Streptococcal

J Invest Dermatol, 2005 Jan, 124(1), 63 - 9
Proteome analysis of skin distinguishes acute guttate from chronic plaque psoriasis; Carlen LM et al.; Psoriasis is a disease with considerable heterogeneity in clinical presentation . This is the first study using two-dimensional gel electrophoresis to compare global protein expression patterns in lesional and non-lesional skin from subjects with acute guttate psoriasis associated with streptococcal throat infection and chronic plaque psoriasis . Samples from experimentally induced contact eczema and normal skin from healthy controls were also included . Proteins with statistically significant differences in expression were used in hierarchical cluster analyses resulting in separation of the different samples into groups . Chronic plaque and guttate psoriasis samples were distinctly separated, indicating that they represent discrete phenotypes at the protein expression level . Interestingly, there was a trend in which guttate psoriasis lesions clustered closer to eczema than to chronic plaque psoriasis lesions, indicating that the duration of the inflammatory reaction may affect clustering . Several of the differentially expressed proteins were identified by mass spectrometry.

J Biol Chem . 2005 Jan 12; {Epub ahead of print}
A streptococcal collagen-like protein interacts with the alpha 2beta 1 integrin and induces intracellular signaling; Humtsoe JO et al.; Streptococcal collagen-like proteins, Scl1 and Scl2 are prokaryotic members of a large protein family with domains containing the repeating amino acid sequence (Gly-Xaa-Yaa)n that form a collagen-like triple-helical structure . Here, we test the hypothesis that Scl variant might interact with mammalian collagen binding integrins . We show that recombinant Scl protein, p176, promotes adhesion and spreading of human lung fibroblasts cells through an alpha(2)beta(1) integrin mediated interaction as shown in cell-adhesion inhibition assays using anti-alpha(2)beta(1) and anti-beta(1) integrins monoclonal antibodies . Accordingly, C2C12 cells stably expressing alpha(2)beta(1) integrin as the only collagen binding integrin, show productive cell adhesion activities on p176 that can be blocked by an anti-alpha(2)beta(1) integrin antibody . In addition, p176 promotes tyrosine phosphorylation of p125FAK of C2C12 cell expressing alpha(2)beta(1) integrin, while parental C2C12 cells does not . Furthermore, adhesion of human lung fibroblast cells to p176 induces phosphorylation of p125FAK, p130CAS, and p68Paxillin proteins . In a domain swapping experiment, we show that integrin binds to the collagenous domain of the Scl protein . Moreover, the recombinant I-domain of the alpha(2) integrin interacts with p176 with a relatively high affinity (KD=17 nM) . Attempts to identify the integrin sites in p176 suggest that more than one site may be involved . These studies, for the first time, suggest that the collagen like proteins of prokaryotes retained not only structural, but also functional characteristics of their eukaryotic counterparts.

Arthritis Res Ther, 2005, 7(1), 20 - 8 Epub 2004 Nov 30.
The role and clinical implications of G6PI in experimental models of rheumatoid arthritis; Kamradt T et al.; The antigens that trigger the pathogenic immune response in rheumatoid arthritis (RA) remain unknown . Until recently it was assumed that either viral or microbial antigens, or joint-specific antigens were the target of arthritogenic T and B lymphocytes in RA . Consequently, murine models of arthritis are induced by immunization with either joint-specific antigens such as type II collagen or microbial products such as streptococcal cell wall . In the K/BxN T-cell receptor transgenic mouse model arthritis is caused by a systemic autoimmune response to the ubiquitously expressed glycolytic enzyme glucose-6-phosphate isomerase (G6PI) . The autoreactive transgenic T cells recognize G6PI and provide help for the production of arthritogenic IgG antibodies against G6PI . More recently it was shown that G6PI immunization induces severe symmetrical peripheral polyarthritis in genetically unaltered DBA/I mice . In that model CD4+ T cells are necessary not only for the induction but also for the effector phase of arthritis . Here we review the pathomechanisms that lead from systemic autoreactivity to arthritis in these models, consider the relevance of anti-G6PI immune reactivity for RA, and discuss the insights into the pathogenesis of RA and possibly other autoimmune conditions that can be gained from these models.

