir. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. A. McCutchan	Yokohama Med. Bull.
581	Comparative studies of antibacterial activity in vitro and absorption and excretion of lincomycin and clinimycin		R. F. McGehee, C. B. Smith, C. Wilcox and M. Finland	The American journal of the medical sciences
71	Effect of infant immunisation with meningococcus serogroup C-CRM(197) conjugate vaccine on diphtheria immunity and reactogenicity in pre-school aged children	The majority of Men C conjugate vaccines given in the UK use CRM(197), a mutant diphtheria toxoid, as their protein carrier. We studied the effects of prior immunisation with Men C-CRM(197) conjugate vaccine on immunity to diphtheria in 193 children before and after a booster dose of Men C at 4 years. Baseline diphtheria antibodies were higher in children given four previous doses of Men C (P<0.0001) and tended to be higher following boosting in those who had received three or four doses. This enhanced immunity was not associated with increased reactogenicity.	J. McVernon, J. MacLennan, E. Clutterbuck, J. Buttery and E. R. Moxon	Vaccine
650	Metabolites of the kynurenine pathway of tryptophan metabolism in the cerebrospinal fluid of Malawian children with malaria	A retrospective study of 100 Malawian children (87 with malaria and 13 with a diagnosis other than malaria) was conducted to determine the relationship between levels of metabolites of the kynurenine pathway in cerebrospinal fluid (CSF) and disease outcome. Three metabolites were measured: quinolinic acid (QA), an excitotoxin; kynurenic acid (KA), a neuroprotective receptor antagonist; and picolinic acid (PA), a proinflammatory mediator. Elevated levels of QA and PA in CSF were associated with a fatal outcome in Malawian children with cerebral malaria (CM). QA was associated with a history of convulsions. An increase in the QArcolon;KA ratio, which favors neurotoxicity, was observed only in the 3 patients with tuberculosis meningitis. Compared with Vietnamese adults with malaria, Malawian children with malaria had higher concentrations of KA. Elevated levels of KA in children with CM may serve to contain injury in the developing brain, which is more susceptible to excitotoxic damage than is the adult brain.	I. M. Medana, N. P. Day, H. Salahifar-Sabet, R. Stocker, G. Smythe, L. Bwanaisa, A. Njobvu, K. Kayira, G. D. Turner, T. E. Taylor and N. H. Hunt	The Journal of infectious diseases
648	Antimicrobial prophylaxis to prevent opportunistic infections in patients with chronic lymphocytic leukemia after allogeneic blood or marrow transplantation	Opportunistic infections have been a problem after BMT in CLL. We have allografted seven patients with B-CLL (n = 6) or B-prolymphocytic leukemia (n = 1) from matched siblings (n = 6) or a mismatched unrelated donor (n = 1). Amongst the first six, we saw two cases of recurrent or prolonged cytomegaloviremia and CMV disease, one listeria meningitis, and one fatal toxoplasma encephalitis. The latter two developed in the setting of steroid therapy of GVHD with extensive prior fludarabine therapy. Prophylaxis for opportunistic infections was developed on an ongoing basis as new infectious complications were seen. The current drug prophylaxis, which has been successful for eight months in the last patient despite pretreatment with fludarabine and steroid therapy for GVHD, is directed against pneumocystis, toxoplasma, fungi, and pneumococci. It includes immunoglobulin (for 3 1/2 months), pyrimethamine-sulfadiazine (for 4 months and during steroids), fluconazole (for 2 1/2 months), cotrimoxazole or pentamidine (for 2 years) and penicillin (lifelong). Dietary precautions are followed for 4 months and during steroids to prevent listeriosis. Four patients are alive in remission with no active infectious problems 8-44 months (median 29) after BMT. We recommend adoption of these or similar prophylactic measures for BMT in CLL as a baseline which can be modified if new infections are identified and according to individual needs.	J. Mehta, R. Powles, S. Singhal, U. Riley, J. Treleaven and D. Catovsky	Leukemia & lymphoma
138	Immunogenicity of a single dose of tetravalent meningococcal serogroups A, C, W-135, and Y conjugate vaccine administered to 2- to 10-year-olds is noninferior to a licensed-ACWY polysaccharide vaccine with an acceptable safety profile	BACKGROUND: Meningococcal disease remains an important cause of invasive bacterial infections in children less than 5 years of age. Immunogenicity and safety of the investigational ACWY vaccine conjugated with tetanus toxoid (ACWY-TT, GlaxoSmithKline Biologicals) were evaluated in 1501 healthy 2- to 10-year-old children in the Philippines, India, Lebanon, and Saudi Arabia.METHODS: Children were randomized (3:1) to receive ACWY-TT or licensed tetravalent meningococcal polysaccharide vaccine (Mencevax, GlaxoSmithKline, Men-PS). Diary cards were used to collect solicited symptoms for 4 days after vaccination. Serious adverse events were reported for 6 months. Serum bactericidal activity (rSBA, rabbit complement) was measured before and 1 month after vaccination in the first 75% of subjects enrolled in each country.RESULTS: The statistical criteria for noninferiority in terms of rSBA vaccine responses were reached. Exploratory analyses showed that postvaccination rSBA titers ? 1:8 and ? 1:128 were significantly higher after ACWY-TT than Men-PS for serogroups C, W-135, and Y, and rSBA vaccine responses and geometric mean antibody titers were significantly higher for all 4 serogroups after administration of ACWY-TT. Noninferiority in terms of incidences of grade 3 general symptoms was not demonstrated. ACWY-TT was well tolerated with grade 3 events reported in <1% of subjects per group. No serious adverse events were considered related to vaccination.CONCLUSION: ACWY-TT was immunogenic in children between 2 to 10 years of age with a clinically acceptable safety profile that resembled licensed Men-PS. These data support a positive benefit/risk ratio for the ACWY-TT vaccine.	Z. A. Memish, G. Dbaibo, M. Montellano, V. P. Verghese, H. Jain, A. P. Dubey, V. Bianco, M. Wielen, S. Gatchalian and J. M. Miller	The Pediatric infectious disease journal
448	Immunogenicity and safety of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis conjugate vaccine in 7.5 microg liquid formulation: A comparison of three lots with the 15.0 microg lyophilized formulation	We conducted a multicenter, single-blind, randomized comparison of the immunogenicity and safety of three manufacturing-scale lots of 7.5 microg liquid Haemophilus influenzae type b polysaccharide-Neisseria meningitidis conjugate vaccine (PRP-OMPC) and a single lot of 15.0 microg lyophilized PRP-OMPC. A total of 908 infants were entered into the study. Each infant received two primary injections intramuscularly 2 months apart beginning at age 2-6 months and a booster injection at 12-15 months. Blood samples for serology were obtained before each injection and 1 month after the second and the booster dose. Immune responses were measured by radioimmunoassay. Approximately 80% of the infants achieved a titer >1.0 microg ml-1 after the second primary dose of all four lots tested; the geometric mean titer (GMT) was ca 3 microg ml-1 for each vaccine group. After the booster dose, more than 90% of infants from each vaccine group had a titer > 1.0 microg ml-1; GMTs ranged from 8 to 10 microg ml- 1. No serious vaccine-associated adverse reactions were reported. Thus the 7.5 microg liquid PRP-OMPC vaccine was at least as immunogenic and well tolerated as the 15.0 microg lyophilized vaccine. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. M. Mendelman, L. Feeley, S. Bird, T. Staub, H. Matthews, B. A. Del, G. Overturf, A. Lee, R. Ellis, J. Staub, S. Szymanski, J. Donnelly, J. P. Hennessey and P. Kniskern	Vaccine
157	Cerebrospinal fluid and serum ampicillin levels in bacterial meningitis patients after intravenous and intramuscular administration	28 patients with bacterial meningitis received ampicillin by the intramuscular (IM) route and 16 patients by the intravenous (IV) route. The mean cerebrospinal fluid (CSF) ampicillin levels were similar in the two groups 1 h after a dose given on the first or second day of treatment, but they were higher in the IM group on both days 4 h after a dose. CSF/serum ratios were similar in both groups but considerably higher at 4 h than at 1 h.	I. A. Mikhail, J. E. Sippel, N. I. Girgis and M. W. Yassin	Scandinavian journal of infectious diseases
440	Fluconazole alone or combined with flucytosine for the treatment of AIDS-associated cryptococcal meningitis	An all oral treatment for cryptococcal meningitis is attractive, particularly where amphotericin B use is impractical. Both fluconazole and flucytosine are available in oral formulations and have activity against Cryptococcus neoformans. We conducted a prospective phase II dose escalation study employing doses of fluconazole ranging from 800 to 2000 mg daily for 10 weeks used alone or combined with flucytosine at 100 mg/kg per day for the first 4 weeks. We found that increasing doses of fluconazole were associated with an increase in survival and a decrease in the time to conversion of the cerebrospinal fluid from culture positive to culture negative. Addition of flucytosine to fluconazole improved outcomes in each dosing cohort. High doses of fluconazole alone or combined with flucytosine were well tolerated.	E. Milefchik, M. A. Leal, R. Haubrich, S. A. Bozzette, J. G. Tilles, J. M. Leedom, J. A. McCutchan and R. A. Larsen	Medical Mycology
216	Effect of community-wide conjugate pneumococcal vaccine use in infancy on nasopharyngeal carriage through 3 years of age: a cross-sectional study in a high-risk population	BACKGROUND: A 7-valent pneumococcal conjugate vaccine (PnCRM7) has been shown to be highly effective in preventing invasive pneumococcal disease. Pneumococcal conjugate vaccines also protect against nasopharyngeal carriage of vaccine serotypes, but the duration of protection against nasopharyngeal carriage is not known. METHODS: A group-randomized efficacy trial of PnCRM7 (vaccine serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) was conducted on the Navajo and White Mountain Apache reservations from April 1997 to October 2000. A group C meningococcal conjugate vaccine was used as the control vaccine. Infants enrolled between 6 weeks and 7 months of age received 3 doses of vaccine 2 months apart and a fourth dose at 12-15 months of age. Vaccinees were enrolled in a nasopharyngeal carriage study from February 2001 to January 2002 to assess the duration of protection against pneumococcal carriage induced by PnCRM7. RESULTS: We included 749 children in the analysis, including 468 children vaccinated with PnCRM7 and 281 children vaccinated with group C meningococcal conjugate vaccine. The median age was 3.3 years (range, 1-7 years), and the median time since last dose of study vaccine was 27 months (range, 12-48 months). Frequencies of overall pneumococcal carriage were similar among PnCRM7 and group C meningococcal conjugate vaccine recipients (63.9% vs. 60.5%, respectively). The absolute frequency of vaccine-type pneumococcal carriage was lower among PnCRM7 recipients (10.3%) than among controls (17.1%; P = .01). This reduction was offset by an increase of nonvaccine-type pneumococcal carriage among PnCRM7 recipients (39.2% vs. 29.8%; P = .01). CONCLUSION: Community-wide PnCRM7 vaccination in infancy reduces the prevalence of vaccine-type carriage and increases the prevalence of nonvaccine-type carriage through at least 3 years of age.	E. V. Millar, K. L. O'Brien, J. P. Watt, M. A. Bronsdon, J. Dallas, C. G. Whitney, R. Reid and M. Santosham	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
541	Immunogenicity and Safety of an Investigational CombinedHaemophilus influenzaeType B andNeisseria meningitidisSerogroups C and Y Conjugate Vaccine in Healthy Infants Compared to Licensed Controls		Miller	Pediatric Academic Society
85	Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age	The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ?8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ?0.15 ?g/ml, PCV serotype-specific IgG concentrations of ?0.35 ?g/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ?11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.	E. Miller, N. Andrews, P. Waight, H. Findlow, L. Ashton, A. England, E. Stanford, M. Matheson, J. Southern, E. Sheasby, D. Goldblatt and R. Borrow	Clinical and vaccine immunology : CVI
500	Serose Meningitis in childhood: The pharmacokinetic of Cefritiaxon and Sodium Penicillin G		M. Millner, G. H. Thalhammer, K. D. Spork, P. Dittrich and A. Georgopoulos	Monatsschrift fur Kinderheilkunde
596	Neuroborreliosis in childhood: Treatment with penicillin sodium and ceftriaxone	Beta-lactam antibiotics like ceftriaxone and penicillin G sodium have been shown to be active against Borrelia burgdorferi in vitro. Results of quantitative determinations of both antibiotic substances in cerebrospinal fluid of children are limited. 75 children (median age 96 months, range 10 to 176 months) with probable or definite neuroborreliosis were treated with ceftriaxone (1 x 50-90 mg/kg/day) or penicillin G sodium (4 x 80,000-120,000 I.U./kg/day) intravenously for 14 days. On day ten of therapy levels of penicillin G sodium (1, 1.5, 2, 3, 4, 5, or 6 hours after intravenous administration), and ceftriaxone (1, 2, 4, 6, 12, or 24 hours after intravenous administration) in serum and cerebrospinal fluid were measured using a micro agar diffusion bioassay. Results demonstrate that penicillin G sodium concentrations in cerebrospinal fluid were above minimum inhibitory concentration after five hours, but below the limit of determination in 60% after six hours. All ceftriaxone results in cerebrospinal fluid - even after 24 hours - were above minimum inhibitory concentration. Penicillin G sodium serum values ranged from 46.6 to 0.1 mug/ml (1 to 6 hours post dose) and ceftriaxone serum values from 261 to 5 mug/ml (1 to 24 hours post dose). The role of administration intervals in antibiotic therapy of neuroborreliosis in children is discussed. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. M. Millner and G. H. Thalhammer	Acta Dermatovenerologica Alpina, Panonica Et Adriatica.
556	Role of antiplatelet drug in preventing ischemic stroke in tuberculosis meningitis: a randomized plaebo controlled trial	61st Annual Meeting of the American Academy of Neurology, 25 April-2 May 2009, Seattle, USA	U. K. Misra, J. Kalita and P. Nair	Neurology
250	Role of aspirin in tuberculous meningitis: a randomized open label placebo controlled trial	OBJECTIVE: To evaluate the efficacy and safety of aspirin in preventing stroke and mortality in tuberculous meningitis (TBM). METHODS: Patients with TBM diagnosed on the basis of clinical, MRI and cerebrospinal fluid (CSF) criteria were randomized into aspirin 150 mg daily or placebo. All the patients received four drug antitubercular treatment- RHZE (rifampicin, isoniazide, pyrazinamide and ethambutol) with or without corticosteroid. The primary endpoint was MRI proven stroke at 3 months and secondary end points were mortality and functional outcome assessed by Barthel Index score at 3 months. The adverse drug reactions were also analyzed. RESULTS: 118 TBM patients were randomized into aspirin and placebo groups. The baseline demographic, clinical (severity of meningitis, MRI and CSF changes) were not significantly different between the two groups. 19 (16.1%) patients lost from follow up. 21 (33.3%) patients developed stroke after randomization which was insignificantly lesser in aspirin (24.2%) compared to the placebo group (43.3%; OR 0.42, 95%CI 0.12-1.39). Aspirin resulted in absolute risk reduction of stroke in 19.1% and significant reduction in mortality compared to placebo (21.7% Vs 43.4%, P=0.02). On binary logistic regression analysis, the age (OR 1.09, CI 1.03-1.14, P=0.001) was the only independent risk factor of stroke and aspirin was significantly related to survival (OR 3.17, 95% CI 1.21-8.31). Aspirin was well tolerated and was not withdrawn in any patient because of side effects. INTERPRETATION: Aspirin resulted in insignificantly lesser strokes and significantly reduced 3 month mortality in patients with TBM.	U. K. Misra, J. Kalita and P. P. Nair	Journal of the neurological sciences
547	Liposomal cytarabine (DepoCyte? Injection) is cost-effective compared with standard cytarabine for the intrathecal treatment of patients with lymphomatous meningitis	46th Annual Meeting of the American Society of Hematology, San Diego, California, 4-7 December 2004. Abstract No. 267	K. Moeremans, L. Annemans and J. Morris	Blood
299	Regional cerebral blood flow during hyperventilation in patients with acute bacterial meningitis	Mechanical hyperventilation is often instituted in patients with acute bacterial meningitis when increased intracranial pressure is suspected. However, the effect on regional cerebral blood flow (CBF) is unknown. In this study, we measured regional CBF (rCBF) in patients with acute bacterial meningitis before and during short-term hyperventilation. In 17 patients with acute bacterial meningitis, absolute rCBF (in ml/100 g min-1) was measured during baseline ventilation and hyperventilation by single-photon emission computed tomography (SPECT) using intravenous 133Xe bolus injection. Intravenous 99mTc-HMPAO (hexamethylpropyleneamine oxime) was subsequently given during hyperventilation. In 12 healthy volunteers, rCBF was measured by SPECT and 99mTc-HMPAO during spontaneous ventilation. Using standard templates to identify regions of interest (ROIs), we calculated rCBF in percentage of cerebellar (99mTc-HMPAO images) or mean hemispheric (133Xe images) flow for each ROI, the degree of side-to-side asymmetry for each ROI, and the anterior-to-posterior flow ratio. On 133Xe images, absolute rCBF decreased significantly during hyperventilation compared to baseline ventilation in all regions, but the relative rCBF did not change significantly from baseline ventilation (n=14) to hyperventilation (n=12), indicating that the perfusion distribution was unchanged. On 99mTc-HMPAO images (n=12), relative rCBF and the anterior-to-posterior flow ratio were significantly lower in patients than in controls in the frontal and parietal cortex as well as in the basal ganglia. Focal perfusion abnormalities were present in 10 of 12 patients. Regional cerebral blood flow abnormalities are frequent in patients with acute bacterial meningitis. Short-term hyperventilation does not enhance these abnormalities.	K. Møller, P. Høgh, F. S. Larsen, G. I. Strauss, P. Skinhøj, B. K. Sperling and G. M. Knudsen	Clinical physiology (Oxford, England)
151	Antibody responses to polysaccharide and polysaccharide-conjugate vaccines after treatment of Hodgkin disease	OBJECTIVE: To compare the immunogenicity of polysaccharide-conjugate vaccines with that of polysaccharide vaccines in patients previously treated for Hodgkin disease. DESIGN: All patients were immunized with Haemophilus influenzae type b (HIB)-conjugate and 4-valent meningococcal polysaccharide vaccines. Subgroups of patients were randomly assigned to receive either 23-valent pneumococcal polysaccharide vaccine or a 7-valent pneumococcal-conjugate vaccine that links seven pneumococcal serotypes to the outer membrane protein complex of Neisseria meningitidis. PATIENTS: 144 patients who had completed treatment for Hodgkin disease, which had been diagnosed at least 2 years before the study. MEASUREMENTS: Antigen-specific antibody concentrations before and 3 to 6 weeks after immunization; number of persons who achieved anti-HIB antibody concentrations considered to be in the protective range. RESULTS: The geometric mean anti-HIB antibody concentration increased from 1.79 micrograms/mL before immunization to 54.1 micrograms/mL after; the percentage of persons with antibody concentrations in the protective range increased from 62% before immunization to 99% after. Patients immunized with 23-valent pneumococcal vaccine had a geometric mean pneumococcal antibody concentration after immunization (9.15 micrograms/mL) that was similar to that of healthy controls (10.0 micrograms/mL) for the seven serotypes measured. In contrast, patients who received 7-valent pneumococcal-conjugate vaccine had a significantly lower mean response compared with patients who received 23-valent; their geometric mean antibody concentration after immunization was 4.95 micrograms/mL (P = 0.005). CONCLUSION: A single dose of HIB-conjugate vaccine was immunogenic in patients who had completed treatment for Hodgkin disease diagnosed at least 2 years before immunization. In addition, responses to the 23-valent pneumococcal and 4-valent meningococcal vaccines were equivalent to those seen in healthy controls. Finally, patients had a significantly lower response to a single dose of 7-valent pneumococcal-conjugate vaccine than to 23-valent vaccine.	D. C. Molrine, S. George, N. Tarbell, P. Mauch, L. Diller, D. Neuberg, R. C. Shamberger, E. L. Anderson, N. R. Phillips, K. Kinsella and D. M. Ambrosino	Annals of internal medicine
144	5 versus 10 days of treatment with ceftriaxone for bacterial meningitis in children: a double-blind randomised equivalence study	BACKGROUND: Bacterial meningitis is an important cause of morbidity and mortality in developing countries, but the duration of treatment is not well established. We aimed to compare the efficacy of 5 and 10 days of parenteral ceftriaxone for the treatment of bacterial meningitis in children.METHODS: We did a multicountry, double-blind, placebo-controlled, randomised equivalence study of 5 versus 10 days of treatment with ceftriaxone in children aged 2 months to 12 years with purulent meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae type B, or Neisseria meningitidis. Our study was done in ten paediatric referral hospitals in Bangladesh, Egypt, Malawi, Pakistan, and Vietnam. We randomly assigned children who were stable after 5 days of treatment, through site-balanced computer-generated allocation lists, to receive a further 5 days of ceftriaxone or placebo. Patients, their guardians, and staff were masked to study-group allocation. Our primary outcomes were bacteriological failure or relapse. Our analysis was per protocol. This study is registered with the International Standard Randomised Controlled Trial Number Register, number ISRCTN38717320.FINDINGS: We included 1004 of 1027 children randomly assigned to study groups in our analyses; 496 received treatment with ceftriaxone for 5 days, and 508 for 10 days. In the 5-day treatment group, two children (one infected with HIV) had a relapse; there were no relapses in the 10-day treatment group and there were no bacteriological failures in either study group. Side-effects of antibiotic treatment were minor and similar in both groups.INTERPRETATION: In children beyond the neonatal age-group with purulent meningitis caused by S pneumoniae, H influenzae type b, or N meningitidis who are stable by day 5 of ceftriaxone treatment, the antibiotic can be safely discontinued.FUNDING: United States Agency for International Development.	E. Molyneux, S. Q. Nizami, S. Saha, K. T. Huu, M. Azam, Z. A. Bhutta, R. Zaki, M. W. Weber and S. A. Qazi	Lancet
290	The outcome of non-typhoidal salmonella meningitis in Malawian children, 1997-2006	INTRODUCTION: The clinical course and outcome of non-typhoidal salmonella (NTS) meningitis in Malawian children over a 10-year period (1997-2006) is described. METHODS: Demographic, clinical and laboratory data were collected for all children over 2 months of age admitted with salmonella meningitis to Queen Elizabeth Central Hospital from 1997 to 2006. In the 1st year, salmonellae were susceptible to chloramphenicol, and children received 2 weeks of chloramphenicol treatment. When NTS resistance to chloramphenicol started to appear in 1998, treatment was changed to ceftriaxone. From 2002, the duration of antibiotic therapy was extended to 4-weeks which included 2 weeks of intravenous ceftriaxone and a further 2 weeks of oral ciprofloxacin. RESULTS: The in-hospital case fatality rate (CFR) was 52.3% (48.2% until 2002 and 53.9% after prolonged antibiotic therapy was introduced). Of the survivors, one in 12 (8.3%) became completely well (sequelae-free) in the period 1997-2001 while 18 of 31 survivors (58.1%) made a complete recovery during 2002-2006 (p<0.01). After the 4-week course of antimicrobial therapy was introduced, the number of relapses or recurrences fell from nine in 15 (60%) survivors treated with chloramphenicol or ceftriaxone to three in 35 (8.7%) survivors who received 4 weeks of antibiotics (p<0.0001). CONCLUSION: In Malawi, salmonella meningitis has a CFR of approximately 50%, which has remained constant over many years. Residual morbidity, however, has decreased over 10 years, despite rising numbers of multi-drug-resistant cases of NTS. This improvement might be owing to better treatment and management and/or reduced pathogenicity of the multi-drug-resistant bacteria.	E. M. Molyneux, L. A. Mankhambo, A. Phiri, S. M. Graham, H. Forsyth, A. Phiri, A. L. Walsh, L. K. Wilson and M. E. Molyneux	Annals of tropical paediatrics
657	Ineraid cochlear implant in the ossified cochlea: surgical techniques and results	Extensive ossification of the cochlea is a common finding in patients with total deafness caused by meningitis, labyrinthitis, or otosclerosis. When the cochlea is totally ossified, the prognosis for achieving free-running speech without lip reading is poor. However, subtotal ossification with residual cochlear patency in the upper basal turn, the middle turn, or the apical turn can be maximally exploited by selective insertion of electrodes. Results can be surprisingly adequate in spite of the poor anatomic conditions. Computed tomography and exploratory cochleotomy, in which electrically evoked auditory brainstem responses are elicited and recorded by intracochlear stimulation are good diagnostic indicators of ossification and residual auditory nerve excitability. "Apical cochleostomy" is an adequate procedure to help penetrate the basal turn in retrograde insertion of the cochlear implant electrode array. Results of this study indicate that the surgical technique and placement of the Ineraid electrode array play a major role in the ability of the patient to achieve understanding of free-running speech.	P. B. Montandon, C. Boëx and M. Pelizzone	The American journal of otology
275	The efficacy of fluconazole 600 mg/day versus itraconazole 600 mg/day as consolidation therapy of cryptococcal meningitis in AIDS patients	UNLABELLED: Cryptococcal meningitis is one of the major complications affecting the central nervous system of patients suffering from AIDS. The results of treatment, when following current recommendation are still unsatisfactory. OBJECTIVE: This study aimed to evaluate the efficacy of a higher than recommended dose of oral fluconazole and itraconazole as consolidation therapy for cryptococcal meningitis in AIDS patients. DESIGN AND METHOD: HIV infected patients with primary cryptococcal meningitis, who had been treated initially with amphotericin B for 2 weeks were included in this study. They were randomized into two groups, to receive either fluconazole 600 mg daily or itraconazole 600 mg daily for 10 weeks. The response towards the two different treatments was clinically defined to be successful, if after 10 weeks of treatment no clinical symptoms and signs of meningitis remained and the cerebrospinal fluid (CSF) fungal culture was negative. RESULTS: The trial was performed from April 1999 to April 2000 at Srinagarind Hospital, Khon Kaen, Thailand. At the beginning of the trial 44 cases were selected, but only 35 patients proved to be suitable for the final evaluation of the study. Out of those, 19 cases were assigned to the fluconazole and 16 cases to the itraconazole group. Ten weeks after treatment, all patients clinically recovered completely. The CSF sterilization rate for the fluconazole group and for the itraconazole group were 100 and 94 per cent respectively. The Fisher's exact test showed no significant difference in the CSF sterilization rate between both groups (p = 0.26). CONCLUSION: The result of this study indicates that treatment with either 600 mg per day of fluconazole or itraconazole as consolidation treatment have the same efficacy for AIDS patients suffering from cryptococcal meningitis. The results of this study also suggest, comparing the result of this trial with the results of similar trials published somewhere else, that treatment with the higher doses may be superior to treatment regimens using lower doses, as can be judged from the clinical outcome and the results of the mycological cultures.	P. Mootsikapun, P. Chetchotisakd, S. Anunnatsiri and K. Choksawadphinyo	Journal of the Medical Association of Thailand = Chotmaihet thangphaet
365	[The vaccine against meningococcal B disease]		B. Mørland	Tidsskrift for den Norske lægeforening : tidsskrift for praktisk medicin, ny række
493	Damaged hearing in Meningitides under treatment with Ampicillin		W. Mortier, G. Stemman and G. Esser	Monatsschrift fur Kinderheilkunde
656	[Pharmacokinetic, bacteriological and clinical studies on cefozopran in the pediatric field]	Cefozopran (CZOP, SCE-2787), a newly developed parenteral cephem antibiotic, was administered to children with bacterial infections. We determined its antibacterial activity, pharmacokinetics, efficacy and safety in these patients. 1. Antibacterial activity MICs of cefmetazole, ceftazidime, cefuzonam, flomoxef and CZOP were determined against a total of 19 strains. For Gram-positive cocci, MICs of CZOP ranged from 0.39 to 0.78 microgram/ml against Staphylococcus aureus (3 strains), from 0.05 to 6.25 micrograms/ml against Streptococcus pneumoniae (5 strains), and 12.5 micrograms/ml against Enterococcus faecalis (1 strain). These MICs were generally similar to those of other cephems, but the MIC of CZOP against E. faecalis was lower than those of the other cephems examined. For Gram-negative bacilli, MICs of CZOP were 25 micrograms/ml against Citrobacter freundii (1 strain), and 6.25 micrograms/ml against Pseudomonas aeruginosa (1 strain). These values were similar to or lower than those of other cephems, MICs of CZOP against Haemophilus influenzae (7 strains) ranged from 0.1 to 0.39 microgram/ml. However, the MIC of CZOP against Serratia marcescens (1 strain) was higher than 100 micrograms/ml, and CZOP was as ineffective as the other cephems against this organism. 2. Pharmacokinetics CZOP was administered to children at 20 or 40 mg/kg via intravenous injection, and determinations were made for its serum concentrations, urinary concentrations and concentrations in cerebrospinal fluid (CSF) using the bioassay. Serum concentrations at 30 minutes after administration were 60.4 micrograms/ml with a dose of 20 mg/kg to one patient and 93.9 and 99.0 micrograms/ml with 40 mg/kg to two patients. The corresponding half-lives were 1.55 hours for 20 mg/kg administration, and 1.10 and 3.41 hours for 40 mg/kg, while the AUCs were 136.5 micrograms.hr/ml for 20 mg/kg, and 194.4 and 264.5 micrograms.hr/ml for 40 mg/kg. The rates of urinary recovery in the first 8 hours after administration were 45.0% in the patient receiving 20 mg/kg, and 84.6 and 97.6% in the two patients receiving 40 mg/kg. The concentrations in the CSF determined in 3 patients with purulent meningitis ranged from 2.6 to 16.0 micrograms/ml 1 hour after administration, and the CSF/serum concentration ratio ranged from 6.5 to 39.0%. These values for pharmacokinetic parameters obtained in the bioassay were similar to those obtained using HPLC. 3. Clinical evaluation Forty-eight patients were clinically evaluated. Of these patients, 75% were less than 3 years of age and there were slightly more male children than female children.(ABSTRACT TRUNCATED AT 400 WORDS)	T. Motohiro, S. Handa, S. Yamada, H. Sasaki, S. Oki, Y. Yoshinaga, K. Oda, M. Aramaki, Y. Sakata and F. Yamashita	The Japanese journal of antibiotics
526	[Basic and clinical study of meropenem in pediatric field]	Meropenem (MEPM), a novel parenteral carbapenem antibiotic, was examined in a cooperative study involving 12 pediatric and 1 neonatologic facilities. The results are summarized as follows. 1. Antibacterial activity Antibacterial activity of MEPM against stock organisms including 31 strains of Streptococcus agalactiae, 14 of Listeria monocytogenes, 4 of Bordetella pertussis and 3 of Neisseria meningitidis ranged from 0.025 to 0.10 micrograms/ml in MIC90's, which were equal or lower than those of control drugs such as imipenem cefazolin, cefotiam, cefotaxime, ceftazidime and latamoxef. MICs against clinical isolates were as follows: In Gram-positive bacteria, MICs were 0.20 micrograms/ml to 6.25 micrograms/ml against 3 strains of Staphylococcus aureus, and 0.025 micrograms/ml or less against 4 of Streptococcus pneumoniae. In Gram-negative bacilli, MICs were 0.10 micrograms/ml to 0.20 micrograms/ml against 3 strains of Haemophilus influenzae and 0.78, 0.10 and 0.78 micrograms/ml, respectively, against one strain each of Enterobacter cloacae, Morganella morganii and Pseudomonas aeruginosa. MIC against 1 strain of Peptococcus saccharolyticus was < or = 0.025 micrograms/ml. 2. Pharmacokinetics Maximum plasma concentrations after intravenous infusion of MEPM over 30 minutes at doses of 10, 20 and 40 mg/kg, respectively, to 3 different groups of 3 children (total 9 cases) were observed at the completion of the treatment. Mean maximum concentrations in the 3 groups were 36.3, 69.5 and 129.8 micrograms/ml, respectively, exhibiting clear dose response. Mean plasma half lives in beta phase were 0.94, 0.86 and 0.94 hours, respectively, exhibiting no difference by doses, and this trend was observed also by HPLC. Urinary excretion rates in the first 6 hours after dose in the 10, 20 and 40 mg/kg groups were 67.3, 65.6 and 68.4%, respectively. Concentrations of MEPM in cerebrospinal fluid were determined in 2 cases of pyogenic meningitis. In 1 case, 500 mg (5.9 mg/kg) of MEPM was infused intravenously over 30 minutes and concentrations on Days 6, 8 and 15 observed at 190, 60 and 100 minutes after respective doses were 0.13, 0.10 micrograms/ml and less than the detection limit. Cerebrospinal fluid-plasma concentration ratio was determinable only on Day 8 and was 2.8%. In another case to which 250 mg (38.5 mg/kg) of MEPM was infused intravenously over 30 minutes, the concentration at Days 6, 7 and 10, 1 hour after the dose were less than the detection limit on day 6, and 2.04 and 2.62 micrograms/ml, respectively on days 7 and 10. 3. Clinical efficacy Clinical efficacies were evaluated in 49 cases and the efficacy rate was 93.9%.(ABSTRACT TRUNCATED AT 400 WORDS)	T. Motohiro, S. Oki, N. Tsumura, H. Sasaki, K. Oda, T. Koga, Y. Sakata, F. Yamashita, N. Takajo and K. Aida	The Japanese journal of antibiotics
523	[Fundamental and clinical studies of sulbactam/cefoperazone in the pediatric field]	To 6 cases of children in 2 groups of 3 each, newly developed sulbactam/cefoperazone (SBT/CPZ) was given at 20 and 40 mg/kg by intravenous bolus injection, respectively, and the serum and urinary concentrations and recoveries of SBT and CPZ were determined. To 1 case of purulent meningitis, this drug was given at 40 mg/kg by intravenous bolus injection, and the cerebrospinal fluid and serum concentrations of SBT and CPZ were determined. Susceptibility tests to SBT/CPZ and CPZ of total 289 strains were conducted; Gram-positive cocci tested consisted of 26 S. aureus strains, 20 S. pyogenes strains and 21 S. pneumoniae strains, and Gram-negative bacilli consisted of 24 H. influenzae strains, 22 E. coli strains, 26 K. pneumoniae strains, 24 E. cloacae strains, 21 E. aerogenes strains, 19 Citrobacter sp. strains, 20 S. marcescens strains, 23 P. mirabilis strains, 23 indole-positive Proteus sp. strains and 20 P. aeruginosa strains. SBT/CPZ was given to total 43 cases at a mean daily dosage of 80.4 mg/kg, in 3 or 4 divided doses (6 cases in 3 and 37 cases in 4), 1 case receiving the drug by drip infusion over 30 minutes (in 3 divided doses) and all the other 42 cases by intravenous bolus injection, for 7 days on an average. They consisted of 2 cases of tonsillitis, 1 case of otitis media, 1 case of otitis media associated with mastoiditis, 30 cases of pneumonia, 1 case of suspected septicemia, 1 case of purulent meningitis, 5 cases of urinary tract infection, 1 case of purulent lymphadenitis and 1 case of submaxillaritis. And the clinical and bacteriological effects were evaluated. Also, side reactions and laboratory examinations for abnormal values due to administration of this drug were made on 47 cases including 4 drop-outs. The following results were obtained: After administration of this drug to 2 groups of 3 children each at 20 and 40 mg/kg by intravenous bolus injection, mean serum concentrations of both SBT and CPZ reached the peaks in 5 minutes; SBT levels were 60.9 and 124.7 micrograms/ml for the 2 groups and CPZ levels were 105.0 and 214.1 micrograms/ml, respectively. In either group, CPZ levels were 1.7 times as high as SBT levels, and there was observed a dose-response in both. In the 20 mg/kg group, mean half-lives of SBT and CPZ were 0.96 and 1.24 hours, respectively, and in the 40 mg/kg group, they were 1.01 and 1.32 hours, CPZ values tending to be longer.(ABSTRACT TRUNCATED AT 400 WORDS)	T. Motohiro, K. Tanaka, T. Koga, Y. Shimada, N. Tomita, Y. Sakata, T. Fujimoto, T. Nishiyama, K. Ishimoto and K. Tominaga	The Japanese journal of antibiotics
195	Evaluation of the indirect effects of a pneumococcal vaccine in a community-randomized study	When a sufficiently high proportion of a population is immunized with a vaccine, reduction in secondary transmission of disease can confer significant protection to unimmunized population members. We propose a straightforward method to estimate the degree of this indirect effect of vaccination in the context of a community-randomized vaccine trial. A conditional logistic regression model that accounts for within-randomization unit correlation over time is described, which models risk of disease as a function of community-level covariates. The approach is applied to an example data set from a pneumococcal conjugate vaccine study, with study arm and immunization levels forming the covariates of interest for the investigation of indirect effects.	L. H. Moulton, K. L. O'Brien, R. Reid, R. Weatherholtz, M. Santosham and G. R. Siber	Journal of biopharmaceutical statistics
472	Immunogenicity and safety of a NeuGcGM3 based cancer vaccine: results from a controlled study in metastatic breast cancer patients	Increased levels of NeuGc-containing gangliosides have been described in human breast cancer. A controlled Phase II clinical trial was conducted in patients with metastatic breast cancer to evaluate immunogenicity, safety and to identify evidences of biological activity of a cancer vaccine composed by NeuGcGM3 in a proteoliposome of Neisseria meningitidis together with Montanide ISA 51 as adjuvant. After first line czhemotherapy, 79 women were randomized 1:1 to receive the vaccine candidate or best supportive care. All patients achieved at least stable disease to the first line therapy for the metastatic condition. Treatment consisted on 5 vaccine doses every 2 weeks and then, monthly re-immunization to complete 15 doses. Vaccination with the NeuGcGM3 based vaccine was safe and the most frequent adverse events consisted on injection site reactions, fever, arthralgia and chills. The vaccine was immunogenic and a sustained increase of both IgG and IgM antibody titters against NGcGM3 was observed after the second vaccination month. Antibodies were able to recognize the NeuGcGM3+ murine tumor cell line L1210 and the myeloma cell line P3X63. Humoral response was specific since vaccination did not result in Neu-Acetyl GM3 or GM2-antibody response. Hyperimmune sera from vaccinated patients were able to prevent the NeuGcGM3 mediated CD4 down-modulation on T lymphocytes. In the intent to treat analysis, there was a trend toward a survival advantage for the vaccine group and this effect was significant for women bearing non-visceral metastasis. Two phase III clinical studies with this vaccine candidate are ongoing. 2010 Landes Bioscience.	V. Mulens, A. Torre, P. Marinello, R. Rodriguez, J. Cardoso, R. Diaz, M. O'Farrill, A. Macias, C. Viada, G. Saurez, A. Carr, T. Crombet, Z. Mazorra, R. Perez and L. E. Fernandez	Human Vaccines
562	Safety and immunogenicity of Haemophilus influenzae type B-Neisseria meningitidis group B outer membrane protein complex conjugate vaccine mixed in the syringe with diphtheria-tetanus-pertussis vaccine in young Gambian infants	To ensure compliance and to reduce costs it is important, especially in less developed countries, that programs of child immunization should require as few clinic attendances and as few injections as possible. Therefore we have investigated whether a Haemophilus influenzae type b conjugate vaccine could be given safely and effectively with diphtheria-tetanus-pertussis vaccine (DTP). One hundred twenty-six Gambian infants were given both polyribosylribitol phosphate (PRP)-outer membrane protein complex (PedvaxHIB) and DTP on the same day at 8, 12 and 16 weeks of age; 60 were given the vaccines mixed in the syringe and 66 were given the vaccines separately. To minimize the injection volume the dose of PRP-OMPC used in both groups was 7.5 micrograms, which is half the usual dose. There were no significant differences in anti-PRP antibody titers between the groups after 1, 2 or 3 doses. The geometric mean titers of antibody for the two groups combined were 0.29 micrograms/ml 1 month after the first dose, 1.03 micrograms/ml after the second dose and 1.11 micrograms/ml after the third dose. Concentrations of antibodies to diphtheria, tetanus and pertussis 1 month after the third dose were not significantly different between the two groups. Systemic side effects were reported with equal frequency in the two groups and were similar to those reported elsewhere for DTP. Tenderness at the injection site was more common where the combined injection (0.75 ml) had been given than where DTP alone (0.5 ml) had been given. The main drawback to the use of these 2 vaccines together is the complexity of the mixing procedure used in this clinical trial.	E. K. Mulholland, V. I. Ahonkhai, A. M. Greenwood, L. C. Jonas, L. J. Lukacs, C. M. Mink, J. M. Staub, J. Todd, P. P. Vella and B. M. Greenwood	The Pediatric infectious disease journal
391	Randomised trial of Haemophilus influenzae type-b tetanus protein conjugate for prevention of pneumonia and meningitis in Gambian infants	Background. In developing countries, pneumonia and meningitis due to Haemophilus influenzae type b (Hib) are common in children under age 12 months and the mortality from meningitis is high. Protein-polysaccharide conjugate vaccines have brought Hib disease under control in industrialised countries. We did a double-blind randomised trial in The Gambia to assess the efficacy of a Hib conjugate vaccine for the prevention of meningitis, pneumonia, and other invasive diseases due to Hib. Methods. Between March, 1993, and October, 1995, 42,848 infants were randomly allocated the conjugate vaccine Hib polysaccharide tetanus protein (PRP-T) mixed with diphtheria-tetanus-pertussis vaccine (DTP), or DTP alone at age 2 months, 3 months, and 4 months. Children who presented with signs of invasive Hib were investigated by blood culture and, where appropriate, by lumbar puncture, chest radiograph, or percutaneous lung aspirate. Children were followed up for between 5 and 36 months. Findings. The median ages at which children received the study vaccine were 11 weeks, 18 weeks, and 24 weeks. 83% of children enrolled received all three doses of vaccine. 17 cases of culture-positive Hib pneumonia, 28 of Hib meningitis, and five of other forms of invasive Hib disease were detected amongst the study children. The efficacy of the vaccine for the prevention of all invasive disease after three doses was 95% (PRP-T vaccinees 1, controls 19 (95% CI 67-100)), for the prevention of Hib pneumonia after two or three doses, 100% (vaccinees 0, controls 10 (55-100)), and for the prevention of radiologically defined pneumonia at any time after enrolment, 21.1% (PRP-T vaccinees 198, controls 251 (4.6-34.9)). Interpretation. PRP-T conjugate Hib vaccine prevented most cases of meningitis and pneumonia due to Hib in Gambian infants. The reduction in the overall incidence of radiologically defined pneumonia in PRP-T vaccinees suggests that about 20% of episodes of pneumonia in young Gambian children are due to Hib. The introduction of Hib vaccines into developing countries should substantially reduce childhood mortality due to pneumonia and meningitis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	K. Mulholland, S. Hilton, R. Adegbola, S. Usen, A. Oparaugo, C. Omosigho, M. Weber, A. Palmer, G. Schneider, K. Jobe, G. Lahai, S. Jaffar, O. Secka, K. Lin, C. Ethevenaux and B. Greenwood	Lancet
240	Relationship between short-term outcome and occurrence of cerebral artery stenosis in survivors of bacterial meningitis	To evaluate the influence of cerebral artery stenosis on the outcome of patients with bacterial meningitis we examined prospectively 47 consecutive patients [33 men, 14 women, mean (SD) age, 53 (17) years, range 18-81] with bacterial meningitis caused by various bacterial pathogens. The patients were examined with the use of the Glasgow Coma Scale (GCS) on days 1, 3, 5, 8, 14 and with the use of the Glasgow Outcome Scale (GOS) on day 21 after admission. In addition, focal cerebral signs were recorded separately. At each clinical examination, the patients underwent transcranial Doppler sonography recordings of the mean blood velocity (MBV) and the pulsatility index in all of the main intracranial arteries and in the submandibular internal carotid artery (ICA). A stenosis of the middle cerebral artery (MCA) was diagnosed by an MBV of > or = 120 cm/s or by an MBV ratio > 3 between the MCA and the ICA. An anterior cerebral artery (ACA) stenosis was indicated by an MBV > or = 100 cm/s, a posterior cerebral artery (PCA) stenosis by an MBV of > or = 85 cm/s, and a basilar artery (BA) stenosis by an MBV of > or = 95 cm/s. Twenty-five patients developed stenosis of the cerebral arteries (apart from 1, all within 8 days), 22 patients remained without stenosis. Of 29 focal cerebral signs, 27 occurred within 8 days. For outcome analysis, outcome was classified into two groups: not handicapped (GOS 5) versus handicapped (GOS 2-4) and dead (GOS 1). Based on the disease course up to day 8, risk factors for a handicapped/dead outcome after day 8 were advancing age (odds ratio per year, 1.06; 95% confidence interval (CI), 1.01-1.11; P = 0.03) and the presence of arterial stenosis (odds ratio, 7.3; 95% CI, 1.1-45) using a multivariate logistic regression analysis model. GCS on day 1, cerebrospinal fluid total protein content and the presence of focal cerebral signs were not significantly related to outcome in this series. The patients with stenosis exhibited significantly more frequently a poorer GCS on days 1-5 (Mann-Whitney U test; P < 0.05). In conclusion, the early occurrence of stenosis of the cerebral arteries in bacterial meningitis predicted a worse clinical course of the disease and a poorer short-term outcome of the survivors.	M. Müller, S. Merkelbach, M. Hermes, J. König and K. Schimrigk	Journal of neurology
191	[Nitric oxide (NO) in children with meningitis]	Twenty seven children with a documented bacterial (BM)-, 73 with viral (mumps and enteroviral) meningitis and 51 controls were included. CSF white blood cell counts, glucose and protein concentrations were determined routinely. CSF nitrite and nitrate levels (the stable degradation product of NO) were determined by a modified Griess reaction. The mean +/- levels of nitrite and nitrate in CSF on admission were higher in patients with BM in comparison with controls and in children with viral meningitis. In 10 patients dexamethasone therapy was started about 10 minutes before the first antibiotic dose and given every 12 hours of 0.4 mg/kg for 2 days. At 24 to 48 hours those who received dexamethasone therapy had a significantly lower mean +/- SD CSF nitrite concentration compared with that in non-steroid treated patients. In all patients with meningitis a significant positive correlation was found between CSF nitrite and CSF granulocyte counts and also CSF protein concentration. Increased production of NO in the CSF compartment during the acute phase of BM may contribute to the inflammatory process and tissue injury. Dexamethasone therapy administered before the first parenteral antibiotic dose reduces the production of NO in the CSF during BM.	E. Murawska, Z. Szychowska and B. Trebusiewicz	Przegla?d epidemiologiczny
220	Remission maintenance therapy for meningeal leukaemia: intrathecal methotrexate and dexamethasone versus intrathecal craniospinal irradiation with a radiocolloid	Thirty-two patients with meningeal leukaemia who achieved meningeal remission with intrathecal methotrexate (MTX) plus dexamethasone (DMT) were entered in a randomized study of two maintenance treatments: (a) I6 patients received intermittent intrathecal doses of MTX plus DMT, and (b) I6 patients received intermittent intrathecal doses of radioactive chromic phosphate (CROP). The population and clinical characteristics of the cases assigned to each maintenance regimen were similar. The duration of meningeal remission was 55-600 + d (median 550 d) for the MTX and DMT group and 56-555 d (median 360 d) for the CROP group. There was no statistical difference (P greater than 0.05) between the curves of the two groups. Intrathecal CROP seems to be as effective as intrathecal MTX plus DMT as maintenance treatment for intrathecal MTX plus DMT induced meningeal remission. Further uses of this compound should be explored but it seems to be dangerous to administer it by lumbar puncture.	F. S. Muriel, D. Schere, A. Barengols, M. Eppinger-Helft, J. L. Braier, S. Pavlovsky, G. H. Macchi and L. Guman	British journal of haematology
618	The benefits of the very early introduction of powdered rice and dried edible seeds (Dal moong) in the oral rehydration solution during the treatment of acute infectious diarrhoea of infancy	We have examined whether the addition of powdered rice and pulses (Dal moong) to oral rehydration solution will decrease the purging rate and thereby increase the efficacy of the oral rehydration therapy. The study was carried out on 60 male infants, with acute watery diarrhoea, moderate dehydration but without fever, vomiting, or other conditions like septicaemia and meningitis. The infants were treated with either the standard WHO oral rehydration salt solution (ORS) or with a modified solution where glucose was removed and powdered rice and Dal moong were added. We found that the infants receiving ORS with powdered rice and Dal moong had significantly lower fluid losses in the stools, a significant and more rapid weight gain, and needed significantly less fluid than the infants receiving ORS only.	A. Murtaza, I. Zulfiqar, S. R. Khan, B. S. Lindblad, B. A. Sahlgren and A. Aperia	Acta paediatrica Scandinavica
248	Initial and subsequent response to pneumococcal polysaccharide and protein-conjugate vaccines administered sequentially to adults who have recovered from pneumococcal pneumonia	BACKGROUND: Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) for adults at high risk for pneumococcal disease. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), and immunologic "priming" with PCV followed by "boosting" with PPV in adults who had recovered from pneumococcal pneumonia.METHODS: Subjects received PPV followed by PCV 6 months later, or vice versa. The levels of IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline and at 4-8 weeks and 6 months after each vaccination.RESULTS: PPV and PCV stimulated similar IgG levels and OPK at 4-8 weeks after vaccination. Six months after receipt of PPV, the antibody levels declined to baseline but remained modestly elevated after receipt of PCV. PCV administered 6 months after PPV stimulated modest increases in IgG level that failed to reach the peaks observed after receipt of PPV. In contrast, PPV administered 6 months after PCV caused dramatic increases in the levels of IgG and OPK for all polysaccharides at 4-8 weeks, consistent with a booster effect. Six months after receipt of the second vaccination, however, levels of IgG and OPK fell precipitously in all patients, approaching baseline levels.CONCLUSIONS: In these high-risk subjects who have recovered after treatment for pneumonia, the effect of PPV is short-lived; PCV stimulates a more prolonged response. The use of PPV as a booster following PCV causes early increases in antibody levels, but the level of IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.	D. M. Musher, A. M. Rueda, M. H. Nahm, E. A. Graviss and M. C. Rodriguez-Barradas	The Journal of infectious diseases
97	Increased endotoxin and interleukin-1 beta concentrations in cerebrospinal fluid of infants with coliform meningitis and ventriculitis associated with intraventricular gentamicin therapy	Intraventricular gentamicin therapy in infants with gram-negative enteric bacillary meningitis and ventriculitis is associated with increased mortality. Therefore, endotoxin, interleukin-1 beta, and cachectin (tumor necrosis factor) concentrations in ventricular cerebrospinal fluid from 21 infants (11 received intravenous antibiotics alone and 10 received intraventricular gentamicin also) were determined and correlated with outcome and other ventricular cerebrospinal fluid indexes of inflammation. Mean interleukin-1 beta concentrations in ventricular cerebrospinal fluid correlated significantly with adverse outcome and with mean concentrations of endotoxin, white blood cells, and protein and inversely with glucose concentrations. Mean and peak endotoxin and interleukin-1 beta concentrations were significantly higher in infants who received intraventricular gentamicin and intravenous antibiotics than in infants given intravenous antibiotics alone. Intraventricular gentamicin may have caused release of endotoxin from gram-negative bacilli in ventricular cerebrospinal fluid, resulting in increased interleukin-1 beta concentrations and inflammation, which could have contributed to the poor outcome in these patients.	M. M. Mustafa, J. Mertsola, O. Ramilo, X. Sáez-Llorens, R. C. Risser and G. H. McCracken	The Journal of infectious diseases
411	Prostaglandins E2 and I2, interleukin 1-beta, and tumor necrosis factor in cerebrospinal fluid in infants and children with bacterial meningitis		M. M. Mustafa, O. Ramilo, X. Saez-Llorens, J. Mertsola, R. R. Magness and G. H. McCracken	Pediatric Infectious Disease Journal
232	Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants with human immunodeficiency virus type 1 infection	OBJECTIVE: Heptavalent pneumococcal conjugate vaccine (PCV) has been shown to be safe and effective in healthy infants and children. However, little is known about its use in children who have human immunodeficiency virus (HIV) infection and are known to be at increased risk of developing pneumococcal infections. This study was conducted to evaluate the safety and immunogenicity of heptavalent PCV in infants with HIV infection. METHODS: The Pediatric AIDS Clinical Trials Group Study 292 Team randomized infants with HIV infection 2:1 to receive heptavalent PCV or placebo in a double-blinded manner. Infants were vaccinated with 3 doses at 2-month intervals, starting at ages 56 to 180 days. A booster dose was given at 15 months of age. Immunogenicity was evaluated after the third dose of vaccine, before and after the booster dose, and at 24 months of age. RESULTS: Thirty infants with HIV infection received PCV, and 15 received placebo. No differences in baseline characteristics were found across arms. Five severe acute reactions were experienced by 4 subjects: 3 in the PCV arm and 1 in the placebo arm; all occurred among subjects with symptomatic disease at study entry. No differences were found in the 2 arms with respect to the number or timing of new diagnoses through 24 months of age, including diagnoses of otitis media. However, when symptomatic subjects were examined separately, the first new diagnosis occurred more rapidly among PCV recipients. Three deaths, all judged to be unrelated to study vaccine, occurred during follow-up: 2 in the PCV arm and 1 in the placebo arm. The primary immunogenicity measures were based on composites of 4-fold changes in serotype-specific immunoglobulin G titers from preimmunization levels. We found a highly significant difference between the vaccine and placebo arms, with the PCV arm showing higher rates of response. Asymptomatic and symptomatic subjects who received PCV had similar immunologic responses for all serotypes. CONCLUSIONS: This study demonstrates that heptavalent PCV was well tolerated and not associated with vaccine-associated adverse reactions. Most important, this vaccine was immunogenic in the infant with HIV infection. However, additional studies of this vaccine (or others) must pay special attention to patients with symptomatic HIV disease, as they seem to be at higher risk for adverse events to any antigen.	S. Nachman, S. Kim, J. King, E. J. Abrams, D. Margolis, A. Petru, W. Shearer, E. Smith, J. Moye, S. Blanchard, E. Hawkins, P. Bouquin, P. Vink, M. Benson, S. Estep and F. Malinoski	Pediatrics
395	Human T-cell responses after vaccination with the Norwegian group B meningococcal outer membrane vesicle vaccine	We have analyzed human T-cell responses in parallel with serum immunoglobulin G (IgG) antibody levels after systemic vaccination with the Norwegian group B Neisseria meningitidis outer membrane vesicle (OMV) vaccine. Ten adult volunteers, with no or very low levels of serum IgG antibodies against meningococci, received three doses intramuscularly of the OMV vaccine (at weeks 0, 6, and 46). T-cell proliferation against the OMV vaccine, purified outer membrane proteins (PorA and PorB), and control antigens (Mycobacterium bovis BCG vaccine and tetanus toxoid) was measured by thymidine incorporation of peripheral blood mononuclear cells before and after vaccination. The results showed that vaccination with OMV elicits strong primary and booster T-cell responses specific to OMV as well as the PorA (class 1) protein and significant, but markedly lower, responses against the PorB (class 3) protein. The median responses to OMV and PorA were 26 and 16 times the prevaccination levels, respectively. Most of the vaccinees showed low T-cell responses against OMV and PorA before vaccination, and the maximum T-cell responses to all vaccine antigens were usually obtained after the second vaccine dose. We found a positive correlation between T-cell responses and anti-OMV IgG antibody levels (r = 0.50, P < 0.0001, for OMV and PorA). In addition, we observed a progressive increase in the percentage of CD45R0+ (memory) CD4-positive T cells (P = 0.002). In conclusion, we have shown that the Norwegian OMV vaccine against meningococcal B disease induced antigen-specific T-cell responses, kinetically accompanied by serum IgG responses, and that vaccination increased the proportion of memory T-helper cells. [References: 37]. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	L. M. Naess, F. Oftung, A. Aase, L. M. Wetzler, R. Sandin and T. E. Michaelsen	Infection & Immunity
339	A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection	BACKGROUND AND PURPOSE: Shunt infection represents a particularly morbid condition, which can also result in mortality. In order to decrease the high morbidity and mortality rates, prevention is an essential step. The purpose of this study was to compare the prophylactic use of ceftriaxone and trimethoprim-sulfamethoxazole (SXT) for the prevention of ventriculoperitoneal (VP) shunt infection. METHODS: In this prospective, single-institution, randomized clinical trial, 107 children with hydrocephalus and an indication for shunting were randomly assigned to prophylaxis with ceftriaxone (n = 50) or SXT (55), each administered as a single dose during anesthesia and two divided doses postoperatively. Patients were followed up for at least one year. RESULTS: The mean age of patients was 15 months, and 85% were aged 6 months or younger. During the first postoperative year, meningitis occurred in 13.5% of patients receiving ceftriaxone and 14.5% of the SXT group, with no statistically significant difference between the groups. Younger age, presence of cerebrospinal fluid leakage and aqueductal stenosis as a cause of hydrocephalus showed significant correlation with meningitis occurrence on univariate analysis. However, only the latter 2 factors were associated with meningitis on multivariate analysis. The risk of shunt infection did not correlate with the gender of the patient, time of VP shunt surgery, or duration of hospitalization for shunting. CONCLUSION: Ceftriaxone and SXT showed similar efficacy in preventing shunt infection. Cerebrospinal fluid leakage before or after VP shunt placement and aqueductal stenosis were independent risk factors for meningitis after VP shunt.	F. Nejat, P. Tajik, M. Khashab, S. S. Kazmi, G. T. Khotaei and S. Salahesh	Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi
334	Treatment of Hemophilus influenzae meningitis: a comparison of chloramphenicol and tetracycline		K. E. Nelson, S. Levin, H. W. Spies and M. H. Lepper	The Journal of infectious diseases
28	[Therapeutic value of immunoglobulins in central nervous system infections]	From 218 patients aged 15 to 72 years suffering from inflammatory infectious diseases of the central nervous system, 162 patients were treated with high doses of immunoglobulins (Ig). The therapeutic results were compared with those of the 56 patients without an additive therapy, separately for bacterial and viral infections. If we compare recoveries and deaths or survivals but defective recoveries, the chi-square test reveals that treatment with Ig at the 0.1 percent level is superior to treatment without Ig in a highly significant manner in favor of the use of Ig. Using other criteria, such as the duration of fever and the length of hospital confinement, calculations using Student's t-test also show significant results in favor of Ig. Early beginning of therapy with high doses of Ig given intravenously, or if necessary intrathecally, proved to be of great therapeutic value in lowering the number of fatalities and defective recoveries.	I. Neu	Medizinische Klinik
441	Intravenous and intrathecal immune substitution in bacterial and viral infections of the central nervous system with gammaglobulins	The efficacy of additional intravenous and intrathecal immunoglobulin (Ig) therapy was investigated in a randomized clinical trial with 68 patients divided with the aid of a list of random numbers into two groups according to their infection. The group of bacterial infections of the CNS included 29 patients and the group of virus infections of the CNS 39 patients. The statistical evaluation of patients with bacterial infections and of those with virus infections was done separately. Group 1 received 10 g Ig each as a short infusion on two consecutive days. Patients with bacterial infections received in addition on every second day and patients with viral infections on every fifth day 500 mg of the same preparation by intrathecal injection. In contrast to this, a control group received the usual therapy only, principally antibiotics for purulent meningitis. The following characteristics were investigated and compared as variable criteria of the course of the disease and consequently of the efficacy of the additional therapy with Ig: CSF- cell count, CSF protein, pyrexia, general condition, paralyses, neuropsychological defects, vigilance and EEG recording. As overall criteria of the course of the disease the length of stay in hospital and the rise in temperature were considered. The results of the statistical analysis showed a statistically significant superiority for the Ig-treatment which was most marked in the regression of CSF pleocytosis, total CSF protein and pyrexia.For the subjectively- graded clinical evaluations, such as general condition, disturbances of vigilance, transient paralyses, neuropsychological defects and EEG tracings, the statistical significance still applied, even if not so pronounced as for the previously mentioned criteria. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	I. S. Neu and R. B. Pelka	Fortschr-Med
12	PCR of peripheral blood for diagnosis of meningococcal disease	Meningococcal disease is normally suspected on clinical grounds and is confirmed by isolation of Neisseria meningitidis bacteria from blood or cerebrospinal fluid or, more recently, by serology or PCR of cerebrospinal fluid. Achieving confirmation of a clinical diagnosis of meningococcal disease has become more difficult in the last few years. The pre-hospitalization administration of parenteral benzylpenicillin normally renders blood cultures sterile, and lumbar puncture is undertaken less frequently, especially in young children. We evaluated PCR for the detection of meningococcal DNA in 80 blood samples taken from patients with known or suspected meningococcal disease or from patients with other diagnoses (negative controls). Both the sensitivity and the specificity of the test were 100% for patients with confirmed cases of meningococcal disease when the blood buffy coat was used (83 to 100% sensitivity and 87 to 100% specificity with 95% confidence limits). Positive PCR results could be obtained from both blood buffy coat and serum samples. Sensitivity was unaffected by prior antibiotic treatment. PCR is a rapid, sensitive test that may be used to confirm a diagnosis of meningococcal disease by using peripheral blood samples. Introduction of this test into clinical laboratories may in some cases obviate the need for lumbar puncture to be performed on patients with suspected meningococcal disease. Our results demonstrate that a substantial number of cases of meningococcal disease are not confirmed by conventional techniques and remain undiagnosed. If the PCR test described here was widely applied, the number of cases of meningococcal disease ascertained might rise by as much as 60% greater than that recognized at present. It is likely that we are in a prevaccination era for meningococcal disease. Better case ascertainment is urgently required to assess the need for vaccines, to determine their costs and benefits, and to monitor their efficacies.	J. Newcombe, K. Cartwright, W. H. Palmer and J. McFadden	Journal of clinical microbiology
261	A randomized, double-blind, placebo-controlled trial of acetazolamide for the treatment of elevated intracranial pressure in cryptococcal meningitis	We conducted a trial of oral acetazolamide for the treatment of cryptococcal meningitis in 22 Thai adults with headache and an opening cerebrospinal fluid pressure of >/=200 mm H(2)0. The trial was terminated prematurely because patients who received acetazolamide developed significantly lower venous bicarbonate levels and higher chloride levels and had more-frequent serious adverse events than did subjects who received placebo.	P. N. Newton, H. Thai le, N. Q. Tip, J. M. Short, W. Chierakul, A. Rajanuwong, P. Pitisuttithum, S. Chasombat, B. Phonrat, A. N. W. Maek, R. Teaunadi, D. G. Lalloo and N. J. White	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
122	Pneumococcal conjugate vaccination in adults: circulating antibody secreting cell response and humoral antibody responses in saliva and in serum	The results from our previous study showed IgA dominated ASC responses to pneumococcal polysaccharide vaccine and to pneumococcal polysaccharide meningococcal outer membrane protein conjugate vaccine (PncOMPC) in adult volunteers. The results indicated that a high IgA ASC response is a useful indicator of a secretory IgA response in saliva. We believe that the mucosal immune responses is potentially an important characteristic of the pneumococcal vaccines and should thus be measured when the new pneumococcal conjugate vaccines are evaluated. In the present study, we studied two new tetravalent pneumococcal conjugate vaccines: the diphtheria toxoid and tetanus toxoid conjugates. In contrast to PncOMPC, these conjugates induced higher responses than the polysaccharide vaccine. Furthermore, the different structure of the two conjugate vaccines might affect the nature of the response. Thus a different vaccine may be optimal for induction of a mucosal response than is of systemic responses.	T. Nieminen, J. Eskola and H. Käyhty	Vaccine
139	[Immunoglobulins in the treatment of bacterial meningitis in childhood]	In a prospective, clinical study forty-four children with bacterial meningitis were treated with antibiotics and underwent a special intravenous treatment with 7-S-immunoglobulins. The children's age ranged between two days and thirteen years. Two of the children died. The other forty-two children did not show any signs of neurological deficiencies upon release from the hospital. The apparently improved prognosis, due to the immunoglobulin therapy, was confirmed by a retrospective study of thirty-six patients, that had an unfavorable prognosis of pneumococcal meningitis. All fourteen patients that had acquired pneumococcal meningitis, and had been treated with immunoglobulins, were clinically cured, whereas in comparison, the sixteen patients of the other group exhibited severe sequelae, and two of them died.	R. Noack, C. Szugs and H. Scholz	Infection
668	Inhaled budesonide for chronic wheezing under 18 months of age	The role of budesonide in controlling chest symptoms in infants was assessed. It was administered from a metered dose inhaler into a large volume spacer (Nebuhaler) with attached Laerdal mask. Twenty nine infants were recruited into a double blind crossover trial. Five defaulted. The remaining 24 (mean age 11 months) were assessed for the tolerance of the device, adverse effects, treatment failures, parental opinion, and daily symptom and treatment records. Twenty tolerated the modified Nebuhaler. One developed meningitis on placebo. Two experienced exacerbations on placebo. Eleven of 18 parents whose children completed the maximum treatment preferred budesonide to placebo and one preferred placebo. Mean symptom scores on budesonide were better than on placebo for the 15 children with complete symptom records. Fewer bronchodilator doses were used while taking budesonide. Our findings indicate that budesonide given in this way is an effective treatment for infants who may need prophylaxis for their wheezing.	V. Noble, N. R. Ruggins, M. L. Everard and A. D. Milner	Archives of disease in childhood
197	The Norwegian meningococcal group B outer membrane vesicle vaccine: side effects in phase II trials	In order to establish the safety of the Norwegian meningococcus B vaccine we have focused on detailed reporting of side effects in several phase II trials. We report here the results of the largest single phase II study, (step II-6) including 877 school children. The incidence of local side effects was significantly higher in the vaccine than in the placebo group, but most of them were mild and short-lasting. Mild systemic side effects were commonly reported in both groups, but more severe side effects were rare and almost equally distributed between the groups.	H. Nøkleby and B. Feiring	NIPH annals
412	A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine is immunogenic and induces immune memory when co-administered with DTPa-HBV-IPV and conjugate pneumococcal vaccines in infants	Immunogenicity and safety of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus-toxoid conjugate vaccine (Hib-MenCY-TT) candidate was evaluated when co-administered with DTPa-HBV-IPV(Pediarix)+PCV7(Prevnar) at 2-4-6 months of age. Anti-PRP concentrations >or= 1.0 microg/mL were observed in 92.9-98.7%, rSBA-MenC/Y titres >or= 1:8 in >98%, rSBA-MenC/Y titres >or= 1:128 in >95.8 and >89.9% subjects. PRP and MenC responses were similar to respective controls (ActHIB and Menjugate) including for antibody persistence. Response to co-administered vaccines was not impaired. Polysaccharide challenge (PRP, PSC, PSY at 11-14 months of age) evidenced immune memory was induced for Hib, MenC/Y conjugate components. The safety profile of Hib-MenCY-TT was similar to controls. Hib-MenCY-TT administered according to the current US Hib vaccine schedule has the potential to induce protective antibodies against Hib and meningococcal-CY disease in infants and toddlers.	T. Nolan, S. Lambert, D. Roberton, H. Marshall, P. Richmond, C. Streeton, J. Poolman and D. Boutriau	Vaccine
508	Immunogenicity and Reactogenicity of a Novel Haemophilus influenzae Type b-Meningococcal Serogroups C and Y Conjugate (Hib-MenCY-TT) Vaccine After a 3-Dose Primary Vaccination Series		T. Nolan, D. Roberton, P. Richmond, S. Waite, C. Streeton, G. Maechler and D. Boutriau	Pediatric Academic Societies Annual Meeting; 2006 April 29-May 2; San Francisco CA, United States
516	A Novel Haemophilus influenzae Type b Meningococcal Serogroups C and Y Conjugate (Hib-MenCY-TT) Vaccine Induces Persistent Immune Responses and Immune Memory		T. Nolan, D. Robertson, P. Richmond, S. Waite, C. Streeton, G. Maechler and D. Boutriau	Pediatric Academic Societies Annual Meeting; 2006 April 29-May 2; San Francisco CA, United States
548	Combining mortality, mycological and neurological measures in a study in the treatment of acquired immune deficiency syndrome associated cryptococcal meningitis [abstract]	29th Meeting of the Society of Clinical Trials; 2008 18-21 May; St Louis, USA.	T. Nolen, B. Eggleston, D. Wallace and P. Pappas	Clinical Trials
535	A Bayesian approach to a phase III study in the treatment of acquired immune deficiency syndrome associated cryptococcal meningitis [absttract]	28th Meeting of the Society for Clinical Trials; 2007 May 20-23; Montreal, Canada.	T. Nolen, D. Wallace, L. Zimmer and P. Pappas	Clinical Trials
477	Safety profile of meropenem: international clinical experience based on the first 3125 patients treated with meropenem	Data from 3125 patients (3220 patient exposures) treated with meropenem were compared with those from 2886 patients (2960 patient exposures) treated with a variety of comparator agents including cephalosporins (alone or in combination with aminoglycosides or an anti-anaerobe agent) and imipenem/cilastatin. Patients treated included those with bacterial infections of the lower respiratory tract, urinary tract and skin and soft tissues, abdominal, obstetric and gynaecological infections, meningitis, febrile episodes in neutropenic patients and paediatric patients with infections. In three studies, meropenem was administered intramuscularly; in the remainder, meropenem was given by 15-30 min iv infusion or by bolus injection over approximately 5 min. The usual dosages were 500 mg or 1 g 8 hourly in adults and 10 or 20 mg/kg 8 hourly in children. In bacterial meningitis, the meropenem dosage in adults was 2 g 8 hourly and 40 mg/kg 8 hourly in children. The overall pattern and frequency of adverse events with meropenem were similar to those of the other beta-lactam antibiotics with which it was compared. The most frequently reported adverse events were diarrhoea, rash, nausea and vomiting, thrombocytosis, eosinophilia and changes in hepatic biochemistry. Abnormal laboratory tests occurred with similar frequencies between meropenem and the comparator agents. The safety profile of meropenem was similar in adults and children, and the presence of renal impairment did not alter the safety profile of meropenem. Experience in clinical studies in 3220 patient exposures has revealed no unusual or unexpected toxicity. The possibility of administration by either iv infusion or bolus injection with a low incidence of nausea and vomiting also provides flexibility in the clinical management of patients. Moreover, the low incidence of reported seizures and good tolerability at high doses, make meropenem particularly useful for the treatment of meningitis and other indications which carry a risk of seizures, or in the treatment of serious infections where high doses of antibiotics are frequently indicated.	S. R. Norrby, P. A. Newell, K. L. Faulkner and W. Lesky	The Journal of antimicrobial chemotherapy
194	Salivary antibodies induced by the seven-valent PncCRM conjugate vaccine in the Finnish Otitis Media Vaccine Trial	We studied salivary antibodies induced by a seven-valent pneumococcal conjugate vaccine (PncCRM). Healthy Finnish children (n=115), a subcohort of the Finnish Otitis Media (FinOM) Vaccine Trial, were immunised either with the PncCRM or a control vaccine (hepatitis B) at the age of 2, 4, 6, and 12 months. Salivary IgG, IgA, IgA1, IgA2 and sIg for serotypes 6B, 14, 19F, and 23F were measured at 7 and 13 months of age, and IgG and IgA also at 4-5 years of age. The PncCRM could induce both salivary anti-Pnc polysaccharide IgG and IgA. However, by the age of 4-5 years IgA concentrations had increased in both groups and were similar. The increases in IgA concentrations were mostly of IgA1 subclass. The difference between the PncCRM and the control group was more notable for serotypes 6B, 14 and 23F than for serotype 19F. We could not find evidence for the development of mucosal immunologic memory after vaccination with the PncCRM.	A. Nurkka, M. Lahdenkari, A. Palmu and H. Käyhty	Vaccine
274	Salivary antibodies induced by the seven-valent PncOMPC conjugate vaccine in the Finnish Otitis Media Vaccine Trial	BACKGROUND: Mucosal antibodies have been suggested to have a role in defence against pneumococcal infections. We investigated here the ability of a seven-valent pneumococcal conjugate vaccine, PncOMPC, to induce mucosal immune response. METHODS: Healthy Finnish children (n = 111), a subcohort of the Finnish Otitis Media Vaccine Trial, were recruited and 56 of them were immunised with the PncOMPC at the age of 2, 4, and 6 months. At 12 months of age, 49 of them received the PncOMPC and 7 were vaccinated with the pneumococcal polysaccharide vaccine (PncPS) as a booster. The control group of 55 children received a hepatitis B vaccine at the same ages. Salivary anti-Pnc IgG, IgA, IgA1, and IgA2 antibodies to serotypes 6B, 14, 19F, and 23F were measured in both groups at the age of 7 and 13 months. RESULTS: Salivary anti-Pnc IgG and IgA were detected more often in the PncOMPC than in the control group. However, the difference between groups was significant only for 19F and 23F IgA concentrations at the age of 7 months. At the age of 13 months, antibody concentrations did not differ between PncOMPC and control groups. The rises in IgA concentrations between 7 and 13 months of age were mainly of subclass IgA1. Further, there is a clear trend that PncPS booster induces higher salivary anti-Pnc PS antibody concentrations than the PncOMPC. CONCLUSION: We found that PncOMPC can induce a mucosal IgA response. However, the actual impact of mucosal antibodies in protection against pneumococcal infections is not clear.	A. Nurkka, M. Lahdenkari, A. A. Palmu and H. Käyhty	BMC infectious diseases
295	Combination flucytosine and high-dose fluconazole compared with fluconazole monotherapy for the treatment of cryptococcal meningitis: a randomized trial in Malawi	BACKGROUND: Cryptococcal meningitis is a major cause of human immunodeficiency virus (HIV)-associated morbidity and mortality in Africa. Improved oral treatment regimens are needed because amphotericin B is neither available nor feasible in many centers. Fluconazole at a dosage of 1200 mg per day is more fungicidal than at a dosage of 800 mg per day, but mortality rates remain unacceptably high. Therefore, we examined the effect of adding oral flucytosine to fluconazole.METHODS: From 13 February through 2 December 2008, HIV-seropositive, antiretroviral-naive patients experiencing their first episode of cryptococcal meningitis were randomized to receive (1) 14 days of fluconazole (1200 mg per day) alone or (2) in combination with flucytosine (100 mg/kg per day) followed by fluconazole (800 mg per day), with both groups undergoing 10 weeks of follow-up. The primary end point was early fungicidal activity, derived from quantitative cerebrospinal fluid cultures on days 1, 3, 7, and 14. Secondary end points were safety and 2- and 10-week mortality.RESULTS: Forty-one patients were analyzed. Baseline mental status, cryptococcal burden, opening pressure, CD4(+) cell count, and HIV load were similar between groups. Combination therapy was more fungicidal than fluconazole alone (mean early fungicidal activity +/- standard deviation -0.28 +/- 0.17 log colony-forming units [CFU]/mL per day vs -0.11 +/- 0.09 log CFU/mL per day; P < .001). The combination arm had fewer deaths by 2 weeks (10% vs 37%) and 10 weeks (43% vs 58%). More patients had grade III or IV neutropenia with combination therapy (5 vs 1, within the first 2 weeks; P = .20), but there was no increase in infection-related adverse events.CONCLUSIONS: The results suggest that optimal oral treatment for cryptococcal meningitis is high-dose fluconazole with flucytosine. Efforts are needed to increase availability of flucytosine in Africa. Clinical trials registration. isrctn.org Identifier: ISRCTN02725351.	J. C. Nussbaum, A. Jackson, D. Namarika, J. Phulusa, J. Kenala, C. Kanyemba, J. N. Jarvis, S. Jaffar, M. C. Hosseinipour, D. Kamwendo, C. M. Horst and T. S. Harrison	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
272	Effect of pneumococcal conjugate vaccine on nasopharyngeal colonization among immunized and unimmunized children in a community-randomized trial	BACKGROUND: Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects. METHODS: We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot. RESULTS: We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07]). CONCLUSIONS: PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.	K. L. O'Brien, E. V. Millar, E. R. Zell, M. Bronsdon, R. Weatherholtz, R. Reid, J. Becenti, S. Kvamme, C. G. Whitney and M. Santosham	The Journal of infectious diseases
451	Immunization with a pneumococcal capsular polysaccharide vaccine during pregnancy	The feasibility of preventing invasive pneumococcal infections during the first few months of life by immunization during pregnancy has been investigated. One hundred and fifty Gambian women were immunized with either a 23-valent pneumococcal polysaccharide vaccine or a meningococcal polysacchnride vaccine during the last trimester of pregnancy. Pregnant women showed a good antibody response to Jive of the six pneumococcal polysaccharides tested (types 1, 3, 5, 6, 14 and 19) but not to type 6 polysaccharide. Mean cord blood/maternal blood IgG antibody ratios varied from 24% (type 1) to 49% (type 3) and differed substantially between individual mother/infant pairs. Pneumococcal antibody levels were higher at birth in infants of women immunized with pneumococcal polysaccharide vaccine than in control infants. However, these antibodies disappeared rapidly during the first few months of life and it is uncertain how much clinical protection against pneumococcal infection maternal immunization would have provided. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	T. J. D. O'Dempsey, T. McArdle, S. J. Ceesay, W. A. S. Banya, E. Demba and O. Secka	Vaccine.
405	Cefotaxime for treatment of neonatal sepsis and meningitis	Neonatal sepsis is a clinical syndrome characterized by systemic signs and symptoms, and bacteremia during the first month of life. The incidence is relatively low (one to eight cases/1000 live births), yet the risk of mortality is approximately 25%. Meningitis in the neonate is usually a sequela of bacteremia; however, it is discussed with neonatal sepsis, because they commonly share etiology and pathogenesis. The incidence of meningitis is usually a fraction of the number of infants with sepsis, varying in different settings from one-fourth to one-third. The mortality rate is high, varying in some series from 15%-50%. There are two major forms of presentation of neonatal sepsis. Early-onset disease presents as a fulminant, multisystemic illness during the first 5-7 days of life; late-onset disease is more commonly recognized after the first weeks of life. Because different microorganisms are responsible for the two forms of disease, the choice of antimicrobial agents also differs. Some organisms such as Escherichia coli, group B streptococci, and Listeria monocytogenes may be responsible, whereas other pathogens such as Staphylococcus aureus and S. epidermidis, and Pseudomonas aeruginosa are usually associated with late-onset disease. Classic initial (empiric) treatment of neonatal sepsis and meningitis consists of ampicillin and an aminoglycoside. With the advent of the third-generation cephalosporins, however, the empiric antimicrobial approach for neonatal sepsis and meningitis has changed in most centers. Third-generation cephalosporins cover more of the pathogens implicated in neonatal sepsis and meningitis, except for the enterococci and L. monocytogenes. In the Fourth Neonatal Meningitis Collaborative Study, neonates were assigned to receive saline or dexamethasone before parenteral cefotaxime and ampicillin. The preliminary data from 37 neonates from six Latin American countries show a low mortality rate and no side effects attributable to the study drugs. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. M. Odio	Diagnostic Microbiology & Infectious Disease
42	Cefotaxime vs. conventional therapy for the treatment of bacterial meningitis of infants and children	Eighty-five infants and children were prospectively randomized to receive cefotaxime or ampicillin and chloramphenicol for therapy of bacterial meningitis. The two therapy groups of patients were comparable as to sex, age, clinical status on admission, prior administration of antibiotics and etiology. Three infants (7%) died in each therapy group. Mean number of days of positive cerebrospinal fluid cultures, time to defervescence and duration of treatment and of hospital stay and complications developing during treatment were similar for the two treatment regimens. Median cerebrospinal fluid bactericidal titers against the patients' pathogens in cefotaxime-treated patients (1:64) were larger than those in patients who received conventional therapy (1:8). Mild to moderate motor sequelae were more frequent in those given conventional therapy at the time of discharge only, and not at 4 months or longer of follow-up. We conclude that cefotaxime has similar efficacy when compared with conventional therapy for the management of bacterial meningitis in pediatric patients.	C. M. Odio, I. Faingezicht, J. L. Salas, J. Guevara, E. Mohs and G. H. McCracken	Pediatric infectious disease
416	Prospective, randomized, investigator-blinded study of the efficacy and safety of meropenem vs. cefotaxime therapy in bacterial meningitis in children	Objectives. To compare the efficacy and safety of meropenem with cefotaxime for the treatment of infants and children with bacterial meningitis. Methods. Infants and children with strongly suspected or documented bacterial meningitis were randomly assigned in a prospective multicenter study to receive either meropenem or cefotaxime. Patients were assessed at the end of therapy and at 5 to 7 weeks and 5 to 7 months after the end of treatment for the presence of neurologic and sensory neural sequelae. Results. A total of 258 children were randomized to either treatment group. A further 8 patients with suspected pneumococcal meningitis were treated with meropenem without randomization. Of the randomized patients 154 were fully evaluable, 79 in the meropenem group and 75 in the cefotaxime group. At the end of treatment there were no significant differences in clinical outcome between the two treatment groups. Clinical cure with or without sequelae was achieved in 97 and 96% of the meropenem- and cefotaxime- treated patients, respectively. At the end of treatment and at 5 to 7 weeks, 46 and 54% of meropenem patients were cured with no sequelae, respectively. Corresponding results for cefotaxime patients were 56 and 58%. All pathogens were eradicated. In total 37 patients had seizures during treatment, 15 (12%) in the meropenem and 22 (17%) in the cefotaxime group. None of the seizures was considered to be drug-related. Conclusions. This trial shows that meropenem is suitable therapy for bacterial meningitis in infants and children and that it offers an efficacy and safety profile similar to that of cefotaxime. Number of References 28. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. M. Odio, J. R. Puig, J. M. Feris, W. N. Khan, W. J. Rodriguez, G. H. McCracken and J. S. Bradley	Pediatric Infectious Disease Journal
655	Vaccinoprophylaxis of mumps using mumps vaccine, strain Sofia 6, in Bulgaria	A mumps vaccine, using strain Sofia 6 prepared in guinea-pig kidney primary cell cultures, was gradually introduced in Bulgaria to vaccinate 1- to 12-year-old children between 1972 and 1976. It was included in the national vaccine programme in 1977. The vaccine showed a slight reactogenicity, a good immunogenicity and a high epidemiological efficacy. Due to the increased morbidity of mumps, revaccination was carried out in 4- to 12-year-old children in 1982. A high level of side-effects, mainly meningitis, was registered, and led to suspension of the mumps vaccine in Bulgaria.	H. Odisseev and N. Gacheva	Vaccine
653	Phenytoin pharmacokinetics and clinical effects in African children following fosphenytoin and chloramphenicol coadministration	AIMS: Some children with malaria and convulsions also have concurrent bacterial meningitis. Chloramphenicol is used to treat the latter whereas phenytoin is used for convulsions. Since chloramphenicol inhibits the metabolism of phenytoin in vivo, we studied the effects of chloramphenicol on phenytoin pharmacokinetics in children with malaria. METHODS: Multiple intravenous (i.v.) doses of chloramphenicol succinate (CAP) (25 mg kg-1 6 hourly for 72 h) and a single intramuscular (i.m.) seizure prophylactic dose of fosphenytoin (18 mg kg-1 phenytoin sodium equivalents) were concomitantly administered to 15 African children with malaria. Control children (n = 13) with malaria received a similar dose of fosphenytoin and multiple i.v. doses (25 mg kg-1 8 hourly for 72 h) of cefotaxime (CEF). Blood pressure, heart rate, respiratory rate, oxygen saturation, level of consciousness and convulsion episodes were monitored. Cerebrospinal fluid (CSF) and plasma phenytoin concentrations were determined. RESULTS: The area under the plasma unbound phenytoin concentration-time curve (AUC(0, infinity ); means (CAP, CEF): 58.5, 47.6 micro g ml-1 h; 95% CI for difference between means: -35.0, 11.4), the peak unbound phenytoin concentrations (Cmax; medians: 1.12, 1.29 micro g ml-1; 95% CI: -0.5, 0.04), the times to Cmax (tmax; medians: 4.0, 4.0 h; 95% CI: -2.0, 3.7), the CSF:plasma phenytoin ratios (means: 0.21, 0.22; 95% CI: -0.8, 0.10), the fraction of phenytoin unbound (means: 0.06, 0.09; 95% CI: -0.01, 0.07) and the cardiovascular parameters were not significantly different between CAP and CEF groups. However, mean terminal elimination half-life (t1/2,z) was significantly longer (23.7, 15.5 h; 95% CI: 1.71, 14.98) in the CAP group compared with the CEF group. Seventy per cent of the children had no convulsions during the study period. CONCLUSIONS: Concomitant administration of chloramphenicol and a single i.m. dose of fosphenytoin alters the t1/2,z but not the other pharmacokinetic parameters or clinical effects of phenytoin in African children with severe malaria. Moreover, a single i.m. dose of fosphenytoin provides anticonvulsant prophylaxis in the majority of the children over 72 h. However, a larger study would be needed to investigate the effect of concomitant administration of multiple doses of the two drugs in this population of patients.	B. R. Ogutu, C. R. Newton, S. N. Muchohi, G. O. Otieno and G. O. Kokwaro	British journal of clinical pharmacology
10	Combined Haemophilus Influenzae type B-Neisseria meningitidis serogroup C vaccine is immunogenic and well tolerated in preterm infants when coadministered with other routinely recommended vaccines	BACKGROUND: Preterm infants are at greater risk of morbidity from vaccine-preventable diseases. Therefore, their responses to vaccination are of particular interest. METHODS: In this open, controlled, Spanish multicenter study, we assessed immunogenicity and safety following primary vaccination of 163 preterm infants (n = 56, <31 weeks' gestation; n = 107, 31-36 weeks' gestation) and 150 full-term infants (>36 weeks' gestation), with Haemophilus Influenzae type B (Hib)-MenC-TT, DTaP(diphtheria-tetanus-acellular pertussis vaccine)-HepB-IPV, and PCV7 at 2 to 4-6 months of age followed by booster vaccination at 16 to 18 months of age. Serum bactericidal activity (rabbit complement) against MenC, and antibodies to Hib and hepatitis b (anti-HBs) were determined. Local/general symptoms were assessed after each vaccination via diary cards. Serious adverse events were recorded throughout the study. RESULTS: There were no statistically significant differences between preterm and full-term infants in either Hib or MenC seroprotection rates or geometric mean concentrations at 1 month postdose 3, before or 1 month postbooster. Postdose 3, >99% of participants had seroprotective anti-HBs antibody concentrations. Anti-HBs geometric mean concentrations was significantly lower in the <31-week group compared with other groups and this difference persisted until 16 to 18 months of age. Hib-MenC-TT vaccine was well tolerated at all ages. There was one death caused by meningococcal serogroup-B sepsis (full term). No serious adverse events were assessed by the investigator as being vaccine related. CONCLUSIONS: Hib-MenC-TT vaccine had a similar immunogenicity and safety profile in preterm and full-term infants. These results demonstrate that preterm infants can be safely vaccinated with Hib-MenC-TT at the recommended chronologic age without impacting the responses to the Hib and MenC antigens.	F. Omeñaca, J. Arístegui, J. C. Tejedor, D. Moreno-Perez, J. Ruiz-Contreras, J. M. Merino, M. Muro Brussi, T. Sánchez-Tamayo, J. Castro Fernandez, L. Cabanillas, K. Peddiraju, N. Mesaros and J. M. Miller	The Pediatric infectious disease journal
94	Treatment of meningococcal meningitis in children in Khartoum		M. I. Omer, H. O. Omer, A. Khidir and M. M. Hassan	Indian pediatrics
124	Subacute meningoencephalitis in a subset of patients with AD after Abeta42 immunization	BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.	J. M. Orgogozo, S. Gilman, J. F. Dartigues, B. Laurent, M. Puel, L. C. Kirby, P. Jouanny, B. Dubois, L. Eisner, S. Flitman, B. F. Michel, M. Boada, A. Frank and C. Hock	Neurology
617	Mycophenolate mofetil versus azathioprine in patients with chronic active ulcerative colitis: a 12-month pilot study	OBJECTIVE: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) of unknown etiology frequently requiring long-term therapy for control of symptoms and prevention of relapse. Azathioprine (AZA) has been shown to be effective and safe in the treatment of chronic active UC. However, the alternatives to treatment with AZA are limited. Our aim was to compare the efficacy and safety of treatment with mycophenolate mofetil (MMF)/prednisolone versus standard immunosuppressive treatment with azathioprine (AZA)/prednisolone in patients with chronic active UC. METHODS: The study was designed as an open comparison of MMF versus AZA. Twenty-four patients with active UC (Rachmilewitz score > or =6 points) were randomly assigned to the MMF (20 mg/kg)/prednisolone or AZA (2 mg/kg)/prednisolone group. The initial prednisolone dosage was 50 mg and was tapered according to a standard protocol. Treatment was scheduled for 1 yr. RESULTS: The rates of remission were higher in the AZA/prednisolone group (n = 12) than in the MMF/prednisolone group (n = 12) throughout the study. Remission rates were 92% versus 67% after 4 wk, 92% versus 67% after 3 months, 92% versus 67% after 6 months, 83% versus 78% after 9 months, and 100% versus 88% after 1 yr. The number of patients not requiring steroids was higher in the AZA/prednisolone group than in the MMF/prednisolone group. Moreover, in the AZA/prednisolone group no severe adverse events were recorded, whereas in the MMF/prednisolone group two severe adverse events were observed: one patient discontinued MMF after 6 months because of recurrent upper airway infections, and one patient exhibited a bacterial meningitis after 9 months. CONCLUSIONS: Treatment with AZA/prednisolone appears to be more effective and safe compared to MMF/prednisolone in patients with chronic active UC. MMF might be an alternative treatment for patients with contraindications to AZA. To further evaluate the effects of MMF in active UC, a placebo-controlled double-blinded study appears warranted.	T. Orth, M. Peters, J. F. Schlaak, F. Krummenauer, R. Wanitschke, W. J. Mayet, P. R. Galle and M. F. Neurath	The American journal of gastroenterology