Arthritis Res Ther, 2005, 7(1), R101 - 17 Epub 2004 Nov 19.
Gene expression profiles in the rat streptococcal cell wall-induced arthritis model identified using microarray analysis; Rioja I et al.; Experimental arthritis models are considered valuable tools for delineating mechanisms of inflammation and autoimmune phenomena . Use of microarray-based methods represents a new and challenging approach that allows molecular dissection of complex autoimmune diseases such as arthritis . In order to characterize the temporal gene expression profile in joints from the reactivation model of streptococcal cell wall (SCW)-induced arthritis in Lewis (LEW/N) rats, total RNA was extracted from ankle joints from naive, SCW injected, or phosphate buffered saline injected animals (time course study) and gene expression was analyzed using Affymetrix oligonucleotide microarray technology (RAE230A) . After normalization and statistical analysis of data, 631 differentially expressed genes were sorted into clusters based on their levels and kinetics of expression using Spotfire profile search and K-mean cluster analysis . Microarray-based data for a subset of genes were validated using real-time PCR TaqMan analysis . Analysis of the microarray data identified 631 genes (441 upregulated and 190 downregulated) that were differentially expressed (Delta > 1.8, P < 0.01), showing specific levels and patterns of gene expression . The genes exhibiting the highest fold increase in expression on days -13.8, -13, or 3 were involved in chemotaxis, inflammatory response, cell adhesion and extracellular matrix remodelling . Transcriptome analysis identified 10 upregulated genes (Delta > 5), which have not previously been associated with arthritis pathology and are located in genomic regions associated with autoimmune disease . The majority of the downregulated genes were associated with metabolism, transport and regulation of muscle development . In conclusion, the present study describes the temporal expression of multiple disease-associated genes with potential pathophysiological roles in the reactivation model of SCW-induced arthritis in Lewis (LEW/N) rat . These findings improve our understanding of the molecular events that underlie the pathology in this animal model, which is potentially a valuable comparator to human rheumatoid arthritis (RA).

Epidemiol Infect, 2004 Dec, 132(6), 1083 - 90
Invasive group B streptococcal disease in infants: a 19-year nationwide study . Serotype distribution, incidence and recurrent infection; Ekelund K et al.; During the period 1984-2002, 472 cases of invasive group B streptococcal (GBS) disease in infants aged 0-90 days in Denmark were registered . The overall incidence was 0.4/1000 live births . Most infants (73%) had early-onset GBS infection with 53% registered within the first day . Serotype III predominated (59%) with other serotypes as follows: Ia (16%), Ib (8%), NT (7%), II (6%), other serotypes (5%) . Recurrence of GBS infection was registered in six infants, and the interval with no antibiotic therapy varied from 2 to 39 days . The serotypes of the isolates obtained from first and second episodes were identical (serotype III in five, and serotype Ia in one infant) . Paired isolates were indistinguishable by PFGE and antibiotic susceptibility testing . Invasive GBS infections in infants are still a problem in Denmark, and recurrent infections are registered in 1% of these infants.

J Clin Microbiol, 2005 Jan, 43(1), 84 - 8
Performance of the new VITEK 2 GP card for identification of medically relevant gram-positive cocci in a routine clinical laboratory; Funke G et al.; The VITEK 2 gram-positive (GP) identification card (bioMerieux, Marcy l'Etoile, France) has been redesigned to achieve greater accuracy in the identification of gram-positive cocci . A total of 43 biochemical tests, including 17 enzymatic tests, are present in the card and interpreted in a kinetic mode, for up to 8 h . The VITEK 2 database, used in conjunction with the GP identification card, allows the identification of 115 different taxa . A total of 364 strains of GP cocci (217 Streptococcaceae strains and 147 Micrococcaceae strains) belonging to 31 taxa were tested with the new VITEK 2 GP identification card . Of the 364 strains, 105 were taken from routine primary plating media . A total of 344 strains (94.5%) were correctly identified to the species level and 17 strains (4.7%) were identified with low discrimination, requiring additional tests, whereas 1 strain (0.3%) was incorrectly identified and 2 strains (0.5%) remained unidentified . Within 7 h of the start of incubation, more than 90% of all strains were identified . Of the 105 primary cultures, 97% were correctly identified to the species level, 2% were identified with low discrimination, and 1% remained unidentified . Identification performance data were independent of each of the three plating media used . It is concluded that the new VITEK 2 GP identification card provides reliable results for the identification of GP cocci under routine laboratory conditions.

J Comp Pathol, 2005 Jan, 132(1), 101 - 5
Cowpox virus infection associated with a streptococcal septicaemia in a foal; Ellenberger C et al.; Cowpox virus infection associated with a streptococcal septicaemia was diagnosed in a weak German Warmblood filly, born 29 days prematurely, and humanely destroyed on the sixth day of life . At necropsy, ulcerative lesions in the alimentary tract, colitis, polyarthritis and nephritis were observed . Transmission electron microscopical examination of specimens from ulcerative lesions revealed typical orthopox virions . Cowpox virus was unequivocally identified by virological and molecular-biological methods.