663	A multicenter, single-blind, prospective randomized trial to evaluate the safety of a polyethylene glycol hydrogel (duraseal dural sealant system) as a dural sealant in cranial surgery	Objective: Incisional cerebrospinal fluid (CSF) leakage after cranial surgery is a significant cause of morbidity due to poor wound healing and infection, meningitis, and pseudomeningocele formation. Many common dural closure techniques, such as sutures, autologous grafts, gelatin or collagen sponges, and fibrin glues, are used to achieve watertight closure, although none are US Food and Drug Administration approved for this use. DuraSeal Dural Sealant System is a polyethylene glycol (PEG) hydrogel approved by the U.S. Food and Drug Administration for obtaining watertight dural closure when applied after standard dural suturing. This multicenter, prospective randomized study further evaluated the safety of a PEG hydrogel compared with common dural sealing techniques. Methods: A total of 237 patients undergoing elective cranial surgery at 17 institutions were randomized to dural closure augmented with the PEG hydrogel or a control "standard of care" dural sealing technique after Valsalva maneuver demonstrated an intraoperative nonwatertight dural closure. Data were collected on complications resulting in unplanned postoperative interventions or reoperations, surgical site infections, CSF leaks, and other neurological complications within 30 days. Surgeons also provided data on the ease of use of the dural sealing techniques, as well as preparation and application times. Results: The incidences of neurosurgical complications, surgical site infections, and CSF leaks were similar between treatment and control groups, with no statistically significant difference between the measures. In the PEG hydrogel group (n = 120), the incidence of neurosurgical complications was 5.8% (n = 7), the incidence of surgical site infections was 1.7% (n = 2), and the incidence of CSF leak was 0.8% (n = 1). In the control group (n = 117), the incidence of neurosurgical complications was 7.7% (n = 9), the incidence of surgical site infection was 2.6% (n = 3), and the incidence of CSF leak was 1.7% (n = 2). Sealant preparation time was less than 5 minutes in 96.6% of the PEG hydrogel group compared with 66.4% of controls (P < 0.001). The dural augmentation was applied in less than 1 minute in 85.7% of the PEG hydrogel group compared with 66.4% of the control group (P < 0.001). Conclusions: The PEG hydrogel dural sealant used in this study has a similar safety profile to commonly used dural sealing techniques when used as dural closure augmentation in cranial surgery. The PEG hydrogel dural sealant demonstrated faster preparation and application times than other commonly used dural sealing techniques. 2012 Elsevier Inc	J. W. Osbun, R. G. Ellenbogen, R. M. Chesnut, L. S. Chin, P. J. Connolly and G. R. Cosgrove	World neurosurgery
256	Stages and syndromes of neuroborreliosis	To ascertain the varieties of neuroborreliosis, 330 patients were identified at the Departments of Neurology in Würzburg and Giessen from 1979 to 1994. Patients who fullfilled at least one of three strict case definitions based on clinical and laboratory criteria were included in the study. Ninety-one per cent of the patients had second-stage neuroborreliosis (duration of symptoms < or = 6 months). The most common syndrome was a painful spinal meningoradiculitis, alone (37%) or in combination with a cranial radiculitis (29%). Meningoradiculitis cranialis (9%), isolated meningitis (4%) and erythema chronica migrans-associated mono/polyneuritis (3%) were further stage II features. Central nervous system involvement occurred either as an acute meningomyelitis or meningomyeloradiculitis (5%) and meningoencephalitis or meningenocephaloradiculitis (4%). Less than 9% of the patients ran a chronic course (stage III) with a disease duration between 6 months and 9 years, either as acrodermatitis chronica atrophicans associated mono- or polyneuritis (2%) or a chronic progressive encephalomyelitis (6%). Cerebrovascular neuroborreliosis (1%) occurred in both stages; however, the primary nature of the course was a chronic one. Involvement of other organs except the skin was rare (joints 3%, heart 1%) but elevated hepatic enzymes were frequent. Our study demonstrates that neuroborreliosis has to be considered in the differential diagnosis of a wide variety of neurological conditions. Cerebrospinal fluid analysis and the search for specific intrathecal antibody production are important diagnostic procedures.	P. Oschmann, W. Dorndorf, C. Hornig, C. Schäfer, H. J. Wellensiek and K. W. Pflughaupt	Journal of neurology
78	Expression of tumor necrosis factor-alpha and transforming growth factor-beta 1 in cerebrospinal fluid cells in meningitis	Meningitis is an acute inflammatory disease of the pia and arachnoid and the fluid in the subarachnoid space, in which a participation of cytokines can be expected. While tumor necrosis factor-alpha (TNF alpha) promotes inflammatory reactions, transforming growth factor-beta 1 (TGF beta 1) has antagonistic effects and suppresses the inflammation in the subarachnoid space. We investigated the protein concentration and mRNA expression of TNF alpha and TGF beta 1 in cerebrospinal fluid (CSF) by ELISA and intracellularly by non-radioactive in situ hybridization in 23 patients with bacterial or viral meningitis. A higher amount of both cytokines on protein and mRNA level, especially of TNF alpha, could be detected in bacterial infection. While an imbalance of both cytokines with a preponderance of TNF alpha- compared to TGF beta 1-mRNA was visible in CSF cells of patients with bacterial meningitis, a balance of TNF alpha- and TGF beta 1-mRNA or a higher expression of TGF beta 1-mRNA could be detected in viral meningitis. In the acute phase of the disease neutrophil granulocytes expressed more TNF alpha- and TGF beta 1-mRNA than lymphocytes and monocytes/macrophages, while these cell types were dominating the cytokine synthesis during the healing phase. These data indicate that immunomodulatory mechanisms take place in the CSF compartment itself, regulated by CSF cells in different but specific ways. In addition, TGF beta 1 seems to be involved in the down-regulation of the inflammatory activity and to be one factor in the cytokine network, which could contribute to a lower rate of complications and positive outcomes. Moreover this study favors the possibility to monitor the immunomodulatory mechanisms by non-radioactive in situ hybridization.	L. M. Ossege, E. Sindern, B. Voss and J. P. Malin	Journal of the neurological sciences
413	MeNZB: a safe and highly immunogenic tailor-made vaccine against the New Zealand Neisseria meningitidis serogroup B disease epidemic strain	Clinical studies have been conducted in New Zealand evaluating the safety and immunogenicity of an outer membrane vesicle (OMV) vaccine, MeNZB, developed to control epidemic disease caused by group B meningococci, subtype P1.7b,4. MeNZB, administered in a three-dose regimen, was well tolerated and induced a seroresponse, defined as a four-fold rise (> or =titre 8) in serum bactericidal antibodies against the vaccine strain 4-6 weeks after the third vaccination, in 96% (95% confidence interval (CI): 79-100%) of adults, 76% (95% CI: 72-80%) of children, 75% (95% CI: 69-80%) of toddlers and 74% (95% CI: 67-80%) of infants receiving MeNZB. In conclusion, these findings suggest that MeNZB is safe and is likely to confer protection against systemic group B meningococcal disease caused by the epidemic strain.	P. Oster, D. Lennon, J. O'Hallahan, K. Mulholland, S. Reid and D. Martin	Vaccine
84	Immunogenicity, reactogenicity and persistence of meningococcal A, C, W-135 and Y-tetanus toxoid candidate conjugate (MenACWY-TT) vaccine formulations in adolescents aged 15-25 years	Development of meningococcal serogroups A, C, W-135 and Y conjugate vaccines could expand coverage against devastating meningococcal diseases. The immunogenicity of one dose of each one of five MenACWY-TT formulations versus a licensed ACWY polysaccharide vaccine was evaluated in 175 healthy subjects of 15-25 years. Serum bactericidal titers (rSBA) were evaluated before and after vaccination. The percentage of rSBA responders to each serogroup A, C, W-135 and Y did not statistically differ from the control for each of the five formulations except for serogroup A that was lower after administration of one formulation. In the 3-year follow-up of the first study where the latter formulation was assessed, bactericidal antibody persistence was similar to the licensed ACWY polysaccharide vaccine for MenA and MenC and higher for MenW-135 and MenY. Our results present five investigational MenACWY-TT conjugate vaccine formulations which are well tolerated and highly immunogenic in adolescents.	L. Ostergaard, E. Lebacq, J. Poolman, G. Maechler and D. Boutriau	Vaccine
576	Pneumococcal antibody concentrations of subjects in communities fully or partially vaccinated with a seven-valent pneumococcal conjugate vaccine	BACKGROUND: A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes. METHODS: A single-blind, cluster-randomized (by village) trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group); in 10 control villages only children <30 months old or those born during the study received PCV-7. Subjects over the age of 30 months resident in vaccine villages received a single dose of PCV-7 whilst those in control villages received a single dose of a serogroup C meningococcal conjugate vaccine. Serum antibody concentrations against specific pneumococcal polysaccharides were measured in approximately 200 age-stratified subjects before, 4-6, 12 and 24 months following vaccination. RESULTS: Baseline pneumococcal antibody concentrations were generally high and increased with age up to 10 years. One dose of PCV-7 increased geometric mean antibody concentrations (GMC) in vaccinated versus control villages for vaccine serotypes 6B and 18C, and 4 and 18C, in the young (under 5 years) and older age groups (5+ years) respectively. There were significantly higher proportions of subjects in the vaccinated than in the control communities with an antibody concentration believed to protect against carriage (>5.0 µg/mL) for all but serotype 9V of the PCV-7 serotypes in the older group, but not in the younger age group. CONCLUSION: Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN51695599 51695599.	M. O. Ota, A. Roca, C. Bottomley, P. C. Hill, U. Egere, B. Greenwood and R. A. Adegbola	PloS one
549	Dexamethasone in tuberculous meningitis. Relationship of cerebrospinal fluid effects to therapeutic efficacy		R. D. O'Toole, G. F. Thornton, M. K. Mukherjee and R. L. Nath	Ann Intern Med
36	Comparative trial of carbenicillin and ampicillin therapy for purulent meningitis	A randomized therapeutic trial of carbenicillin (CB) or ampicillin (AMP) in purulent meningitis was performed in 86 pediatric and adult patients (41 Haemophilus influenzae, 22 Streptococcus pneumoniae, 13 Neisseria meningitidis, and 10 of unknown etiology). All isolates, incuding H. influenzae, were susceptible to CB and AMP. Median cerebrospinal fluid (CSF) antibiotic concentrations were 0.85 and 1.60 mug/ml for CB and AMP, respectively, during administration of daily doses of 400 mg/kg and 0.65 and 0.45 mug/ml, respectively, on daily doses of 200 mg/kg. Higher CSF concentrations, up to a median concentration of 4.5 mug/ml, were observed in patients with CSF protein concentrations >/=75 mg/100 ml. Clinical responses were equivalent on either antibiotic regimen. Among AMP patients (45), 8 had significant residua and 3 died; among CB patients (41), 5 had residua and none died. However, 38% of H. influenzae patients treated with CB had positive CSF cultures on day 1 follow-up lumbar punctures, compared with only 5.8% of AMP patients with H. influenzae. The significance of a delay of CSF sterilization among CB-treated patients is unknown, since there was no correlation between persistence of hemophilus organisms and the frequency of adverse outcome. AMP and CB are equivalent for the treatment of bacterial meningitis due to susceptible organisms.	G. D. Overturf, E. A. Steinberg, A. E. Underman, J. Wilkins, J. M. Leedom, A. W. Mathies and P. F. Wehrle	Antimicrobial agents and chemotherapy
630	[Intravascular laser irradiation of the blood in the treatment of suppurative septic complications in otorhinolaryngology]	The paper reviews the results of intravascular laser radiation (ILR) for pyoseptic complications in 8 patients with otogenic and 2 patients with rhinogenic meningitis, 1 patient with cavernous sinus thrombosis and 5 patients with Dupuytren's phlegmon. The adjuvant to conventional treatment use of ILR activates immune system, improves rheological blood characteristics, enhances tissue regeneration.	V. T. Pal?hun, A. S. Lapchednko and A. G. Kucherov	Vestnik otorinolaringologii
86	[Activity of creatine phosphokinase in cerebrospinal fluid in bacterial and lymphocytic meningoencephalitis]		S. Pancewicz	Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
306	Recombinant interferon- gamma 1b as adjunctive therapy for AIDS-related acute cryptococcal meningitis	We conducted a phase 2, double-blind, placebo-controlled study to evaluate the safety and antifungal activity of adjuvant recombinant interferon (rIFN)- gamma 1b in patients with acquired immunodeficiency syndrome and acute cryptococcal meningitis. Patients received 100 or 200 microg of rIFN- gamma 1b or placebo, thrice weekly for 10 weeks, plus standard therapy with intravenous amphotericin B, with or without flucytosine, followed by therapy with fluconazole. End points included conversion of cerebrospinal fluid fungal cultures from positive to negative at 2 weeks, resolution of symptoms, and survival. Among 75 patients, 2-week culture conversion occurred in 13% of placebo recipients, 36% of rIFN- gamma 1b (100 microg) recipients, and 32% of rIFN- gamma 1b (200 microg) recipients. There was a trend toward improved combined mycologic and clinical success in rIFN- gamma 1b recipients (26% vs. 8%; P=.078). Therapy with rIFN- gamma 1b was well tolerated, and there was no apparent influence on serial CD4 cell counts and human immunodeficiency virus load measurements. Adjunctive therapy with rIFN- gamma 1b holds promise for patients with acute cryptococcal meningitis and warrants further study.	P. G. Pappas, B. Bustamante, E. Ticona, R. J. Hamill, P. C. Johnson, A. Reboli, J. Aberg, R. Hasbun and H. H. Hsu	The Journal of infectious diseases
370	A phase II randomized trial of amphotericin B alone or combined with fluconazole in the treatment of HIV-associated cryptococcal meningitis	BACKGROUND: Cryptococcosis is a life-threatening infection among patients with human immunodeficientcy virus (HIV) infection. Therapeutic options for the treatment of central nervous system cryptococcosis are limited, especially in resource-limited settings. METHODS: We conducted a randomized, open-label, phase II trial in Thailand and the United States that compared the safety and efficacy of intravenous amphotericin B deoxycholate (AmB) 0.7 mg/kg (the standard therapy) with that of AmB 0.7 mg/kg plus fluconazole 400 mg (the low-dosage combination) or AmB 0.7 mg/kg plus fluconazole 800 mg (the high-dosage combination) administered daily for 14 days, followed by fluconazole alone at the randomized dosage (400 or 800 mg per day) for 56 days. The primary safety end point was the number of severe or life-threatening treatment-related toxicities; the primary efficacy end point was a composite of survival, neurologic stability, and negative cerebrospinal fluid culture results after 14 days of therapy. RESULTS: A total of 143 patients were enrolled. There were no differences in treatment-related toxicities among the 3 arms. Toxicity was predictable and was most often related to AmB, and it included electrolyte abnormalities, anemia, nephrotoxicity, and infusion-related events. At day 14, 41%, 27%, and 54% of patients in the standard therapy, low-dosage combination, and high-dosage combination therapy arms, respectively, demonstrated successful outcomes. A trend towards better outcomes in the combination therapy arms was seen at days 42 and 70. CONCLUSIONS: AmB plus fluconazole administered at a dosage of 800 mg for 14 days, followed by fluconazole administered at a dosage of 800 mg daily for 56 days, is well-tolerated and efficacious among HIV-positive patients with central nervous system cryptococcosis. These results have significant treatment implications and should be validated in a randomized phase III trial.	P. G. Pappas, P. Chetchotisakd, R. A. Larsen, W. Manosuthi, M. I. Morris, T. Anekthananon, S. Sungkanuparph, K. Supparatpinyo, T. L. Nolen, L. O. Zimmer, A. S. Kendrick, P. Johnson, J. D. Sobel and S. G. Filler	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
514	Effect of donor immunization with meningococcal polysaccharide vaccine on the response of the recipient after allogeneic bone marrow transplantation - a randomized study [abstract]	29th Annual Meeting of the European Group for Blood and Marrow Transplantation, 19th Meeting of the EBMT Nurses Group, Istanbul, Turkey, Mar 23-26,2003 [Abstract NO: P682]	T. Parkkali, H. Ahman, H. Käyhty, T. Ruutu, L. Volin and P. Ruutu	Bone Marrow Transplantation
190	Tetravalent meningococcal polysaccharide vaccine is immunogenic in adult allogeneic BMT recipients	Forty-four adult BMT recipients transplanted from an HLA-identical sibling donor were randomized to receive meningococcal polysaccharide (Men PS) vaccine either 8 (early group; 22 patients) or 20 (late group; 22 patients) months after BMT. The geometric mean concentrations (GMC) of antibodies to serogroup A Neisseria meningitidis (Men A) and serogroup C Neisseria meningitidis (Men C), determined by an EIA method, decreased during the first 6 months after BMT but remained at a stable level thereafter. Before vaccination the GMCs of anti-Men A were 1.53 microg/ml and 1.61 microg/ml, but 1 month after vaccination they were significantly higher, 3.46 microg/ml and 6.39 microg/ml, in the early and late groups. The GMCs of anti-Men C increased from 0.37 microg/ml and 0.44 microg/ml before vaccination to 3.31 microg/ml and 4.62 microg/ml at 1 month after vaccination in the early and late groups, respectively. By 6 months after vaccination the GMCs of Men antibodies had decreased to levels of about 50% of those measured at 1 month after vaccination. Two-fold responses to Men A PS were seen in 52% and 74% and to Men C PS in 76% and 89% of the BMT recipients in the early and late groups, respectively. Chronic GVHD had no influence on the vaccination response. In the present study, Men PS vaccine induced good and equal antibody responses to Men A and Men C PSs in allogeneic BMT recipients regardless of timing after BMT. Vaccination against Neisseria meningitidis should be considered, especially in the event of travelling or military service > or = 8 months after BMT.	T. Parkkali, H. Käyhty, H. Lehtonen, T. Ruutu, L. Volin, J. Eskola and P. Ruutu	Bone marrow transplantation
509	Immunogenicity of tetravalent meningococcal polysaccharide vaccine in adult allogeneic BMT recipients [abstract]	26th Annual Meeting of the European Group for Blood and Marrow Transplantation, 16th Meeting of the Nurses Group, Austria, Innsbruck, Mar 5-8,2000 [Abstract No: 621]	T. Parkkali, H. Käyhty, T. Ruutu, L. Volin, J. Eskola and P. Ruutu	Bone Marrow Transplantation
488	Emergence in Vietnam of Streptococcus pneumoniae resistant to multiple antimicrobial agents as a result of dissemination of the multiresistant Spain(23F)-1 clone	Surveillance for Streptococcus pneumoniae resistant to penicillin and other antimicrobial agents is necessary to define the optimal empirical antibiotic therapy for meningitis in resource-poor countries such as Vietnam. The clinical and microbiological features of 100 patients admitted to the Centre for Tropical Diseases in Ho Chi Minh City, Vietnam, between 1993 and 2002 with invasive pneumococcal disease were studied. A penicillin-nonsusceptible pneumococcus (MIC, > or =0.1 micro g/ml) was isolated from the blood or cerebrospinal fluid of 8% of patients (2 of 24) between 1993 and 1995 but 56% (20 of 36) during 1999 to 2002 (P < 0.0001). Pneumococcal isolates resistant to penicillin (MIC, > or =2.0 micro g/ml) increased from 0% (0 of 24) to 28% (10 of 36) (P = 0.002). Only one isolate was ceftriaxone resistant (MIC, 2.0 micro g/ml). Penicillin-nonsusceptible pneumococci were isolated from 78% of children younger than 15 years (28 of 36) compared with 25% of adults (16 of 64) (P = 0.0001). Isolation of a penicillin-nonsusceptible pneumococcus in adults with meningitis was independently associated with referral from another hospital (P = 0.005) and previous antibiotic therapy (P = 0.025). Multilocus sequence typing showed that 86% of the invasive penicillin-resistant pneumococcus isolates tested (12 of 14) were of the Spain(23F)-1 clone. The serotypes of >95% of the penicillin-nonsusceptible pneumococci were included in the currently available pneumococcal vaccines. Our findings point to the recent introduction and spread of the Spain(23F)-1 clone of penicillin-resistant pneumococci in Vietnam. Simple clinical predictors can be used to guide empirical antibiotic therapy of meningitis. Pneumococcal vaccination may help to control this problem.	C. M. Parry, N. M. Duong, J. Zhou, N. T. Mai, T. S. Diep, Q. Thinh le, J. Wain, N. Vinh Chau, D. Griffiths, N. P. Day, N. J. White, T. T. Hien, B. G. Spratt and J. J. Farrar	Antimicrobial agents and chemotherapy
175	Ampicillin-cloxacillin in purulent meningitis		L. Partana, J. S. Partana, E. Prajogo, S. Thahir and K. Satjadibrata	Paediatrica Indonesiana
371	Amphotericin B: the higher the dose, the higher the toxicity		A. C. Pasqualotto	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
402	Evaluation of the use of dexamethasone in the therapeutic schedule for purulent meningitis		J. N. Passos and J. L. Baldy	Rev-Inst-Med-Trop-Sao-Paulo
285	Significance of mycobacterial immune complexes (IgG) in the diagnosis of tuberculous meningitis	SETTING: Tuberculous meningitis (TBM) has high mortality, especially in children. Early accurate diagnosis and adequate treatment would reduce this mortality. Diagnosis of TBM remains an enigma because of low cerebrospinal fluid (CSF) culture positivity for Mycobacterium tuberculosis and weak clinical correlation with conventional immunoassays. OBJECTIVE: To evaluate significance of mycobacterial immune complexes (IgG) and anti-mycobacterial antibodies in the diagnosis of TBM. METHOD: CSF from TBM patients and various types of other neurological (both infectious and non-infectious) and non-neurological cases was studied for the presence of IgG and anti-mycobacterial antibodies using antigen capture (by anti-BCG) and multilayered ELISA (using M. tuberculosis soluble extract), respectively. RESULTS: IgG in CSF could be detected in 33 of 55 (60%) and anti-mycobacterial antibodies in 30 of 55 (55%) TBM cases. Presence of IgG, anti-mycobacterial antibodies or both could be detected in 45 of 55 (82%) of the TBM cases. Excepting three of the pyogenic meningitis CSF, none of the infectious (49), non-infectious neurological cases (30) and non-neurological controls (32) showed the presence of IgG or anti-mycobacterial antibodies. CONCLUSION: Detection of IgG along with anti-mycobacterial antibodies aids in diagnosis of a large proportion of TBM cases.	S. A. Patil, M. Gourie-Devi, A. R. Anand, A. N. Vijaya, N. Pratima, K. Neelam and A. Chandramuki	Tubercle and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease
342	Risk factors in postoperative neurosurgical infection. A prospective study	Four hundred and seventy patients who had undergone neurosurgical operations were studied prospectively. After defining post-operative infection so that is included all the infective complications irrespective of location occurring after surgery, the overall infection rate was 17%. The infection rate in 413 cases without pre-existing infection was 15%. Wound infection was recorded in 5% and meningitis in 6%. Risk factors which lead to a significant increase in the incidence of postoperative infection were found to be altered sensorium, multiple operations, pre-existing infection, emergency surgery, duration of surgery more than 4 hours, urinary catheterisation, cerebrospinal fluid leak, and ventilatory support.	R. Patir, A. K. Mahapatra and A. K. Banerji	Acta neurochirurgica
683	Immunoglobulin prophylaxis does not prevent nosocomial infections in very low birth weight neonates	Neonates with birth weight less than 1500 g (VLBW), being almost always premature, are immunocompromised hosts. They have profound hypogammaglobulinaemia because there is little transfer of maternal IgG to the foetus before 32 weeks of gestation. It was hypothesized that the commercially available intravenous preparations of IgG, when given as prophylaxis, could reduce the incidence of nosocomial infections among these neonates. The Neonatal Research Network of the National Institute of Child Health and Human Development (NICHHD) undertook this study to test this hypothesis through a prospective, multicentre, randomized clinical trial. A total of 2416 infants with birth weights between 501 g to 1500 g were randomly assigned to the intravenous immunoglobulin (n = 1204) or control group (n = 1212). The study group received a commercial intravenous globulin preparation (Sandoglobulin, Sandoz Pharmaceuticals, East Hanover, New Jersey, USA) in a dose of 700 mg per kg for infants weighing 501-1000 g and 900 mg per kg for those with a weight of 1001-1500 g with the aim of achieving a serum IgG concentration of 700 mg/dl. The immunoglobulin infusions were repeated every 14 days until the infants weighed 1800 g, were discharged or died. Control infants were given placebo infusions during phase I of the study (n = 623), but no infusion during phase II (n = 589). The sample size was estimated on the assumption that the use of immunoglobulin would reduce the incidence of confirmed nosocomial infections by at least 33%. The primary outcome variable of the trial was the development of confirmed nosocomial infection including septicaemia, meningitis or urinary tract infection from 96 hours of birth to 120 days of life. Nosocomial infections occurred with comparable frequency in the two groups, 17% of infants (208/1204) in the study group and 19% (231 /1212) in the control group (Relative risk, RR 0.91, 95% CI 0.77-1.08, p=0.25). The morbidity pattern (patent ductus arteriosus, intraventricular haemorrhage, necrotizing enterocolitis, bronchopulmonary dysplasia), duration of ventilation, days of hospitalization and mortality rates were similar in the two groups. The study concludes that 'prophylactic use of intravenous immunoglobulin failed to reduce the incidence of hospital acquired infections in very low birth weight infants.'. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	V. Paul	National Medical Journal of India.
394	Phase I clinical trial with a hexavalent PorA containing meningococcal outer membrane vesicle vaccine	A meningococcal outer membrane vesicle (OMV) vaccine was prepared from two production strains designed to express three serosubtype-specific class 1 outer membrane proteins or PorA. The resulting hexavalent PorA OMV vaccine contained the serosubtypes P1.7,16; P1.5,2; P1.19,15; P1.7(h),4; P1.5(c),10; P1.12,13 and were used to immunize adult volunteers. A single immunization with two dosages, 7.5 and 15 microg of the individual PorAs, was studied The vaccine was considered safe for further use. Approximately half of the volunteers demonstrated a fourfold increase in bactericidal antibody activity against six test strains expressing the specific PorAs when given the higher dosage. This bactericidal activity was found to be directed against PorA. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. Peeters, H. C. Rumke, L. C. Sundermann, V. M. Rouppe v, J. Meulenbelt, M. Schuller, A. J. Kuipers, L. P. Van d and J. T. Poolman	Vaccine
298	Slow initial ?-lactam infusion and oral paracetamol to treat childhood bacterial meningitis: a randomised, controlled trial	BACKGROUND: New antimicrobials or adjunctive treatments have not substantially reduced mortality from acute childhood bacterial meningitis. Paracetamol seems to have beneficial effects in bacteraemic adults and some experts recommend initial slow ?-lactam infusion. We investigated whether these treatments had benefits in children with bacterial meningitis. METHODS: We did a prospective, double-blind, single-centre study with a two-by-two factorial design in Luanda, Angola. 723 participants aged 2 months to 13 years were randomly assigned two 12 h intravenous infusions, without loading doses, of 125 mg/kg bodyweight cefotaxime (total dose 250 mg/kg) given over 24 h, or 250 mg/kg bodyweight cefotaxime given as four boluses, one every 6 h over 24 h. Patients also received oral paracetamol at an initial dose of 30 mg/kg then 20 mg/kg every 6 h for 48 h or placebo. Two primary endpoints, death or severe neurological sequelae and deafness, were analysed by intention to treat. The study was registered as ISRCTN62824827. FINDINGS: 183 patients were assigned cefotaxime infusion plus paracetamol and 180 patients to each of the other three treatment groups. Causative agents were identified in 63% of cases and were mostly Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Death or severe neurological sequelae were seen in 340 (47%) of 723 children and deafness in 45 (12%) of 374 tested, both distributed similarly across treatment groups. In a predefined subgroup analysis of death or any sequelae, by causative agent, a benefit was seen in favour of infusion over bolus in children with pneumococcal meningitis (infusion plus placebo, odds ratio 0·18, 95% CI 0·03-0·90, p=0·04). A similar effect was seen for children receiving cefotaxime infusion plus paracetamol, but the difference was not significant (OR 0·22, 95% CI 0·04-1·09, p=0·06). A post-hoc analysis suggested that cefotaxime infusion plus paracetamol lowered mortality at least during the first 3 days, irrespective of cause. INTERPRETATION: Although no tested regimen improved the final outcomes of these very ill children, studies of longer courses of ?-lactam infusion plus paracetamol seem warranted. FUNDING: The Päivikki and Sakari Sohlberg, the Sigrid Jusélius, and the Paediatric Research Foundations, and the daily newspaper Helsingin Sanomat.	T. Pelkonen, I. Roine, M. L. Cruzeiro, A. Pitkäranta, M. Kataja and H. Peltola	The Lancet infectious diseases
503	Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland	A recently developed Haemophilus influenzae type b capsular polysaccharide vaccine was given to 48,977 children 3 months to 5 years of age; an equal number of children receiving group A meningococcal vaccine served as controls. The protection as well as serum antibody response was strongly age-dependent. Among children who had received the H. influenzae type b vaccine when 18 months of age or older, there were no cases of bacteremic disease caused by H. influenzae type b in the first year after vaccination. At the same time 11 such cases were seen in the control group of the same age, a highly significant difference. In the second year after vaccination two cases occurred in the H. influenzae type b-vaccinated group, five in the meningococcal-group A vaccinated group. No protection was seen among children who had been younger than 18 months when vaccinated, even if they received a booster dose of the vaccine. The serum antibody response to the H. influenzae type b polysaccharide, measured by radioimmunoassay, was poor in children below 18 months of age and good in those above it. No effect of the vaccine could be seen on the nasopharyngeal carriage of H. influenzae type b, which was approximately 6% in this age group. Adverse effects of the vaccine were mild.	H. Peltola, H. Käyhty, A. Sivonen and H. Mäkelä	Pediatrics
480	(Meningococcal vaccine: first results)		H. Peltola and P. Mäkelä	Suomen Lääkärilehti
156	Hearing impairment in childhood bacterial meningitis is little relieved by dexamethasone or glycerol	OBJECTIVE: Several studies have evaluated dexamethasone for prevention of hearing loss in childhood bacterial meningitis, but results have varied. We compared dexamethasone and/or glycerol recipients with placebo recipients, and measured hearing at 3 threshold levels. METHODS: Children aged 2 months to 16 years with meningitis were treated with ceftriaxone but were double-blindly randomly assigned to receive adjuvant dexamethasone intravenously, glycerol orally, both agents, or neither agent. We used the Glasgow coma scale to grade the presenting status. The end points were the better ear's ability to detect sounds of >40 dB, >or=60 dB, and >or=80 dB, with these thresholds indicating any, moderate-to-severe, or severe impairment, respectively. All tests were interpreted by an external audiologist. Influence of covariates in the treatment groups was examined by binary logistic regression. RESULTS: Of the 383 children, mostly with meningitis caused by Haemophilus influenzae type b or Streptococcus pneumoniae, 101 received dexamethasone, 95 received dexamethasone and glycerol, 92 received glycerol, and 95 received placebo. Only the presenting condition and young age predicted impairment independently through all threshold levels. Each lowering point in the Glasgow scale increased the risk by 15% to 21% (odds ratio: 1.20, 1.21, and 1.15 [95% confidence interval: 1.06-1.35, 1.07-1.37, and 1.01-1.31]; P = .005, .003, and .039) for any, moderate-to-severe, or severe impairment, respectively. Each increasing month of age decreased the risk by 2% to 6% (P = .0001, .0007, and .041, respectively). Neither dexamethasone nor glycerol prevented hearing loss at these levels regardless of the causative agent or timing of antimicrobial agent. CONCLUSIONS: With bacterial meningitis, the child's presenting status and young age are the most important predictors of hearing impairment. Little relief is obtained from current adjuvant medications.	H. Peltola, I. Roine, J. Fernández, A. González Mata, I. Zavala, S. Gonzalez Ayala, A. Arbo, R. Bologna, J. Goyo, E. López, G. Miño, S. Dourado de Andrade, S. Sarna and T. Jauhiainen	Pediatrics
31	C-reactive protein in childhood meningitides	Utility of C-reactive protein (CRP) latex agglutination test in meningitis was evaluated. Serum CRP test was positive in 100% cases of meningitic groups and 53% cases of "no meningitis (NM)" group. Cerebrospinal fluid (CSF) CRP test was positive in 100% cases of pyogenic meningitis, whereas it was negative in 95% cases of tuberculous meningitis and 100% cases of NM group. CSF CRP test showed 100% sensitivity and negative predictive values, 95-100% specificity and 94-100% positive predictive values for various inter-group differentiations. This study concluded that CSF CRP positive cases should be considered as pyogenic meningitis unless proved otherwise. Routine use of this simple, reliable and inexpensive test is recommended for rapid diagnosis and differential diagnosis f meningitis.	H. K. Pemde, K. Harish, Y. P. Thawrani, S. Shrivastava and K. M. Belapurkar	Indian journal of pediatrics
421	Safety and preliminary immunogenicity of the recombinant outer membrane protein P64k of Neisseria meningitidis in human volunteers	P64k is a meningococcal protein from Neisseria meningitidis that has been obtained by recombinant DNA technology. Recombinant P64k has been extensively characterized by physicochemical and immunological methods. Lately this protein has been found to act as a versatile immunological carrier for weak antigens in mice. In the present work, a Phase I clinical trial was carried out in healthy volunteers who received three inoculations of either placebo or recombinant P64k (20 or 50 microg). No severe adverse events occurred during the trial. Only mild adverse events in ten volunteers were observed. At 1 month after the third dose, 15 out of 18 volunteers (83.3%) who received the recombinant antigen had a P64k-specific antibody titre > or =1:100, as detected by ELISA. A fourth dose, given 9 months after the third one, elicited a potent booster immune response in P64k vaccinees. Accordingly, these P64k formulations were considered safe and immunogenic in healthy human volunteers.	A. Pérez, F. Dickinson, Z. Cinza, A. Ruíz, T. Serrano, J. Sosa, S. González, Y. Gutiérrez, C. Nazábal, O. Gutiérrez, D. Guzmán, M. Díaz, M. Delgado, E. Caballero, G. Sardiñas, A. Alvarez, A. Martín, G. Guillén and R. Silva	Biotechnology and applied biochemistry
698	Pharmacokinetics of daclizumab and mycophenolate mofetil with cyclosporin and steroids in renal transplantation	Daclizumab and mycophenolate mofetil (MMF) decrease the incidence of acute allograft rejection. This double-blind, randomized, placebo-controlled trial was performed primarily to assess the pharmacokinetics of MMF in an immunosuppressive regimen incorporating daclizumab. At five centers, 75 renal transplant recipients were randomized 2 : 1 to receive either daclizumab 1 mg/kg or placebo pre-transplantation and every other week, for a total of five doses. All patients received cyclosporine, steroids, and MMF. Levels of mycophenolic acid (MPA), its glucuronide metabolite, and daclizumab were measured after dosing on days 28 and 56. Safety parameters evaluated included: adverse events, laboratory abnormalities, infections, patient/graft survival, incidence of lymphoproliferative disorders, and incidence of acute rejection at 12 months. The concomitant administration of daclizumab and MMF had no effect on the pharmacokinetics of MPA: AUC0-8 values ([mu]g h/mL +/- SD) on day 28 were 30.1 +/- 13.3 for daclizumab-treat patients vs. 31.1 +/- 12.4 for placebo and on day 56, 37.7 +/- 18.2 for daclizumab-treated patients vs. 35.7 +/- 14.0 for placebo. Adverse events were similar between the two groups. Acute rejection at 12 months occurred in 14% of patients receiving daclizumab and 20% of patients receiving placebo. The coadministration of daclizumab did not result in a pharmacokinetic interaction with MPA, the active metabolite of MMF. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. D. Pescovitz, G. Bumgardner, R. S. Gaston, R. L. Kirkman, S. Light, I. H. Patel, K. Nieforth and F. Vincenti	Clinical Transplantation
501	[Diffusion of amoxicillin and ampicillin intraenous administration in acute meningitis of children]		G. Pesnel, F. Squinazi, S. Lemerle-Gruson, C. Lassale, P. Geslin and P. Reinert	Medecine et Maladies Infectieuses
631	Double-blind comparison of cefamandole and penicillin in pneumococcal pneumonia	We conducted a prospective, randomized, double-blind comparison of intravenous penicillin and cefamandole in the therapy of pneumococcal pneumonia. Patients received either 1 g of cefamandole or 600,000 U of aqueous penicillin G every 6 h. Of the 100 patients entered into the study, 96 had clinical and radiographic evidence of pneumonia. Microbial etiology was determined from the results of sputum and blood cultures and/or sputum Gram stains. Streptococcus pneumoniae was pathogenic in 49 patients, of whom 24 received cefamandole and 25 received penicillin. There was no statistically significant difference in the response or cure rate. Of the 100 patients, 93 were treated for 3 days or more and were evaluated for adverse effects and toxicity. There was no significant difference between cefamandole-treated and pencillin-treated patients in the incidence of colonization, superinfection, phlebitis, thrombocytosis, decrease in hematocrit, or elevated liver function tests. Eosinophilia occurred more frequently in patients treated with penicillin (20 of 42) than in those treated with cefamandole (11 of 42 (chi square, P < 0.05). Only one patient receiving cefamandole developed a positive direct Coombs test. No patient in either group developed meningitis. We conclude that, with the doses and route of administration employed in this study, cefamandole is as effective as penicillin in the therapy of pneumococcal pneumonia without an increased incidence of colonization, superinfection, or adverse effects.	B. G. Petty, C. R. Smith, J. C. Wade, G. L. Conrad, J. J. Lipsky, J. J. Ellner and P. S. Lietman	Antimicrobial agents and chemotherapy
613	Cefotaxime vs penicillin G for acute neurologic manifestations in Lyme borreliosis. A prospective randomized study	We randomly assigned 21 patients with painful Lyme neuroborreliosis radiculitis (Bannwarth's syndrome) and neuroborreliosis meningitis to a 10-day treatment with either penicillin G. 4 x 5 million U/d (n = 10) or cefotaxime sodium, 3 x 2 g/d (n = 11), intravenously. We were not able to demonstrate clinical differences between groups, either during the 10-day treatment period or at follow-up examination a mean of 7.7 months after antibiotic therapy. Cerebrospinal fluid cefotaxime concentrations reached the minimum inhibitory concentration at the 90% level for Borrelia burgdorferi in all patients, while none of the patients treated with penicillin G had cerebrospinal fluid concentrations above the minimum inhibitory concentration at the 90% value. We conclude that patients with acute neurologic manifestations of Lyme borreliosis may benefit from a 10-day treatment with cefotaxime or penicillin G. Cerebrospinal fluid antibiotic concentrations above the minimum inhibitory concentration at the 90% value, as observed in all patients treated with cefotaxime, offer the most hope for long-term prognosis.	H. W. Pfister, V. Preac-Mursic, B. Wilske and K. M. Einhäupl	Archives of neurology
522	[Intercellular adhesion molecules sICAM-1, sICAM-2, sICAM-3 and IFNgamma in neuroborreliosis and tick-borne encephalitis]	OBJECTIVE: The aim of this study was to evaluate the serum and CSF concentration of soluble intercellular adhesion molecules sICAM-1, sICAM-2, sICAM-3 and proinflammatory cytokine IFNgamma in patients with tick-borne encephalitis (TBE) and neuroborreliosis.METHODS: The study group consisted of 40: 20 with TBE meningitis and 20 with Lyme meningitis. The serum and CSF levels of adhesion molecules and IFNgamma were determined by ELISA assay twice: before and after treatment.RESULTS: Before treatment the concentrations of adhesion molecules and IFNgamma in serum as well as in CSF were significantly higher in both studied groups than in control group (with the exception of the serum level of sICAM-2 in TBE group). After the treatment, the serum parameters in TBE group decreased to the control level. CSF levels were also reduced, but still remained higher than in the control group. In patients with neuroborreliosis serum concentration of sICAM-1 and sICAM-2 did not change as compared with its level before treatment but other studied parameters in serum and CSF decreased significantly.CONCLUSIONS: The results of our study confirm the participation of intercellular adhesion molecules in the pathogenesis of viral (TBE) and bacterial (neuroborreliosis) neuroinfections.	M. Pietruczuk, A. Pietruczuk, S. Pancewicz, J. Zajkowska, R. Swierzbi?ska and T. Hermanowska-Szpakowicz	Przegla?d epidemiologiczny
627	Role of local anesthesia during lumbar puncture in neonates	Local anesthesia decreases physiologic responses to pain in neonates but has not been used routinely during lumbar punctures in newborns, as it might obscure anatomical landmarks. However, local anesthesia may decrease newborns' struggling during lumbar puncture, thus facilitating the procedure and increasing its success rate. The success rate of lumbar punctures was compared in neonates allocated prospectively to 0.2 to 0.5 mL of 1% lidocaine anesthesia (n = 48) or a control group (n = 52). Newborns were held in a modified lateral recumbent position (neck not flexed) and their struggling response to the various steps in the lumbar puncture was scored by the holder. The newborns' struggling motion score increased in response to lidocaine injection, but response to the subsequent spinal needle insertion was significantly decreased. Despite this decreased motion, no differences were noted in the number of attempts per lumbar puncture (1.9 +/- 0.2 [SEM] in lidocaine and 2.1 +/- 0.2 in control groups), rate of lumbar puncture failure (15% in lidocaine and 19% in control groups), or the number of traumatic lumbar punctures (46% in both groups). The success rate of lumbar puncture was not dependent on level of training of physicians performing the procedure. No acute complications, cerebrospinal fluid contamination, or subsequent meningitis was noted in either group. It is concluded that local anesthesia with lidocaine decreases the degree of struggling but does not alter the success rate of lumbar puncture in neonates. The practice of withholding lidocaine anesthesia from neonates undergoing lumbar punctures cannot be justified by arguing that it makes the procedure more difficult to perform.	J. M. Pinheiro, S. Furdon and L. F. Ochoa	Pediatrics
456	Prevention of meningeal leukemia: Review of 20 years of research and current recommendations	By use of prophylactic CNS therapy, the incidence of meningeal relapse has been dramatically reduced and the length of the initial bone marrow remission has been greatly prolonged in children with acute lymphoblastic leukemia. Pinkel performed a controlled study in which 94 patients were randomized to one of two regimens of presymptomatic CNS therapy, or received no prophylactic CNS therapy. This crucial study showed that prophylactic CNS therapy was very useful both in preventing meningeal relapse and in prolonging the duration of complete remission. Then, many additional regimens for prophylactic CNS therapy were tried on thousands of children worldwide in an effort to improve upon these results. Among the many CNS therapy regimens that were tried, none gave results better than the original St. Jude regimen. Our knowledge of CNS leukemia in general has greatly increased, but the last 20 years have brought us no further significant progress as to improved results in preventing meningeal leukemia. The many novel and innovative CNS therapy regimens that have been tried have yielded essentially the same results as to prevention of meningeal leukemia and as to duration of disease-free survival. Five to ten percent, or fewer in patients at low risk, still show meningeal relapse, and nearly one half of children with ALL still have hematologic relapse within the first 5 years following initiation of therapy. The goal now is to reduce neurotoxicity. Thus, progress has been stymied and we now await some new addition to therapy that will dramatically improve our results. Nonetheless, there are still many promising avenues of research yet to be explored. Meningeal leukemia remains a fascinating and satisfying field of clinical research. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	C. Pochedly	Hematol Oncol Clin North Am
378	Ceftizoxime versus vancomycin and gentamicin in neurosurgical prophylaxis: a randomized, prospective, blinded clinical study	In a prospective, randomized, blinded study, 826 patients undergoing clean neurosurgical procedures received single intravenous doses of ceftizoxime (2 g) (n = 422) or a combination of vancomycin (1 g) and gentamicin (80 mg) (n = 404) 1 hour before an incision was made. Patients with infected or contaminated wounds and those receiving shunts or other implants were excluded. Primary wound infections occurred within 30 days in five patients in each group and were most common after spinal surgery and procedures through previous incisions. Secondary infections (pneumonias, urinary tract infections, and intravenous line-related bacteremia) occurred in 24 patients in the ceftizoxime group and 25 in the vancomycin/gentamicin group. The infection rates after transsphenoidal procedures (n = 129) were remarkably low in both groups. Ceftizoxime caused no adverse drug reactions, but six patients in the vancomycin/gentamicin group had clinically significant infusion-related hypotension or flushing. Placement of a temporary external drain, use of an operating microscope, preoperative steroids, and diabetes were not associated with increased infection rates. Analysis of routinely encountered ventricular cerebrospinal fluid and simultaneously obtained peripheral blood showed low but detectable levels of all three antibiotics within 2 hours; only ceftizoxime, however, achieved cerebrospinal fluid levels sufficient to inhibit the staphylococcus and Gram-negative bacilli most often associated with postneurosurgical infections. We conclude that ceftizoxime is as effective as vancomycin and gentamicin in neurosurgical prophylaxis but is less toxic and penetrates cerebrospinal fluid better.	V. G. Pons, S. L. Denlinger, B. J. Guglielmo, J. Octavio, J. Flaherty, P. A. Derish and C. B. Wilson	Neurosurgery
377	CSF antibiotic prophylaxis for neurosurgical patients with ventriculostomy: a randomised study	The value of prophylactic antibiotics for patients with ventricular catheter for monitoring and CSF drainage is uncertain. 228 patients were randomised to receive perioperative antibiotics only (Unasyn, Group I) or prolonged antibiotics for the presence of the ventricular catheter (Unasyn and Aztreonam, Group II). The incidence of intracranial and extracranial infection was documented prospectively. Group II patients had a significantly reduced incidence of CSF infection [3/115 (3%) vs 12/113 (11%), p = 0.01] and extracranial infections [23/115 (20%) vs 48/113 (42%), p = 0.002]. CSF pathogens in Group II patients were MRSA and Candida, whereas in Group I, Staphylococci, E coli and Klebsiella. Although prolonged antibiotic prophylaxis significantly reduced the incidence of serious CSF infection as well as extracranial infections, this policy did select resistant or opportunistic pathogens such as Candida and MRSA.	W. S. Poon, S. Ng and S. Wai	Acta neurochirurgica. Supplement
681	The effects of treatment with antibiotics, laser and acupuncture upon chronic maxillary sinusitis in children	In a clinical study we compared three different types of therapy in chronic maxillary sinusitis. 45 patients, 3-40 years old, were treated, 19 with antibiotics, 18 with acupuncture and 8 with Laser-acupuncture. There was no statistical difference of results between Laser- therapy and antibiotics (Chi-Square-Test). Compared to previous treatments with antibiotics, results and duration of improvement was significantly better after acupuncture. Conclusion: acute sinusitis, especially of frontal sinus and in younger children, will better be treated by antibiotics because of the danger of osteomyelitis and meningitis. Acupuncture should be tried in chronic and recurrent stages after exclusion of large adenoids in children or bone inhibition of sinus clearance, especially before an invasive operation like removal of sinus mucosa is carried out.	R. Pothman and Yh	American Journal of Chinese Medicine
685	A randomized trial comparing fluconazole with clotrimazole troches for the prevention of fungal infections in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group	BACKGROUND: Cryptococcal meningitis and other serious fungal infections are common complications in patients infected with the human immunodeficiency virus (HIV). Fluconazole is effective for long-term suppression of many fungal infections, but its effectiveness as primary prophylaxis had not been adequately evaluated. METHODS: We conducted a prospective, randomized trial that compared fluconazole (200 mg per day) with clotrimazole troches (10 mg taken five times daily) in patients who were also participating in a randomized trial of primary prophylaxis for Pneumocystis carinii pneumonia. RESULTS: After a median follow-up of 35 months, invasive fungal infections had developed in 4.1 percent of the patients in the fluconazole group (9 of 217) and in 10.9 percent of those in the clotrimazole group (23 of 211; relative hazard, as adjusted for the CD4+ count, 3.3; 95 percent confidence interval, 1.5 to 7.6). Of the 32 invasive fungal infections, 17 were cryptococcosis (2 in the fluconazole group and 15 in the clotrimazole group; adjusted relative hazard, 8.5; 95 percent confidence interval, 1.9 to 37.6). The benefit of fluconazole was greater for the patients with 50 or fewer CD4+ cells per cubic millimeter than for the patients with higher counts. Fluconazole was also effective in preventing esophageal candidiasis (adjusted relative hazard, 5.8; 95 percent confidence interval, 1.7 to 20.0; P = 0.004) and confirmed and presumed oropharyngeal candidiasis (5.7 and 38.1 cases per 100 years of follow-up in the fluconazole and clotrimazole groups, respectively; P < 0.001). Survival was similar in the two groups. CONCLUSIONS: Fluconazole taken prophylactically reduces the frequency of cryptococcosis, esophageal candidiasis, and superficial fungal infections in HIV-infected patients, especially those with 50 or fewer CD4+ lymphocytes per cubic millimeter, but the drug does not reduce overall mortality.	W. G. Powderly, D. Finkelstein, J. Feinberg, P. Frame, W. He, C. Horst, S. L. Koletar, M. E. Eyster, J. Carey and H. Waskin	The New England journal of medicine
302	A controlled trial of fluconazole or amphotericin B to prevent relapse of cryptococcal meningitis in patients with the acquired immunodeficiency syndrome. The NIAID AIDS Clinical Trials Group and Mycoses Study Group	BACKGROUND: After primary treatment for cryptococcal meningitis, patients with the acquired immunodeficiency syndrome (AIDS) require some form of continued suppressive therapy to prevent relapse. METHODS: We conducted a multicenter, randomized trial that compared fluconazole (200 mg per day given orally) with amphotericin B (1 mg per kilogram of body weight per week given intravenously) in patients with AIDS who had completed primary therapy for cryptococcal meningitis with amphotericin B (greater than or equal to 15 mg per kilogram). To be eligible, patients had to have at least two negative cultures of cerebrospinal fluid immediately before randomization. The primary end point was relapse of cryptococcal disease as confirmed by biopsy or culture. RESULTS: Of 218 patients initially enrolled, 119 were assigned to fluconazole and 99 to amphotericin B. Twenty-three patients were found not to have met the entry criteria; six other patients assigned to amphotericin B did not receive it and were lost to follow-up. Of the remaining 189 patients, after a median follow-up of 286 days 14 of 78 receiving amphotericin B (18 percent) and 2 of 111 assigned to fluconazole (2 percent) had relapses of symptomatic cryptococcal disease (P less than 0.001 by Fisher's exact test). There was a difference of 19 percent in the estimated probability of remaining relapse-free at one year between the fluconazole group (97 percent) and the amphotericin B group (78 percent) (95 percent confidence interval, 7 percent to 31 percent; P less than 0.001). Serious drug-related toxicity was more frequent in the amphotericin B group (P = 0.02), as were bacterial infections (P = 0.004) and bacteremia (P = 0.002). CONCLUSIONS: Fluconazole taken by mouth is superior to weekly intravenous therapy with amphotericin B to prevent relapse in patients with AIDS-associated cryptococcal meningitis after primary treatment with amphotericin B.	W. G. Powderly, M. S. Saag, G. A. Cloud, P. Robinson, R. D. Meyer, J. M. Jacobson, J. R. Graybill, A. M. Sugar, V. J. McAuliffe and S. E. Follansbee	The New England journal of medicine
369	[Pefloxacin mesylate--clinical effectiveness in various forms of infectious-inflammatory diseases]	Pefloxacin mesylate is a broad spectrum fluoroquinolone active against pathogens with multiple resistance. Due to its high therapeutic efficacy (at last 90 per cent) and good tolerance pefloxacin mesylate is considered as the most promising drug in the therapy of severe infections and infections difficult for the treatment such as wound infection, meningitis and particularly perilous infections. Prolonged pharmacokinetics and high bioavailability of the drug provided its administration in the treatment of in- and outpatients with severe infection twice a day in a daily dose of 0.8 to 1.2 g. Pefloxacin proved to be a drug of choice in the treatment of infection due to intracellular pathogens.	V. P. Pozdniakova, L. Nestetrova, L. B. Smirnova, V. P. Iakovlev, L. A. Blatun, O. I. Koshil, S. M. Fedorov, L. A. Bakalova, L. S. Strachunski and K. B. Kurmanova	Antibiotiki i khimioterapii?a = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinsko? i mikrobiologichesko? promyshlennosti SSSR
467	Enoxacin in acute exacerbations of chronic bronchitis: a comparison with amoxycillin	A total of 43 hospitalized adult patients with acute exacerbations of chronic bronchitis or bronchiectasis due to Gram-negative bacteria were randomized to receive either enoxacin (400 mg bd) or amoxycillin (1,000 mg tid) for 7-12 days. Micro-organisms isolated included 24 Haemophilus influenzae (three beta-lactamases positive), 11 Branhamella catarrhalis (six beta-lactamase positive), two Pseudomonas aeruginosa and two Neisseria meningitidis in 37 evaluable patients. In the enoxacin group (23 patients) 82.6% of the patients were clinically cured or improved against 93% of patients in the amoxycillin group (14 patients). In the enoxacin group 76% of the pathogens were eradicated with two failures (P. aeruginosa), one relapse (H. influenzae) and three superinfections (Streptococcus pneumoniae). In the amoxycillin group, 71% of the pathogens were eradicated with 29% relapses. The differences between the two groups were not statistically significant. An increase in theophylline concentration occurred in 15 of 16 patients receiving simultaneous administration of theophylline, without clinical evidence of toxicity when theophylline dosage was reduced and enoxacin continued. Enoxacin appears to be as effective as amoxycillin in the treatment of acute exacerbations of chronic bronchitis due to susceptible Gram-negative bacteria.	T. Prigogine, Y. Glupczynski, J. P. Carpiaux, M. Blogie, E. Yourassowsky and J. S. Schmerber	The Journal of antimicrobial chemotherapy
453	Efficacy of ciprofloxacin in the treatment of nasopharyngeal carriers of Neisseria meningitidis		M. P. Pugsley, D. L. Dworzack, E. A. Horowitz, T. A. Cuevas, W. E. Sanders and C. C. Sanders	The Journal of infectious diseases
106	Evaluation of Sch 29,482 in the eradication of Neisseria meningitidis from nasopharyngeal carriers	Fifty-eight chronic carriers of Neisseria meningitidis were given 250 mg of Sch 29,482 or placebo orally every 6 h for 4 days. Although 22 of 29 subjects taking Sch 29,482 became culture negative while taking the drug, only five were culture negative 2 weeks posttherapy. There were no significant adverse reactions.	M. P. Pugsley, D. L. Dworzack, C. C. Sanders and W. E. Sanders	Antimicrobial agents and chemotherapy
584	Ceftazidime in the treatment of infective complications of spinal cord lesions	The use and the abuse of the antibiotics are certainly a subject of great concern, particularly for the increasing incidence of multiresistent bacteria. Since these resistent organisms may be sensitive to cephalosporin, we have tested the effectiveness of a new cephalosporin, ceftazidime, in the treatment of resistent infection in spinal cord injuried patients. A randomized study of ceftazidime versus amikacin was carried out on twenty patients. The preliminary results are presented. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Punzo, D. Squillante and M. Natale	Journal of Neurosurgical Sciences
372	Clinical applications of ethambutol		M. M. Pyle	Tubercle
229	Rapid diagnosis of acute bacterial meningitis: role of a broad range 16S rRNA polymerase chain reaction	BACKGROUND: Acute bacterial meningitis is a significant cause of morbidity and mortality throughout the world. It can be difficult to diagnose, as the symptoms and signs are often non-specific. STUDY OBJECTIVE: To evaluate the performance of an in-house semi-nested polymerase chain reaction (PCR) assay targeting the 16S rRNA gene of Eubacteria for the rapid diagnosis of acute bacterial meningitis using cerebrospinal fluid (CSF) specimens. METHODS: A total of 112 CSF samples from 112 patients were used in the study. Among these, 32 samples were obtained from confirmed cases of Streptococcus pneumoniae, six samples were obtained from confirmed cases of Haemophilus influenzae, one sample from a confirmed case of Neisseria meningitidis, and 10 cases of clinically suspected acute bacterial meningitis. The remaining 63 CSF samples were obtained from patients with non-infectious illnesses (n = 47) of the central nervous system (CNS) and autopsy-confirmed tuberculous meningitis (n = 16). RESULTS: The assay had an overall sensitivity of 93% (95% confidence interval [CI] 0.81-0.98, negative predictive value = 95%) and a specificity of 98% (95% CI 0.92-1.0, positive predictive value = 98%). CONCLUSION: These preliminary findings suggest that the semi-nested PCR assay targeting the 16S rRNA gene may be used as a rapid test for the diagnosis of acute bacterial meningitis.	W. Rafi, A. Chandramuki, R. Mani, P. Satishchandra and S. K. Shankar	The Journal of emergency medicine
445	The treatment of tuberculosis meningitis in children with a combination of isoniazid rifampicin and streptomycin- preliminary report [abstract]	Twenty-two children with tuberculous meningitis were treated with isoniazid, streptomycin and rifampicin and 19 were treated with, isoniazid, PAS and streptomycin for at least 18 months. Both groups received corticosteroids at the beginning of the treatment. The rate of recovery in the first 2 months of treatment was slightly more rapid in group-I than in group-Il and neurological sequelae were less frequent in group-I than in group-Il, but the differences were not statistically significant. There was very little difference in the death rate in both groups. A high incidence of jaundice was found amongst the children who received rifampicin.	N. N. Rahjoc, N. Rahjoo, I. Bocdiman, M. Said and S. Lazuardi	Indian Journal of Tuberculosis
542	Dexamethasone - a useful adjunct in treatment of acute meningitis in adults [abstract no:95]		R. Rajput, Jagdish, R. Gupta, S. B. Siwach, V. K. Katyal and D. Chaudhry	Journal of the Association of Physicians of India
280	Three chemotherapy studies of tuberculous meningitis in children	Chemotherapy studies were undertaken in 180 patients with tuberculous meningitis. They were treated for 12 months with 1 of 3 regimens: the first consisted of streptomycin, isoniazid and rifampicin daily for the first 2 months, followed by ethambutol plus isoniazid for 10 months; in the second, pyrazinamide was added for the first 2 months, and in the third, rifampicin was reduced to twice weekly in the first 2 months. Steroids were prescribed for all the patients in the initial weeks of treatment. Approximately 50% of the patients were aged less than 3 years. On admission, 13% of the patients were classified as stage I, 77% as stage II and 9% as stage III. Cerebrospinal fluid (CSF) culture results were available for all the 180 patients and M. tuberculosis was isolated in 59 (33%). CSF smear results for acid fast bacilli were available only for the 103 patients admitted to the second and the third studies, and of these in 60 (58%) the CSF was positive either by smear or culture. The response to therapy was similar in the 3 studies. Despite administration of rifampicin for 2 months, the mortality was high. In all, 27% of the patients died of tuberculous meningitis, 39% had neurological sequelae and 34% recovered completely. There was a strong association between the stage on admission and the mortality rate, the deaths being highest in stage III. In the first study, when isoniazid was prescribed daily in a dosage of 20 mg/kg, 39% of the patients developed jaundice; however, when the dosage was reduced to 12 mg/kg, the incidence fell to 16%. In the third study, where rifampicin was administered twice a week, the incidence of jaundice was much lower (5%).	P. Ramachandran, M. Duraipandian, M. Nagarajan, R. Prabhakar, C. V. Ramakrishnan and S. P. Tripathy	Tubercle
72	Role of interleukin 1-beta in meningeal inflammation		O. Ramilo, M. M. Mustafa, X. Sáez-Llorens, J. Mertsola, S. Ohkawara, M. Yoshinaga, E. J. Hansen and G. H. McCracken	The Pediatric infectious disease journal
199	Observed costs and health care use of children in a randomized controlled trial of pneumococcal conjugate vaccine	BACKGROUND: Pneumococcal conjugate vaccine for infants has recently been found to be effective for prevention of meningitis, bacteremia, pneumonia and otitis media, but it is more costly than previously introduced vaccines. AIM: We sought to determine the savings in medical costs through 36 months of life attributable to the use of the vaccine in healthy infants in a large randomized trial. METHODS: We analyzed the actual medical costs of 36 471 children involved in a randomized trial of heptavalent pneumococcal conjugate vaccine conducted in the Northern California Kaiser Permanente Medical Care Program. The costs of the vaccine and vaccine administration were excluded. RESULTS: Compared with the control group, the vaccinated group experienced a 2% reduction in clinic related costs [$48; 95% confidence interval (CI), $10 to $83] and a nearly significant 14% reduction in outpatient hospitalization costs ($32; CI -$1 to $66). The savings in total medical costs were 1.2%, but this difference was not significant ($41; CI -$204 to $270). Inpatient hospital costs were highly variable and were responsible for the lack of precision in the difference in total cost. In a post hoc analysis that excluded hospital costs not believed to be potentially pneumococcal related, savings in medical costs were $78 and significant (CI $5 to $158). CONCLUSIONS: The pneumococcal conjugate vaccine reduced ambulatory care costs in children in the first 36 months of life, but without a larger trial, the magnitude of the savings in total medical costs is uncertain. These results indicate, however, that any medical cost savings that are associated with the vaccine are unlikely to be high enough to offset the cost of the vaccine at its current price.	G. T. Ray, J. C. Butler, S. B. Black, H. R. Shinefield, B. H. Fireman and T. A. Lieu	The Pediatric infectious disease journal
609	Single-dose plasma and cerebrospinal fluid pharmacokinetics of ceftriaxone in infants and children	Pharmacokinetic variables were studied in children with central nervous system infections who received a single dose of ceftriaxone sodium. After initial lumbar puncture of children with documented or suspected bacterial meningitis, ventriculitis, or both, therapy was initiated with i.v. ampicillin and chloramphenicol. Children were randomly selected to receive a single i.v. dose of ceftriaxone. Concentrations of ceftriaxone were measured in plasma at intervals from 0 to 720 minutes after the beginning of the infusion and in cerebrospinal fluid (CSF) at one to five hours after the dose. Blood samples were obtained immediately after the second lumbar puncture for assessement of drug penetration into CSF. Elimination rate constant, elimination half-life, apparent volume of distribution, and plasma clearance were determined from samples obtained 30-720 minutes after the start of the infusion. In two children with ventriculoperitoneal shunts, serial determinations of ceftriaxone in CSF were obtained. All eight children who received 75 mg/kg and five of eight who received 50 mg/kg had positive CSF cultures. Volume of distribution was less after the 50 mg/kg dose than after the 75 mg/kg dose. In the children with shunts, adequate CSF drug concentrations were maintained throughout 12 hours of testing. These data support a 12-hour dosage interval, but clinical studies are needed to evaluate efficacy of the drug at both 12-hour and 24-hour dosage regimens. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. D. Reed, H. L. Rekate and S. C. Aronoff	Clin Pharm
48	Quadrivalent meningococcal vaccination of adults: phase III comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra	Neisseria meningitidis is a leading cause of bacterial meningitis in the United States, with the highest case fatality rates reported for individuals > or = 15 years of age. This study compares the safety and immunogenicity of the Novartis Vaccines investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, to those of the licensed meningococcal conjugate vaccine, Menactra, when administered to healthy adults. In this phase III multicenter study, 1,359 adults 19 to 55 years of age were randomly assigned to one of four groups (1:1:1:1 ratio) to receive a single dose of one of three lots of MenACWY-CRM or a single dose of Menactra. Serum samples obtained at baseline and 1 month postvaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA). The hSBA titers following vaccination with MenACWY-CRM and Menactra were compared in noninferiority and prespecified superiority analyses. Reactogenicity was similar in the MenACWY-CRM and Menactra groups, and neither vaccine was associated with a serious adverse event. When compared with Menactra, MenACWY-CRM met the superiority criteria for the proportions of recipients achieving a seroresponse against serogroups C, W-135, and Y and the proportion of subjects achieving postvaccination titers of > or = 1:8 for serogroups C and Y. MenACWY-CRM's immunogenicity was statistically noninferior (the lower limit of the two-sided 95% confidence interval was more than -10%) to that of Menactra for all four serogroups, with the postvaccination hSBA geometric mean titers being consistently higher for MenACWY-CRM than for Menactra. MenACWY-CRM is well tolerated in adults 19 to 55 years of age, with immune responses to each of the serogroups noninferior and, in some cases, statistically superior to those to Menactra.	K. S. Reisinger, R. Baxter, S. L. Block, J. Shah, L. Bedell and P. M. Dull	Clinical and vaccine immunology : CVI
118	Safety, tolerability, and immunogenicity of gardasil given concomitantly with Menactra and Adacel	OBJECTIVES: Multinational phase III trials of a human papillomavirus vaccine, Gardasil, have shown the vaccine to be generally well-tolerated, efficacious, and immunogenic. We evaluated the immunogenicity and safety of Gardasil administered concomitantly with Menactra and Adacel. METHODS: In this open-label study, boys (n = 394) and girls (n = 648) aged 10 to 17 were randomly assigned in a 1:1 ratio as follows: group A (concomitant administration) received a 0.5-mL dose of Gardasil at day 1, month 2, and month 6 and a 0.5-mL dose of Menactra and Adacel on day 1; group B (nonconcomitant administration) received Gardasil at day 1, month 2, and month 6 and Menactra and Adacel at month 1. Antibody levels for all vaccine components were measured. Systemic, injection-site, and serious adverse experiences (AEs) were monitored. RESULTS: Immune responses after concomitant administration of the 3 vaccines were noninferior to nonconcomitant administration. Seroconversion for Gardasil was > or = 99% in both groups A and B. For Menactra and Adacel, concomitant administration of the vaccines was demonstrated to be noninferior to nonconcomitant administration. Concomitant administration was generally well-tolerated. No participants withdrew because of an AE. One serious AE of transient muscular weakness of <24 hours' duration after the third Gardasil injection was reported in group B and was deemed possibly vaccine-related by the investigator. CONCLUSIONS: Overall, concomitant administration was generally well-tolerated and did not interfere with the immune response to the respective vaccines. Concomitant administration should minimize the number of visits required to deliver each vaccine individually, leading to increased compliance and more effective disease prevention.	K. S. Reisinger, S. L. Block, M. Collins-Ogle, C. Marchant, M. Catlett, D. Radley, H. L. Sings, R. M. Haupt and E. I. Garner	Pediatrics
57	Dosage escalation, safety and immunogenicity study of four dosages of a tetravalent meninogococcal polysaccharide diphtheria toxoid conjugate vaccine in infants	BACKGROUND: Young children have the highest incidence of meningococcal infection. Approximately 50% of disease in United States children less than 2 years of age is caused by serogroups C and Y. In the developing world, serogroups A and W-135 cause outbreaks and epidemics of infection. METHODS: Three groups of 30 infants were enrolled. The first group of infants was given 3 doses of a quadrivalent (group A, C, Y, W-135) polysaccharide meningococcal vaccine conjugated to diphtheria toxoid (MCV-4) at a dosage of 1 microg of each serogroup polysaccharide. The second group of infants was given MCV-4 at a dosage of 4 microg, and the last group of children received a 10-microg dosage. Vaccinations were given at 2, 4 and 6 months of age.A subset of these children was vaccinated at 15 to 18 months of age with licensed meningococcal polysaccharide (A, C, Y, W-135) vaccine. Serum bactericidal antibody (SBA) titers were measured with baby rabbit complement. RESULTS: The proportion of infants with local reactions increased significantly with increasing dosages after Injection 1 and 3. Approximately 1 month after completion of the primary series, the proportion of infants with an SBA titer > or = 1/8 ranged from 54 to 92%, depending on the serogroup and dose of polysaccharide contained in the vaccine. The SBA geometric mean titer varied from 17.4 to 101.6. There was no statistically significant difference between the SBA responses among the 3 dosage groups. After vaccination with polysaccharide vaccine at 15 to 18 months of age, mean fold increases in SBA of 4.9 to 170.3 were observed, suggesting an anamnestic response. CONCLUSIONS: MCV-4 appears to have a reactogenicity profile acceptable to parents and health care providers. It was only modestly immunogenic in infants, but it appeared to prime the immune system of the majority of infants given three doses in infancy. There is no statistically significant immunologic advantage conferred by increasing the dosage beyond 4 microg/ml, and local reactions are more frequent after the 10-microg/ml dosage.	M. Rennels, J. King, R. Ryall, T. Papa and J. Froeschle	The Pediatric infectious disease journal
423	Dose escalation, safety and immunogenicity study of a tetravalent meninogococcal polysaccharide diphtheria conjugate vaccine in toddlers	Two injections of tetravalent (Groups A, C, Y and W-135) meningococcal polysaccharide vaccine conjugated to diphtheria were given to 30 toddlers at dosages of 1, 4 and 10 [mu]g/ml polysaccharide of each serogroup. Reactogenicity was acceptable at all dosages. The 4-[mu]g/ml dose appears to be immunologically optimal. Number of References 1. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. Rennels, J. King Jr, R. Ryall, S. Manoff, T. Papa, A. Weddle and J. Froeschle	Pediatric Infectious Disease Journal
22	Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine conjugated to CRM197 in United States infants	BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria meningitidis likely will become the leading cause of bacterial sepsis and meningitis in US children. This report describes the safety and immunogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM197 via reductive amination (MnCC). METHODS: One hundred six healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized, controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal vaccine. Parents reenrolled 64 of these children at 12 to 15 months to receive a fourth dose of MnCC. Routine childhood vaccines, including DTP, were coadministered. Temperatures and symptoms were recorded for 3 days after each immunization. Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4. RESULTS: Moderate to severe local reactions, defined as erythema or induration > or =2.4 cm or pain that interfered with limb movement was reported after 0 to 3.2% of MnCC injections, depending on the reaction and dose. Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown. Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 microg/ml after Dose 3 and 8.03 microg/ml after the booster. Geometric mean functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively. One hundred percent of children had a serum bactericidal antibody titer of > or =1:64 after three doses and > or = 1:128 after the booster. CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and generated high titers of bactericidal antibody in immunized US infants and toddlers. It appears to be an attractive candidate vaccine for the prevention of serogroup C meningococcal disease in young children.	M. B. Rennels, K. M. Edwards, H. L. Keyserling, K. Reisinger, M. M. Blatter, S. A. Quataert, D. V. Madore, I. Chang, F. J. Malinoski, J. G. Hackell and P. R. Paradiso	The Pediatric infectious disease journal
694	Role of gastric colonization in nosocomial infections and endotoxemia: a prospective study in neurosurgical patients on mechanical ventilation	The role of gastric microbial colonization in nosocomial infections and endotoxemia was investigated prospectively in 40 neurosurgical patients requiring mechanical ventilation for greater than 48 h. Each was studied up to 7 d. Swabs from the nose and oropharynx were cultured at admission, and aspirates from the stomach and trachea were cultured daily until enteral alimentation was started. Patients were evaluated every second day for endotoxemia and coagulation activation. Of 153 gastric aspirates, 66.7% contained microorganisms at a mean quantity of 10(7) cfu/ml. Nosocomial pneumonia occurred in 15 patients, septicemia in 5, and meningitis in 1. The stomach was the evident source of infection in only 1 patient with pneumonia. Of 140 plasma samples, 12 (8.6%) from 10 patients showed detectable endotoxin levels, but there was no association between endotoxemia or coagulation activation and the presence of microorganisms in the stomach. The stomach was not an important source for nosocomial infections or endotoxemia, even in patients with high gastric pH.	P. Reusser, W. Zimmerli, D. Scheidegger, G. A. Marbet, M. Buser and K. Gyr	The Journal of infectious diseases
474	Comparison of isolates of Neisseria gonorrhoeae causing meningitis and report of gonococcal meningitis in a patient with C8 deficiency [abstract]		C. Rio, D. S. Stephens, J. S. Knapp and R. J. Rice	Genitourinary Medicine
534	Design issues of an international study in the treatment of acquired immune deficiency syndrome associated cryptococcal meningitis [abstract]	25th Annual Meeting of the Society for Clinical Trials; 2004 May 23-26; New Orleans, Louisiana, USA	T. L. Robinson, S. Rosanbalm, D. Wallace and L. Zimmer	Clinical Trials. Supplement
228	Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial	BACKGROUND: Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia. METHODS AND FINDINGS: A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4-6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively). A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (?15 y of age) at CSS-2 (odds ratio [OR]?=?0.15 [95% CI 0.04-0.57] and OR?=?0.32 [95% CI 0.10-0.98], respectively) and at CSS-3 (OR?=?0.37 [95% CI 0.15-0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small. CONCLUSIONS: Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a "herd effect" in non-vaccinated older children and adults. No significant serotype replacement was detected. Please see later in the article for the Editors' Summary.	A. Roca, P. C. Hill, J. Townend, U. Egere, M. Antonio, A. Bojang, A. Akisanya, T. Litchfield, D. E. Nsekpong, C. Oluwalana, S. R. Howie, B. Greenwood and R. A. Adegbola	PLoS medicine
123	Aseptic meningoencephalitis in adults: liberal or restrictive treatment?	39 adult patients suffering from aseptic meningoencephalitis were admitted to hospital during April-December 1976 and were divided into 2 groups, according to birth date. One group (n = 24) was treated with bed rest in the febrile stage and recommended to avoid for some weeks activities that promote headache. The other group (n = 15) was encouraged to resume daily life as soon as possible. No pertinent difference was found between the groups in admission. The patients were followed for 9 months by questionnaires and registration of sick leave. The average number of days away from work was 32 in the "restrictive" and 15 in the "liberal" group. No untoward effects were found from a shorter sick leave and a rapid resumption of normal physical activity.	L. Rombo, G. Lindh and P. Lundbergh	Scandinavian journal of infectious diseases
158	Effect of aluminium hydroxide and meningococcal serogroup C capsular polysaccharide on the immunogenicity and reactogenicity of a group B Neisseria meningitidis outer membrane vesicle vaccine	Three different formulations of an outer membrane vesicle (OMV) vaccine against group B meningococcal disease have been prepared and tested for immunogenicity and reactogenicity in adult volunteers. The vaccines were prepared with or without aluminium hydroxide and serogroup C-polysaccharide (C-ps). Doses from 12.5 to 100 micrograms protein were given twice at a six weeks' interval. All three formulations were well tolerated and highly immunogenic, inducing bactericidal and opsonizing antibodies in humans. Adsorption of OMVs to aluminium hydroxide reduced the pyrogenicity in rabbits. The differences in immunogenicity between the formulations were relatively small, but after the second dose a stronger booster response was observed when the vaccines were adsorbed. Thus, a formulation with OMVs and C-ps represents a safe and highly immunogenic vaccine, even without aluminium hydroxide.	E. Rosenqvist, E. A. Høiby, G. Bjune, A. Aase, A. Halstensen, A. K. Lehmann, J. Paulssen, J. Holst, T. E. Michaelsen, H. Nøkleby, L. O. Frøholm and O. Closs	Developments in biological standardization
189	Human antibody responses to meningococcal outer membrane antigens after three doses of the Norwegian group B meningococcal vaccine	The antibody kinetics in sera from 27 adults after three doses of the Norwegian group B meningococcal outer membrane vesicle (OMV) vaccine was studied. The vaccinees received the third dose 4 to 5 years after the first two. Antibody responses against outer membrane proteins (OMPs) and lipopolysaccharides were studied by enzyme-linked immunosorbent assay and immunoblotting and with serum bactericidal assays (SBA) with three variants of the vaccine strain, 44/76. Six weeks after the second injection, the geometric mean (GM) of the levels of immunoglobulin G (IgG) against OMVs was about sevenfold higher than that of prevaccination levels, and 74% of the vaccinees developed a greater-than-twofold rise in SBA titer. After 6 months, the GM of IgG levels declined to about threefold higher, and after 4 to 5 years it declined to about twofold higher, than that before vaccination. The third dose induced a rapid increase in SBA titers in 96% of the vaccinees, and the GM of levels of IgG against OMVs rose to about 14-fold the prevaccination level. One year later, the IgG antibody levels had dropped to 4.6-fold the prevaccination level, but 88% of the vaccinees still showed bactericidal activity. The response after the two first doses was higher in individuals with prevaccination antibodies, but no such effect was found after three doses. The use of defined mutants in SBA and linear multiple regression analyses indicated that among the major OMPs, antibodies to the Opc and class 1 proteins made the most important single contributions to the bactericidal activity against the vaccine strain, but it also demonstrated the importance of antibodies against other antigens. After three doses, 68% of the vaccinees showed a significant SBA response against a strain lacking both the Opc and the class 1 proteins. Three doses converted almost all subjects to SBA responders and gave higher antibody levels and relatively less serosubtype-specific bactericidal activity than did two doses, probably indicating a broader cross-protection against heterologous strains.	E. Rosenqvist, E. A. Høiby, E. Wedege, K. Bryn, J. Kolberg, A. Klem, E. Rønnild, G. Bjune and H. Nøkleby	Infection and immunity
208	Three-year follow-up of children with postmeningitic deafness and partial cochlear implant insertion	OBJECTIVES: To evaluate the long-term outcome of children with postmeningitic deafness and partial insertion of the Nucleus electrode array, and to compare their speech perception performance with that of children with full insertion of the electrode array. DESIGN: A battery of seven speech perception tests was administered to 25 children with a cochlear implant (CI). Results were reduced into one score: equivalent hearing loss (EHL). SETTING: Tertiary referral centre. PARTICIPANTS: The partial insertion group comprised seven children, mean age at implantation 5.5 years, mean duration of deafness 3.6 years. The full-insertion control group comprised 18 children. Mean age at implantation: 4.4 years; mean duration of deafness: 2.9 years. All the children became deaf between 0 and 3 years of age. MAIN OUTCOME MEASURES: Over a 3-year follow-up period, the children with partial insertion showed continuing progress, although there was wide variation in performance and the rate of progression. Some open-set comprehension could even be achieved with the insertion of only eight electrodes of a nucleus device. RESULTS: Three years after implantation, speech perception in the partial insertion children was poorer than that in the control groups with long (P < 0.01; 95% confidence interval 7-43 dB EHL) and short duration of deafness (P < 0.0001; 95% confidence interval 28-53 dB EHL). They showed slower progress and reached a poorer EHL plateau. Four of the seven children acquired open-set word recognition. CONCLUSIONS: Patients with partial insertion of the electrode array benefit from a CI, although less than patients with complete insertion.	L. J. Rotteveel, A. F. Snik, A. M. Vermeulen and E. A. Mylanus	Clinical otolaryngology : official journal of ENT-UK ; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery
260	Choosing a route of administration for quadrivalent meningococcal polysaccharide vaccine: intramuscular versus subcutaneous	A clinical trial was conducted to compare intramuscular (im) with subcutaneous (sc) routes for administration of quadrivalent meningococcal polysaccharide vaccine in 141 adults. Safety assessment showed the im route had reduced erythema (P<.01) and reduced headache on days 1 and 2 (P<.05). Serological testing for serum bactericidal antibody titers against capsular groups A and C did not detect significant differences.	F. L. Ruben, J. E. Froeschle, C. Meschievitz, K. Chen, J. George, M. K. Reeves-Hoché, P. Pietrobon, M. Bybel, W. C. Livingood and L. Woodhouse	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
343	H. influenzae meningitis: therapeutic trials		D. Rush	The New England journal of medicine
277	Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial	BACKGROUND: Intensified antibiotic treatment might improve the outcome of tuberculous meningitis. We assessed pharmacokinetics, safety, and survival benefit of several treatment regimens containing high-dose rifampicin and moxifloxacin in patients with tuberculous meningitis in a hospital setting. METHODS: In an open-label, phase 2 trial with a factorial design in one hospital in Indonesia, patients (aged >14 years) with tuberculous meningitis were randomly assigned to receive, according to a computer-generated schedule, first rifampicin standard dose (450 mg, about 10 mg/kg) orally or high dose (600 mg, about 13 mg/kg) intravenously, and second oral moxifloxacin 400 mg, moxifloxacin 800 mg, or ethambutol 750 mg once daily. All patients were given standard-dose isoniazid, pyrazinamide, and adjunctive corticosteroids. After 14 days of treatment all patients continued with standard treatment for tuberculosis. Endpoints included pharmacokinetic analyses of the blood and cerebrospinal fluid, adverse events attributable to tuberculosis treatment, and survival. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01158755. FINDINGS: 60 patients were randomly assigned to receive rifampicin standard dose (12 no moxifloxacin, ten moxifloxacin 400 mg, and nine moxifloxacin 800 mg) and high dose (ten no moxifloxacin, nine moxifloxacin 400 mg, and ten moxifloxacin 800 mg). A 33% higher dose of rifampicin, intravenously, led to a three times higher geometric mean area under the time-concentration curve up to 6 h after dose (AUC(0-6); 78·7 mg.h/L [95% CI 71·0-87·3] vs 26·0 mg.h/L [19·0-35·6]), maximum plasma concentrations (C(max); 22·1 mg/L [19·9-24·6] vs 6·3 mg/L [4·9-8·3]), and concentrations in cerebrospinal fluid (0·60 mg/L [0·46-0·78] vs 0·21 mg/L [0·16-0·27]). Doubling the dose of moxifloxacin resulted in a proportional increase in plasma AUC(0-6) (31·5 mg.h/L [24·1-41·1] vs 15·1 mg.h/L [12·8-17·7]), C(max) (7·4 mg/L [5·6-9·6] vs 3·9 mg/L [3·2-4·8]), and drug concentrations in the cerebrospinal fluid (2·43 mg/L [1·81-3·27] vs 1·52 mg/L [1·28-1·82]). Intensified treatment did not result in increased toxicity. 6 month mortality was substantially lower in patients given high-dose rifampicin intravenously (ten [35%] vs 20 [65%]), which could not be explained by HIV status or severity of disease at the time of presentation (adjusted HR 0·42; 95% CI 0·20-0·91; p=0·03). INTERPRETATION: These data suggest that treatment containing a higher dose of rifampicin and standard-dose or high-dose moxifloxacin during the first 2 weeks is safe in patients with tuberculous meningitis, and that high-dose intravenous rifampicin could be associated with a survival benefit in patients with severe disease. FUNDING: Royal Dutch Academy of Arts and Sciences, Netherlands Foundation for Scientific Research, and Padjadjaran University, Bandung, Indonesia.	R. Ruslami, A. R. Ganiem, S. Dian, L. Apriani, T. H. Achmad, A. J. Ven, G. Borm, R. E. Aarnoutse and R. Crevel	The Lancet infectious diseases
332	A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. National Institute of Allergy and Infectious Diseases Mycoses Study Group	This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P = .006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P = .04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS-associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy.	M. S. Saag, G. A. Cloud, J. R. Graybill, J. D. Sobel, C. U. Tuazon, P. C. Johnson, W. J. Fessel, B. L. Moskovitz, B. Wiesinger, D. Cosmatos, L. Riser, C. Thomas, R. Hafner and W. E. Dismukes	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
425	A comparison of itraconazole versus fluconazole as maintenance therapy for AIDS-associated cryptococcal meningitis	This study was designed to compare the effectiveness of fluconazole vs. itraconazole as maintenance therapy for AIDS-associated cryptococcal meningitis. HIV-infected patients who had been successfully treated (achieved negative culture of CSF) for a first episode of cryptococcal meningitis were randomized to receive fluconazole or itraconazole, both at 200 mg/d, for 12 months. The study was stopped prematurely on the recommendation of an independent Data Safety and Monitoring Board. At the time, 13 (23%) of 57 itraconazole recipients had experienced culture-positive relapse, compared with 2 relapses (4%) noted among 51 fluconazole recipients (P =.006). The factor best associated with relapse was the patient having not received flucytosine during the initial 2 weeks of primary treatment for cryptococcal disease (relative risk = 5.88; 95% confidence interval, 1.27-27.14; P =.04). Fluconazole remains the treatment of choice for maintenance therapy for AIDS- associated cryptococcal disease. Flucytosine may contribute to the prevention of relapse if used during the first 2 weeks of primary therapy. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. S. Saag, G. A. Cloud, J. R. Graybill, J. D. Sobel, C. U. Tuazon, P. C. Johnson, W. J. Fessel, B. L. Moskovitz, B. Wiesinger, D. Cosmatos, L. Riser, C. Thomas, R. Hafner, W. E. Dismukes and R. Larsen	Clinical Infectious Diseases
320	Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis. The NIAID Mycoses Study Group and the AIDS Clinical Trials Group	BACKGROUND: Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. METHODS: In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. RESULTS: Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 [14 percent] vs. 24 of 131 [18 percent]; P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P less than 0.0001). CONCLUSIONS: Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined.	M. S. Saag, W. G. Powderly, G. A. Cloud, P. Robinson, M. H. Grieco, P. K. Sharkey, S. E. Thompson, A. M. Sugar, C. U. Tuazon and J. F. Fisher	The New England journal of medicine
410	Comparison of amphotericin B with fluconazole in the treatment of acute AIDS-associated cryptococcal meningitis	Background. Intravenous amphotericin B, with or without flucytosine, is usually standard therapy for cryptococcal meningitis in patients with the acquired immunodeficiency syndrome (AIDS). Fluconazole, an oral triazole agent, represents a promising new approach to the treatment of cryptococcal disease. Methods. In a randomized multicenter trial, we compared intravenous amphotericin B with oral fluconazole as primary therapy for AIDS-associated acute cryptococcal meningitis. Eligible patients, in all of whom the diagnosis had been confirmed by culture, were randomly assigned in a 2:1 ratio to receive either fluconazole (200 mg per day) or amphotericin B. Treatment was considered successful if the patient had had two consecutive negative cerebrospinal fluid cultures by the end of the 10-week treatment period. Results. Of the 194 eligible patients, 131 received fluconazole and 63 received amphotericin B (mean daily dose, 0.4 mg per kilogram of body weight in patients with successful treatment and 0.5 mg per kilogram in patients with treatment failure; P = 0.34). Treatment was successful in 25 of the 63 amphotericin B recipients (40 percent; 95 percent confidence interval, 26 percent to 53 percent) and in 44 of the 131 fluconazole recipients (34 percent; 95 percent confidence interval, 25 percent to 42 percent) (P = 0.40). There was no significant difference between the groups in overall mortality due to cryptococcosis (amphotericin vs. fluconazole, 9 of 63 (14 percent) vs. 24 of 131 (18 percent); P = 0.48); however, mortality during the first two weeks of therapy was higher in the fluconazole group (15 percent vs. 8 percent; P = 0.25). The median length of time to the first negative cerebrospinal fluid culture was 42 days (95 percent confidence interval, 28 to 71) in the amphotericin B group and 64 days (95 percent confidence interval, 53 to 67) in the fluconazole group (P = 0.25). Multivariate analyses identified abnormal mental status (lethargy, somnolence, or obtundation) as the most important predictive factor of a high risk of death during therapy (P<0.0001). Conclusions. Fluconazole is an effective alternative to amphotericin B as primary treatment of cryptococcal meningitis in patients with AIDS. Single-drug therapy with either drug is most effective in patients who are at low risk for treatment failure. The optimal therapy for patients at high risk remains to be determined. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. S. Saag, W. G. Powderly, G. A. Cloud, P. Robinson, M. H. Grieco, P. K. Sharkey, S. E. Thompson, A. M. Sugar, C. U. Tuazon, J. F. Fisher, N. Hyslop, J. M. Jacobson, R. Hafner and W. E. Dismukes	New Engl. J. Med.
258	Quinolone treatment for pediatric bacterial meningitis: a comparative study of trovafloxacin and ceftriaxone with or without vancomycin	BACKGROUND: Trovafloxacin is a new fluoroquinolone that exhibits good penetration into the central nervous system and excellent antimicrobial activity against common meningeal pathogens, including beta-lactam-resistant pneumococci. PURPOSE AND DESIGN: A multicenter, randomized clinical trial was conducted in children with bacterial meningitis to compare the safety and efficacy of trovafloxacin with that of ceftriaxone with or without vancomycin therapy. RESULTS: A total of 311 patients, ages 3 months to 12 years, were enrolled, of whom 203 were fully evaluable, 108 treated with trovafloxacin and 95 with the conventional regimen. Both groups were comparable with regard to baseline characteristics: age; cerebrospinal fluid findings; use of dexamethasone; history of seizures; and etiologic agents. No significant differences between trovafloxacin and the comparator, respectively, were detected in any of the following outcome measures: clinical success at 5 to 7 weeks after treatment (79% vs. 81%); deaths (2% vs. 3%); seizures after enrollment (22% vs. 21%); and severe sequelae (14% vs. 14%). Only 4 of 284 children developed joint abnormalities up to 6 months after treatment, 1 (0.9%) child received trovafloxacin and 3 (3.1%) received the comparator regimen. None of the evaluable patients experienced significant abnormalities of liver function during treatment. One nonevaluable patient who received trovafloxacin for 5 days and ceftriaxone for 11 days was readmitted to the hospital with hepatitis of unknown etiology 1 day after discharge. The episode resolved with liver function tests returning to normal within 2 months. CONCLUSIONS: We conclude that trovafloxacin is an effective antibiotic for treatment of pediatric bacterial meningitis. These favorable results support further evaluation of fluoroquinolone therapy for children with meningitis or other serious bacterial infections.	X. Sáez-Llorens, C. McCoig, J. M. Feris, S. L. Vargas, K. P. Klugman, G. D. Hussey, R. W. Frenck, L. H. Falleiros-Carvalho, A. G. Arguedas, J. Bradley, A. C. Arrieta, E. R. Wald, S. Pancorbo, G. H. McCracken and S. R. Marques	The Pediatric infectious disease journal
692	Short course versus 7-day course of intravenous antibiotics for probable neonatal septicemia: a pilot, open-label, randomized controlled trial	OBJECTIVE: To compare a short course of antibiotics (48 to 96 hours) and a standard course of antibiotics (7 days) for probable neonatal sepsis.DESIGN: Randomized, controlled, open-labeled trial with blocking and stratification according to birth weight. Setting: Tertiary care, referral, teaching hospital in Northern India.PARTICIPANTS: Neonates >30 wks gestation and >1000 g at birth, with probable sepsis (clinical signs of sepsis, raised C reactive protein) were enrolled. Babies with major malformations, severe birth asphyxia, meningitis, bone or joint or deep-seated infection, those who were already on antibiotics, and those undergoing surgery were excluded. Neonates, who had clinically remitted on antibiotic therapy by the time a sterile blood culture report was received were randomized.INTERVENTION: In the intervention arm, antibiotics were stopped after the 48 hour culture was reported sterile. In the control arm, antibiotics were continued to a total of 7 days.MAIN OUTCOME MEASURE: Treatment failure defined as reappearance of signs suggestive of sepsis within 15 days of stopping antibiotics, supported by laboratory evidence and adjudicated by a blinded expert committee.RESULTS: 52 neonates were randomized to receive a short course or 7 day course (n=26 each). Baseline variables were balanced in the 2 groups. There was no significant difference in the treatment failures between the 2 groups (3 babies in the 7-day group vs none in short course group, P=0.23).CONCLUSION: No difference in the treatment failure rates could be identified between short course and 7-day groups among neonates >30 weeks and > 1000 grams with probable sepsis.	S. S. Saini, S. Dutta, P. Ray and A. Narang	Indian pediatrics
396	Therapeutic management of purulent meningitis in children. A prospective study of 101 cases. <ORIGINAL> MODALITES THERAPEUTIQUES DES MENINGITES PURULENTES DE L'ENFANT. A PROPOS DE 101 OBSERVATIONS	One hundred and one cases of purulent meningitis without any sign of immediate severity have been prospectively treated. Cefotaxime was given until the results of bacteriological tests; when possible, a randomisation separated one group in which cefotaxime was continued and another group in which cefotaxime was replaced by ampicillin. IV treatment was stopped at the 10th day even in cases with persisting fever. All patients less than or equal to2 years of age were given phenobarbitone. Serious complications consisted of 4 cases of hypoacousia, equally distributed in either therapeutic group of Haemophilus meningitis. No child developed convulsions when receiving phenobarbitone. Late examination of CSF was uncontributive, even in patients with persisting fever. The following simplifications could be proposed in purulent meningitis with usual clinical picture and course: initial treatment with IIIrd generation cephalosporin; substitution by ampicillin or amoxicillin as soon as bacteriological tests make it possible; discontinuation of IV treatment by the 10th day maximun, without CSF control; prevention of convulsions in young children by phenobarbitone given during the acute stage of meningitis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. K. Samra and P. J. Cohen	Arch Fr Pediatr
263	Role of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with bacterial meningitis	OBJECTIVE: To investigate the efficacy of dexamethasone and oral glycerol in reducing hearing and neurological sequelae in children with acute bacterial meningitis (ABM). DESIGN: Prospective double blind, placebo controlled randomized study. SETTING: Pediatric services of a tertiary care teaching and referral hospital. SUBJECTS: Children 2 months to 12 years with a diagnosis of acute bacterial meningitis admitted between June 2002 to September 2003. INTERVENTION: Subjects were assigned randomly to receive dexamethasone, glycerol, dexamethasone+glycerol or placebo. Neurological and hearing impairment was assessed at discharge and after 1 month. RESULTS: 58 children (48 boys, 10 girls), mean age 50.2 +/- 41.0 months, were studied. Twelve patients received dexamethasone, 13 glycerol, 20 dexamethasone + glycerol and 13 placebo. Bacterial etiology was ascertained in 24 patients: Streptococcus pneumoniae-10, H influenzae b-7, Staph. aureus-5 and others-2. Three (5.2%) children died during hospital stay and 55 survived. Seven (12%) patients had neurological sequelae (3 in glycerol, 3 in dexamethasone+glycerol, 1 in placebo group, P = 0.29), and 10 patients (17%) had hearing sequelae (2 in glycerol, 3 in dexamethasone, 2 dexamethasone + glycerol and 3 in placebo group, P = 0.68). CONCLUSION: No significant difference was seen in neurological or hearing outcome with use of either glycerol or dexamethasone in children with acute bacterial meningitis.	J. Sankar, P. Singhi, A. Bansal, P. Ray and S. Singhi	Indian pediatrics
66	Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study	BACKGROUND: Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. METHODS: We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. FINDINGS: Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (p<0·0145) and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose; seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified. INTERPRETATION: On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys. FUNDING: Novartis Vaccines and Diagnostics.	M. E. Santolaya, M. L. O'Ryan, M. T. Valenzuela, V. Prado, R. Vergara, A. Muñoz, D. Toneatto, G. Graña, H. Wang, R. Clemens and P. M. Dull	Lancet
100	Importance of complement source in measuring meningococcal bactericidal titers	Complement-mediated bactericidal antibodies in serum confer protection against meningococcal disease. The minimum protective titer is estimated to be between 1:4 and 1:8 when measured by the Goldschneider assay performed with human complement, the assay used in the 1960s to establish the correlation between bactericidal antibodies and protection. A more recently described bactericidal assay standardized by an international consortium uses rabbit complement, which is known to augment bactericidal titers. To define a protective titer measured by the standardized assay, we compared bactericidal titers against serogroup C strains measured by this assay to titers measured by the assay described by Goldschneider et al. A titer of > or =1:128 measured by the standardized assay was needed to predict with > or =80% certainty a positive titer of > or =1:4 as measured by the Goldschneider assay. However, the majority of samples with titers of 1:4 measured by the Goldschneider assay had titers of <1:128 when measured by the standardized assay. Therefore, by the results of the standardized assay such persons would be falsely categorized as being susceptible to disease. In conclusion, high bactericidal titers measured with the standardized assay performed with rabbit complement are predictive of protection, but no threshold titer is both sensitive and specific for predicting a positive titer measured by the Goldschneider assay using human complement. Up to 10% of the U.S. adult population lacks intrinsic bactericidal activity against serogroup C strains in serum and can serve as complement donors. Therefore, use of the Goldschneider assay or an equivalent assay performed with human complement is preferred over assays that use rabbit complement.	G. F. Santos, R. R. Deck, J. Donnelly, W. Blackwelder and D. M. Granoff	Clinical and diagnostic laboratory immunology
577	Safety and antibody persistence following Haemophilus influenzae type b conjugate or pneumococcal polysaccharide vaccines given before pregnancy in women of childbearing age and their infants	BACKGROUND: Immunization of healthy women before pregnancy is a potential approach to providing increased levels of maternal antibody to newborns to protect them from infections occurring during the perinatal period and first months of life. METHODS: Healthy nonpregnant Pima Indian women of childbearing age were randomized to receive one of two Haemophilus influenzae type b (Hib) conjugate vaccines [HbOC or Hib-meningococcal outer membrane protein complex (OMP)] or a 23-valent pneumococcal polysaccharide vaccine (PnPs). Infants received Hib-OMP vaccine at 2, 4 and 12 months of age. Vaccine safety and immunogenicity was evaluated in the women and their infants. RESULTS: Anti-polyribose ribitol phosphate antibody titers were significantly higher in women in both Hib conjugate vaccine groups than in the pneumococcal vaccine group throughout the 37-month observation period. Antibody responses to HbOC vaccine were significantly higher than those to Hib-OMP. A subsequent booster dose of each Hib conjugate vaccine induced reactions and antibody responses similar to those of the first dose. Infants born to mothers immunized with Hib vaccines compared with PnPs had significantly higher polyribose ribitol phosphate-specific IgG antibody titers at birth and 2 months of age but lower antibody responses to Hib-OMP at 6 months and similar titers before and after boosting with Hib-OMP at 1 year of age. By contrast women immunized with PnPs did not have significantly elevated concentrations of pneumococcal-specific antibody at delivery, and their infants had pneumococcal antibody titers similar to those of infants born to mothers who did not receive pneumococcal vaccine before pregnancy. CONCLUSION: Hib conjugate vaccine given to women before pregnancy significantly increased the proportion of infants who had protective Hib antibody levels at birth and 2 months of age.	M. Santosham, J. A. Englund, P. McInnes, J. Croll, C. M. Thompson, L. Croll, W. P. Glezen and G. R. Siber	The Pediatric infectious disease journal
645	Passive immunization for infection with Haemophilus influenzae type b	Haemophilus influenzae type b is the leading cause of meningitis in children younger than 5 years of age in the United States. The incidence of infection with H influenzae type b in certain populations, such as Apache and Navajo Indians and Alaskan Eskimos, is 10 to 20 times higher than in the general US population. Another important feature of H influenzae type b infections in these populations is that more than 80% of the cases occur during the first year of life, with 35% to 45% occurring during the first 6 months. One of the currently licensed vaccines that contains the capsular polysaccharide of the H influenzae type b organism is not reliably immunogenic in infants younger than 18 months of age. A number of new H influenzae type b vaccines prepared by covalently coupling the H influenzae type b capsular polysaccharide with a protein carrier antigen are undergoing clinical evaluation. One of these conjugate vaccines was shown to be efficacious in preventing disease caused by H influenzae type b in Finnish infants when they were immunized at 3, 4, and 6 months of age. Unfortunately, in a recently concluded trial, the same vaccine was not found to be efficacious in preventing such disease in infants younger than 1 year of age among the Alaskan Eskimo population. We have evaluated an alternative approach for protecting high-risk infants.(ABSTRACT TRUNCATED AT 250 WORDS)	M. Santosham, R. Reid, G. W. Letson, M. C. Wolff and G. Siber	Pediatrics
359	Prevention of Haemophilus influenzae type b infections in Apache and Navajo children	Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy.	M. Santosham, B. Rivin, M. Wolff, R. Reid, W. Newcomer, G. W. Letson, J. Almeido-Hill, C. Thompson and G. R. Siber	The Journal of infectious diseases
181	Diagnostic value of atypical lymphocytes in cerebrospinal fluid from adults with enteroviral meningitis	We have noted two morphologically distinct types of atypical lymphocytes (AL) in the cerebrospinal fluid (CSF) of adult patients with meningitis: one, which we designate type-I AL, with multilobulated nuclei resembling those of the abnormal cells in adult T-cell leukaemia (ATL); and another, type-II AL, characterized by large lymphocytes with basophilic cytoplasm and nuclei containing coarse chromatin. Type-I AL were detected in 25 of 39 patients (64%) with enteroviral and in 11 of 109 (11%) with aseptic meningitis presumed to be caused by other viruses, but not in meningitis resulting from Cryptococcus neofirmans (n = 14), Mycobacterium tuberculosis (n = 19) or acute bacterial infection (n = 49). Type-I AL were not seen in herpes zoster (n = 15) aseptic meningeal reactions (n = 15), or in leptomeningeal carcinomatosis (n = 14). Type-II AL were often present in meningitis of various aetiologies and in aseptic meningeal reactions, but not in leptomeningeal carcinomatosis. The presence of type-I AL in the CSF was found to be indicative of enteroviral meningitis with the highest predictive value (69%), while type-II AL had a lower diagnostic positive predictive value in meningitis of the five aetiologies above. Type-I AL immunostained for CD4, while type-II AL were stained for CD8. The presence of type-I AL in CSF strongly suggests enteroviral meningitis, which warrants careful follow-up without antifungal, antituberculous or antibacterial agents. However, type-I AL, which are likely to be virally transformed lymphocytes, must be distinguished from ATL cells, which frequently involve the meninges.	Y. Sato, Y. Ohta, Y. Honda, M. Kaji and K. Oizumi	Journal of neurology
697	[Fundamental and clinical evaluation of cefozopran in low birth weight infants and neonates]	We conducted fundamental and clinical evaluations of a cephem antibiotic, cefozopran (SCE-2787, CZOP), in infants with low birth weights and mature infants. (1) Blood concentrations CZOP was intravenously given in bolus dose of 20 mg/kg to the newborn. The blood antibiotic concentrations were 69.7 micrograms/ml at 30 minutes after administration and the elimination half life was 2.99 hours in mature infants aged 1 to 3 days. They were 38.7 micrograms/ml and 2.85 hours in those aged 4 to 7 days, and 40.8 micrograms/ml and 3.81 hours in those aged 8 days or elder, respectively. In infants with lower birth weights aged 4 to 7 days the blood antibiotic concentrations were 48.6 micrograms/ml at 30 minutes after i.v. administration and the elimination half life was 3.77 hours. The blood antibiotic concentrations at 30 minutes after intravenous doses of 10, 20 and 50 mg/kg in mature infants aged 8 days or elder were 21.1, 40.8 and 153.6 micrograms/ml (value at 60 minutes) and the elimination half lives were 2.24, 3.81 and 3. 07 hours, respectively. Administration of CZOP at doses of 20 and 40 mg/kg by intravenous drip infusion over 30 minutes gave the blood drug concentrations of 48.0 and 103.2 micrograms/ml at the end of the infusion and the half lives were 2.60 and 3.33 hours, respectively. (2) Urinary excretion The urinary excretion rates after i.v. bolus doses of 10, 20 and 40 mg/kg were 28.4 to 58.6% of dose. The urinary excretion rate after i.v. drip infusion of 40 mg/kg over 30 minutes was 49.0% of dose. (3) Transfer into cereblospinal fluid The transfer of the antibiotic into cereblospinal fluid in patients with serous meningitis was 4.1 to 15.5 micrograms/ml at 1 hours after administration. (4) Clinical results The clinical efficacy was judged "good" or "excellent" in 2 of the 3 patients with septicemia and in all of the 10 patients with suspected septicemia. It was judged "excellent" in all of the 9 patients with pneumonia, 3 with urinary tract infections and 3 with intrauterine infections. Prophylactic use of the antibiotic was effective in all of the 12 patients. Of the patients in whom bacteriological evaluation was successful, 7 of the 10 causative organisms were confirmed to be eradicated. No adverse drug reactions of signs and symptoms were recognized. Fourteen abnormal alterations of the laboratory test values such as elevation of gamma-GTP and that of GPT were recognized in 8 patients (16.7%). None of them were particularly serious. These results indicate that CZOP is a drug useful for treatment and prevention of infections in infants with lower birth weights as well as in mature infants.	Y. Sato, K. Sunakawa, H. Akita, S. Iwata, T. Yokota and Y. Kusumoto	Jpn J Antibiot
604	Cefepime vs. ceftazidime treatment of pyelonephritis: A European, randomized, controlled study of 300 pediatric cases	Background. Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. Methods. Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual resuLts were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The iv treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. Results. The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of iv study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of iv treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (9%) and in 10 ceftazidime patients (7%). Conclusions. Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	U. B. Schaad, J. Eskola, D. Kafetzis, M. Fishbach, S. Ashkenazi, V. Syriopoulou, J. Boulesteix, P. V. De, J. J. Gres, C. Rollin, J. Astruc, E. Mallet, G. E. Le, J. P. Carriere, I. Marosvari, M. Cizman, F. Asensi-Botet, A. Bensman, P. Francois, K. Boven, J. C. Borderon, G. Syrogiannopoulos, C. Rodrigo, R. Hernandez-Marco, L. B. Le, M. Borte, M. Isacsohn, D. Engelhard, L. Gothefors, J. Guggenbichler, J. C. Pautard, M. Nuutinen, J. Kimpen, J. Roord, Z. Meszner, J. Slany, I. Tessin, J. Misselwitz, A. Bourillon, C. Olivier, J. Cervilla, I. Helin and D. Muller-Wiefel	Pediatric Infectious Disease Journal
678	Cefepine vs. ceftazidime treatment of pyelonephritis: a European, randomized, controlled study of 300 pediatric cases. European Society for Paediatric Infectious Diseases (ESPID) Pyelonephritis Study Group	BACKGROUND: Cefepime has been used in clinical therapeutic trials for meningitis, serious infection and febrile neutropenia, comprising more than 800 pediatric patients. This agent has also been used in patients 12 years of age and older with uncomplicated and complicated urinary tract infections including pyelonephritis, but not in younger patients. In this study the safety and efficacy of cefepime were compared with those of ceftazidime for treatment of pyelonephritis in pediatric patients younger than 12 years of age. METHODS: Two hundred ninety-nine pediatric patients (ages 1 month to 12 years) with pyelonephritis (300 episodes) were enrolled in a randomized, open label, multicenter trial. Individual results were evaluated by a blinded committee of experts. Cefepime was compared with ceftazidime, both administered parenterally at 50 mg/kg every 8 h. Patients were to receive the assigned study drug until at least 48 h after becoming afebrile. The i.v. treatment was then to be continued or replaced by oral trimethoprimsulfamethoxazole for a maximum of 12 to 14 days. RESULTS: The predominant causative pathogens were Escherichia coli, 88%; Proteus spp., 6%; Pseudomonas aeruginosa, 2%; and Klebsiella spp., 2%. Bacteriologic eradication was achieved in 96 and 94% of cefepime and ceftazidime patients, respectively, at the end of i.v. study drug treatment and was maintained in 94 and 91%, respectively, at the end of total study therapy. After study therapy bacteriologic eradication was maintained after 4 to 6 weeks in 86% of cefepime cases and in 83% of ceftazidime cases. A satisfactory clinical response occurred in 98 and 96% of cefepime and ceftazidime patients, respectively, at the end of i.v. treatment and in 93% at the end of total study therapy in both treatment arms. Drug-related clinical adverse events occurred in 14 cefepime patients (91%) and in 10 ceftazidime patients (7%). CONCLUSIONS: Cefepime and ceftazidime are equally safe and efficacious treatment for pyelonephritis in pediatric patients.	U. B. Schaad, J. Eskola, D. Kafetzis, M. Fishbach, S. Ashkenazi, V. Syriopoulou, J. Boulesteix, V. Pril, J. J. Grès and C. Rollin	The Pediatric infectious disease journal
392	An extended experience with cefuroxime therapy of childhood bacterial meningitis	Eighty-four pediatric patients with bacterial meningitis were prospectively evaluated while receiving cefuroxime (200 mg/kg/day in four equal intravenous doses) as single-drug therapy for 9 to 13 days. Six cases were admitted in extremis and died within a few hours because of irreversible central nervous system damage or shock. The remaining 78 patients were cured, and prompt bacteriological and clinical responses were noted. The pathogens were Haemophilus influenzae b (43 cases), Neisseria meningitidis (20 cases), Streptococcus pneumoniae (10 cases) and unknown (five cases). All pathogens were susceptible in vitro to cefuroxime including two strains of beta-lactamase producing H. influenzae. Time to defervescence, incidence and cause of both prolonged and secondary fever, as well as type and frequency of complications and sequelae compared favorably to other series. It is concluded that cefuroxime is effective and safe single-drug therapy for childhood bacterial meningitis beyond the neonatal age group	U. B. Schaad, J. Krucko and J. Pfenninger	Pediatric Infectious Disease
612	Randomized trial of donor human milk versus preterm formula as substitutes for mothers' own milk in the feeding of extremely premature infants	OBJECTIVE: Compared with preterm formula (PF), mother's milk (MM) is associated with lower rates of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) among premature infants. Because not all mothers of premature infants produce sufficient milk to supply their infants throughout hospitalization, we reasoned that pasteurized donor human milk (DM) would be a suitable alternative. METHODS: Extremely premature infants (<30 weeks of gestation) whose mothers intended to breastfeed were assigned randomly to receive either pasteurized DM or PF if the supply of their own MM became insufficient during the study (birth to 90 days of age or hospital discharge). Infection-related events (LOS, NEC, meningitis, presumed sepsis, or urinary tract infection) that occurred after the attainment of a milk intake of 50 mL/kg, dietary intake, growth, skin-to-skin contact, and duration of hospital stay were compared. The primary analysis compared groups DM and PF on an intent-to-treat basis. If no differences were noted, then these groups were combined and compared with the reference group, group MM. If differences were noted, then the subsequent analyses compared each group with group MM. RESULTS: Of 243 infants, 70 (29%) received only MM; group DM included 81 infants and group PF included 92 infants. Because of poor weight gain, 17 infants (21%), all in group DM, were switched to PF. There were no differences in birth weight, gestational age, multiple births, and age at attainment of feeding of 50 mL/kg among groups. There were no differences between group DM and group PF in LOS and/or NEC, other infection-related events, hospital stay, or number of deaths. Group DM received a greater intake of milk and more nutritional supplements but had a slower rate of weight gain, compared with group PF. Compared with groups DM and PF, group MM had fewer episodes of LOS and/or NEC and total infection-related events and a shorter duration of hospital stay. Group MM also had fewer Gram-negative organisms isolated from blood cultures than did the other groups. CONCLUSIONS: In this randomized, blinded trial of feeding of extremely premature infants, we found that, as a substitute for MM, DM offered little observed short-term advantage over PF for feeding extremely premature infants. Advantages to an exclusive diet of MM were observed in terms of fewer infection-related events and shorter hospital stays.	R. J. Schanler, C. Lau, N. M. Hurst and E. O. Smith	Pediatrics
687	Antibiotic prophylaxis in cerebrospinal fluid shunting: a prospective randomized trial in 152 hydrocephalic patients	The authors report a prospective, randomized 18-month study on the effect of prophylactic antibiotic treatment in 152 hydrocephalic patients in whom clean shunt operations or revisions were done. The treated group received methicillin (totally 200 mg/kg) divided into six i.v. doses during 24 hours starting at the induction of anesthesia. Patients allergic to penicillin received erythromycin instead. Seventy-nine patients received antibiotics, and 73 (the control group) received none. All patients were followed at least 6 months after operation or to their death. Eleven patients developed signs of infection, giving an overall infection rate of 7.2%; however, the infection occurred less than 1 month after the operation in only half of these. Six of the patients had septicemia, 4 had peritonitis, and 1 had meningitis. In the treated group, the infection rate was 8.9%; in the control group, the rate was 5.5%. There was no statistically significant difference. The prophylactic antibiotic regimen in this investigation did not reduce the infection rate connected with cerebrospinal fluid shunting procedures.	K. Schmidt, F. Gjerris, O. Osgaard, E. F. Hvidberg, J. E. Kristiansen, B. Dahlerup and C. Kruse-Larsen	Neurosurgery
80	Importance of antibodies to lipopolysaccharide in natural and vaccine-induced serum bactericidal activity against Neisseria meningitidis group B	Analysis of the specificity of bactericidal antibodies in normal, convalescent, and postvaccination human sera is important in understanding human immunity to meningococcal infections and can aid in the design of an effective group B vaccine. A collection of human sera, including group C and group B convalescent-phase sera, normal sera with naturally occurring cross-reactive bactericidal activity, and some postvaccination sera, was analyzed to determine the specificity of cross-reactive bactericidal antibodies. Analysis of human sera using a bactericidal antibody depletion assay demonstrated that a significant portion of the bactericidal activity could be removed by purified lipopolysaccharide (LPS). LPS homologous to that expressed on the bactericidal test strain was most effective, but partial depletion by heterologous LPS suggested the presence of antibodies with various degrees of cross-reactivity. Binding of anti-L3,7 LPS bactericidal antibodies was affected by modification of the core structure, suggesting that these functional antibodies recognized epitopes consisting of both core structures and lacto-N-neotetraose (LNnT). When the target strain was grown with 5'-cytidinemonophospho-N-acetylneuraminic acid (CMP-NANA) to increase LPS sialylation, convalescent-phase serum bactericidal titers were decreased by only 2- to 4-fold, and most remaining bactericidal activity was still depleted by LPS. Highly sialylated LPS was ineffective in depleting bactericidal antibodies. We conclude that natural infections caused by strains expressing L3,7 LPS induce persistent, protective bactericidal antibodies and appear to be directed against nonsialylated bacterial epitopes. Additionally, subsets of these bactericidal antibodies are cross-reactive, binding to several different LPS immunotypes, which is a useful characteristic for an effective group B meningococcal vaccine antigen.	D. H. Schmiel, E. E. Moran, P. B. Keiser, B. L. Brandt and W. D. Zollinger	Infection and immunity
2	Two versus three doses of a meningococcal C conjugate vaccine concomitantly administered with a hexavalent DTaP-IPV-HBV/Hib vaccine in healthy infants	The immunogenicity and reactogenicity of a meningococcal serogroup C (MenC) conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib vaccine according to a two- or three-dose schedule in healthy infants was evaluated. At 1 month post-vaccination, 98% (two doses) and 100% (three doses) of subjects had serum bactericidal antibody using human complement assay (hSBA) titres > or =1:8; at 12 months of age > or =89% of subjects in each group remained seroprotected. Induction of immunological memory, as evaluated by administration of a meningococcal serogroup A/C polysaccharide vaccine challenge dose, was similar for both regimens and no interference was observed in the immune response to MenC or hepatitis B virus antigens. Reactogenicity was similar in each group. MenC conjugate vaccine given concomitantly with DTaP-IPV-HBV/Hib to healthy infants in the first year of life using a two-dose schedule is as safe and immunogenic as a three-dose regimen.	H. J. Schmitt, K. S. Steul, A. Borkowski, F. Ceddia, E. Ypma and M. Knuf	Vaccine
483	Purulent meningitis - Treatment and prognosis		P. Schmuziger and T. Wegmann	Schweiz Med Wochenschr
578	Induction of serum Haemophilus influenzae type B capsular antibodies in adult volunteers fed cross-reacting Escherichia coli 075:K100:H5	Serum Haemophilus influenzae Type b (HITB) anticapsular antibodies were induced in adult volunteers by feeding of either of two strains of a cross-reacting Escherichia coli 075:K100:H5. In all the fed volunteers colonization for a finite period lasting up to eight weeks occurred, without adventitious reactions. Nine of 14 normal volunteers and one of two volunteers previously immunized with the Type 6 H.influenzae polysaccharide responded with a greater than twofold increase in serum Type 6H. influenzae antibodies. These antibodies induced by Esch. coli were specific for the capsular polysaccharide and had bactericidal activity. The safety of this procedure, the comparable results in laboratory animals and the identification of other cross-reacting strains of Esch. coli with meningococcal and pneumococcal capsular polysaccharides suggest that colonization with these nonpathogenic organisms at birth may provide a general method of preventive immunization to diseases caused by encapsulated bacteria.	R. Schneerson and J. B. Robbins	The New England journal of medicine
317	Tuberculous hydrocephalus: comparison of different treatments with regard to ICP, ventricular size and clinical outcome	The effect of different treatment regimes on intracranial pressure (ICP), degree of hydrocephalus and clinical outcome was evaluated in 81 children with tuberculous meningitis. 24 children underwent CSF shunting, while 57 with communicating hydrocephalus were randomly assigned to three treatment groups: antituberculous drugs only; or additional intrathecal hyaluronidase or oral acetazolamide and furosemide in addition to antituberculous treatment. The addition of acetazolamide and furosemide was significantly more effective in achieving normal ICP than antituberculous drugs alone. No difference was found in mortality or number of disabled survivors between groups. Of those surviving, nearly two-thirds with stage II tuberculous meningitis were mildly disabled and nearly one-half with stage III were severely disabled at follow-up, emphasising the need for early diagnosis of tuberculous meningitis in the young child.	J. Schoeman, P. Donald, L. Zyl, M. Keet and J. Wait	Developmental medicine and child neurology
367	Thalidomide therapy in childhood tuberculous menigitis		J. F. Schoeman	Journal of child neurology
292	The effect of adjuvant steroid treatment on serial cerebrospinal fluid changes in tuberculous meningitis	Three recent studies found that corticosteroids improve clinical outcome and mortality in tuberculous meningitis (TBM), although the exact mechanism of action of the drug remains speculative. A number of reports on the effect of corticosteroids on cerebrospinal fluid (CSF) findings in TBM have been published, often with conflicting results regarding serial cell counts and protein levels. As part of a controlled, randomized trial on the effect of oral prednisone on outcome in childhood TBM at our institution, CSF was collected and analysed weekly during the 1st month of treatment. We found no significant difference in serial CSF cell counts between the steroid and non-steroid groups in the study. However, the steroid group had significantly lower CSF protein and globulin levels after the 1st month of treatment, and a more steady rise in CSF glucose levels than the non-steroid group. Knowledge of the different CSF responses during the course of anti-tuberculosis therapy is important in clinical decision-making.	J. F. Schoeman, J. W. Elshof, J. A. Laubscher, A. Janse van Rensburg and P. R. Donald	Annals of tropical paediatrics
286	Effect of corticosteroids on intracranial pressure, computed tomographic findings, and clinical outcome in young children with tuberculous meningitis	OBJECTIVE: To study the effect of highdose prednisone on intracranial pressure (ICP), cranial computed tomographic (CT) findings, and clinical outcome in young children with moderate to severe tuberculous meningitis (TBM). STUDY DESIGN: Prospective, controlled, randomized study. METHODS: Continuous lumbar, cerebrospinal fluid pressure monitoring and contrasted CT scanning were performed in 141 consecutive children with TBM at admission. All children were then randomly allocated to a nonsteroid group (71 children) or a steroid group (70 children) who received prednisone (first 16 children, 2 mg/kg per day; next 54 children, 4 mg/kg per day) for the first month of treatment. ICP monitoring and CT scanning were repeated regularly, and clinical outcome was assessed after 6 months of antituberculosis treatment. RESULTS: No statistically significant difference in ICP or the degree of hydrocephalus (as demonstrated by CT scan) was found between the steroid and nonsteroid groups after the first month of treatment. Basal ganglia infarcts developed in 16% of children in the steroid group and 24% in the nonsteroid group during the first month of treatment. Neither this incidence nor the eventual size of infarcts present at admission differed significantly between the two treatment groups. Single or multiple tuberculomas were seen on the first CT scans of 7 children (5%), whereas tuberculomas developed in 11 children (8%) at treatment. Both the response of the tuberculomas to treatment and the incidence of new tuberculomas were significantly improved by steroid therapy. Basal enhancement was also significantly less in the steroid group after 1 month of treatment. Steroids lowered mortality in stage III TBM significantly. Similarly, more surviving children in the steroid group had IQs of greater than 75 than did the those in the nonsteroid group. No significant difference was found in the incidence of motor deficit, blindness, or deafness. CONCLUSIONS: Corticosteroids significantly improved the survival rate and intellectual outcome of children with TBM. Enhanced resolution of the basal exudate and tuberculomas by steroids was shown by serial CT scanning. Corticosteroids did not affect ICP or the incidence of basal ganglia infarction significantly.	J. F. Schoeman, L. E. Zyl, J. A. Laubscher and P. R. Donald	Pediatrics
666	Causes of death in febrile granulocytopenic cancer patients receiving empiric antibiotic therapy	We reviewed the causes of death of 55 granulocytopenic patients who received empiric antibiotic treatment for fever according to an EORTC cooperative protocol; 53 presented cancer and 2 aplastic anemia. Among the 55 patients, 19 (35%) deaths were attributed to infection: 16 to bacterial and 3 to fungal infections. Among the patients with bacterial infections, 12 died from septic shock, 3 from pneumonia and 1 from Pseudomonas aeruginosa meningitis. The most frequent non-infectious causes of death were the cancer progression (18%) and hemorrhagic complications (27%), most often cerebromeningeal in relationship to thrombocytopenia. A large number of the patients who died from infection (78%) and hemorrhage (74%) had advanced cancer with poor chances to respond to anticancer therapy.	J. P. Sculier, D. Weerts and J. Klastersky	European journal of cancer & clinical oncology
499	Concerning the Treatment of Bacterial Meningitis. Examination Concerning the Crossing of Antibiotics from the Blood into the Cerebrospinal Fluid		K. Seelemann and B. Kornatz-Stegmann	Deutsche Medizinische Wochenschrift
458	Influence of serogroup B meningococcal vaccine antigens on growth and survival of the meningococcus in vitro and in ex vivo and in vivo models of infection		K. L. Seib, F. Oriente, J. Adu-Bobie, P. Montanari, F. Ferlicca, M. M. Giuliani, R. Rappuoli, M. Pizza and I. Delany	Vaccine
462	Vestibular deficits in deaf children	Considerable knowledge has been accumulated regarding acquired and congenital deafness in children. However, despite the intimate relationship between the auditory and vestibular systems, data are limited regarding the status of the balance system in these children. Using a test population of 15 children, aged 8 to 17 years, we performed electronystagmography testing. The test battery consisted of the eye-tracking (gaze nystagmus, spontaneous nystagmus, saccade, horizontal pursuit and optokinetic) tests, positional/positioning (Dix- Hallpike and supine) tests, and rotational chair tests. With age- matched controls, five children were tested in each of the following three categories: normal hearing, hereditary deafness, and acquired deafness. The children in the hereditary deafness category were congenitally deaf and had a family history of deafness. Those subjects in the acquired deafness category had hearing loss before the age of 2 years, after meningitis. Analysis of variance demonstrated significant differences between the two deaf groups and the control subjects in the gaze nystagmus test, saccade latencies, horizontal pursuit phase, and Dix-Hallpike and supine positionally provoked nystagmus. Also, significant differences were found in rotational chair gain and phase between the deaf and normal-hearing children. The children with acquired deafness exhibited the most profound results. In addition, there were significant differences in rotational chair gain between the acquired and congenitally deaf children. No differences were noted in horizontal pursuit gains, saccade accuracies, or saccade asymmetries. These preliminary data demonstrate that the etiologic factors responsible for congenital and acquired deafness in children may indeed affect the balance system as well. These findings of possible balance disorders in conjunction with the profound hearing loss in this patient population will have prognostic implications in the future evaluation, treatment, and rehabilitation of these patients.	P. A. Selz, M. Girardi, H. R. Konrad and L. F. Hughes	Otolaryngol Head Neck Surg
184	Evaluation of therapeutic regimens in pyogenic meningitis		M. D. Shah, M. K. Jain, M. Kulkarni, A. Tiku and U. Mhaiskar	Indian pediatrics
52	Placental and breast transfer of antibodies after maternal immunization with polysaccharide meningococcal vaccine: a randomized, controlled evaluation	We evaluated the strategy of maternal immunization with Neisseria meningitidis (Nm) vaccine in Asian mothers, to assess potential protection of infants, including by breast milk. One hundred and fifty-seven women in the third trimester were randomized to receive a single dose of the polysaccharide Nm (n=75) or a control vaccine (n=82). Group A Nm IgG levels were measured in maternal and infant sera, and specific IgA in breast milk. A 5.6-fold rise of Nm IgG antibody was observed among the Nm vaccinees. At delivery, geometric mean titres (GMTs) of Nm IgG antibody in Nm mothers was 12.5 microg/ml versus 4.97 microg/ml, with a mean infant/maternal antibody ratio of 0.56. Infants of Nm vaccinees had mean IgG levels of 6.9, 2.3, 1.2 and 0.6 microg/ml at 0, 6, 14 and 22 weeks, significantly higher than in control children up to 14 weeks. Anti-Nm IgA levels in milk were 6.8 to 2.0 microg/ml, significantly higher in Nm vaccinees till 6 months. Immunization during pregnancy is safe for both mothers and infants, and provides infants with significantly increased levels of specific IgG for 2-3 months and oral IgA for 6 months.	N. S. Shahid, M. C. Steinhoff, E. Roy, T. Begum, C. M. Thompson and G. R. Siber	Vaccine
102	Rapid diagnosis of tuberculous meningitis by polymerase chain reaction	The polymerase chain reaction (PCR) in cerebrospinal fluid was compared with conventional bacteriology and an enzyme-linked immunosorbent assay (ELISA) for cerebrospinal fluid antibodies in the diagnosis of tuberculous meningitis (TBM). PCR was the most sensitive technique; it detected 15 (75%) of 20 cases of highly probable TBM (based on clinical features), 4 (57%) of 7 probable cases, and 3 (43%) of 7 possible cases. ELISA detected 11 (55%) of the highly probable cases and 2 each of the probable and possible cases. Culture was positive in only 4 of the highly probable cases. Among the controls (14 pyogenic meningitis, 3 aseptic meningitis, 34 other neurological disorders), 6 subjects tested early in the study (2 pyogenic meningitis, 4 other disorders) were PCR positive. Second DNA preparations from their stored cerebrospinal fluid samples were all PCR negative, suggesting that the false-positive results were due to cross-contamination. 18 PCR-positive TBM samples retested were all still PCR positive. The antibody ELISA was positive in 3 controls despite the use of a high cutoff value.	P. Shankar, N. Manjunath, K. K. Mohan, K. Prasad, M. Behari, n. Shriniwas and G. K. Ahuja	Lancet
233	Randomized clinical trial of intra-operative antimicrobial prophylaxis of infection after neurosurgical procedures	A randomized, placebo-controlled, double-blind and sequentially analysed clinical trial to determine the efficacy of intra-operative parenteral gentamicin and vancomycin (with streptomycin in the irrigating solution) in preventing infection at the operative site following neurosurgical procedures is described. Patients receiving prophylaxis had a significantly (P = 0.046) lower operative site infection rate (2/71 = 2.8%) than those receiving placebo (9/77 = 11.7%). This difference was most apparent during an epidemic, the source of which was not evident. Moreover, a total of 13 infections (two operative site, five pneumonia and six urinary tract) occurred among 12 patients receiving prophylaxis, whereas there was a total of 31 infections (nine operative site, nine pneumonia, 10 urinary tract and three septicaemia) among 24 patients receiving placebo. A smaller quantity of antimicrobial drugs was administered postoperatively to patients receiving prophylaxis (3.96 'antibiotic-days' per patient) than to those receiving placebo (6.87 'antibiotic-days' per patient).	M. Shapiro, U. Wald, E. Simchen, S. Pomeranz, D. Zagzag, S. D. Michowiz, E. Samuel-Cahn, Y. Wax, R. Shuval and Y. Kahane	The Journal of hospital infection
543	A randomized phase III/IV study to determine benefit and safety of cytarabine liposome injection for treatment of neoplastic meningitis	42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta,GA, 2-6 June, 2006	W. R. Shapiro, M. Schmid, M. Glantz and J. J. Miller	Journal of Clinical Oncology: ASCO annual meeting proceedings
328	Amphotericin B lipid complex compared with amphotericin B in the treatment of cryptococcal meningitis in patients with AIDS	The study objective was to obtain preliminary information regarding the safety and efficacy of amphotericin B (AmB) lipid complex (ABLC) in the treatment of AIDS-associated cryptococcal meningitis. Of 55 patients randomly assigned to 6 weeks of therapy with ABLC (1.2-5.0 mg/[kg.d], with ascending doses for three sequential cohorts) or AmB (0.7-1.2 mg/[kg.d]), 46 received > or = 12 doses. Transfusion requirements, mean decreases in hemoglobin level, and mean increases in creatinine level were significantly greater with AmB than with ABLC. The total number of adverse events, infusion-related events, and occurrences of hypomagnesemia and hypokalemia associated with each form of therapy were similar. Among 21 recipients of ABLC at a dosage of 5 mg/kg (daily for 2 weeks and then thrice weekly for 4 weeks), symptoms and signs resolved for 18 (86%). Of those receiving > or = 12 doses of ABLC, cultures converted to negative for 8 (42%), were undeterminable for 3 (16%), and remained positive for 8 (42%) despite resolution of symptoms. Although preliminary, these data suggest ABLC has significant activity in patients with AIDS-associated cryptococcal meningitis. Because this formulation has less hematologic and renal toxicity than does AmB, further evaluation of ABLC is warranted.	P. K. Sharkey, J. R. Graybill, E. S. Johnson, S. G. Hausrath, R. B. Pollard, A. Kolokathis, D. Mildvan, P. Fan-Havard, R. H. Eng, T. F. Patterson, J. C. Pottage, M. S. Simberkoff, J. Wolf, R. D. Meyer, R. Gupta, L. W. Lee and D. S. Gordon	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
178	No demonstrable association between the Leningrad-Zagreb mumps vaccine strain and aseptic meningitis in a large clinical trial in Egypt	To address the claim that the Leningrad-Zagreb (L-Z) mumps vaccine strain is causally associated with aseptic meningitis, a prospective, post-marketing safety study was conducted with a measles-mumps-rubella vaccine (MMR) (TRESIVAC(R); Serum Institute of India Ltd., Pune, India), which uses the L-Z strain as its mumps component in Egypt. In all, 453 119 children (65 423 children aged 16-24 months and 329 211 children aged 5-7 years) received MMR. The control groups which, as a result of local health regulations, were slightly younger than vaccinees, comprised 12 253 and 46 232 children, respectively. Using questionnaires, the parents recorded solicited local, systemic and neurological adverse events for up to 42 days post-vaccination. All data were analysed externally on an intention-to-treat basis by individuals not participating in the study. Local and/or systemic reactions were reported in a small percentage of participants, with pain, fever and parotitis being the most common signs among vaccinees in both age groups. No case of aseptic meningitis, encephalitis, anaphylaxis or convulsions was observed in any participant. Thus, in this series of more than 450 000 Egyptian children, the L-Z mumps vaccine strain in this vaccine did not cause aseptic meningitis. The vaccine is considerably cheaper than Western competitors and a valid alternative to other MMR vaccines.	H. J. Sharma, S. A. Oun, S. S. Bakr, S. V. Kapre, S. S. Jadhav, R. M. Dhere and S. Bhardwaj	Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
349	Intravenous chloramphenicol plus penicillin versus intramuscular ceftriaxone for the treatment of pyogenic meningitis in Nepalese children		P. R. Sharma, R. K. Adhikari, M. P. Joshi, M. Lal, T. Chodon, B. M. Pokhrel, R. S. Shrestha and I. B. Shrestha	Tropical doctor
291	Dexamethasone as an adjunctive treatment of bacterial meningitis	This study was conducted on 77 Libyan infants and children aged month to 10 years with acute bacterial meningitis. Upon admission, the patients were divided randomly in two groups. Group I (38 patients) received ceftriaxone plus dexamethasone i.v. Group II (39 patients) received ceftriaxone alone. Both groups were compared for mean changes in CSF sugar, CSF protein and CSF polymorph count at 4th day of treatment. There was a significant difference between the two groups in CSF sugar and protein changes (P < 0.05) but not in CSF polymorph (P > 0.05). Both groups showed prompt clinical response and similar occurrence of acute complications, fatality rate and permanent neurological sequelae. However, group I manifested shorter duration of fever (P < 0.05). Dexamethasone improved the inflammatory reaction in acute bacterial meningitis and shortened the duration of fever but it did not have any significant effect on the fatality and the occurrence of neurological sequelae of this disease.	N. M. Shembesh, S. M. Elbargathy, I. M. Kashbur, B. N. Rao and K. S. Mahmoud	Indian journal of pediatrics
384	[Safety and immunogenicity of groups A + C meningococcal conjugate vaccine] LA: Chi	Objective: To observe the safety and immunogenicity of freeze-dried groups A + C meningococcal conjugate vaccine. Methods: A double-blind, randomized and parallel controlled clinical trial was carried out in the children at ages of 6-9 months and not less than 3 years. The children in trial groups were immunized with freeze-dried groups A + C meningococcal conjugate vaccine. However, in control groups, the children at ages of 6-9 months were immunized with group A meningococcal polysaccharide vaccine, while those at ages of not less than 3 years with groups A + C meningococcal polysaccharide vaccine. The adverse reaction, serum antibody content and antibody positive conversion rate after immunization were observed. Results: The systemic adverse reaction rates in the children at ages of 6-9 months in trial and control groups were 1.67% and 4.58%, while those of local adverse reaction rates were 0.83% and 2.08%, respectively. However, the systemic adverse reaction rates in the children at ages of not less than 3 years in trial and control groups were 2.50% and 3.33% respectively, while those of local adverse reaction rates were both 0.83%. The contents of antibody against group A meningococcus in sera of children at ages of 6-9 months in trial and control groups were 22.27 and 3.61 mug/ml, while the antibody positive conversion rates were 99.01% and 66.67%, respectively, which showed significant difference (P < 0.05). The contents of antibodies against groups A and C menigococcus in sera of children at ages of not less than 3 years in trial group were 21.28 and 17.94 mug/ml, while the antibody positive conversion rates were 99.04% and 98.08%, respectively. However, in the sera of children at ages of not less than 3 years in control group, the contents of antibodies against groups A and C menigococcus were 34.43 and 22.66 mug/ml respectively, while the antibody positive conversion rates were both 98.04%. The antibody contents of children at ages of not less than 3 years in trial and control groups showed significant difference (P < 0.05), while the antibody positive conversion rates showed no significant difference (P > 0.05). Conclusion: Freeze-dried groups A + C meningococcal conjugate vaccine showed high safety and immunogenicity in the children at ages of 6-9 months and not less than 3 years.	N. M. Shi, Y. Qu, X. Ai, R. T. Pang, Y. H. Bai, L. Q. Yang and J. Wu	Chinese Journal of Biologicals
635	Effects of prophylactic intrathecal administrations of nicardipine on vasospasm in patients with severe aneurysmal subarachnoid haemorrhage	Calcium antagonists are currently most widely used for chronic cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). However, the vasodilatory effects of systemically administered calcium antagonists can be limited secondary to hypotension. We previously compared intrathecal and intravenous routes of administration of nicardipine. Intrathecal administration of nicardipine significantly dilated spastic basilar arteries on day 7 in a two-haemorrhage canine model of vasospasm. In the present communication, the effects of prophylactic, serial administration of intrathecal nicardipine on vasospasm was examined in 50 patients. Patients were classified as Fisher SAH group 3 and all had their aneurysms clipped within 3 days of SAH. Following placement of a cisternal drain, 2 mg of nicardipine was injected, three times each day for an average of 10 days. The control group consisted of 91 similar patients with cisternal drainage not treated with nicardipine. Intrathecal administration of nicardipine decreased the incidence of symptomatic vasospasm by 26%, angiographic vasospasm by 20% and increased good clinical outcome at one month after the haemorrhage by 15%. Postoperative angiograms revealed that patients in the nicardipine group showed less vasospasm of major cerebral arteries, near the tip of a drain in the basal cistern, but vasospasm in the A2 and M2 segments was not decreased. Radio-isotope cisternography suggested that nicardipine might not reach the subarachnoid space around A2 and M2 segments. Nine patients complained of headache probably secondary to nicardipine induced vasodilation. Two patients suffered from meningitis, both were successfully treated. Intrathecal administration nicardipine appears to be effective in the treatment of vasospasm, but side effects were significant.	M. Shibuya, Y. Suzuki, H. Enomoto, T. Okada, K. Ogura and K. Sugita	Acta neurochirurgica
182	Efficacy, immunogenicity and safety of heptavalent pneumococcal conjugate vaccine in low birth weight and preterm infants	OBJECTIVE: To determine the efficacy, immunogenicity and safety of the heptavalent CRM197 pneumococcal conjugate vaccine (PCV) in low birth weight (LBW) and preterm (PT) infants against invasive pneumococcal disease caused by vaccine types. METHODS: In a randomized double blind trial of 37,868 infants given either PCV or meningococcal type C conjugate vaccine (MCV), 1756 infants <750 g <2500 g (LBW) and 4340 infants from 32 to <38 weeks old (PT) were identified. Risk of invasive pneumococcal disease in LBW and PT infants was compared with risk in normal birth weight (NBW) and full term (FT) infants. Local and systemic events observed within 48 h of recent vaccine were assessed by telephone interviews and similar comparisons made. Premature infant Emergency Department visits and hospitalization were also identified and compared with FT and NBW infants. RESULTS: Initiation of immunization and intervals between doses were similar for all groups. The risk ratio for invasive pneumococcal diseases for LBW infants compared with NBW infants was 2.6 (P = 0.03), and for PT compared with FT infants the risk ratio was 1.6 (P = 0.06). Vaccine efficacy for both groups was 100%. PCV was as immunogenic in LBW and PT as in NBW and FT infants. Fever and local events after PCV vaccination were similar when adjusted for clustering among multiple doses per child. When stratified for individual doses there was more redness and swelling for LBW infants and more swelling for PT infants after Dose 3. Isolated local and systemic reactions were more commonly seen with PCV than with MCV, a pattern similar to that in NBW and FT infants. Hospitalization rates were similar for PCV and MCV recipients. CONCLUSION: These data support the use of PCV in LBW infants and PT infants.	H. Shinefield, S. Black, P. Ray, B. Fireman, J. Schwalbe and E. Lewis	The Pediatric infectious disease journal
470	A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure	Object. The criteria for the use of mild hypothermia (34[degrees]C) in severely head injured patients have not been standardized. A prospective randomized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure (ICP). Methods. At 11 medical centers, 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided randomly into two groups: the mild hypothermia group (HT group, 45 patients) and the normothermia group (NT group, 46 patients). Patients in the HT group were exposed to mild hypothermia (34[degrees]C) for 48 hours, followed by rewarming at 1[degrees]C per day for 3 days, whereas patients in the NT group were exposed to normothermia (37[degrees]C) for 5 days. The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome at 3 months postinjury. During treatment, there was a significantly greater use of neuromuscular blocking agents in the HT group (p = 0.011). During the initial 2 weeks postinjury, the incidences of pneumonia, meningitis, leukocytopenia, thrombocytopenia, hypernatremia, hypokalemia, and hyperamylasemia were significantly higher in the HT than in the NT group (p < 0.05). Conclusions. Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients. Number of References 9. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	T. Shiozaki, T. Hayakata, M. Taneda, Y. Nakajima, N. Hashiguchi, S. Fujimi, Y. Nakamori, H. Tanaka, T. Shimazu and H. Sugimoto	Journal of Neurosurgery
686	A multicenter prospective randomized controlled trial of the efficacy of mild hypothermia for severely head injured patients with low intracranial pressure. Mild Hypothermia Study Group in Japan	OBJECT: The criteria for the use of mild hypothermia (34 degrees C) in severely head injured patients have not been standardized. A prospective randomized controlled trial was conducted to determine whether mild hypothermia is essential in the treatment of severely head injured patients with low intracranial pressure (ICP). METHODS: At 11 medical centers, 91 severely head injured patients with an admission Glasgow Coma Scale score of 8 or less in whom ICP could be maintained below 25 mm Hg by conventional therapies were divided randomly into two groups: the mild hypothermia group (HT group, 45 patients) and the normothermia group (NT group, 46 patients). Patients in the HT group were exposed to mild hypothermia (34 degrees C) for 48 hours, followed by rewarming at 1 degrees C per day for 3 days, whereas patients in the NT group were exposed to normothermia (37 degrees C) for 5 days. The two groups were similar with respect to prognostic factors, and there was no difference in clinical outcome at 3 months postinjury. During treatment, there was a significantly greater use of neuromuscular blocking agents in the HT group (p = 0.011). During the initial 2 weeks postinjury, the incidences of pneumonia, meningitis, leukocytopenia, thrombocytopenia, hypernatremia, hypokalemia, and hyperamylasemia were significantly higher in the HT than in the NT group (p < 0.05). CONCLUSIONS: Mild hypothermia should not be used for the treatment of severely head injured patients with low ICP because this therapy conveys no advantage over normothermia in such patients.	T. Shiozaki, T. Hayakata, M. Taneda, Y. Nakajima, N. Hashiguchi, S. Fujimi, Y. Nakamori, H. Tanaka, T. Shimazu and H. Sugimoto	Journal of neurosurgery
424	Phase I/II, open-label trial of safety and immunogenicity of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human immunodeficiency virus-infected adolescents	BACKGROUND: Quadrivalent meningococcal polysaccharide conjugate vaccine (MCV4) is routinely recommended for healthy youth in the United States, but there are no data about its use in HIV-infected people. METHODS: P1065 is a Phase I/II trial of MCV4 safety and immunogenicity in HIV-infected children and youth performed at 27 US sites of the IMPAACT network. All youth (11-24 years old) received 1 dose of open-label MCV4 at entry. Standardized questionnaires were used to evaluate safety. Baseline protective immunity was defined as rabbit serum bactericidal antibody (rSBA) titer > or = 1:128. Immunogenic response was defined as a > or = 4-fold rise in rSBA against each meningococcal serogroup. Multivariable logistic regression analysis was used to evaluate the association of demographic and clinical characteristics on immunogenic response to serogroup C. RESULTS: Among 319 subjects who received MCV4, 10 (3.1%) reported immediate adverse events which were local and mild, and 7 (2.2%) experienced Grade > or = 3 adverse events, unrelated to vaccine. The 305 subjects with serologic data had a median age of 17 years and were 59% male, 50% Black, and 38% Latino. Subjects were stratified by entry CD4%: 12%, CD4 <15%; 40%, 15% to 24%; and 48%, > or = 25%. Baseline protective immunity varied by serogroup: A, 41%; C, 11%; W-135, 15%; Y, 35% The immunogenic response rates to serogroups A, C, W-135, and Y were 68%, 52%, 73%, and 63%, respectively. In multivariable logistic regression models, lower entry CD4%, higher entry viral load, and CDC Class B/C diagnosis were associated with significantly lower odds of response to serogroup C. CONCLUSION: Many HIV-infected youth naturally acquire meningococcal immunity. MCV4 is safe and immunogenic in HIV-infected youth, but response rates are lower than in healthy youth, particularly for those with more advanced HIV clinical, immunologic, and virologic status.	G. K. Siberry, P. L. Williams, J. Lujan-Zilbermann, M. G. Warshaw, S. A. Spector, M. D. Decker, B. E. Heckman, E. F. Demske, J. S. Read, P. Jean-Philippe, W. Kabat and S. Nachman	Pediatric infectious disease journal
49	Relationship between serum bactericidal activity and serogroup-specific immunoglobulin G concentration for adults, toddlers, and infants immunized with Neisseria meningitidis serogroup C vaccines	A new meningococcal group C-CRM(197) conjugate vaccine (MnCC; Meningitec) has been evaluated in multiple clinical trials in the United States and most recently has been approved for routine administration in the United Kingdom. Meningococcal serogroup C (MnC)-specific immunoglobulin G (IgG) antibodies in pre- and postimmunization sera obtained from healthy U.S. adults, toddlers, and infants were quantitated by enzyme-linked immunosorbent assay (ELISA) and by an antibody-dependent, complement-mediated serum bactericidal assay (SBA). Serogroup-specific IgG antibody (micrograms per milliliter) in adults immunized either with the quadrivalent polysaccharide (A, C, Y, and W-135) vaccine or with MnCC showed a strong correlation (r = 0.848 and 0.934, respectively) by linear regression analysis with SBA. Sera from infants immunized with the MnCC (n = 30) and an age-matched unimmunized control group (n = 15) were also analyzed. Linear regression analysis of serum bactericidal and IgG ELISA data from sera obtained at 2 months of age (preimmunization) showed no correlation; however, a high degree of correlation was observed at time points after two (r = 0.877) and three (r = 0.951) immunizations, where significant rises in anti-MnC polysaccharide antibodies occurred relative to the age-matched control group. Infants previously primed with 3 doses of MnCC were given a booster dose of conjugate vaccine at 12 to 15 months of age. The correlation coefficient of ELISA to SBA for combined pre- and postbooster data was r = 0.836 (n = 48 pairs). In conclusion, increases in serum bactericidal activity in immunized adult, toddler, and infant populations were found to correlate very well with increases in serogroup-specific IgG concentrations, whereas the correlation between these two assays in nonimmunized 2-month-old infants was poor. Characterizing the relationship between these methods is important for understanding the significance of antigen-specific antibody concentrations relative to vaccine performance and protection from disease.	D. J. Sikkema, K. E. Friedman, B. Corsaro, A. Kimura, S. W. Hildreth, D. V. Madore and S. A. Quataert	Clinical and diagnostic laboratory immunology
647	Interleukin-6 and tumor necrosis factor-alpha levels in plasma and cerebrospinal fluid of term newborn infants with hypoxic-ischemic encephalopathy	OBJECTIVES: To determine plasma and cerebrospinal fluid (CSF) levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in hypoxic-ischemic encephalopathy (HIE). STUDY DESIGN: A controlled, prospective study of 20 control neonates, 19 term newborn infants presenting with sepsis and no meningitis, and 19 asphyxiated term newborn infants. Blood and CSF samples were collected within 48 hours of birth for IL-6 and TNF-alpha determinations. RESULTS: Median plasma IL-6 was similar in sepsis and asphyxia but significantly higher than in control neonates. Median plasma TNF-alpha was similar in asphyxia and control neonates but significantly lower than in sepsis. In asphyxiated newborn infants, median CSF IL-6 and TNF-alpha were significantly higher than in sepsis and control neonates. Median CSF IL-6 was significantly higher in sepsis than in control neonates. Median CSF TNF-alpha was similar in newborn infants with sepsis and control neonates. IL-6 and TNF-alpha CSF/plasma ratios were similar in newborn infants with sepsis and control neonates but lower than in asphyxiated newborn infants. CONCLUSIONS: Term newborn infants with HIE have elevated CSF IL-6 and TNF-alpha levels. Plasma IL-6 is increased in asphyxia and sepsis. Plasma TNF-alpha is increased only in sepsis. High IL-6 and TNF-alpha CSF/plasma ratios in asphyxia suggest that these cytokines are produced in the brain of term newborn infants with HIE.	R. C. Silveira and R. S. Procianoy	The Journal of pediatrics
552	Comparison of ceftriaxone and rifampicin in eliminating nasopharyngeal carriage of serogroup B neisseria meningitidis. [abstract]	Presented at the Annual Scientific Meeting of The Royal Australasian College of Physicians, Perth, Western Australia, 11-14 May, 1999..	G. Simmons, N. Jones and L. Calder	Australian & New Zealand Journal of Medicine
196	Equivalence of ceftriaxone and rifampicin in eliminating nasopharyngeal carriage of serogroup B Neisseria meningitidis	The efficacy of ceftriaxone in eliminating nasopharyngeal carriage of Neisseria meningitidis was compared with that of rifampicin during an epidemic of serogroup B meningococcal disease in Auckland, New Zealand. Household contacts of cases had a throat swab taken and were randomized to treatment. Carriers had a repeat swab taken 6 days later to determine efficacy of treatment. Ceftriaxone (98.2%) was equivalent to rifampicin (97.6%) in eliminating serogroup B N. meningitidis. It is cheaper than rifampicin and has the advantage of full compliance and fewer contraindications, but its acceptability by patients may limit its use as a first-line prophylactic agent.	G. Simmons, N. Jones and L. Calder	The Journal of antimicrobial chemotherapy
163	High resolution proton MR spectroscopy of cerebrospinal fluid in MS patients. Comparison with biochemical changes in demyelinating plaques	Proton magnetic spectroscopy (1H-MRS) investigation was performed on CSF samples of patients with neurological inflammatory diseases including 52 cases of multiple sclerosis (MS). 12 acute idiopathic polyneuropathies, 20 acute meningitides (10 viral and 10 bacterial). Spectra were compared with those acquired in 18 neurological controls. High CSF lactate levels were found in MS patients during clinical exacerbation of relapsing-remitting course (p = 0.036 vs neurological controls). In MS patients with MRI evidence of Gd-enhanced plaques CSF lactate was higher than in patients with MRI inactive plaques (p = 0.017). CSF lactate positivity correlated with number of CSF mononuclear cells in MS patients with clinical activity (p = 0.05) as well as in MS patients with MRI enhancement (p = 0.003). A comparative 1H-MRS investigation in vivo on localized demyelinating areas confirmed an elevated lactate signal in Gd-enhanced (61%) more frequently than in unenhanced (22%) plaques (p = 0.03). MS patients with high lactate signal in active plaques showed high lactate levels in CSF. Increased CSF lactate was found also in patients with acute meningitis and idiopathic polyneuropathy. These data suggest that changes in lactate levels may depend on anaerobic glycolytic metabolism in activated leukocytes during inflammatory diseases. A decrease of CSF formulate levels was found in MS patients during active and inactive clinical phase (p = 0.037, p=0.05 vs neurological controls respectively). Formate changes might be related to a disorder of choline-glycine cycle in MS. 1H-MRS in vivo showed significant increase of choline in acute plaques, whereas a decrease of N-acetyl aspartate was found in chronic plaques; these metabolites are undetectable in CSF. CSF glucose levels were lower in bacterial than in viral meningitis (p = 0.014) and in neurological controls (p = 0.05). These observations suggest that 1H-MRS may be able to detect CSF metabolic impairment in neurological inflammatory diseases. In MS some CSF findings reflect metabolic changes occurring in brain demyelinating areas, and they could be useful foe evaluation of disease activity in different stages of disease evolution.	I. L. Simone, F. Federico, M. Trojano, C. Tortorella, M. Liguori, P. Giannini, E. Picciola, G. Natile and P. Livrea	Journal of the neurological sciences
351	Low diversity Cryptococcus neoformans variety grubii multilocus sequence types from Thailand are consistent with an ancestral African origin	The global burden of HIV-associated cryptococcal meningitis is estimated at nearly one million cases per year, causing up to a third of all AIDS-related deaths. Molecular epidemiology constitutes the main methodology for understanding the factors underpinning the emergence of this understudied, yet increasingly important, group of pathogenic fungi. Cryptococcus species are notable in the degree that virulence differs amongst lineages, and highly-virulent emerging lineages are changing patterns of human disease both temporally and spatially. Cryptococcus neoformans variety grubii (Cng, serotype A) constitutes the most ubiquitous cause of cryptococcal meningitis worldwide, however patterns of molecular diversity are understudied across some regions experiencing significant burdens of disease. We compared 183 clinical and environmental isolates of Cng from one such region, Thailand, Southeast Asia, against a global MLST database of 77 Cng isolates. Population genetic analyses showed that Thailand isolates from 11 provinces were highly homogenous, consisting of the same genetic background (globally known as VNI) and exhibiting only ten nearly identical sequence types (STs), with three (STs 44, 45 and 46) dominating our sample. This population contains significantly less diversity when compared against the global population of Cng, specifically Africa. Genetic diversity in Cng was significantly subdivided at the continental level with nearly half (47%) of the global STs unique to a genetically diverse and recombining population in Botswana. These patterns of diversity, when combined with evidence from haplotypic networks and coalescent analyses of global populations, are highly suggestive of an expansion of the Cng VNI clade out of Africa, leading to a limited number of genotypes founding the Asian populations. Divergence time testing estimates the time to the most common ancestor between the African and Asian populations to be 6,920 years ago (95% HPD 122.96 - 27,177.76). Further high-density sampling of global Cng STs is now necessary to resolve the temporal sequence underlying the global emergence of this human pathogen.	S. P. Simwami, K. Khayhan, D. A. Henk, D. M. Aanensen, T. Boekhout, F. Hagen, A. E. Brouwer, T. S. Harrison, C. A. Donnelly and M. C. Fisher	PLoS pathogens
491	Treatment of meningitis with chloramphenicol		S. A. Singh	East Afr Med J
267	Seven days vs. 10 days ceftriaxone therapy in bacterial meningitis	Ceftriaxone is recommended in children with acute bacterial meningitis (ABM) for 10 days. However, the drug is expensive, and shorter duration of therapy, if equally effective, would cut costs of therapy and hospitalization. The aim of this study was to compare the outcome of 7 days vs. 10 days' ceftriaxone therapy in children with ABM. Seventy-three children aged 3 months to 12 years with ABM, consecutively admitted to hospital were enrolled. Ceftriaxone was given for 7 days to all. Randomization to group I (7 days) and group II (10 days) therapy was done on the seventh day. At the end of 7 days' therapy in group I and 10 days in group II, children were evaluated using a clinical scoring system. Children with a score of more than 10 were labelled as 'treatment failures' and were continued on ceftriaxone. If a score was less than 10, the antibiotic was stopped. Complications were appropriately evaluated and managed. All children were followed-up 1 month after discharge: neurodevelopmental assessment, Denver Development Screening Tests, IQ and hearing assessment were done. After excluding four patients, there were 35 children in group I and 34 in group II. The two groups were comparable with respect to age, sex, nutritional status, presenting clinical features, and CSF parameters. Organism identification was possible in 38 per cent of children: (Streptococcus pneumoniae, 21 per cent; Haemophilus influenzae, 13 per cent; meningococcus, 4 per cent). Treatment failure rate was comparable in both groups (9 in group I and 8 in group II) as was the sequelae at discharge and at 1 month (9 in group I, 15 in group II,p > 0.1). Status epilepticus and focal deficits at presentation were significantly associated with treatment failures and sequelae in both the groups (p < 0.05). Length of hospital stay was shorter in group I (10.8 +/- 6.0 days) as compared with group II (14.4 +/- 7.2 days,p < 0.05) and frequency of nosocomial infection was significantly more in group II (p < 0.05). It was concluded that clinical outcome of patients treated with 7 days' ceftriaxone therapy is similar to that of 10 days' therapy, and is associated with lesser nosocomial infection and earlier hospital discharge. Seven days ceftriaxone therapy may be recommended for uncomplicated ABM in children in developing countries.	P. Singhi, M. Kaushal, S. Singhi and P. Ray	Journal of tropical pediatrics
88	Effect of Neisseria meningitidis group A polysaccharide vaccine on nasopharyngeal carrier rates		A. Sivonen	The Journal of infection
283	[Cytoflavin in the complex treatment of neuroinfections in children]	The results of using cytoflavin in the complex treatment of bacterial purulent meningitis and viral encephalitis in 60 children, aged from 1 month to 18 years, are presented. Clinical efficacy of the drug revealed by the decrease in the frequency of residual presentations and reduction of recovery time was demonstrated. The drug had an effect on the endothelial dysfunction, rheologic blood properties, coagulation blood system as a whole and vascular tone as well. Cytoflavin can be recommended in complex pathogenetic treatment of neuroinfections in children.	N. V. Skripchenko and E. S. Egorova	Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinsko? promyshlennosti Rossi?sko? Federatsii, Vserossi?skoe obshchestvo nevrologov [i] Vserossi?skoe obshchestvo psikhiatrov
87	DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation	AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.	M. H. Slack, S. Cade, D. Schapira, R. J. Thwaites, A. Crowley-Luke, J. Southern, R. Borrow and E. Miller	Archives of disease in childhood
96	Serogroup C meningococcal glycoconjugate vaccine in adolescents: persistence of bactericidal antibodies and kinetics of the immune response to a booster vaccine more than 3 years after immunization	BACKGROUND: The persistence of protection from meningococcal disease following immunization with serogroup C meningococcal (MenC) glycoconjugate vaccines in infancy is short-lived. The duration of protective immunity afforded by these vaccines in other at-risk age groups (i.e., adolescents and young adults) is not known. We evaluated the persistence of bactericidal antibodies following immunization with a MenC glycoconjugate vaccine (MenCV) in adolescents and the kinetics of immune response to a meningococcal AC plain polysaccharide vaccine (MenPS) challenge or a repeat dose of MenCV. METHODS: We conducted a randomized comparative trial of 274 healthy 13-15-year-olds from whom a total of 4 blood samples were obtained (prior to administration of a dose of MenPS or MenCV, again on 2 further occasions at varying times from days 2-7 after vaccination, and finally on day 28 after vaccination. The correlate of protection was a serum bactericidal assay titer > or = 8 (with a serum bactericidal assay using human complement). RESULTS: A serum bactericidal assay using human complement titer > or = 8 was observed in 75% of participants at baseline (mean age, 14.5 years; mean time since routine MenCV vaccination, 3.7 years). No increase in serum bactericidal assay geometric mean titers was detected until day 5 after administration of MenPS. Geometric mean titers following administration of MenCV were significantly higher than those observed following administration of MenPS, at days 5, 7, and 28. CONCLUSIONS: This study showed sustained levels of bactericidal antibodies for at least 3 years after immunization of adolescents with MenCV. After challenge of immunized adolescents with MenPS, there was no increase in serum bactericidal assay observed until day 5 after vaccination, indicating that immunological memory may be too slow to generate protection against this potentially rapidly invasive organism.	M. D. Snape, D. F. Kelly, P. Salt, S. Green, C. Snowden, L. Diggle, A. Borkowski, L. M. Yu, E. R. Moxon and A. J. Pollard	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
198	Demonstration of immunologic memory using serogroup C meningococcal glycoconjugate vaccine	BACKGROUND: Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory. METHODS: Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants. RESULTS: MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068). CONCLUSIONS: Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.	M. D. Snape, J. M. Maclennan, S. Lockhart, M. English, L. M. Yu, R. E. Moxon and A. J. Pollard	The Pediatric infectious disease journal
591	Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost plus or minus hyperthermia for glioblastoma multiforme	Purpose: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. Methods and Materials: Adults with newly-diagnosed, focal, supratentorial glioblastoma less than or equal to 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) plus or minus HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. Results: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ('no heat') and 40 to brachytherapy + HT ('heat'). By intent to treat, TTP and survival were significantly longer for 'heat' than 'no heat' (p = 0.04 and p = 0.04). For the 33 'no heat' patients and 35 'heat' patients who underwent brachytherapy boost, TTP and survival were significantly longer for 'heat' than 'no heat' (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to 'heat' (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on 'no heat' and 6 on the 'heat' arm). Conclusion: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	P. K. Sneed, P. R. Stauffer, M. W. McDermott, C. J. Diederich, K. R. Lamborn, M. D. Prados, S. Chang, K. A. Weaver, L. Spry, M. K. Malec, S. A. Lamb, B. Voss, R. L. Davis, W. M. Wara, D. A. Larson, T. L. Phillips and P. H. Gutin	International Journal of Radiation Oncology Biology Physics
226	[Clinical experiments with a new derivative of 6-aminopenicillanic acid: hetacillin potassium]		M. L. Soranzo and G. Bosio	Minerva medica
510	New Zealand Epidemic Strain Meningococcal B Outer Membrane Vesicle (OMV) Vaccine in Healthy 6 - 8 Month Old Infants		V. Sotutu, D. R. Lennon, F. Chan-Mow, J. O'Hallahan, P. Oster, J. Steward, K. Mulhaolland and D. Martin	Pediatric Academic Societies Annual Meeting; 2005 May 14-17; Washington DC, United States
114	Immunogenicity and safety of a meningococcal A conjugate vaccine in Africans	BACKGROUND: Group A meningococci are the source of major epidemics of meningitis in Africa. An affordable, highly immunogenic meningococcal A conjugate vaccine is needed.METHODS: We conducted two studies in Africa to evaluate a new MenA conjugate vaccine (PsA-TT). In study A, 601 children, 12 to 23 months of age, were randomly assigned to receive PsA-TT, a quadrivalent polysaccharide reference vaccine (PsACWY), or a control vaccine (Haemophilus influenzae type b conjugate vaccine [Hib-TT]). Ten months later, these children underwent another round of randomization within each group to receive a full dose of PsA-TT, a one-fifth dose of PsACWY, or a full dose of Hib-TT, with 589 of the original participants receiving a booster dose. In study B, 900 subjects between 2 and 29 years of age were randomly assigned to receive PsA-TT or PsACWY. Safety and reactogenicity were evaluated, and immunogenicity was assessed by measuring the activity of group A serum bactericidal antibody (SBA) with rabbit complement and performing an IgG group A-specific enzyme-linked immunosorbent assay.RESULTS: In study A, 96.0% of the subjects in the PsA-TT group and 63.7% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline; in study B, 78.2% of the subjects in the PsA-TT group and 46.2% of those in the PsACWY group had SBA titers that were at least four times as high as those at baseline. The geometric mean SBA titers in the PsA-TT groups in studies A and B were greater by factors of 16 and 3, respectively, than they were in the PsACWY groups (P<0.001). In study A, the PsA-TT group had higher antibody titers at week 40 than the PsACWY group and had obvious immunologic memory after receiving a polysaccharide booster vaccine. Safety profiles were similar across vaccine groups, although PsA-TT recipients were more likely than PsACWY recipients to have tenderness and induration at the vaccination site. Adverse events were consistent with age-specific morbidity in the study areas; no serious vaccine-related adverse events were reported.CONCLUSIONS: The PsA-TT vaccine elicited a stronger response to group A antibody than the PsACWY vaccine. (Funded by the Meningitis Vaccine Project through a grant from the Bill and Melinda Gates Foundation; Controlled-Trials.com numbers, ISRCTN78147026 and ISRCTN87739946.).	S. O. Sow, B. J. Okoko, A. Diallo, S. Viviani, R. Borrow, G. Carlone, M. Tapia, A. K. Akinsola, P. Arduin, H. Findlow, C. Elie, F. C. Haidara, R. A. Adegbola, D. Diop, V. Parulekar, J. Chaumont, L. Martellet, F. Diallo, O. T. Idoko, Y. Tang, B. D. Plikaytis, P. S. Kulkarni, E. Marchetti, F. M. LaForce and M. P. Preziosi	The New England journal of medicine
486	Pilot trial of infusional cyclophosphamide, doxorubicin, and etoposide plus didanosine and filgrastim in patients with human immunodeficiency virus- associated non-Hodgkin's lymphoma	Purpose: To determine the following: (1) the feasibility of combining the antiretroviral didanosine (ddl) with a 96-hour continuous intravenous (IV) infusion of cyclophosphamide (800 mg/m2), doxorubicin (50 mg/m2), and etoposide (240 mg/m2) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma (NHL) associated with human immunodeficiency virus (HIV) infection; (2) the effect of ddl on CDE-induced myelosuppression and CD4 lymphopenia; and (3) the effect of CDE on serum p24 antigen and quantitative HIV blood cultures. Methods: Twenty-five patients with HIV-related NHL received CDE every 28 or more days. Consecutive patients were assigned in an alternating fashion to group A (ddl given at a standard dose during cycles one, two, five, and six) or group B (ddl given during cycles three, four, five, and six). Results: ddl use was associated with less leukopenia (mean nadir, 3.33 v 1.49 x 103/muL; P =.03), neutropenia (2.38 v 1.07 x 103/muL; P =.03), and thrombocytopenia (76 v 48 x 103/muL; P =.059), and fewer RBC (1.6 v 3.1 per cycle; P <.01) and platelet transfusions (0.7 v 1.5 per cycle; P <.01), but had no significant effect on CD4 lymphopenia. Furthermore, lymphomatous bone marrow involvement and law CD4 count were associated with significantly greater myelosuppression. Although there was no substantial change in serum p24 antigen, the HIV blood culture became quantitatively more positive or converted from negative to positive in seven patients (64%). Complete response (CR) occurred in 58% of patients (95% confidence interval, 38% to 78%), median CR duration exceeded 18 months, tumor-related mortality was 20%, and median survival was 18.4 months. Conclusion: Our results suggest that the CDE and filgrastim regimen is tolerable and effective for patients with HIV- associated NHL, and that combination with ddl is feasible and may result in less myelosuppression. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. A. Sparano, P. H. Wiernik, X. Hu, C. Sarta, E. L. Schwartz, R. Soeiro, D. H. Henry, B. Mason, H. Ratech and J. P. Dutcher	Journal of Clinical Oncology
50	[Evaluation of systematic anti-meningococcal vaccination strategy in French military recruits]	The objective of the study was to assess the efficacy of meningococcal meningitidis vaccination among French military recruits, two years after the introduction of systematic vaccination. Protective efficacy (PE) was calculated using two epidemiological methods. The first was based on the incidence and density rates among vaccinated and unvaccinated subjects during the period when both groups were simultaneously available: PE = 100% (95% CI: 0-100%). The second was to compare the incidence density rates among vaccinated subjects with expected rates. The expected rates were calculated using a model involving adjustment of incidence rates observed before the introduction of vaccination. This second, more powerful method confirmed the efficacy of systematic vaccination for meningococcal meningitidis: PE = 100% (95% CI 30%-100%).	A. Spiegel, P. Quenel, G. Sperber and M. Meyran	Santé (Montrouge, France)
170	Comparison of ceftriaxone with standard therapy for bacterial meningitis		R. W. Steele and R. W. Bradsher	The Journal of pediatrics
589	Acoustic reflex in patients with cochlear implants (analog stimulation)	Stapedius reflexes were tested in 21 deaf patients with the Vienna cochlear implant using intra- or extracochlear electrodes. Sinusoidal bursts of 125, 500, 1,000, and 2,000 Hz were used as stimuli presented in a randomized sequence. The contralateral acoustic reflex was monitored by synchronized sampling of the acoustic impedance of the ear. Results obtained were compared to psychoacoustic sensation values. The reflex threshold always was located close to the uncomfortable loudness level within the subjective dynamic range, or at least above the most comfortable loudness level. Practical applications of reflex testing and limitations of the method for use in children are discussed. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	K. Stephan, K. Welzl-Muller and H. Stiglbrunner	Am. J. Otol.
682	Therapy for opportunistic fungal infections: past, present and future	The field of antifungal chemotherapy is presently rapidly moving. It began in 1903, with the successful use of potassium iodide (KI). Then there was little progress for 50 years, when in 1951, nystatin was introduced, the first useful polyene. Four years later amphotericin B followed, which is still the historical standard against which new systemic antifungals are compared. Except for the development of flucytosine, there was little progress until the early 1970s and the development of the azole drugs. The present era, which is characterized largely by the modifications of azole drugs, began with ketoconazole and brought agents which can be given orally and have increasing potency, decreasing toxicity and a broader spectrum of activity. Recent studies have examined ways to ameliorate the well-known toxicities of amphotericin B. A new approach has been to complex the drug with lipids or entrap it in liposomes. Itraconazole is a broad-spectrum oral triazole whose greatest advantages over the imidazoles are in its activity against aspergillosis and cryptococcosis, though it is also efficacious against the endemic deep mycoses. Fluconazole is a broad-spectrum triazole. It has been shown to be efficacious in various forms of superficial candidosis, including esophageal disease. We have shown in a randomized, double-blind, placebo-controlled study that maintenance therapy can completely prevent thrush in AIDS patients with recurrent thrush and possibly prevent all deep and superficial mycoses. Other studies have shown efficacy in cryptococcal meningitis in AIDS comparable to conventional therapy and with far less toxicity, and also in prevention of relapse of cryptococcal disease. Early diagnosis of fungal infections in cancer patients is problematic.(ABSTRACT TRUNCATED AT 250 WORDS)	D. A. Stevens	Indian journal of cancer
125	Neuropsychiatric lupus favourable response to low dose i.v. cyclophosphamide and prednisolone (pilot study)	Sixty SLE patients with only primary neuropsychiatric manifestations (NP-SLE), (54 female and six male; mean age 44.5) were compared consecutively. Forty-six of the patients (78.3%) were presented with a combination of neuropsychiatric symptoms. Except for the standard immunoserological test, all patients underwent clinical, neurological and psychiatric examination, electrophysiological tests [EEG (electro-encephalography involves recording and analysis of electrical signals generated by the brain), EP (the evoked potentials method involves analysis of a series of electrical signals generated in parts of the nervous system following stimulation of sense organs and peripheral nerves) and EMNG (electro-myo-neography is a method of measurement of electrical activity arising from muscle fibers and peripheral nerves)]. This method presents a valuable tool for assessment of functional state of peripheral nervous systems and muscles)), and neuroimaging (MRI of the brain). Thirty-seven out of 60 patients with NP-SLE (group I) were treated with a low dose of i.v. cyclophosphamide (200-400 mg per month). The average daily oral dose of prednisone in these patients was 20.5 mg. Group II consisted of 23 patients treated with pridnisone (mean dose 20.5 per day) only or with antimalarials. Patients in the first group showed a considerable clinical and electrophysiological improvement of cerebral function, while there was only a slight or no improvement in the second group. The difference between groups was statistically significant.	L. Stojanovich, R. Stojanovich, V. Kostich and E. Dzjolich	Lupus
638	Balance sensory organization in children with profound hearing loss and cochlear implants	OBJECTIVES: (1) To determine the feasibility of the use of a modified postural control test under altered sensory conditions in children over 8 years of age, and (2) to assess how deaf children use sensory information for postural control when they have normal or abnormal vestibular responses, and if hearing input from a unilateral cochlear implant, changes their postural behavior. PATIENTS: We selected 36 children, 8 to 11 years of age, with congenital or early-acquired profound sensorineural hearing loss, 13 of them with unilateral cochlear implantation and 22 normal-hearing children. METHODS: The Postural Control (PC) test consists of a force platform with 2 stimulation paradigm conditions: (1) standing on the platform with opened eyes; (2) standing on foam placed on the force platform with closed eyes. Implanted children were tested with the implant turn on and turn off in this condition, in order to evaluate eventual change in the postural control parameters when they have hearing habilitation. The body center of pressure distribution area (COP) and the body sway velocity (SV) were the parameter to evaluate the postural control. RESULTS: Deaf children were classified into two groups according with the vestibular responses: group A (n=28) Children with normal vestibular rotary responses; group B (n=8) children with hypoactive responses. Children in group A had diagnoses of syndromic and non-syndromic hereditary deafness, and children in group B had inner ear malformations, post-meningitis deafness, and one child had non-syndromic hereditary deafness with hypoactive vestibular response. In condition 1, when vestibular, somatosensory and visual information were enabled, the COP and SV values did not show any statistically significant differences between groups A, B and control. In condition 2, when visual information was removed and the somatosensory input strongly modified by standing on the foam, group B showed significant higher COP and SV values than groups A and control (p<0.05). In addition, the scalograms by wavelets of children in group B had higher amplitudes increasing the sway frequencies contents up to 3 Hz, not allowing them to maintain the up right stance in similar stimulation than in condition. Implanted children of the group A and B with the implant turn on, in the condition 2, did not show any significant difference in the SV, comparing when they had the implanted turn off. Group A p=0.395 and group B p=0.465 (Wilcoxon ranked test). CONCLUSION: These findings allow us to confirm that this postural test can be performed in children over 8 years old. Also our results suggest that deaf children with associated hypoactive vestibular responses included in our study, despite the etiology of the deafness, primarily use visual and somatosensory information to maintain their postural control. Hearing habilitation with a unilateral cochlear implant has no effect on the observed sensory organization strategy.	H. Suarez, S. Angeli, A. Suarez, B. Rosales, X. Carrera and R. Alonso	International journal of pediatric otorhinolaryngology
676	Correlation of cerebral Near-infrared spectroscopy (cNIRS) and neurological markers in critically ill children	OBJECTIVE: To correlate regional brain saturations (RSO(2)) measured by cerebral Near-infrared spectroscopy (cNIRS) with serological markers indicative of neurological injury (neuron-specific enolase (NSE) and S100beta). METHODS: Children with at least one organ failure who were undergoing cNIRS monitoring were eligible for enrollment, while children with hyperbilirubinemia and cyanotic heart disease were excluded. Children were further analyzed based on the presence of an acute neurological injury (defined as hypoxic/ischemic injury after cardiac arrest, status epilepticus, meningitis, encephalopathy) as well as survival. RSO(2) was measured continuously (every 30 s) and averages were obtained at 6 h and 24 h epochs prior to serum collection (E6 and E24, respectively). Serum was collected for NSE and S100beta, which were both determined by ELISA. Serum from children undergoing evaluation for fever in the Emergency department served as serological controls. Correlations were determined using the Pearson Product Moment Correlations. RESULTS: A total of 26 children underwent cNIRS monitoring for a total of 47 days. Overall NSE was greater in critically ill children compared to controls, as well as in all subsets of children analyzed (acute CNS injuries, no acute CNS injuries, survivors and non-survivors). S100beta tended to be greater in critically ill children, but this did not reach statistical significance. Average RSO(2) in E6 and E24 was 68.0% +/- 1.5 and 68.6% +/- 1.6, respectively, in a total of 131,036 measurements and E6 RSO(2) was strongly, negatively correlated with S100beta in children with acute neurological injuries. CONCLUSIONS: This is the first study to correlate averaged RSO(2) measured by cNIRS with neurological injury markers in critically ill children. We believe that this data can be used to establish thresholds for RSO(2) that can be tested in future trials to determine if this technology is predictive of long-term neurological outcome.	A. Subbaswamy, A. A. Hsu, S. Weinstein and M. J. Bell	Neurocritical care
690	Cryptococcus neoformans-reactive and total immunoglobulin profiles of human immunodeficiency virus-infected and uninfected Ugandans	We determined total and Cryptococcus neoformans glucuronoxylomannan (GXM)-reactive antibody repertoires of human immunodeficiency virus (HIV)-infected and HIV-uninfected Ugandans in a retrospective, case-control study of participants in a randomized controlled trial of pneumococcal vaccination. The study included 192 adults: 48 who subsequently developed cryptococcal meningitis (CM); (HIV+ CM+); 2 individuals who matched them in CD4+ T-cell level, stage of HIV disease, and age but did not develop CM (HIV+ CM-); and 48 HIV-uninfected individuals. Total serum immunoglobulin concentrations and titers of immunoglobulin M (IgM), IgG, and IgA to GXM, pneumococcal polysaccharides, and antibodies expressing certain V(H)3 idiotypes were determined with banked sera obtained before the development of cryptococcosis for HIV+ CM+ subjects. The results showed that HIV-infected subjects had significantly lower levels of IgM to GXM but higher levels of total immunoglobulin and IgG and IgA to GXM than those of HIV-uninfected subjects. HIV-infected subjects with a history of pneumonia had higher levels, and those with a history of herpes zoster had lower levels of GXM-binding antibodies than subjects with no history of either disease. Minimal to no cross-reactivity was demonstrated between antibodies to GXM and polysaccharides in a pneumococcal vaccine. No significant differences between the antibody repertoires of HIV+ CM+ and HIV+ CM- subjects were identified, but among subjects without a history of pneumonia, there was a trend towards lower V(H)3-positive antibody levels among HIV+ CM+ than among HIV+ CM- subjects. Our findings demonstrate an association between previous infectious diseases and differences in the total and GXM-reactive antibody repertoires of HIV-infected subjects and suggest the question of whether certain microbes modulate subsequent antibody responses to GXM deserves further study.	K. Subramaniam, N. French and L. A. Pirofski	Clinical and diagnostic laboratory immunology
693	Pharmacology and toxicity of high-dose ketoconazole	One hundred sixty patients were entered in two multicenter protocols to receive 400 to 2,000 mg of ketoconazole once daily for nonmeningeal or meningeal coccidiodomycosis. For 24 h after administration of all doses, mean concentrations in serum exceeded MICs for Coccidioides immitis (trough concentrations, greater than 1 microgram/ml). Mean peak concentrations occurred 4 to 6 h after administration, ranging from 7 to 17 micrograms/ml for doses of 400 to 2,000 mg. Incremental increases in peak concentrations in serum were greatest at doses of less than or equal to 1,200 mg. To investigate whether long-term therapy altered concentrations in serum, serial data were studied by several methods. The results suggested a trend to increased levels in serum with prolonged therapy, but were not statistically significant. All 168 cerebrospinal fluid (CSF) samples from meningitis patients contained less than or equal to 2.9 micrograms/ml, and only 6 contained greater than 1 microgram/ml. There was no apparent relation between dose, time after dose, site of CSF sampling, or concurrent inflammation and CSF ketoconazole concentration. Neither concentration in serum, toxicity, nor outcome correlated with dose, calculated in milligrams per kilogram at the fixed doses (400-mg increments) under study. Likewise, at the various doses, concentration in serum did not correlate with outcome or toxicity, suggesting that individual drug disposition was not an important factor in outcome or toxicity. Toxicity was reversible, and principal side effects were nausea and vomiting (50%), gynecomastia (21%), decreased libido (13%), alopecia (8%), elevated liver function tests (5%), pruritus (5%), and rash (4%). Gastrointestinal and endocrinologic toxicity were dose related and increased at doses greater than 800 mg. The cumulative percent toxicity requiring discontinuation of drug was 6, 17, 23, and 56% at 400-, 800-, 1,200-, and 1,600-mg doses. Doses of >400 mg are thus markedly more toxic, and efficacy data for nonmeningeal disease have not demonstrated that they are more efficacious.	A. M. Sugar, S. G. Alsip, J. N. Galgiani, J. R. Graybill, W. E. Dismukes, G. A. Cloud, P. C. Craven and D. A. Stevens	Antimicrobial agents and chemotherapy
588	Combination intrathecal (IT) therapy for meningeal leukemia: two versus three drugs	Principles of combination chemotherapy were applied to intrathecal (IT) therapy for meningeal leukemia in a randomized study in children. Diagnosis required a cerebral spinal fluid (CSF) mononuclear cell count > or = 10 mmsup 3 or blast cells in any number. Children in marrow remission and relapse were randomized separately. Two drug therapy consisted of methotrexate 15 mg/Msup 2 + hydrocortisone 15 mg/Msup 2, IT, every 4 to 5 days, until the CSF normalized, followed by maintenance therapy, instituted leukovorin 2 wk and continuing at increasing intervals to 8 wk, to central nervous system (CNS) relapse or death. Three drug therapy added cytosar 30 mg/Msup 2 IT to each treatment as above. All were given keukovorin with each treatment. The median length of CNS remission was 460 days for the 3 drug therapy (N=48) and 317 days for the 2 drug therapy (N=45), p=0.25. Three triple therapy patients in CNS remission had not reached the median at the time of report, all continuing 2 drug patients had passed the median. Triple therapy patients in marrow relapse had not reached their median; the median length of CNS remission for 2 drug patients in marrow relapse was 176 days. Toxicities of the regimens were similar. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	M. P. Sullivan, G. B. Humphrey and T. J. Vietti	Procamerasscancer Res
557	Biochemical characterizations of Escherichia coli-expressed protective antigen Ag473 of Neisseria meningitides group B		J. W. Sung, S. Y. Hsieh, C. L. Lin, C. H. Leng, S. J. Liu, A. H. Chou, L. W. Lai, L. H. Lin, Y. Kwok, C. Y. Yang and P. Chong	Vaccine
340	Efavirenz-based regimen as treatment of advanced AIDS with cryptococcal meningitis		S. Sungkanuparph, A. Vibhagool, P. Mootsikapun, P. Chetchotisakd, S. Tansuphaswaswadikul, C. Bowonwatanuwong and W. Chantratita	Journal of acquired immune deficiency syndromes (1999)
677	Effect of a selective restriction policy on antibiotic expenditure and use: an institutional model	Strictly enforced antibiotic formulary restriction in combination with formulation of agreed guidelines for antibiotic use in common infection problems such as septicemia, febrile neutropenia, urinary tract infection, biliary sepsis, liver abscess, peritonitis, nosocomial pneumonia, soft tissue infection and purulent meningitis, generated a combined savings of 307,748.5 bahts or 13.5 per cent cost reduction over a 6 month period, and improved quality of use, appropriate 54.8 vs 67.5 per cent, statistically significance (P less than 0.002). Although this saving was offset in part by increased spending of unrestricted antibiotics, such as Penicillin and Gentamicin, an overall cost saving remained. In the months during the restrictions, no significant changes occurred regarding patients response and mortality. However, after the onset of the controls, it was revealed that antibiotics were more appropriately used afterwards. This study has shown, most importantly, that savings were achieved with no negative effect on good patient care. Moreover, the antibiotic use control was operationally successful, most house-staff and attending physicians, not only antibiotic evaluating team, have accepted the program in a very positive way. Overall, this program successfully achieved its initial goal, cost saving without compromising good medical practice. We are now continuing our program and also trying to modify so that it will be useful to all departments in the hospital	P. Suwangool, P. Moola-Or, A. Waiwatana, C. Sitthi-Amorn, S. Israsena and M. Hanvanich	Journal of the Medical Association of Thailand
373	Liver function tests during treatment of tuberculosis with short-course regimens containing isoniazid, rifampicin & pyrazinamide		R. Swamy, G. S. Acharyulu, M. Duraipandian, M. S. Jawahar, R. Ramachandran and G. R. Sarma	The Indian journal of medical research
495	Gamma-Venin P in the treatment of bacterial meningitis in children		L. Szenborn, R. Noack, D. Pohl and Z. Rudkowski	Monatsschrift fur Kinderheilkunde
358	[Use of immunoglobulin enriched with class IgM antibodies in treatment of purulent meningitis]		L. Szenborn and Z. Rudowski	Polski tygodnik lekarski (Warsaw, Poland : 1960)
551	Etiology and neurological complications of bacterial meningitis in 189 patients		P. Tabatabaie, S. Sayahtaheri, A. Siadati and O. Alizad	Acta Medica Iranica
438	Management of acute bacterial meningitis [letter; comment]		G. Tamburlini, A. Cattaneo, R. Schindler Maggi, A. Macaluso and S. Pivetta	Lancet
301	Comparison of one week with two week regimens of amphotericin B both followed by fluconazole in the treatment of cryptococcal meningitis among AIDS patients	BACKGROUND: Amphotericin B treatment in cryptococcosis requires daily hospital visits or admission. Its toxicities and hospital costs have been concerned. Short course amphotericin B regimen warrants to be evaluated. OBJECTIVE: To compare the safety and efficacy of one-week (AmB1) with two-week (AmB2) amphotericin B both followed by fluconazole. MATERIAL AND METHOD: 57 AIDS with cryptococcal meningitis were randomly assigned to either AmB1 or AmB2. Microbiological and clinical clearances were the outcomes of the study. RESULTS: The treatment success at 6 weeks was 63.3% in AmB1 and 70.4% in AmB2 (p = 0.574). Clinical assessment at week 10 and renal toxicities were not significantly different between both regimens. Mortality rate was 14% however, 75% of deaths were in AmB2. CONCLUSION: AmB1 was comparably effective and safe as the standard AmB2 regimen in the treatment of AIDS related cryptococcal meningitis. It can be an alternative regimen to lower hospital based care and improve cost effective for source limiting health care centers.	S. Tansuphaswadikul, W. Maek-a-Nantawat, B. Phonrat, L. Boonpokbn, A. G. Mctm and P. Pitisuttithum	Journal of the Medical Association of Thailand = Chotmaihet thangphaet
439	[Study on safety and immunogenicity of group A/C meningococcal polysaccharide conjugate vaccine]	OBJECTIVE: To evaluate the safety and immunogenicity of group A/C meningococcal polysaccharide conjugate vaccine.METHODS: The double-blind, randomized, parellel controlled, single central clinical trial was carried out to evaluat safety and immunogenicity of MCV-A/C.RESULTS: 4-fold rise rate of antibody to group A, C and A/C were more than 90 percent after MCV. The GMTs of antibody serogroup A and C were more than 1:150 in four trial groups aged 3-5 months, 6-23 months, 2-15 years and 16-30 years, for which the susceptive subjects seroprotected. There were no significant differences between MCV and the control group in the systemic and local reactions rates. The systemic and local reactions rates after the first, second and third dose of MCV were low. And no severe systemic and local reactions.CONCLUSION: Group A/C MCV was safe and immunogenic for the population > or =3 months old. Registration National Food drugs Surveillance administrative bureau, Medicine Clinical Experiment Written Directive from a superior" number:2006L04776.	H. Tao, Y. N. Li and C. H. Wu	Zhongguo yi miao he mian yi
63	Treatment of acute meningococcaemia with chemotherapy and immune plasma		A. M. Taqi, J. T. Macfarlane, R. Morton, S. S. Wali and B. M. Greenwood	The Journal of infection
385	Assessment of the protection conferred by anti-group C meningococcal polysaccharide vaccine to 6 to 36-mth-old children. <ORIGINAL> AVALIACAO DO EFEITO PROTETOR DE VACINA POLISSACARIDICA ANTIMENINGOCOCICA DO GRUPO C, EM CRIANCAS DE 6 A 36 MESES	A description is made of the methodology employed to assess the protection conferred by the Merck, Sharp & Dohme anti-meningococcic vaccine which was used in a mass vaccination campaign conducted in the City of Sao Paulo, Brazil, during an epidemic. The etiologic agent of this epidemic was identified as type C Neisseria meningitidis. For the assessment, 6 to 36 mth old children were chosen among those vaccinated from December 12 to 22, 1972. The sample included 67,299 children who received the vaccine and 67,299 who received a placebo (diphtheric- tetanic toxoid). Surveillance of the total 134,549 children was made until June 3, 1974, when it was interrupted because of the occurrence of a new epidemic during which patients were admitted to various hospitals rather than to a single one, as in the study epidemic. It was concluded that those children who were 24 to 36 mth old at the time of vaccination showed a lower attack rate when the agent was type C N. meningitidis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. E. Taunay, R. A. Feldman and B. C. Oliveira	Rev Inst Adolfo Lutz
422	[Assessment of the protection conferred by anti group C meningococcal polysaccharide vaccine to 6 to 36 mth old children]	A description is made of the methodology employed to assess the protection conferred by the Merck, Sharp & Dohme anti-meningococcic vaccine which was used in a mass vaccination campaign conducted in the City of Sao Paulo, Brazil, during an epidemic. The etiologic agent of this epidemic was identified as type C Neisseria meningitidis. For the assessment, 6 to 36 mth old children were chosen among those vaccinated from December 12 to 22, 1972. The sample included 67,299 children who received the vaccine and 67,299 who received a placebo (diphtheric- tetanic toxoid). Surveillance of the total 134, 549 children was made until June 3, 1974, when it was interrupted because of the occurrence of a new epidemic during which patients were admitted to various hospitals rather than to a single one, as in the study epidemic. It was concluded that those children who were 24 to 36 mth old at the time of vaccination showed a lower attack rate when the agent was type C N. meningitidis.	A. E. Taunay, R. A. Feldman and B. C. Oliveira	Rev Inst Adolfo Lutz
443	Immunogenicity and reactogenicity of a booster dose of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine given to toddlers of 13-14 months of age with antibody persistence up to 31 months of age	BACKGROUND: A combined Haemophilus influenzae type b and Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) may be a convenient alternative to separate Hib and MenC conjugate vaccines. METHODS: Healthy infants randomized in a previous study for priming at 2, 4, and 6 months: Hib-MenC-TT primed group, 3 doses of Hib-MenC-TT + DTPa-HBV-IPV (N = 87); MenC-TT primed group, 2 doses of MenC-TT (NeisVac-C; Baxter Healthcare SA, Zuürich, Switzerland) + 3 doses of DTPa/Hib containing vaccines (N = 178); MenC-CRM primed group, 3 doses of MenC-CRM197(Meningitec; Wyeth Corporation Delaware, Madison, NJ) + DTPa-HBV-IPV/Hib (N = 93). At 13-14 months of age, Hib-MenC-TT and MenC-TT primed groups received a Hib-MenC-TT booster dose and the MenC-CRM primed group a booster dose of DTPa-HBV-IPV/Hib. Blood samples were taken before and at 1 and 18 months postbooster. RESULTS: Before the booster dose, persistence of anti-polyribosyl ribitol phosphate (PRP) antibody concentration > or =0.15 microg/mL in the Hib-MenC-TT (96.4%) and MenC-TT (96.1%) primed groups and of MenC bactericidal titers > or =1:8 in the Hib-MenC-TT primed group (96.3%) was statistically significantly higher than in the MenC-CRM primed group (86.4% and 85.4%, respectively). One month after the Hib-MenC-TT booster, 99.2% subjects in the Hib-MenC-TT primed + MenC-TT primed pooled groups had anti-PRP levels > or =1 microg/mL, and 99.6% had SBA-MenC titers > or =1:128. The Hib-MenC-TT booster tended to be less reactogenic than the DTPa-HBV-IPV/Hib control and no serious adverse events related to vaccination were reported. Eighteen months after boosting with Hib-MenC-TT, SBA-MenC titers > or =1:8 persisted in 92.7% subjects and anti-PRP > or =0.15 microg/mL persisted in 99.4%. CONCLUSIONS: Primary immunization with 3 doses of Hib-MenC-TT coadministered with DTPa-HBV-IPV induced antibodies that persisted up to the second year of life. The Hib-MenC-TT booster administered to primed toddlers induced robust and persistent antibody responses to both the Hib and MenC components and had an acceptable safety profile.	J. C. Tejedor, M. Moro, J. M. Merino, J. A. Gómez-Campderá, M. García-del-Rio, A. Jurado, F. J. Díez-Delgado, F. Omeñaca, J. García-Sicilia, J. Ruiz-Contreras, A. Martin-Ancel, J. Roca, R. Boceta, P. García-Corbeira, G. Maechler and D. Boutriau	The Pediatric infectious disease journal
561	Immunogenicity and reactogenicity of primary immunization with a novel combined Haemophilus influenzae Type b and Neisseria meningitidis Serogroup C-tetanus toxoid conjugate vaccine coadministered with a Diphtheria-tetanus-acellular Pertussis-hepatitis B-inactivated poliovirus vaccine at 2, 4 and 6 months Clinical evaluation of a new starter formula for infants containing live Bifidobacterium longum BL999 and prebiotics	BACKGROUND: This phase II study evaluated the immunogenicity and reactogenicity of primary vaccination with a novel Hib-MenC conjugate vaccine (GlaxoSmithKline [GSK] Biologicals) coadministered with DTPa-HBV-IPV (GSK Biologicals) at 2, 4 and 6 months. METHODS: Healthy infants were randomized to receive Hib-MenC coadministered with DTPa-HBV-IPV (N = 117) or MenC-CRM (Wyeth) coadministered with DTPa-HBV-IPV/Hib (GSK Biologicals; N = 120) at 2, 4 and 6 months. Antibody concentrations were measured before vaccination and after doses 2 and 3. Solicited local and general symptoms, unsolicited symptoms and serious adverse events (SAEs) were recorded. RESULTS: All subjects in the Hib-MenC group had seroprotective titers of anti-PRP antibodies (>or=0.15 microg/mL) and SBA-MenC titers (>or=1:8) 1 month after the third dose. These responses were noninferior to those seen in the control group, in which a 99.1% seroprotection rate was observed for both Hib and MenC. At that time, anti-PRP and SBA-MenC GMTs were significantly higher in the Hib-MenC group (12.8 microg/mL and 2467.1 microg/mL, respectively) than in the control group (3.8 microg/mL and 1833.7 microg/mL). High seroprotection rates were already observed after the second dose of Hib-MenC; 96.4% and 100% of subjects were seroprotected to Hib and MenC, respectively. Immune responses to coadministered antigens were unimpaired; seroprotection/vaccine response rates >or=96.5% were recorded postdose 3 in the Hib-MenC group. No differences in reactogenicity were seen between the 2 study groups. CONCLUSIONS: Coadministration of a Hib-MenC conjugate vaccine with DTPa-HBV-IPV is well tolerated and immunogenic, and does not impair the immune response to any of the coadministered antigens OBJECTIVES: The larger number of bifidobacteria in the intestine of breast-fed infants has been associated with their better health compared with formula-fed infants. We assessed the safety and tolerability of an experimental formula containing 2 x 10(7) colony-forming units of Bifidobacterium longum BL999 and 4 g/L of a prebiotic mixture containing 90% galacto-oligosaccharides and 10% fructo-oligosaccharides. METHODS: A 7-mo prospective, randomized, reference-controlled, double-blinded trial was performed in infants who were not breast fed after the 14th day of birth. One hundred thirty-eight infants were enrolled and assigned to receive the control or experimental formula until they were 112 d old. Mean weight gain (primary outcome) and recumbent length, head circumference, tolerability (gastrointestinal symptoms), and overall morbidity (secondary outcomes) were measured at 14, 28, 56, 84, and 112 d of age. RESULTS: Equivalence in mean weight gain between the two groups was shown. The treatment difference in the intention-to-treat and per-protocol populations were within the predefined equivalence boundaries of +/-3.9 g/d. No statistically significant difference in recumbent length, head circumference, or incidence of adverse events was found between the two groups. Infants in the experimental group had fewer incidences of constipation and had stool characteristics that suggest that the experimental formula was tolerated well. Furthermore, these infants showed a trend toward fewer respiratory tract infections. CONCLUSIONS: The starter formula containing BL999 and galacto-oligosaccharides/fructo-oligosaccharides is safe and well-tolerated	J. C. Tejedor, M. Moro, J. Ruiz-Contreras, J. Castro, J. A. Gomez-Campdera, M. L. Navarro, J. M. Merino, A. Martin-Ancel, J. Roca, M. Garcia-Del-Ri, A. Jurado, F. J. ez-Delgado, F. Omenaca, J. Garcia-Sicilia, R. Boceta, P. Garcia-Corbeira, A. Collard, D. Boutriau, L. Schuerman, J. M. Jacquet, G. Puccio, C. Cajozzo, F. Meli, F. Rochat, D. Grathwohl and P. Steenhout	Pediatr Infect Dis J
59	Immunogenicity and reactogenicity of primary immunization with a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type B vaccine coadministered with two doses of a meningococcal C-tetanus toxoid conjugate vaccine	BACKGROUND: This study evaluated the concurrent use of meningococcal C tetanus conjugate (MenC-TT) vaccine (NeisVac-C) with DTaP-based combinations, according to 2 vaccination schedules, one of which included hepatitis B vaccination at birth (Trial DTaP-HBV-IPV/Hib-097). METHODS: Healthy infants were randomized to receive either DTaP-HBV-IPV/Hib (Infanrix hexa) at 2, 4, and 6 months (N = 115) or HBV at birth followed by DTaP-HBV-IPV/Hib at 2 and 6 months and DTaP-IPV/Hib (Infanrix-IPV Hib) at 4 months (N = 115). In both groups 2 doses of MenC-TT conjugate were coadministered at 2 and 4 months, and compared with 3 doses of MenC-CRM197 conjugate (Meningitec) coadministered at 2, 4, and 6 months with DTaP-HBV-IPV/Hib (N = 120). Antibody concentrations were measured at 2, 6 and 7 months. Solicited local and general symptoms, unsolicited symptoms, and serious adverse events (SAEs) were recorded. RESULTS: All MenC-TT recipients had seroprotective concentrations of anti-PRP antibodies (> or = 0.15 microg/mL) 1 month after the third vaccine dose and all had SBA-MenC titers > or = 1:8 after the second dose of MenC-TT. These responses were noninferior to those seen after 3 doses of DTaP-HBV-IPV/Hib and MenC-CRM. Anti-PRP antibody GMCs were significantly higher in MenC-TT than MenC-CRM vaccinees (7.9, 7.3, 3.8 microg/mL, respectively). Immune responses to all other coadministered antigens were unimpaired, with seroprotection/seropositivity rates > or = 98.1% in MenC-TT vaccinees. All schedules studied were well tolerated, with no differences in reactogenicity between the study groups. CONCLUSIONS: Coadministration of DTaP-HBV-IPV/Hib or DTaP-IPV/Hib with 2 doses of MenC-TT conjugate vaccine is safe, well tolerated, and immunogenic, with no impairment of the response to the coadministered antigens.	J. C. Tejedor, M. Moro, J. Ruiz-Contreras, J. Castro, J. A. Gómez-Campderá, M. L. Navarro, J. M. Merino, A. Martín-Ancel, J. Roca, M. García-del-Río, A. Jurado, F. J. Díez-Delgado, F. Omeñaca, J. García-Sicilia, R. Boceta, P. García-Corbeira, J. M. Jacquet, A. Collard and L. Schuerman	The Pediatric infectious disease journal
185	Concentrations of ceftazidime, tobramycin and ampicillin in the cerebrospinal fluid of newborn infants	Thirty-five neonates with suspected septicaemia were randomized to treatment with tobramycin or ceftazidime, both in combination with ampicillin. Concentrations of antibiotics in the CSF were measured 1 h after the third, fourth or fifth injection. In 13 of 17 neonates tobramycin CSF concentrations were below 0.5 mg/l. Ceftazidime CSF concentrations ranged from 2.5 to 17 mg/l, which should be sufficient for treatment of infections with group B streptococci and most aerobic gram-negative bacilli but not all strains of Staphylococcus aureus. Ampicillin CSF concentrations ranged from 1 to 80 mg/l, which should be sufficient for treatment of meningitis caused by enterococci and Listeria monocytogenes, the most important neonatal pathogens not covered by ceftazidime.	I. Tessin, B. Trollfors, K. Thiringer, Z. Thörn and P. Larsson	European journal of pediatrics
321	Influence of antituberculosis drug resistance and Mycobacterium tuberculosis lineage on outcome in HIV-associated tuberculous meningitis	HIV-associated tuberculous meningitis (TBM) has high mortality. Aside from the devastating impact of multidrug resistance (MDR) on survival, little is understood about the influence of other bacterial factors on outcome. This study examined the influence of Mycobacterium tuberculosis drug resistance, bacterial lineage, and host vaccination status on outcome in patients with HIV-associated TBM. Mycobacterium tuberculosis isolates from the cerebrospinal fluid of 186 patients enrolled in two studies of HIV-associated TBM in Ho Chi Minh City, Vietnam, were tested for resistance to first-line antituberculosis drugs. Lineage genotyping was available for 122 patients. The influence of antituberculosis drug resistance and M. tuberculosis lineage on 9-month mortality was analyzed using Kaplan-Meier survival analysis and Cox multiple regression models. Isoniazid (INH) resistance without rifampin resistance was associated with increased mortality (adjusted hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.18 to 2.66; P = 0.005), and multidrug resistance was uniformly fatal (n = 8/8; adjusted HR, 5.21, 95% CI, 2.38 to 11.42; P < 0.0001). The hazard ratio for INH-resistant cases was greatest during the continuation phase of treatment (after 3 months; HR, 5.05 [95% CI, 2.23 to 11.44]; P = 0.0001). Among drug-susceptible cases, patients infected with the "modern" Beijing lineage strains had lower mortality than patients infected with the "ancient" Indo-Oceanic lineage (HR, 0.29 [95% CI, 0.14 to 0.61]; P = 0.001). Isoniazid resistance, multidrug resistance, and M. tuberculosis lineage are important determinants of mortality in patients with HIV-associated TBM. Interventions which target these factors may help reduce the unacceptably high mortality in patients with TBM.	D. Q. Tho, M. E. Török, N. T. Yen, N. D. Bang, N. T. Lan, V. S. Kiet, N. Vinh Chau, N. H. Dung, J. Day, J. Farrar, M. Wolbers and M. Caws	Antimicrobial agents and chemotherapy
65	Risk factors for carriage of meningococcus in the Los Angeles County men's jail system	Ten cases of meningococcal meningitis in the Los Angeles County men's jail system in 1986 were the first known reported cases in this population. New cases have continued into 1990. Nineteen of 21 symptomatic cases identified by serogroup from the men's jail occurring through 1988 had serogroup C. The prevalence of meningococcal carriage and potential risk factors were studied in 1988 among 150 men booked to enter the jail, 350 inmates being released, and 100 jail staff. The prevalence of meningococcal carriage among releases, bookings, and staff were 25.4%, 18.7%, and 5.0%, respectively. Among releases, imprisonment longer than a threshold of 28 days increased carriage of serogroup C 10.0 times (95% confidence interval (CI) 4.6-21.6). Among bookings, household crowding increased serogroup C carriage 8.2 times (95% CI 1.5-45.3). Direct and passive smoking at home increased carriage of any serogroup 5.2 (95% CI 1.2-47.5) and 2.5 (95% CI 1.1-5.8) times, respectively. Feasible potential interventions include banning smoking in the jail and immunization with quadrivalent meningococcal vaccine of booked men sentenced for one month or more.	J. C. Thomas, N. S. Bendana, S. H. Waterman, M. Rathbun, G. Arakere, C. E. Frasch, J. D. Wenger, V. Magsombol and J. H. Clark	American journal of epidemiology
398	Trial of dexamethasone treatment for severe bacterial meningitis in adults	Objective: To evaluate the clinical benefit of early adjunctive dexamethasone therapy for severe bacterial meningitis in adults. Design: Multicenter, double-blind, randomized trial initiated in emergency or intensive care units in France and Switzerland. Within 3 h after initiation of an aminopenicillin therapy, patients received dexamethasone (10 mg q.i.d.) or placebo for 3 days. The primary end-point was the rate of patients cured without any neurologic sequelae on day 30. Results: Sixty patients were enrolled, predominantly with a severe form since 85% required ICU stay and 43% mechanical ventilation. Streptococcus pneumoniae accounted for 31 cases and Neisseria meningitidis for 18 cases. The study had to be stopped prematurely because of a new national recommendation of experts to use third generation cephalosporin and vancomycin as a result of the increasing rate of penicillin-resistant S. pneumoniae in France. After the third sequential analysis by the triangular statistical test, the difference of rate of cured patients without any neurologic sequelae was not statistically significant (p = 0.0711) between the dexamethasone group (74.2%; n = 31) and the placebo group (51.7%; n = 29). Furthermore, the former group was younger and less sick at inclusion. Conclusion: Bacterial meningitis is still a severe disease in adults, since the overall observed rate of death or severe neurologic sequelae was 26.7%. The reported data are inconclusive regarding a systematic use of dexamethasone as an adjunctive therapy for bacterial meningitis in adults. Moreover this treatment impairs antibiotic penetration into the cerebrospinal fluid (CSF) that can lead to therapeutic failure, particularly in areas with high or increasing rates of penicillin-resistant S. pneumoniae. Number of References 20. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	R. Thomas, Y. Tulzo, J. Bouget, C. Camus, C. Michelet, P. Corre, E. Bellissant, P. Regamey, P. Unger, G. Offenstadt, E. Maury, Y. Domart, P. Veyssier, J. C. Bertrand, Y. Page, P. Canton, B. Hoen, P. Auzepy, P. Alquier, J. M. Chennebault, F. Nicolas, P. Leconte, C. Arich, J. P. Cardinaud, F. Costes, J. M. Descamps, P. Gajdos, G. Guivarch, C. Haas, M. Hermes, J. C. Jouan, G. Lelou, P. Lestavel and F. Nouailhat	Intensive Care Medicine
417	Anti-endotoxin therapy for fulminant meningococcal septicaemia - Pilot study	Objective: Evaluation of anti-endotoxin therapy (AET) in fulminant meningococcal septicaemia (FMS). Design: Open study with historical comparison group. Setting: Two children's hospitals, one with a regional referral intensive care unit. Patients: Study patients were 11 children admitted consecutively during 1987. Comparison patients were 21 children seen between 1/1/77-31/12/87, 19 ascertained from hospital clinical and laboratory records. All children had FMS, defined as a Glasgow Meningococcal Septicaemia Prognostic Score of 8 or more. Interventions: Study patients received AET with IV infusion of polymyxin E (2 mg/kg over 20 minutes) and Pentaglobin, a pooled polyvalent immunoglobulin (5 ml/kg over 12 hours) on 2 consecutive days. All children received appropriate antibiotics and intensive care. End point: Survival to discharge. Main results: Eight (72.7%) of 11 patients treated with AET survived, as did 6 (28.6%) of 21 not given AET. Treatment and comparison groups did not differ in terms of sex or age distribution, infecting serogroup or antibiotic therapy. No adverse effects of AET were identified. Conclusions: Survival in the AET-treated group was higher than in the untreated group (p = 0.019, Fisher's exact test). A prospective, double-blind, placebo-controlled trial is indicated. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. P. J. Thomson, C. A. Hart, J. A. Sills and F. Harris	Pediatr Rev Commun
330	Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis	Tuberculous meningitis (TBM) is the most lethal form of tuberculosis, and new treatments that improve outcomes are required. We randomly assigned adults with TBM to treatment with standard antituberculosis treatment alone or in combination with ciprofloxacin (750 mg/12 h), levofloxacin (500 mg/12 h), or gatifloxacin (400 mg/24 h) for the first 60 days of therapy. Fluoroquinolone concentrations were measured with plasma and cerebrospinal fluid (CSF) specimens taken at predetermined, randomly assigned times throughout treatment. We aimed to describe the pharmacokinetics of each fluoroquinolone during TBM treatment and evaluate the relationship between drug exposure and clinical response over 270 days of therapy (Controlled Trials number ISRCTN07062956). Sixty-one patients with TBM were randomly assigned to treatment with no fluoroquinolone (n = 15), ciprofloxacin (n = 16), levofloxacin (n = 15), or gatifloxacin (n = 15). Cerebrospinal fluid penetration, measured by the ratio of the plasma area under the concentration-time curve from 0 to 24 h (AUC(0-24)) to the cerebrospinal fluid AUC(0-24), was greater for levofloxacin (median, 0.74; range, 0.58 to 1.03) than for gatifloxacin (median, 0.48; range, 0.47 to 0.50) or ciprofloxacin (median, 0.26; range, 0.11 to 0.77). Univariable and multivariable analyses of fluoroquinolone exposure against a range of different treatment responses revealed worse outcomes among patients with lower and higher plasma and CSF exposures than for patients with intermediate exposures (a U-shaped exposure-response). TBM patients most likely to benefit from fluoroquinolone therapy were identified, along with exposure-response relationships associated with improved outcomes. Fluoroquinolones add antituberculosis activity to the standard treatment regimen, but to improve outcomes of TBM, they must be started early, before the onset of coma.	G. E. Thwaites, S. M. Bhavnani, T. T. Chau, J. P. Hammel, M. E. Török, S. A. Wart, P. P. Mai, D. K. Reynolds, M. Caws, N. T. Dung, T. T. Hien, R. Kulawy, J. Farrar and P. G. Ambrose	Antimicrobial agents and chemotherapy
224	Serial MRI to determine the effect of dexamethasone on the cerebral pathology of tuberculous meningitis: an observational study	BACKGROUND: Adjunctive dexamethasone increases survival from tuberculous meningitis, but the underlying mechanism is unclear. We aimed to determine the effect of dexamethasone on cerebral MRI changes and their association with intracerebral inflammatory responses and clinical outcome in adults treated for tuberculous meningitis. METHODS: Cerebral MRI was undertaken, when possible, at diagnosis and after 60 days and 270 days of treatment in adults with tuberculous meningitis admitted to two hospitals in Vietnam. Patients were randomly assigned either dexamethasone (n=24) or placebo (n=19) and received 9 months of treatment with standard first-line antituberculosis drugs. We assessed associations between MRI findings, treatment allocation, and resolution of fever, coma, cerebrospinal fluid inflammation, and neurological outcome. FINDINGS: 83 scans were done for 43 patients: 19 given placebo, 24 given dexamethasone. Basal meningeal enhancement (82%) and hydrocephalus (77%) were the most common presenting findings. Fewer patients had hydrocephalus after 60 days of treatment with dexamethasone than after placebo treatment (p=0.217). Tuberculomas developed in 74% of patients during treatment and in equal proportions in the treatment groups; they were associated with long-term fever, but not relapse or poor clinical outcome. The basal ganglia were the most common site of infarction; the proportion with infarction after 60 days was halved in the dexamethasone group (27%vs 58%, p=0.130). INTERPRETATION: Dexamethasone may affect outcome from tuberculous meningitis by reducing hydrocephalus and preventing infarction. The effect may have been under-estimated because the most severe patients could not be scanned.	G. E. Thwaites, J. Macmullen-Price, T. H. Tran, P. M. Pham, T. D. Nguyen, C. P. Simmons, N. J. White, T. H. Tran, D. Summers and J. J. Farrar	Lancet neurology
202	The first use of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB) in humans	BACKGROUND: Neisseria meningitidis serogroup B is a well-recognized cause of bacterial meningitis and sepsis for which no broadly protective vaccine exists. Whole genome sequencing was used to identify three antigens: factor H binding protein (fHbp), Neisserial adhesin A (NadA), and Neisseria heparin binding antigen (NHBA) for an investigational vaccine candidate (rMenB). This was the first trial of an investigational multicomponent meningococcal serogroup B vaccine (4CMenB), containing rMenB and outer membrane vesicles (OMV) from the New Zealand epidemic strain in humans. RESULTS: Seventy adults enrolled and received study vaccine. All vaccines were generally well tolerated. Immune responses were observed to multiple serogroup B strains following all investigational vaccines, suggesting the potential for broad coverage against this serogroup. Immunogenicity was enhanced by the addition of OMV; the 4CMenB displayed the optimal profile for further investigation. METHODS: In a phase I, observer blind, randomized trial, healthy adults (18-40 years of age) were randomized 2:2:1 to receive 3 doses of 4CMenB, rMenB with OMV from the Norwegian outbreak strain, or rMenB alone. Pre- and postvaccination sera were evaluated in a serum bactericidal assay using human complement (hSBA) against a panel of 15 serogroup B strains, with titers ? 4 considered protective. Solicited injection site and systemic reactions were evaluated for 7 days following each vaccination and adverse events were reported throughout the study. CONCLUSION: In this trial, 4CMenB displayed a favorable profile for further clinical development. 4CMenB demonstrated immunogenicity against multiple heterologous serogroup B strains. All vaccines were generally well tolerated in this study.	D. Toneatto, S. Ismaili, E. Ypma, K. Vienken, P. Oster and P. Dull	Human vaccines
8	Early clinical experience with a candidate meningococcal B recombinant vaccine (rMenB) in healthy adults	BACKGROUND: The development of a broadly protective vaccine against meningococcal serogroup B is a well-recognized public health need. Whole-genome sequencing was used to identify meningococcal surface proteins that are conserved across strains. These proteins were incorporated into two investigational vaccines. METHODS: Three randomized studies were performed to evaluate a three-component recombinant meningococcal serogroup B vaccine (rMenB) and rMenB plus outer membrane vesicles from the Norwegian outbreak strain 44/76 (rMenB+OMVNW). Participants were randomized to receive 3 or 4 doses of rMenB or rMenB+OMVNW or control vaccines and provided sera for exploratory immunogenicity testing against a panel of meningococcal serogroup B strains. A booster dose was administered 12 months after the initial primary series in one of the studies. The control cohort received a licensed quadrivalent meningococcal polysaccharide vaccine against serogroups A, C, W-135 and Y as well as hepatitis B vaccine as safety comparators. Solicited reactions within 7 days of any vaccination and adverse events throughout the studies were recorded. RESULTS: One hundred four participants enrolled into the clinical trials. Both rMenB and rMenB+OMVNW induced immune responses to multiple serogroup B strains in the majority of participants. Compared with rMenB, rMenB+OMVNW appeared somewhat more immunogenic and reactogenic; the study was not adequately powered for statistical assessment of these small differences. Both investigational vaccines were more reactogenic than the licensed vaccines. Few vaccinees discontinued any study due to reactogenicity to any study vaccine administered. CONCLUSION: Based on the immunogenicity and reactogenicity results in these participants, both rMenB and rMenB+OMVNW were promising candidates for further investigation.	D. Toneatto, P. Oster, A. C. deBoer, A. Emerson, G. F. Santos, E. Ypma, L. DeTora, M. Pizza, A. Kimura and P. Dull	Human vaccines
288	Dexamethasone and long-term outcome of tuberculous meningitis in Vietnamese adults and adolescents	BACKGROUND: Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown. METHODS: Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability. RESULTS: 545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32). CONCLUSIONS: Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM. TRIAL REGISTRATION: ClinicalTrials.gov NCT01317654.	M. E. Török, D. B. Nguyen, T. H. Tran, T. B. Nguyen, G. E. Thwaites, T. Q. Hoang, H. D. Nguyen, T. H. Tran, T. C. Nguyen, H. T. Hoang, M. Wolbers and J. J. Farrar	PloS one
430	Timing of initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-associated tuberculous meningitis	(See the editorial commentary Lawn and Wood, on pages 1384-1387.) Background. The optimal time to initiate antiretroviral therapy (ART) in human immunodeficiency virus (HIV)-associated tuberculous meningitis is unknown. Methods. We conducted a randomized, double-blind, placebo-controlled trial of immediate versus deferred ART in patients with HIV-associated tuberculous meningitis to determine whether immediate ART reduced the risk of death. Antiretroviral drugs (zidovudine, lamivudine, and efavirenz) were started either at study entry or 2 months after randomization. All patients were treated with standard antituberculosis treatment, adjunctive dexamethasone, and prophylactic co-trimoxazole and were followed up for 12 months. We conducted intention-to-treat, per-protocol, and prespecified subgroup analyses. Results. A total of 253 patients were randomized, 127 in the immediate ART group and 126 in the deferred ART group; 76 and 70 patients died within 9 months in the immediate and deferred ART groups, respectively. Immediate ART was not significantly associated with 9-month mortality (hazard ratio [HR], 1.12; 95% confidence interval [CI], .81-1.55; P = .50) or the time to new AIDS events or death (HR, 1.16; 95% CI, .87-1.55; P = .31). The percentage of patients with severe (grade 3 or 4) adverse events was high in both arms (90% in the immediate ART group and 89% in the deferred ART group; P = .84), but there were significantly more grade 4 adverse events in the immediate ART arm (102 in the immediate ART group vs 87 in the deferred ART group; P = .04). Conclusions. Immediate ART initiation does not improve outcome in patients presenting with HIV-associated tuberculous meningitis. There were significantly more grade 4 adverse events in the immediate ART arm, supporting delayed initiation of ART in HIV-associated tuberculous meningitis. Clinical Trials Registration. ISRCTN63659091.	M. E. Torok, N. T. Yen, T. T. Chau, N. T. Mai, N. H. Phu, P. P. Mai, N. T. Dung, N. V. Chau, N. D. Bang, N. A. Tien, N. H. Minh, N. Q. Hien, P. V. Thai, D. T. Dong, T. T. Anh do, N. T. Thoa, N. N. Hai, N. N. Lan, N. T. Lan, H. T. Quy, N. H. Dung, T. T. Hien, N. T. Chinh, C. P. Simmons, M. Jong, M. Wolbers and J. J. Farrar	Clinical infectious diseases
563	Immunogenicity and safety of an inactivated hepatitis a vaccine administered concomitantly with a pneumococcal conjugate vaccine in healthy children 15 months of age	The immunogenicity and safety of hepatitis A vaccine and pneumococcal conjugate vaccine, administered separately or concomitantly in children 15 months of age, were evaluated. After completed vaccinations, antihepatitis A and antipneumococcal geometric mean concentrations were similar across groups. Both vaccines were well-tolerated when given concomitantly during the second year of life	A. F. Trofa, M. Levin, C. D. Marchant, J. Hedrick and M. M. Blatter	Pediatr Infect Dis J
24	Once daily ceftriaxone for meningococcemia and meningococcal meningitis	Twenty children with meningococcal disease (15 with meningococcal meningitis and 5 with meningococcemia without meningitis) were treated with ceftriaxone, 80 to 100 mg/kg/day for 4 days. An additional 22 patients with meningococcal disease (13 with meningitis, 9 with meningococcemia without meningitis) were treated with penicillin G. On the basis of the Damrosch-Stiehm scoring system, 19 patients were classified in the poor prognostic group and were treated with antishock therapy. Clinical recovery time and normalization of CSF were compared in two groups. When the complications were compared, necrotic skin lesions were more frequently seen in the penicillin G group than in those who received ceftriaxone. Ceftriaxone is an effective and safe drug and offers the advantage of once daily administration for treatment of meningococcal disease in pediatric patients.	A. M. Tuncer, I. Gür, U. Ertem, A. Ece, S. Türkmen, B. Deniz, I. Gürman and S. Tuncer	The Pediatric infectious disease journal
104	A clinical trial examining the effect of increased total CRM(197) carrier protein dose on the antibody response to Haemophilus influenzae type b CRM(197) conjugate vaccine	CRM(197) is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid/tetanus toxoid/acellular pertussis vaccine (DTaP) received either diphtheria CRM(197)-based Haemophilus influenzae type b conjugate vaccine (HbOC) or HbOC and a diphtheria CRM(197)-based combination 9-valent pneumococcal conjugate vaccine/meningococcal group C conjugate vaccine. Administration of conjugate vaccines with CRM(197) carrier protein load >50 microg did not reduce response to CRM(197) conjugate vaccines or immunogenicity to immunologically cross-reactive diphtheria toxoid.	V. Usonis, V. Bakasenas, S. Lockhart, S. Baker, W. Gruber and F. Laudat	Vaccine
120	Cerebrospinal fluid nitric oxide levels in childhood bacterial meningitis	The role of nitric oxide (NO) in childhood bacterial meningitis was investigated by determining the levels of nitrate/nitrite, stable end products of NO metabolism, in cerebrospinal fluid (CSF). Eighteen children with bacterial meningitis and 18 as a control group were included in the study. Mean (+/- SD) CSF nitrate/nitrite levels were 27.6 +/- 26 micromol/l in the bacterial meningitis group and 3.2 +/- 1.8 micromol/l in the control group (p = 0.0005). We found no correlation between CSF nitrate/nitrite levels and CSF white blood cell count (r = 0.22), protein (r = 0.26) or tumour necrosis factor alpha (TNF-alpha) levels (r = 0.046), but a moderate negative correlation between CSF nitrate/nitrite and glucose levels (r = -0.46).	G. Uysal, G. Yüksel, B. Sinav, S. Yüksel and H. Uysal	Scandinavian journal of infectious diseases
117	Penetration of antibiotics into the cerebro-spinal fluid in inflammatory conditions. 1. Preface and comparative study of ampicillin with hetacillin		V. Vacek, M. Hejzlar and M. Skálová	Internationale Zeitschrift für klinische Pharmakologie, Therapie, und Toxikologie. International journal of clinical pharmacology, therapy, and toxicology
107	[The relationship of the therapeutic efficacy of immunoglobulin against tick-borne encephalitis to the specific activity of the preparation and the times of its administration]	A controlled clinical trial included 115 patients with meningeal and focal tick-borne encephalitis, 38 of them received nonspecific treatment alone, 77 were given adjuvant intramuscular immunoglobulin against tick-borne encephalitis. The latter are shown to improve much more rapidly than patients treated only symptomatically. When calculating adequate immunoglobulin doses, it is necessary to take in consideration not only the amount of the compound, but also the concentration of the specific antibodies. The authors propose treatment schemes for patients with meningeal and focal tick-borne encephalitis.	L. A. Vereta, T. A. Zakharycheva, V. I. Aleksandrov, V. V. Skupchenko and S. P. Nikolaeva	Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova / Ministerstvo zdravookhraneniia i meditsinsko? promyshlennosti Rossi?sko? Federatsii, Vserossi?skoe obshchestvo nevrologov [i] Vserossi?skoe obshchestvo psikhiatrov
203	Pathophysiological aspects of hyperglycemia in children with meningococcal sepsis and septic shock: a prospective, observational cohort study	INTRODUCTION: The objective of this study was to investigate the occurrence of hyperglycemia and insulin response in critically ill children with meningococcal disease in the intensive care unit of an academic children's hospital. METHODS: Seventy-eight children with meningococcal disease were included. The group was classified into shock non-survivors, shock survivors and sepsis survivors. There were no sepsis-only non-survivors. The course of laboratory parameters during 48 hours was assessed. Insulin sensitivity and ?-cell function on admission were investigated by relating blood glucose level to insulin level and C-peptide level and by homeostasis model assessment (HOMA) [?-cell function (HOMA-%B) and insulin sensitivity (HOMA-%S)]. RESULTS: On admission, hyperglycemia (glucose >8.3 mmol/l) was present in 33% of the children. Shock and sepsis survivors had higher blood glucose levels compared with shock non-survivors. Blood glucose level on admission correlated positively with plasma insulin, C-peptide, cortisol, age and glucose intake. Multiple regression analysis revealed that both age and plasma insulin on admission were significantly related to blood glucose. On admission, 62% of the hyperglycemic children had overt insulin resistance (glucose >8.3 mmol/l and HOMA-%S <50%); 17% had ?-cell dysfunction (glucose >8.3 mmol/l and HOMA-%B <50%) and 21% had both insulin resistance and ?-cell dysfunction. Hyperglycemia was present in 11% and 8% of the children at 24 and 48 hours after admission, respectively. CONCLUSIONS: Children with meningococcal disease often show hyperglycemia on admission. Both insulin resistance and ?-cell dysfunction play a role in the occurrence of hyperglycemia. Normalization of blood glucose levels occurs within 48 hours, typically with normal glucose intake and without insulin treatment.	J. J. Verhoeven, M. Brinker, A. C. Hokken-Koelega, J. A. Hazelzet and K. F. Joosten	Critical care (London, England)
41	Antibody avidity and immunoglobulin G isotype distribution following immunization with a monovalent meningococcal B outer membrane vesicle vaccine	The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.	C. L. Vermont, H. H. Dijken, C. J. Limpt, R. Groot, L. Alphen and G. P. Dobbelsteen	Infection and immunity
605	Perispinal analgesia for labour followed by patient-controlled infusion with bupivacaine and sufentanil: combined spinal-epidural vs. epidural analgesia alone	BACKGROUND AND OBJECTIVE: Combined spinal-epidural is an alternative technique to epidural analgesia for labour, but its benefits are not clearly identified. METHODS: A prospective, blinded, randomized study was undertaken involving 113 women attending a university hospital obstetric department. Analgesia was initiated with intrathecal bupivacaine 0.25% 1 mL + sufentanil 5 microg in the combined spinal-epidural group (n = 54), and with bupivacaine 0.125% + epinephrine 2.5 microg mL(-1) + sufentanil 7.5 microg in the epidural group (n = 59). In both cases this was followed by patient-controlled epidural analgesia with bupivacaine 0.125% (+ sufentanil 0.25 microg mL(-1)). Duration of labour, quality of analgesia and side-effects were compared between groups. RESULTS: In the combined spinal-epidural group, the onset of analgesia was faster (5 vs. 15 min, P < 0.001), the consumption of bupivacaine was lower (7.5 vs. 11.3 mg h(-1), P = 0.003) and there was less unilateral analgesia (14.8% vs. 40.7%, P = 0.002) than in the epidural group. The characteristics of labour were similar in both groups. However, in the combined spinal-epidural group, there was a higher incidence of posterior presentation (25.9% vs. 10%, P = 0.03), pruritus (P < 0.001), hypotension (P = 0.002), somnolence (P = 0.01), nausea (P = 0.02) and one case of meningitis. CONCLUSIONS: The combined spinal-epidural technique provided more effective analgesia during labour than epidural analgesia alone but offered no other advantage. It induced more adverse effects and this should be considered before routinely using the combined spinal-epidural technique.	L. Vernis, C. Dualé, B. Storme, J. P. Mission, B. Rol and P. Schoeffler	European journal of anaesthesiology
91	Tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered with measles-mumps-rubella-varicella vaccine during the second year of life: An open, randomized controlled trial	Co-administration of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT) with MMRV vaccine was investigated in 1000 12-23-month old children randomized (3:3:1:1) to receive co-administered ACWY-TT+MMRV, or a single dose of ACWY-TT, MMRV or MenC-CRM(197). Non-inferiority of ACWY-TT to MenC-CRM(197) and non-inferiority of ACWY-TT+MMRV to ACWY-TT and MMRV alone, and the immunogenicity of serogroups AWY were demonstrated according to pre-defined criteria. Fever reactions in ACWY+MMRV and MMRV groups were comparable. ACWY-TT can be co-administered with MMRV without affecting immunogenicity or safety profiles of either vaccine. This study has been registered at www.clinicaltrials.gov NCT00474266.	T. Vesikari, A. Karvonen, V. Bianco, M. Wielen and J. Miller	Vaccine
513	Tetravalent meningococcal serogroups A, C, W-135 and Y conjugate vaccine is well tolerated and immunogenic when co-administered with measles-mumps-rubella-varicella vaccine during the second year of life: An open, randomized controlled trial		T. Vesikari, A. Karvonen, V. Bianco, M. Wielen and J. Miller	Vaccine
142	Results from a randomized clinical trial of coadministration of RotaTeq, a pentavalent rotavirus vaccine, and NeisVac-C, a meningococcal serogroup C conjugate vaccine	RotaTeq (Merck & Co. Inc./Sanofi Pasteur MSD) is a three-dose, oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis. The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine (MenCC; NeisVac-C; Baxter Healthcare) to healthy infants without impairing the protective immune responses to MenCC. This was an open-label, randomized, comparative study conducted in Finland. The study was designed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines. Healthy infants (n = 247), aged 6 to 7 weeks, were recruited. Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C (the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ? 8 was 100% in both groups). The other responses to MenCC (titer of ? 1:128, ? 4-fold increase in titer, and geometric mean titers [GMTs]) and the responses to RotaTeq (IgA and SNA response to G1 to G4 and P1A[8], GMTs, and ? 3-fold increase in titer) were comparable between groups, including a ? 3-fold IgA increase in >96% of the infants in both groups. Concomitant administration of the first doses of MenCC, diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib), and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib, but that was not observed after the second concomitant administration. The convenience of concomitant administration of RotaTeq and MenCC may, however, outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine. These results support the coadministration of RotaTeq and MenCC.	T. Vesikari, A. Karvonen, R. Borrow, N. Kitchin, M. Baudin, S. Thomas and A. Fiquet	Clinical and vaccine immunology : CVI
475	Immunogenicity and safety of the human rotavirus vaccine Rotarix co-administered with routine infant vaccines following the vaccination schedules in Europe	This study assessed the immunogenicity and safety of a human rotavirus vaccine RIX4414; the effect of co-administration of childhood vaccines on the immune responses was also assessed. Healthy infants aged 6-14 weeks received two doses of RIX4414/placebo concomitantly with the primary childhood vaccination (Infanrix hexa, Infanrix quinta,Meningitec and/or Prevnar), respecting the vaccination schedule of each country. Anti-rotavirus IgA seroconversion rate (ELISA cut-off 20 U/ml) was measured pre-vaccination and 1-2 months post-Dose 2. Immune response against diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b, inactivated polio virus, pneumococcal polysaccharide conjugate (France and Germany) and meningococcal group C conjugate vaccines (Spain) were measured approximately 1-month post-Dose 3. An overall anti-rotavirus IgA seroconversion rate of 86.5%(95% CI: 83.9-88.8) was observed in the RIX4414 group 1-month post-Dose 2. The seroconversion rate in Finland and Italy (3 and 5-month schedule) was 94.6%(95% CI: 90.0-97.5) and 92.3%(95% CI: 64.0-99.8), respectively. Immune response to the childhood vaccines was unaffected following co-administration with RIX4414. Reactogenicity profile was similar for RIX4414 and placebo groups. RIX4414 was immunogenic and well tolerated in European infants and the co-administration of routine childhood vaccines with RIX4414 did not negatively impact the immune responses to these vaccines.	T. Vesikari, A. Karvonen, R. Prymula, V. Schuster, J. C. Tejedor, F. Thollot, P. Garcia-Corbeira, S. Damaso, H. H. Han and A. Bouckenooghe	Vaccine
390	Reactivity and immunogenicity of bivalent (AC) and tetravalent (ACW135Y) meningococcal vaccines containing O-acetyl-negative or O-acetyl-positive group C polysaccharide	The immunogenicity and the reactivity of two bivalent (AC) and two tetravalent (ACW135Y) meningococcal vaccines containing either the O-acetyl-positive or the O-acetyl-negative group C polysaccharide were compared in healthy adolescent and adult volunteers. The vaccines contained high-molecular-weight, purified capsular meningococcal polysaccharides and were administered subcutaneously at a dose of 50 mug for each polysaccharide. Reactivity was low for all vaccines, and the tetravalent vaccines were not significantly more reactive than the bivalent vaccines. Immunogenicity was measured by assay of bactericidal antibodies in pre- and postvaccination sera. More than 90% of the vaccinees had at least a 4-fold increase in the bactericidal antibody titer against each group of meningococcus represented in the vaccines. Addition of polysaccharide W135 and polysaccharide Y to polysaccharides A and C did not alter the immunogenicity of the latter polysaccharides. Thus, there is no evidence of antigenic competition with the tetravalent vaccine. Comparison of the antibody response to the O-acetyl-positive and the O-acetyl-negative variants of group C polysaccharide in the bivalent vaccines, as measured by both bactericidal and enzyme-linked immunosorbent assays, indicates that in adults, the two types of group C polysaccharide are similarly immunogenic. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	I. Vodopija, Z. Baklaic and P. Hauser	Infection & Immunity
19	Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults	In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults (n=21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC polysaccharide vaccine. Blood samples were collected prior to immunization and at 6 additional time points, from 3 to 25 days post-immunization. Secondary immunization resulted in 5-10-fold higher IgG titers compared to the primary immunization group, 25 days post-immunization. Prior to the secondary immunization, but 5 years after the first immunization, protective bactericidal antibodies and levels of MenC-specific IgG and IgM were still present. Furthermore, IgG antibodies present before secondary immunization were of higher avidity compared to antibodies produced one month after primary immunization. In addition, secondary immunization with nonconjugated MenC polysaccharide seemed to induce a higher IgG2 response compared to MenCC immunization. The kinetics of the observed secondary immune responses were not really faster than the observed primary responses. However, the rate of increase in antibodies seemed faster than the primary responses, representing a booster response. As the course of infection by Neisseria meningitidis can be very rapid, these data support the idea that sustainment of high antibody levels induced by MenCC are important for immediate protection.	R. M. Voer, F. R. Klis, C. W. Engels, R. M. Schepp, J. Kassteele, E. A. Sanders, G. T. Rijkers and G. A. Berbers	Vaccine
79	Specificity of human bactericidal antibodies against PorA P1.7,16 induced with a hexavalent meningococcal outer membrane vesicle vaccine	A set of isogenic strains was constructed from the meningococcal reference strain H44/76 (B:15:P1.7,16) which differed only in their outer membrane protein (OMP) compositions. First, three isogenic strains lacking the expression of either class 3 (PorB) or class 4 (RmpM) OMP or both were obtained. Second, three isogenic class 1 OMP loop-deficient strains of H44/76 lacking the predicted loop 1 or 4 or both of class 1 OMP (PorA) were obtained. Third, three isogenic class 1 OMP strains which differed by point mutations in the predicted loop 4 of subtype P1.16 were constructed. Strains were constructed through transformation with gene constructs made in Escherichia coli and their homologous recombination into the meningococcal chromosome. This study describes the contribution of one of the six class 1 OMPs, PorA P1.7,16, in the development of bactericidal antibodies after a single immunization of adult volunteers with 50 or 100 micrograms of protein within a hexavalent PorA outer membrane vesicle vaccine. PorA-, PorB-, and RpmM-deficient isogenic strains were used to define the human immune response against PorA. The loop-deficient isogenic strains were used to define the contribution of loops 1 and 4 of PorA in the development of bactericidal anti-PorA antibodies. The isogenic strains carrying a point mutation in loop 4 were used to study the cross-reactivity of the induced bactericidal antibodies against target strains showing microheterogeneity. The results indicate that a single immunization with the hexavalent PorA vaccine induced a dose-dependent bactericidal immune response, which is directed mainly against PorA. The epitope specificity of antibodies is directed mostly against loop 1, although loop 4 and as-yet-unidentified epitopes of PorA P1.7,16 are also involved.	E. R. Voort, P. Ley, J. Biezen, S. George, O. Tunnela, H. Dijken, B. Kuipers and J. Poolman	Infection and immunity
133	CD4 and CD8 lymphocyte subsets in cerebrospinal fluid and peripheral blood from patients with multiple sclerosis, meningitis and normal controls	OBJECTIVES: To study the distribution of CD4+ and CD8+ T-cell subsets in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (MS), meningitis, other neurological diseases and healthy controls. MATERIAL AND METHODS: The expression of markers for naive and memory cells (CD45RA+ and CD45R0+), and helper/inducer cells (CD29+) on CD4+ cells as well as CD45R0+ and killer/effector (S6F1+) on CD8+ cells was investigated in cerebrospinal fluid (CSF) and peripheral blood from patients with multiple sclerosis (n=28), meningitis (n=13), other neurological diseases (n=16), and healthy controls (n=16) by 2-color flow cytometry. RESULTS: The majority of T cells in the CSF of the 4 groups exhibited the phenotype of memory cells (CD45R0+) on both CD4+ and CD8+ cells. The proportion of helper/inducer (CD29+CD4+ in CD4+) cells was also larger in the CSF compared to peripheral blood in the 3 patient groups and controls investigated. In contrast, CD8+ cells with killer/effector (S6F1+) phenotype were fewer in CSF compared to peripheral blood in all 4 groups. There were no significant differences between patients and controls regarding the distribution of these activation markers in the CSF or peripheral blood. CONCLUSION: Our observations support the notion that activated T cells of both CD4+ and CD8+ phenotype selectively pass the blood-brain barrier under both pathological and normal conditions.	M. Vrethem, C. Dahle, C. Ekerfelt, P. Forsberg, O. Danielsson and J. Ernerudh	Acta neurologica Scandinavica
74	Single injection treatment of meningococcal meningitis. 2. Long-acting chloramphenicol	A single injection of a long-acting oily preparation of chloramphenicol (Tifomycine) was compared with a five-day course of crystalline and procaine penicillin in the treatment of 131 adult patients with meningococcal meningitis. The clinical response to treatment was similar in the two groups of patients. Serial lumbar punctures showed a parallel fall in CSF cell count, protein and lactate and all posttreatment cultures were sterile. Single injection chloramphenicol treatment was cheaper and much easier to administer than penicillin. Long-acting chloramphenicol is thus an effective form of treatment for meningococcal meningitis and is likely to prove of particular value in the management of epidemics in areas with limited medical resources.	S. S. Wali, J. T. Macfarlane, W. R. Weir, P. G. Cleland, P. A. Ball, M. Hassan-King, H. C. Whittle and B. M. Greenwood	Transactions of the Royal Society of Tropical Medicine and Hygiene
659	[Effect comparison of arachnoid cysts in sacral canal]	OBJECTIVE: To evaluate the clinical outcomes of two different surgical treatments for arachnoid cysts in sacral canal. METHODS: From January 2004 to March 2009, 55 cases of arachnoid cysts in the sacral canal were treated by traditional simple sacral laminectomies with resection of the cysts (group A, 25 cases) and novel CT-guided percutaneous fibrin glue therapy of arachnoid cysts (group B, 30 cases). Of them, there were 23 males and 32 females, aging 15-66 years with an average of 42.6 years; the duration of symptoms was 6 months to 15 years with an average of 3.5 years. L5-S1 was involved in 22 cases, S1,2 in 25 cases, S2,3 in 12 cases, S2 in 8 cases, and presacral in 2 cases. The size of cysts was 1.5 cm x 1.0 cm to 6.0 cm x 2.8 cm. The MRI examination showed that all patients had cysts in the sacral canal. There were no significant difference (P > 0.05) in sex, ages, disease duration and cysts size between two groups. Preoperative data and postoperative lumbosacral pain and function improvement were analyzed and compared between two groups. RESULTS: All operations were performed successfully. The operative time, blood loss and hospitalization days of group B were significantly less than those of group A (P < 0.01). All 55 cases were followed up from 9 to 61 months (mean 23 months). In group A, postoperative cerebrospinal fluid leakage (25 cases), intracranial infection (2 cases), nerve injury (3 cases), and nerve root irritation (8 cases) occurred; in group B, mild meningitis (3 cases) and low grade fever (5 cases) occurred. Except for nerve injury, other complications were cured after symptomatic management. During the follow-up, 2 recurrent cases were found in group A and 1 case in group B. Of them, 2 recurrent cases were treated with CT-guided percutaneous fibrin glue therapy of arachnoid cysts, and cysts disappeared. For two groups, there were significant differences in Oswestry functional disability index and visual analogue scale score between preoperation and postoperation (P < 0.01), and in the rate of score improvement between two groups (P < 0.01). According to the rating scale, the excellent and good rates of pain improvement were 64% in group A and 100% in group B; the excellent and good rates of function improvement were 24% in group A and 97% in group B. CONCLUSION: CT-guided percutaneous fibrin glue therapy for arachnoid cysts in the sacral canal is a mini-invasive, safe, effective, and economical method, it may be better choices for the treatment of arachnoid cysts in the sacral canal.	B. Wang, Z. Shao, H. Wu, S. Yang, Y. Wu, Z. Ma and P. Yu	Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery
414	[Cerebral spinal fluid replacement plus intrathecal administration in treatment of acute bacterial meningitis]	Objective: To study clinical effects of cerebral spinal fluid replacement plus intrathecal administration in bacterial meningitis. Methods: One hundred and twenty-five patients aged 17 to 71 years old with acute bacterial meningitis were randomly divided into two groups. Patients in control group (47 patients) received routine treatment. Patients in experiment group (78 patients) received cerebral spinal fluid replacement plus intrathecal administration (antibiotics and desamethason) besides routine treatment. The clinical effects were compared between the two groups. Results: The mean durations of hospitalization, and for temperature and for leukocytes returning to normal in the experiment group were shortened by 9 days, and the mean duration for peripheral blood returning to normal was shortened by 7 days. Conclusion: The cerebral spinal fluid replacement plus intrathecal administration might be useful to treat bacterial menineitis. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	S. P. Wang, G. Y. Zhao and H. Wang	Chinese Journal of Emergency Medicine
592	Invasive Haemophilus influenzae type b disease in Alaska: Background epidemiology for a vaccine efficacy trial	In a previous study we demonstrated that Alaskan Eskimos had the highest endemic incidence of invasive Haemophilus influenzae type b (Hib) disease. In 1980 we established a prospective surveillance program for all invasive Hib disease throughout Alaska to (1) characterize additional epidemiological features of disease in Native Alaskans to plan for a vaccine efficacy trial and (2) define the epidemiology of Hib disease in all population groups in the state. For the three-year period, 1980-1982, 287 confirmed episodes of invasive Hib disease occurred. For children less than five years of age, the incidences for Eskimos, Indians, and non-Natives were 705, 401, and 129 cases per 100,000 population, respectively. The Native population represents only 16% of the population of Alaska but has 51% of all invasive Hib disease. Disease differed significantly among Eskimos, Indians, and non-Natives with regard to risk, age of onset, disease type, antibiotic susceptibility of strains, and regional incidence, but mortality and seasonal occurrence were similar. For Native Alaskans the cumulative Hib disease risk for the first two years of life was 4% (range, 1%-7% by region). This high endemic disease risk, concentrated in the first two years of life, provides a unique opportunity to prospectively evaluate the protective efficacy of a vaccine in a randomized, blinded, and placebo-controlled trial. Such a trial was initiated in December 1984. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. I. Ward, M. K. W. Lum and D. B. Hall	J-Infect-Dis
601	Safety and efficacy of low-dose intravenous immune globulin (IVIG) treatment for infants and children with immune thrombocytopenic purpura. Low-Dose IVIG Study Group	PURPOSE: This report presents pooled data from two multicenter studies conducted to assess the efficacy, safety, and tolerance of lower-dose intravenous immune globulin (IVIG) regimens of 250 mg/kg/day, 400 mg/kg/day, and 500 mg/kg/day for 2 days, compared to an established higher-dose regimen of 1 g/kg/day for 2 days, in children with immune thrombocytopenic purpura (ITP). PATIENTS AND METHODS: A total of 24 children received IVIG (Gammar i.v.). In Study 1, 10 centers enrolled 12 children between 5 and 12 years old who received IVIG at either 400 mg/kg/day or 1 g/kg/day for 2 days. In Study 2, five centers enrolled 12 infants and children younger than 5 years old who received IVIG at 250 mg/kg/day or 500 mg/kg/day for 2 days. Both studies were prospective and randomized. RESULTS: IVIG treatment was effective (platelets increased at least 30,000/cu mm over baseline) in 94% (16 of 17) of the evaluable patients in the low-dosage group. Platelet increases occurred rapidly: by 48 hours, total platelet counts ranged from 32,000/cu mm to 256,000/cu mm, and peak platelet counts reached 38,000/cu mm to 551,000/cu mm. Adverse events (AEs) were most often mild, lasted less than 3 hours, and were usually those typically associated with immunoglobulin administration-headache, nausea, vomiting, and fever. There were two serious AEs-an anaphylactoid reaction in one patient in the 400 mg/kg group and aseptic meningitis in one patient in the 1 g/kg high-dosage group. Both patients recovered without sequelae and were responders. Although the incidence of AEs varied by dosage groups, this difference was not significant. However, the incidence of AEs was affected by age. AEs were significantly lower in patients younger than 5 years of age. CONCLUSIONS: In this small, randomized trial, low-dose IVIG in 2-day regimens of 250, 400, or 500 mg/kg/day rapidly reversed thrombocytopenia just as effectively as 1 g/kg/day in infants and young children with ITP. Lower-dosage regimens are safe and well-tolerated; the incidence of AEs is lower in children younger than 5 years of age.	I. Warrier, J. B. Bussel, L. Valdez, J. Barbosa and D. S. Beardsley	Journal of pediatric hematology/oncology
640	Single dose cefazolin prophylaxis for postcesarean infections: before vs. after cord clamping	The objective of this study was to test the hypothesis that 1 g of cefazolin administered preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity. Ninety consecutive laboring subjects undergoing cesarean delivery at > or = 37 weeks gestation were randomized by computer to receive 1 g of cefazolin intravenously preoperatively or after cord clamping in a double-blinded, placebo-controlled study. The 2 groups were compared for differences in maternal and neonatal demographics, and intrapartum and operative characteristics associated with postcesarean infection. Primary maternal outcome variables were endometritis or wound infection. Secondary outcomes included intra-abdominal abscess formation, septic pelvic thrombophlebitis, pneumonia, or urinary tract infection. Neonatal outcomes included sepsis screens, sepsis, pneumonia, and meningitis. Subjects were followed 6 weeks postoperatively for late complications. Subjects receiving cefazolin preoperatively or after cord clamping had similar maternal and neonatal demographics, and intrapartum and operative characteristics. One patient in the former group experienced both endometritis and wound infection. In the latter group, 2 wound infections and 1 case of endometritis occurred (P = 0.35). There were no secondary maternal infections. Two infants treated for pneumonia and 2 other infants readmitted with febrile illnesses were born to mothers receiving cefazolin preoperatively. Overall, 8 neonates were evaluated for suspected sepsis and all had negative studies. Six of these infants' mothers received cefazolin preoperatively (P = 0.28). In conclusion, 1 gram of cefazolin preoperatively is no more effective than the same dose administered after cord clamping in preventing postcesarean infectious morbidity, but is associated with a trend toward increased suspected sepsis in the newborn. However, this trend may be related to differences between the study groups' risk factors for infection.	J. R. Wax, K. Hersey, C. Philput, M. S. Wright, K. V. Nichols, M. K. Eggleston and J. F. Smith	The Journal of maternal-fetal medicine
496	On streptomycin therapy of tuberculous meningitis and miliary tuberculosis		K. Wechselberg and E. Weidenbusch	Klinische Wochenschrift
679	[Experiences using acylureido-penicillins (azlocillin, mezlocillin) in pediatrics]	The acylureidopenicillins azlocillin and mezlocillin cover a broad spectrum of bacteria, including gramnegative and grampositive species as well as anaerobes. Azlocillin is especially active against P. aeruginosa. Mezlocillin has a good activity against Klebsiella. Both antibiotics inhibit Hemophilus, N. meningitidis and D. pneumoniae in low concentrations. Clinical and kinetic studies were made in more than 300 pediatric patients. Elimination-constant halflife, distribution volume and area under the curve were determined to propose dosage recommendations. Concentrations of azlocillin (44) and mezlocillin (77) were measured in the bronchial secretions. Up to hour 5 after i.v. injection a wide range of concentration values were observed. Azlocillin was found in the meconium in different concentrations after a single injection into the newborn. Mezlocillin diffused into the CSF even in uninflamed meninges, 3 h after injection the mean concentrations were 5.5 mg/l. 39 patients, 35 of them infected by P. aeruginosa, were treated by azlocillin. Urinary tract infections, wound infections and dacryocystitis were cured with one exception. Less convincing were the results in complicated bronchopulmonary diseases. The clinical efficacy of mezlocillin was similar. In a group of 59 patients there were only 3 without effect and some with improvement again in complicated pulmonary diseases. Side effects worth to be mentioned were not seen. In 2 patients the azlocillin injection caused nausea. Mezlocillin led to some minor transitory elevations of the transaminases and dyspepsia in some patients.	L. Weingärtner, U. Sitka, R. Patsch and H. H. Thiemann	Klinische Pädiatrie
460	Infectious toxic hypotension. Effect and dosage of midodrine. <ORIGINAL> INFEKTIOS-TOXISCHE HYPOTENSION. DOSIERUNG UND WIRKUNG VON MIDODRIN	A new alpha-sympathicomimetic drug with peroral effect is midodrine. The effective oral dosage in infancy and childhood is 0.06 mg/kg/dosi. The therapeutic effect, comparing the drug with etilefrin, is shown in 120 children with pneumonia, enteritis, meningitis in a random study. The results give an increase in blood pressure and a decrease in heart frequency, statistically proved, on the first day of treatment. Therefore, it seems that midodrine is qualified for the treatment of hypotension in infectious diseases. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	G. Weippl	Padiatr Padol
606	[Infectious toxic hypotension--effect and dosage of midodrine (author's transl)]	A new alpha-sympathicomimetic drug with peroral effect is midodrine. The effective oral dosage in infancy and childhood is 0.06 mg/kg/dosi. The therapeutic effect, comparing the drug with etilefrin is shown in 120 children with pneumonia, enteritis, meningitis in a random study. The results give an increase in blood pressure and a decrease in heart frequency, statistically proved, on the first day of treatment. Therefore it seems that midodrine is qualified for the treatment of hypotension in infectious diseases.	G. Weippl	Pädiatrie und Pädologie
646	[Infectious toxic hypotension effect and dosage of midodrine]	A new alpha-sympathicomimetic drug with peroral effect is midodrine. The effective oral dosage in infancy and childhood is 0.06 mg/kg/dosi. The therapeutic effect, comparing the drug with etilefrin is shown in 120 children with pneumonia, enteritis, meningitis in a random study. The results give an increase in blood pressure and a decrease in heart frequency, statistically proved, on the first day of treatment. Therefore it seems that midodrine is qualified for the treatment of hypotension in infectious diseases.	G. Weippl	Padiatrie und Padologie
450	Ceftriaxone versus cefuroxime for treatment of bacterial meningitis	Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	D. Weiss and J. H. Glaser	Journal of Pediatrics
219	Neutral and acidic oligosaccharides in preterm infants: a randomized, double-blind, placebo-controlled trial	BACKGROUND: Serious infectious morbidity is high in preterm infants. Enteral supplementation of prebiotics may reduce the incidence of serious infections, especially infections related to the gastrointestinal tract. OBJECTIVE: The objective was to determine the effect of enteral supplementation of a prebiotic mixture consisting of neutral oligosaccharides ((SC)GOS/(LC)FOS) and acidic oligosaccharides (AOS) on serious infectious morbidity in preterm infants. DESIGN: In a randomized controlled trial, preterm infants (gestational age <32 wk and/or birth weight <1500 g) received enteral supplementation of 80% (SC)GOS/(LC)FOS and 20% AOS (1.5 g . kg(-1) . d(-1)) or placebo (maltodextrin) between days 3 and 30 of life. Serious infectious morbidity was defined as a culture positive for sepsis, meningitis, pyelonephritis, or pneumonia. The analysis was performed by intention-to-treat and per-protocol, defined as > or =50% supplementation dose during the study period. RESULTS: In total, 113 preterm infants were included. Baseline and nutritional characteristics were not different between groups. In the intention-to-treat analysis, the incidence of > or =1 serious infection, > or =1 serious endogenous infection, or > or =2 serious infectious episodes was not significantly different in the (SC)GOS/(LC)FOS/AOS-supplemented and placebo groups. In the per-protocol analysis, there was a trend toward a lower incidence of > or =1 serious endogenous infection and > or =2 serious infectious episodes in the (SC)GOS/(LC)FOS/AOS-supplemented group than in the placebo group (P = 0.09 and P = 0.07, respectively). CONCLUSIONS: Enteral supplementation of (SC)GOS/(LC)FOS/AOS does not significantly reduce the risk of serious infectious morbidity in preterm infants. However, there was a trend toward a lower incidence of serious infectious morbidity, especially for infections with endogenous bacteria. This finding suggests a possible beneficial effect that should be evaluated in a larger study. This trial was registered at isrctn.org as ISRCTN16211826.	E. A. Westerbeek, J. P. Berg, H. N. Lafeber, W. P. Fetter, G. Boehm, J. W. Twisk and R. M. Elburg	The American journal of clinical nutrition
40	Persistence of serum bactericidal antibody one year after a booster dose of either a glycoconjugate or a plain polysaccharide vaccine against serogroup C Neisseria meningitidis given to adolescents previously immunized with a glycoconjugate vaccine	BACKGROUND: Bactericidal antibody induced by immunization of infants with serogroup C Neisseria meningitidis (MenC) vaccines wanes rapidly during childhood. Adolescents are at particular risk from meningococcal disease, therefore they might benefit from a booster dose of vaccine. The duration of serologic response to such a booster in adolescents is unknown. METHODS: In a previous study, English schoolchildren, aged 9 to 12 years, who had received a monovalent MenC glycoconjugate vaccine in 1999-2000, were given either a plain polysaccharide vaccine (MenC-PS group, n = 150) or a glycoconjugate vaccine (MenC-CRM group, n = 95) at 13 to 15 years of age. In this follow-up study, serum bactericidal antibody titers and specific immunoglobulin G concentrations were assessed 1 year later. Results were compared with unboosted controls of similar age (control group, n = 298). RESULTS: Compliance with study protocol was achieved for 146 of the MenC-PS group, 92 of the MenC-CRM group, and 293 of the control group. Compared with the control group, both the MenC-PS and MenC-CRM groups had a significantly higher (P < 0.0001) geometric mean serum bactericidal antibody titers 1 year after the booster dose (geometric mean titers for MenC-PS group 3388 [95% confidence interval {CI}: 2460-4665]; MenC-CRM group 4417 [95% CI: 2951-6609]; control group 316 [95% CI: 252-396]). Specific immunoglobulin G concentration also rose and remained elevated 1 year after the booster. CONCLUSIONS: A booster dose of MenC vaccine given to adolescents produced a marked rise in bactericidal antibody, which remained elevated 1 year later. Introduction of an adolescent booster of MenC vaccine might provide enhanced long-term population control of the disease.	P. C. Whalley, M. D. Snape, D. F. Kelly, C. Banner, S. Lewis, L. Diggle, T. M. John, L. M. Yu, O. Omar, A. Borkowski and A. J. Pollard	The Pediatric infectious disease journal
401	Immunogenicity and safety of human papillomavirus-16/18 AS04-adjuvanted vaccine coadministered with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine and/or meningococcal conjugate vaccine to healthy girls 11 to 18 years of age: Results from a randomized open trial		C. M. Wheeler, B. M. Harvey, M. E. Pichichero, M. W. Simon, S. P. Combs and M. M. Blatter	Pediatric infectious disease journal
621	Neutrophil storage pool depletion in septic, neutropenic neonates	A prospective study was done to determine the incidence of neutrophil storage pool (NSP) depletion in clinically septic neonates with peripheral neutropenia (< 1500/mmsup 3). Infants with NSP depletion were then randomized in a controlled study of polymorphonuclear leukocyte transfusions. Bone marrow examinations were done in 13 patients, and NSP depletion was noted in 3 (23%) patients. All patients with no NSP depletion had peripheral neutrophil recovery and 8 of 10 survived. Complications of meningitis contributed to both deaths. Two of the three patients with NSP depletion died. Neither the initial severity of illness nor the degree of peripheral neutropenia were predictive either of NSP depletion or of mortality. Most neonates with severe peripheral neutropenia and clinical sepsis had peripheral neutrophil recovery and survived with conservative management. Those at high risk could be identified by examination of the NSP. Only those patients with NSP depletion should be considered for controlled studies of polymorphonuclear leukocyte transfusions. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. G. Wheeler, A. R. Chauvenet and C. A. Johnson	Pediatr-Infect-Dis
137	Disseminated herpes zoster in the immunocompromised host: a comparative trial of acyclovir and vidarabine. The NIAID Collaborative Antiviral Study Group	Seventy-three immunocompromised patients with disseminated herpes zoster were evaluated in a double-blind controlled trial of acyclovir (n = 37) versus vidarabine (n = 36) therapy. Acyclovir was administered at 30 mg/kg/day at 8-h intervals and vidarabine was given as a continuous 12-h infusion at 10 mg/kg/day for 7 days (longer if resolution of cutaneous or visceral disease was incomplete). No demographic differences existed between treatment groups. No deaths attributable to varicella-zoster virus infection occurred within 1 month of treatment. Neither rates of cutaneous healing, resolution of acute neuritis, and frequency of postherpetic neuralgia nor adverse clinical and laboratory events differed between treatment groups. Acyclovir recipients were discharged from the hospital more promptly than vidarabine recipients (P = .04, log rank test). These data indicate that disseminated herpes zoster is amenable to therapy with either acyclovir or vidarabine; resultant mortality is low.	R. J. Whitley, J. W. Gnann, D. Hinthorn, C. Liu, R. B. Pollard, F. Hayden, G. J. Mertz, M. Oxman and S. J. Soong	The Journal of infectious diseases
70	Trial of chloramphenicol for meningitis in northern savanna of Africa	In a controlled trial chloramphenicol proved as effective and much cheaper than penicillin for the treatment of group A meningococcal meningitis in Zaria, Nigeria. A short course of five days cured most patients. Adults and older children were soon able to take chloramphenicol by mouth, which reduced the cost and simplified treatment.It is suggested that chloramphenicol is a suitable alternative to sulphonamides for the treatment of meningococcal meningitis in those parts of Africa where the organism is sulphonamide-resistant.	H. C. Whittle, N. M. Davidson, B. M. Greenwood, D. A. Warrell, A. Tomkins, P. Tugwell, A. Zalin, A. D. Bryceson, E. H. Parry, M. Brueton, M. Duggan and A. D. Rajkovi	British medical journal
544	A revival of the older methods of diagnosis and treatment of pyogenic meningitis. A seminar on pratical difficulties in applying existing knowledge about nutrition and infections		H. C. Whittle and B. M. Greenwood	J Trop Pediatr Environ Child Health
34	[Acid-base balance and electrolytes in cerebrospinal fluid of patients with bacterial and lymphocytic meningitis]	Acid-base balance and electrolytes concentration in cerebrospinal fluid (CSF) of patients with bacterial and lymphocytic meningitis were assessed. Inflammatory process causing the damage of blood-brain barrier and brains hypoxia leads to statistically significant changes of pH, pO2, bicarbonates and K+ concentrations in CSF of patients with bacterial meningitis, which in lymphocytic meningitis were not observed. Patients with fatal; outcome of bacterial meningitis showed higher CSF's acidosis and lover bicarbonates with higher K+ concentrations, which suggest deeper damage of brain hemostasis regulating mechanisms in those patients.	A. Wiczkowski, L. Dyla, L. Kepa and T. Sawaryn	Przegla?d lekarski
664	[Magnetic resonance imaging and spectroscopic metabolites assessment in brain cryptococcosis]	Cryptococcus neoformans is the causative agent of cryptococcosis and cryptococcal meningitis, which are serious pathological conditions affecting up to 10% of patients with AIDS. In this paper we present results magnetic resonance imaging and spectroscopic metabolites (1H MR) in brain cryptococcosis. In 1 HMR spectroscopy we find decreased metabolic ratios to nonsaturated water (H2O) signal N-acetylaspartate (NA/H2O, creatine (Cr/H20), choline (Cho/H2O). We show increased mioinositol to H2O ratio. Spectroscopy results suggest about massive neuronal injury and accompanying gliosis in brain cryptococcosis.	A. Wierci?ska-Drapa?o and E. Tarasow	Wiadomo?ci parazytologiczne
247	Crossover vaccination with quadrivalent meningococcal vaccine (against A/C/Y/W-135) following recent application of bivalent meningococcal vaccine (against A/C): Assessment of safety and side effect profile	Background: Until May 2000, bivalent A/C meningococcal vaccine was the only available vaccine in Singapore for hajj travelers to Saudi Arabia. Recent worldwide reports of serogroup W-135 meningococcal meningitis associated with hajj returnees necessitated switching to quadrivalent A/C/Y/W-135 vaccine and crossover vaccination of travelers to Saudi Arabia. No safety data are available for quadrivalent vaccine following recent vaccination with bivalent vaccine. We assessed the safety and side effect profile of bivalent, quadrivalent, and quadrivalent meningococcal vaccine after recent vaccination with bivalent vaccine. Methods: A postvaccination telephone questionnaire survey was performed for all travelers who received either bivalent (B), quadrivalent (Q), or quadrivalent with recent (as defined by less than 6 months before) bivalent meningococcal vaccine (BQ) between 22 May and 8 June 2000 in preparation for the umrah (minor pilgrimage). Patients were asked about local reactions (pain, erythema, swelling at injection site graded in mild, moderate, and severe) and systemic reactions (fever, headache, graded in mild and severe). Results: Of 546 persons vaccinated, 323 were interviewed. Median time interval between interview and vaccination was 10 days. Of those interviewed, 64 patients received bivalent (B), 213 quadrivalent (Q), and 46 quadrivalent after recent bivalent vaccine (BQ). The median interval time between previous bivalent and quadrivalent vaccine was 5 weeks. There was no statistically significant difference in the prevalence of side effects between the three groups. Mild pain at injection site was recorded in B as 21.8%, Q as 23%, BQ as 21.7%; low grade fever in B as 7.8%, Q as 9.8%, and BQ as 15.2%. Conclusions: Bivalent and quadrivalent meningococcal vaccine are well tolerated. Crossover vaccination of quadrivalent meningococcal vaccine after recent vaccination with bivalent vaccine does not increase the prevalence of adverse reactions and is therefore safe. Number of References 14. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	A. Wilder-Smith and N. I. Paton	Journal of Travel Medicine
497	Acute evoked potentials in patients with bacterial meningitis with and without Dexamethasonotherapy with regard to liquorelastase		B. Wilken, J. Wees, F. K. Tegtmeyer and F. Aksu	Monatsschrift fur Kinderheilkunde
83	Further characterization of responses of infants and children to meningococcal A polysaccharide vaccine	The responses to 10 or 50 microgram doses of meningococcal group A polysaccharide vaccine were evaluated in infants and children. Although the 50 microgram dose was shown to be more effective in the induction of detectable anti-A antibody in vaccinees of all ages, only 6.5% (7/108) of infants smaller than or equal to 12 months demonstrated a "protective level" (greater than or equal to 2 mug/ml antibody protein) at 28 or 35 days postinoculation. Unexpected variations in the response to different lots, supplied by three different manufactures, were observed. These findings indicate the need for additional studies before routine immunization of young infants can be recommended.	J. Wilkins and P. F. Wehrle	The Journal of pediatrics
234	Correlation of group C meningococcal conjugate vaccine response with B- and T-lymphocyte activity	Despite the success of conjugate vaccination against meningococcal group C (MenC) disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation.	J. B. Wing, L. Smart, R. Borrow, J. Findlow, H. Findlow, A. Lees, R. A. Foster, J. Carlring, R. C. Read and A. W. Heath	PloS one
251	Surgical intervention and heparin-anticoagulation improve prognosis of rhinogenic/otogenic and posttraumatic meningitis	It is still controversial, whether early surgical removal of infectious material and heparin-anticoagulation to reduce vascular complications will improve outcome in acute meningitis. In the present pilot-study 40 patients with acute or delayed post-traumatic or oto-/rhinogenic purulent bacterial meningitis were analysed for neurological outcome by using the Glasgow outcome score (GOS) and the Tuthill functional score; patients were treated either by early surgical revision of the septic focus (Group 1, within 6 days, n = 15), late surgery (Group 2, later than 6 days, n = 19), or no surgery at all (Group 3, n = 6). All patients, independent of surgical approach, received therapeutic heparin-anticoagulation. Patient groups were otherwise comparable for antibiotic treatment, osmotherapy, microbiology, CSF-findings, CT-scans and prognostic factors. Outcome according to GOS was superior in Group 1 compared with Groups 2/3 (non-significant). Although there was no significant difference on admission in the Tuthill functional score, Group 1 achieved a superior final outcome of 96 points compared with Groups 2 and 3, who gained 72 points (p < 0.01). In addition, Group 1 patients had significantly less intracranial complications (8/15 patients versus 21/25 patients in Groups 2/3, p < 0.01) and were dependent upon respirator treatment for fewer days (10.2 days) than Groups 2/3 (12.5 days, non-significant). In 31 patients CSF-leakage was identified: among these, 17 patients had CSF-leakage, which had not been anticipated by clinical/neuroradiological examinations and revealed only by surgery. The overall mortality in this study population was very low (2.5%), therefore, therapeutic heparin seems to represent an additional favorable treatment measure.(ABSTRACT TRUNCATED AT 250 WORDS)	J. Winkler, U. Bogdahn, G. Becker, W. Durant, F. X. Brunner, M. Eckstein, A. Brawanski, M. Warmuth and H. G. Mertens	Acta neurologica Scandinavica
314	Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis	BACKGROUND: In certain diseases clinical experts may judge that the intervention with the best prospects is the addition of two treatments to the standard of care. This can either be tested with a simple randomized trial of combination versus standard treatment or with a 2 x 2 factorial design.METHODS: We compared the two approaches using the design of a new trial in tuberculous meningitis as an example. In that trial the combination of 2 drugs added to standard treatment is assumed to reduce the hazard of death by 30% and the sample size of the combination trial to achieve 80% power is 750 patients. We calculated the power of corresponding factorial designs with one- to sixteen-fold the sample size of the combination trial depending on the contribution of each individual drug to the combination treatment effect and the strength of an interaction between the two.RESULTS: In the absence of an interaction, an eight-fold increase in sample size for the factorial design as compared to the combination trial is required to get 80% power to jointly detect effects of both drugs if the contribution of the less potent treatment to the total effect is at least 35%. An eight-fold sample size increase also provides a power of 76% to detect a qualitative interaction at the one-sided 10% significance level if the individual effects of both drugs are equal. Factorial designs with a lower sample size have a high chance to be underpowered, to show significance of only one drug even if both are equally effective, and to miss important interactions.CONCLUSIONS: Pragmatic combination trials of multiple interventions versus standard therapy are valuable in diseases with a limited patient pool if all interventions test the same treatment concept, it is considered likely that either both or none of the individual interventions are effective, and only moderate drug interactions are suspected. An adequately powered 2 x 2 factorial design to detect effects of individual drugs would require at least 8-fold the sample size of the combination trial.TRIAL REGISTRATION: Current Controlled Trials ISRCTN61649292.	M. Wolbers, D. Heemskerk, T. T. Chau, N. T. Yen, M. Caws, J. Farrar and J. Day	Trials
375	Failure of regular external ventricular drain exchange to reduce cerebrospinal fluid infection: result of a randomised controlled trial	BACKGROUND: It is controversial whether regular changes of external ventricular drains can reduce cerebrospinal fluid (CSF) infection. OBJECTIVE: To carry out a randomised controlled clinical trial over a two year period to determine whether a regular change of ventricular catheter every five days could reduce CSF infection and improve outcome. METHODS: 103 patients requiring external ventricular drains for more than five days and with no evidence of concurrent CSF infection were studied. The patients were randomised to regular change of ventricular catheter (every five days) and no change unless clinically indicated. RESULTS: The CSF infection rates were 7.8% for the catheter change group and 3.8% for the no change group, respectively (rate ratio = 1.80, 95% confidence interval 0.33 to 9.81, p = 0.50). No significant difference was found in intensive care unit stay, ward stay, or clinical outcome between the two groups. CONCLUSIONS: Regular changes of ventricular catheter at five day intervals did not reduce the risk of CSF infection. A single external ventricular drain can be employed for as long as clinically indicated.	G. K. Wong, W. S. Poon, S. Wai, L. M. Yu, D. Lyon and J. M. Lam	Journal of neurology, neurosurgery, and psychiatry
637	Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial	BACKGROUND: Treatment of patients with early Lyme disease has trended toward longer duration despite the absence of supporting clinical trials. OBJECTIVE: To evaluate different durations of oral doxycycline treatment and the combination of oral doxycycline and a single intravenous dose of ceftriaxone for treatment of patients with early Lyme disease. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Single-center university hospital. PATIENTS: 180 patients with erythema migrans. INTERVENTION: Ten days of oral doxycycline, with or without a single intravenous dose of ceftriaxone, or 20 days of oral doxycycline. MEASUREMENTS: Outcome was based on clinical observations and neurocognitive testing. Efficacy was assessed at 20 days, 3 months, 12 months, and 30 months. RESULTS: At all time points, the complete response rate was similar for the three treatment groups in both on-study and intention-to-treat analyses. In the on-study analysis, the complete response rate at 30 months was 83.9% in the 20-day doxycycline group, 90.3% in the 10-day doxycycline group, and 86.5% in the doxycycline-ceftriaxone group (P > 0.2). The only patient with treatment failure (10-day doxycycline group) developed meningitis on day 18. There were no significant differences in the results of neurocognitive testing among the three treatment groups and a separate control group without Lyme disease. Diarrhea occurred significantly more often in the doxycycline-ceftriaxone group (35%) than in either of the other two groups (P < 0.001). CONCLUSIONS: Extending treatment with doxycycline from 10 to 20 days or adding one dose of ceftriaxone to the beginning of a 10-day course of doxycycline did not enhance therapeutic efficacy in patients with erythema migrans. Regardless of regimen, objective evidence of treatment failure was extremely rare.	G. P. Wormser, R. Ramanathan, J. Nowakowski, D. McKenna, D. Holmgren, P. Visintainer, R. Dornbush, B. Singh and R. B. Nadelman	Annals of internal medicine
463	Immunologic response of man to group B meningococcal polysaccharide vaccines		F. A. Wyle, M. S. Artenstein, B. L. Brandt, E. C. Tramont, D. L. Kasper, P. L. Altieri, S. L. Berman and J. P. Lowenthal	The Journal of infectious diseases
607	Perioperative antimicrobial prophylaxis in neurosurgery: clinical trial of systemic flomoxef administration and saline containing gentamicin for irrigation	The efficacy of a new protocol consisting of a prophylactic antibiotic regimen of peri- and postoperative intravenous administration of flomoxef and irrigation of the operative field with saline containing gentamicin was assessed by comparing infection rates in two consecutive series of patients who underwent neurosurgical procedures. Group A received postoperative flomoxef administration, with saline containing no antibiotics for irrigation, from July 1988 to December 1989. Group B received the new protocol from January 1990 to December 1991. For further evaluation, this protocol was continued in most patients who underwent surgery from January 1992 through December 1993 (Group C). Only adult or adolescent patients who underwent clean neurosurgical procedures were included. The number of patients and procedures in each group were: 76 patients (97 procedures) in Group A, 103 (133) in Group B, and 107 (137) in Group C. There were no significant differences between Groups A and B in age, sex, clinical category, coexistent disease, clinical outcome, surgical procedures, general anesthesia, emergency operation, steroid administration, and the timing (season), duration, and frequency of surgery. Meningitis developed in three patients and subcutaneous infection in one in Group A. None of the patients in Group B experienced postoperative infection. This difference in infection rates (4.1% vs. 0%) was statistically significant (p = 0.0305). Furthermore, no postoperative infections developed in the Group C patients. The most appropriate interval for multiple dose administration was determined by analyzing intraoperative time-related changes in the serum flomoxef concentration during surgery in 21 recent patients. Serum flomoxef concentrations fell below therapeutic levels (3.0 micrograms/ml) by the 6th post-administration hour in 70% of patients. We conclude that this antibiotic regimen significantly reduces the postoperative infection rate following neurosurgical procedures. Multiple dose administration of flomoxef is recommended when the duration of surgery is 6 hours or more.	M. Yamamoto, M. Jimbo, M. Ide, N. Tanaka, Y. Umebara and S. Hagiwara	Neurologia medico-chirurgica
13	A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; expanding the use of Vi polysaccharide vaccine in southeast China: a cluster-randomized trial	BACKGROUND: One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. METHODS: The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. RESULTS: The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged < or = 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. CONCLUSION: The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China.	J. Yang, C. J. Acosta, G. A. Si, J. Zeng, C. Y. Li, D. B. Liang, R. L. Ochiai, A. L. Page, M. C. Danovaro-Holliday, J. Zhang, B. D. Zhou, H. Z. Liao, M. L. Wang, D. M. Tan, Z. Z. Tang, J. Gong, J. K. Park, M. Ali, B. Ivanoff, G. C. Liang, H. H. Yang, T. Pang, Z. Y. Xu, A. Donner, C. M. Galindo, B. Q. Dong and J. D. Clemens	BMC public health
383	[Immediate adverse reaction after mass vaccination of groups A+C meningococcal polysaccharide vaccine]	Objective: To observe the immediate adverse reaction after mass vaccination of groups A+C meningococcal polysaccharide vaccine. Methods: The populations in field were divided into 108 clusters consisting of 54 trial and 54 control clusters according to the principle of cluster randomization stratified and paired sampling, and vaccinated with groups A+C meningococcal polysaccharide vaccine and typhoid Vi polysaccharide vaccine respectively. An adverse event surveillance system was established to monitor the immediate reactions following vaccination campaign. Results: A total of 34 543 persons were vaccinated, of whom 18 167 with groups A+C meningococcal polysaccharide vaccine and 16 376 with typhoid Vi polysaccharide vaccine. The immediate adverse reaction rates after vaccination with groups A+C meningococcal polysaccharide vaccine and typhoid Vi polysaccharide vaccine were 0.44[per mille] and 0.79[per mille] respectively, which showed no significant difference. All the immediate adverse reactions appeared within 15 min after vaccination, of which the earliest one within 5 min. Two cases of abnormal reactions were observed, but on severe reaction. Conclusion: The immediate adverse reaction rate after vaccination of groups A+C meningococcal polysaccharide vaccine was low, indicating good safety of the vaccine. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	J. Yang, Q. Ye and B. Q. Dong	Chinese Journal of Biologicals
357	[Use of meropenem in the treatment of severe infections in newborns]	Meropenem was used in the treatment of 15 newborns (8 preterm) with sepsis, pneumonia or meningitis by intravenous infusion of 15-20 mg/kg daily divided to 3 equal doses. Clinical improvement was achieved in all the cases. No side effects were recorded.	G. V. Yatsyk	Antibiotiki i khimioterapii?a = Antibiotics and chemoterapy [sic] / Ministerstvo meditsinsko? i mikrobiologichesko? promyshlennosti SSSR
146	Heptavalent pneumococcal vaccine conjugated to outer membrane protein of Neisseria meningitidis serogroup b and nasopharyngeal carriage of Streptococcus pneumoniae in infants	BACKGROUND: Streptococcus pneumoniae (Sp) is an important bacterial pathogen in children. Nasopharyngeal (NP) colonization of S. pneumoniae is necessary for person-to-person transmission and often precedes invasive disease. METHODS: NP carriage of Sp was studied in 49 infants following administration of a heptavalent pneumococcal conjugate vaccine (PCV) conjugated to the outer membrane protein of serogroup b Neisseria meningitidis (vaccine serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F). The vaccine was administered at 2, 4, 6, and 12 months of age and carriage rates were compared to a concurrent group of 32 infants not given PCV and evaluated over the first 15 months of life. RESULTS: Overall, Sp was isolated in 86/367 (23%) of NP cultures and 49% of infants. Serotype 23F was significantly less prevalent in the PCV group (1.9%) than the control group (16.1%) (P<0.05). Analysis of the proportion of children with prevalent carriage or acquisition of carriage did not differ between groups when evaluated by age or serotype. We noted, however, decreased acquisition and carriage in the vaccine group 1 month following the 12 month dose of PCV for vaccine serotypes (76 and 52% reduction, respectively), but this did not reach statistical significance (P=0.3). Adjustment for age, daycare and antibiotic use by multivariate modeling revealed no difference in carriage of vaccine containing serotypes or non-vaccine serotypes between groups. CONCLUSION: We did not show a significant effect of this heptavalent PCV on NP carriage. Further study of this issue, including a larger population size, is needed.	S. H. Yeh, K. M. Zangwill, H. Lee, S. J. Chang, V. I. Wong, D. P. Greenberg and J. I. Ward	Vaccine
397	[Immune response and post inoculation reactions of simultaneous administration of hepatitis B vaccine with routine vaccine in children, III. Immune response and post inoculation reactions of simultaneous administration of hepatitis B vaccine and BCG, meningococcus group A polysaccharide vaccine]	The results of the immune response and post inoculation reactions of simultaneous administration of BCG, meningococcus group A polysaccharide vaccine and hepatitis B vaccine were reported. 360 newborn babies (1-3 days of age) were divided into five groups. The babies in group No. 1 were vaccinated with hepatitis B vaccine alone, babies in group No. 2 were vaccinated with BCG for scarification within 3 days after delivery and meningococcus group A polysaccharide vaccine in 6 months of age; babies in group No. 3 were vaccinated with hepatitis B vaccine, BCG for scarification and Meningococcus group A polysaccharide vaccine simultaneously, babies in group No. 4 were vaccinated with intradermal BCG and Meningococcus group A polysaccharide vaccine separately, babies in group No. 5 were vaccinated with hepatitis B vaccine, intradermal BCG and meningococcus group A polysaccharide vaccine simultaneously. The results of the immune response of the combination of hepatitis B vaccine with BCG, meningococcus group A polysaccharide vaccine were similarly to the immune response observed after immunization of each vaccine alone in children. The general post inoculation reactions of all vaccines were mild. There was no significant difference among all 5 groups. The data showed that children could be immunized with hepatitis B vaccine, BCG and meningococcus group A polysaccharide vaccine simultaneously.	C. Yuan	Chung-Hua-Liu-Hsing-Ping-Hsueh-Tsa-Chih// Chinese Journal of Epidemiology
109	[Albumin and immunoglobulin levels in cerebrospinal fluid and serum in tick borne meningoencephalitis]	The levels of albumin and immunoglobulins G, A, M were determined by using nephelometry technique in the cerebrospinal fluid and serum in 14 adults with tick borne meningoencephalitis at the beginning and after four weeks of disease. Intra blood-brain synthesis of IgG, IgA, IgM was evaluated by indexes of synthesis (Tibbling formula). The blood-brain integrity was estimated by CSF/serum albumin ratio. Increased albumin and immunoglobulins G, A, M levels were demonstrated in first examination and only elevated levels of albumin and immunoglobulin M lasted after four weeks. Albumin level in cerebrospinal fluid and albumin ratio were elevated in both examinations. The serum levels of albumin and immunoglobulins were similar in first and second examination. On the basis these results we conclude that in tested patients blood-brain integrity was disturbed still after four weeks of disease.	J. M. Zajkowska, S. A. Pancewicz, B. Kucharewicz, T. Hermanowska-Szpakowicz, M. Szmitkowski and W. Krupa	Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego
205	Safety and immunogenicity of a heptavalent pneumococcal conjugate vaccine in infants	OBJECTIVE: To evaluate the safety and immunogenicity of two lots of a heptavalent Streptococcus pneumoniae conjugate vaccine (PCV) containing seven capsular polysaccharide serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to the outer membrane complex of Neisseria meningitidis serogroup B (OMPC) and administered to infants at 2, 4, 6, and 12 months of age. METHODS: One hundred twenty infants were randomly assigned to concurrently receive PCV-OMPC and one of two Haemophilus influenzae type b (Hib) conjugate-DTwP combination vaccines: (1) Hib with a heterologous protein carrier (CRM(197), TETRAMUNE, Group 1) or (2) an experimental Hib-hepatitis b combination vaccine with the homologous carrier (OMPC, Group 2). All infants in Groups 1 and 2 received PCV-OMPC (lot 1) at 12 months of age. Another separate group of 120 infants (Group 3) received a different lot of PCV-OMPC concurrently with Hib-CRM(197) (TETRAMUNE) at 2, 4, and 6 months of age and then were randomized to receive either PCV-OMPC or a 23-valent polysaccharide (PS) pneumococcal vaccine at 12 months of age. RESULTS: Each PCV-OMPC lot was generally well tolerated and no vaccine-related serious adverse events were reported. Following the primary series, serotype-specific anti-pneumococcal geometric mean concentrations (GMC) were highest for serotypes 14, 19F, and 4 and lowest for serotypes 6B and 23F. GMC and seroconversion rates in Group 3 (lot 2) were lower than in Group 1 (lot 1) for serotypes 6B, 14, 18C, and 23F. Antibody responses to serotypes 6B, 14, and 18C were significantly lower in Group 2 compared to Group 1. Following a booster dose of PCV-OMPC at 12 months of age, each lot was immunogenic with at least a 5-10-fold increase in antibody levels, and responses were significantly higher among those who received the PS vaccine. CONCLUSIONS: PCV-OMPC is generally safe in infants, displays variable immune response by serotype, and concomitant receipt of Hib vaccine with homologous carrier may impact on its immunogenicity.	K. M. Zangwill, D. P. Greenberg, C. Y. Chiu, P. Mendelman, V. K. Wong, S. J. Chang, S. Partridge and J. I. Ward	Vaccine
642	Safety and reactogenicity of a novel DTPa-HBV-IPV combined vaccine given along with commercial Hib vaccines in comparison with separate concomitant administration of DTPa, Hib, and OPV vaccines in infants	OBJECTIVE: Combination vaccines simplify vaccine administration and have the potential to promote compliance and cost-effectiveness by decreasing the number of injections needed to immunize a child. The objective of this study was to assess the safety and reactogenicity of the diphtheria-tetanus toxoid-acellular pertussis-hepatitis B virus-inactivated polio virus (DTPa-HBV-IPV) vaccine when coadministered with different Haemophilus influenzae type B (Hib) vaccines in comparison with separate, commercially available, control vaccines in a 3-dose primary vaccination series. METHODS: An open-label, randomized, parallel-group study in 5318 infants who were 8 to 16 weeks of age at enrollment was conducted in 90 centers in Germany. The incidence of adverse events that occurred in infants who received the DTPa-HBV-IPV candidate vaccine coadministered with 1 of 4 different Hib vaccines (given in separate sites; groups 1-4) was compared with the incidence that occurred in infants who received commercially available control vaccines (DTPa, Hib, and oral polio virus [OPV] vaccine; group 5) administered separately. The vaccines were given as a 3-dose primary series at 3, 4, and 5 months of age. Infants were assessed for solicited local and general adverse events for 4 days and for unsolicited adverse events for 30 days after each vaccine dose. The primary endpoint was to rule out a 7.5% increase in infants who experienced grade 3 (defined as preventing normal everyday activities unless otherwise specified) solicited local and general adverse events over the 3-dose primary course after the combined DTPa-HBV-IPV vaccine coadministered with Hib as compared with commercially available vaccines. RESULTS: During the 3-dose primary course, 490 of 3029 infants (16.2%) in the pooled DTPa-HBV-IPV vaccine groups and 151 of 744 (20.3%) in the control vaccine group experienced a grade 3 adverse event (rate difference [control minus combination] 4.1%; 90% confidence interval, 1.41-7.13). The lower limit of the 90% confidence interval of the observed difference remained above the prespecified -7.5% limit for noninferiority, thereby meeting the primary endpoint. The incidences of local injection-site reactions were similar for the DTPa-HBV-IPV and DTPa injection sites. Significant differences in the incidence of both local and general adverse events were observed depending on which of the Hib vaccines was coadministered. Infants who received Hib N meningitidis outer-membrane complex protein conjugate vaccine had greater incidences of fever and, to a lesser extent, greater reactions at the Hib injection site than did infants who received other Hib vaccines. CONCLUSIONS: The combination DTPa-HBV-IPV vaccine administered concomitantly with Hib vaccine at separate sites was at least as safe as coadministration of individual DTPa, Hib, and OPV vaccines in terms of the defined endpoints for safety.	F. Zepp, A. Schuind, C. Meyer, R. Sänger, A. Kaufhold and P. Willems	Pediatrics
37	Primary and booster mucosal immune responses to meningococcal group A and C conjugate and polysaccharide vaccines administered to university students in the United Kingdom	Meningococcal group A+C capsular polysaccharide (PS) conjugate vaccines may prime for serum immunoglobulin G (IgG) memory responses to meningococcal capsular PS. It is not known whether these vaccines induce immunological memory at the mucosal level, which may be important in reducing nasopharyngeal carriage. Mucosal immune responses to meningococcal conjugate and PS vaccines in young adults were investigated. Healthy university students were randomized to receive either a groups A+C meningococcal conjugate vaccine (MACconj, n = 100) or a group A+C meningococcal PS vaccine (MACPS, n = 95). One year after the primary immunization, both groups were randomized again to receive a MACconj or a MACPS booster vaccination. Saliva samples were collected before and 1 month after the primary and booster vaccinations. Anti-meningococcal A (MenA) and C (MenC) PS IgA and IgG antibody levels were measured by a standard enzyme-linked immunosorbent assay. After the primary vaccination, salivary MenA and MenC IgG and MenA IgA concentrations were significantly increased after immunization with both MACconj and MACPS vaccines, but the salivary Men C IgA level was increased only after MACPS vaccine (P < 0.01). IgA responses to both serogroups were greater for MACPS than MACconj vaccine (P < 0.05), whereas no significant differences were seen for IgG responses. MenA IgG titers were higher after the MACPS booster in MACconj-primed subjects than after the MACPS primary vaccination, suggesting the presence of IgG memory. Antibody responses to a dose of either MACPS or MACconj were not significantly reduced in those previously given MACPS compared to the primary responses to those vaccines. Meningococcal A+C conjugate and PS vaccines induce significant mucosal responses in young adults. MACconj priming may induce IgG memory at the mucosal level, which is likely to be a reflection of an anamnestic serum IgG response. No evidence of mucosal hyporesponsiveness was observed after MACPS priming in this study.	Q. Zhang, R. Lakshman, R. Burkinshaw, S. Choo, J. Everard, S. Akhtar and A. Finn	Infection and immunity
333	Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in infants	Background. Serogroup C meningococcal conjugate polysaccharide vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx, local mucosal immune responses may play an important role in host defense against infection and carriage. We have investigated the mucosal IgA and IgG antibody responses to two meningococcal C conjugate vaccines in the saliva of healthy infants. Methods. Specific salivary IgA and IgG antibodies to two meningococcal C polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in infants after parenteral vaccinations at the ages of 2, 3 and 4 months. Unstimulated saliva samples were collected immediately before the first immunization and 1 month after the third immunizations. Forty healthy infants receiving the same routine vaccines but no meningococcal C vaccine were recruited as controls. Results. There were significant increases in meningococcal C polysaccharide-specific IgG antibody concentrations postvaccination compared with prevaccination concentrations in both vaccinated groups (both P < 0.001), but no change in the control group. There were no significant increases in specific IgA postvaccination geometric mean concentrations in either the vaccine or the control groups. The number of IgA positives postvaccination increased slightly in the Wyeth vaccine group vs. controls (P < 0.05). Conclusions. Significant salivary IgG antibodies to meningococcal C polysaccharide were observed after parenteral immunization with two meningococcal C conjugate vaccines, whereas there was no significant increase in specific IgA antibody levels for these two vaccines. Number of References 30. Copyright © 2011 Elsevier B. V., Amsterdam. All Rights Reserved.	Q. Zhang, E. Pettitt, R. Burkinshaw, G. Race, L. Shaw and A. Finn	Pediatric Infectious Disease Journal
336	International collaboration between US and Thailand on a clinical trial of treatment for HIV-associated cryptococcal meningitis	BACKGROUND: International clinical trials can provide scientific and logistic benefits in spite of the many challenges. Determining whether a country, especially a developing country, is an appropriate location for the research should include in-country consultation and partnering to assess its social value for the population; that treatments are relevant for the population under study; and that the research infrastructure and ethical oversight are adequate. Collaboration increases the likelihood of study success and helps ensure that benefits accrue to recruited populations and their community.PURPOSE: This paper describes our experiences on a bi-national study and may provide guidance for those planning to engage in future collaborations.METHODS: A Thai and United States team collaborated to develop and implement a phase II clinical trial for HIV-associated cryptococcal meningitis to assess safety and tolerability of combination therapy vs. standard treatment. Clinical and cultural differences, regulatory hurdles and operational issues were addressed before and during the study to ensure a successful collaboration between the 2 groups.RESULTS: The international multicenter study allowed for more rapid enrollment, reduced costs to complete the study, sharing of the benefits of research, greater generalizability of results and capacity building in Thailand; quality metrics in Thailand were equivalent to or better than those in the U.S.CONCLUSIONS: Conducting successful clinical trials internationally requires early and ongoing collaboration to ensure the study meets sites' requirements and expectations, conforms to varying national regulations, adheres to data quality standards and is responsive to the health needs of studied populations.	L. O. Zimmer, T. L. Nolen, S. Pramanpol, D. Wallace, M. E. Walker, P. Pappas and P. Chetchotisakd	Contemporary clinical trials
187	Meningococcal serogroup B vaccine protection trial and follow-up studies in Chile. The Chilean National Committee for Meningococcal Disease		W. D. Zollinger, J. Boslego, E. Moran, J. Garcia, C. Cruz, S. Ruiz, B. Brandt, M. Martinez, J. Arthur and P. Underwood	NIPH annals
641	Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial	BACKGROUND: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. METHODS AND FINDINGS: A5164 was a randomized strategy trial of "early ART"--given within 14 days of starting acute OI treatment versus "deferred ART"--given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) >or=50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. THE DIFFERENCE IN THE PRIMARY ENDPOINT DID NOT REACH STATISTICAL SIGNIFICANCE: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27-0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30-0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. CONCLUSIONS: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. TRIAL REGISTRATION: ClinicalTrials.gov NCT00055120.	A. Zolopa, J. Andersen, W. Powderly, A. Sanchez, I. Sanne, C. Suckow, E. Hogg and L. Komarow	PloS one