Surg Today, 2005, 35(1), 60 - 6
Effect of Intraperitoneal Neutrophils Induced by OK432 on Malignant Ascites; Hosoya Y et al.; PURPOSE: To evaluate the efficacy of a streptococcal preparation, OK432, on malignant ascites in mice . METHODS: PC-C203U (PC203) is a preparation of another strain of the streptococcal family, with the lowest antineoplastic action . To examine the survival curves of mice after the inoculation of BAMC-1 tumor cells, we gave intraperitoneal OK432, PC203, or saline as a control . Intraperitonal neutrophils were counted by cytospin, and interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and macrophage inflammatory protein (MIP)-1alpha were measured by enzyme-linked immunosorbent assay, and 8 h after the administration of OK432, PC203, and saline . Using electron microscopy, we examined the greater omental milky spots, where the in situ proliferation of neutrophils or macrophages takes place . RESULTS: The OK432 group had the best survival and the control group the worst . The ratio of intraperitoneal neutrophils to BAMC-1 was highest in the OK432 group and lowest in the control group . Quantitative IL-1beta, IL-6 and MIP-1alpha levels were correlated closely with survival . Electron microscopic examination of the milky spots revealed massive proliferation of neutrophils in the OK432 group, but not in the PC203 or control groups . CONCLUSION: OK432 effectively activated intraperitoneal neutrophils and a series of immunological chain reactions through an increase in IL-1beta, IL-6, and MIP-1alpha levels . Milky spots could have important antitumor effects in terms of the spread of neutrophils.

Clin Exp Nephrol, 2004 Dec, 8(4), 351 - 5
Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy; Horita Y et al.; We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N) . The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition . Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection . A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli . Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased . Electron microscopy revealed "hump" electron-dense deposits on the epithelial side of the glomerular basement membrane . These features were consistent with PSAGN superimposed on IgA-N . After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy . Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.

Pediatr Infect Dis J, 2004 Oct, 23(10), 961 - 3
Antibodies to type III group B streptococcal polysaccharide in breast milk; Edwards MS et al.; We compared concentrations of type III group B streptococcal capsular polysaccharide (CPS)-specific IgG and IgA in archived 2-month-postpartum breast milk from 9 women with > or =1 microg/ml and 9 with < 1 microg/ml type III CPS-specific IgG in serum . Type III CPS-specific antibodies were not detectable consistently but were measurable in breast milk from some women in both groups, indicating their potential for a role in prevention or amelioration of late onset group B streptococcal disease.

Pediatr Blood Cancer . 2004 Dec 8; {Epub ahead of print}
Early bacteremia in pediatric hematopoietic stem cell transplant patients on oral antibiotic prophylaxis; Kersun LS et al.; BACKGROUND: Bacteremia occurs during hematopoietic stem cell transplant (HSCT) in 20%-25% of patients and the use of gut decontamination (GD) to decrease this risk is controversial . Our purpose was to determine the incidence of bacteremia and antimicrobial resistance post-HSCT in pediatric patients receiving GD, and to identify risk factors associated with infection . PROCEDURES: This was a retrospective cohort study of 182 pediatric patients undergoing first HSCT for malignant disease at The Children's Hospital of Philadelphia from January, 1999 to December, 2002 . We examined the impact of age, sex, race, diagnosis, disease status, conditioning regimen, recent bacteremia, stem cell source, donor, graft versus host disease prophylaxis agents, and mucositis severity using Cox proportional hazard models . GD consisted of amoxicillin (azithromycin, if penicillin allergic) and oral gentamicin . Outcome was first episode of bacteremia prior to absolute neutrophil count (ANC) 500/mm(3) . Antibiotic susceptibilities were performed on all isolates . RESULTS: Seventy-four patients (41%) developed bacteremia . The majority were Gram-positive cocci, with Staphylococcal (50%) and Streptococcal species (28%) the most common . Gram-negative organisms were identified in 22% with Pseudomonas (5.7%) and Klebsiella species (3.4%) the most common . Of the Streptococcal infections, 72% were resistant to ampicillin; only 25% of the Gram-negative bacteria were resistant to gentamicin . Race was the only factor associated with early bacteremia (hazard ratio 2.3 for non-Caucasian, non-African-American patients, CI 1.3-4.3, P = 0.007) CONCLUSIONS: Early bacteremia is common after HSCT, despite the use of GD . Resistant Gram-positive organisms predominate, consistent with recent trends in immunocompromised patients . Although used in practice, there is no clear evidence for the efficacy of GD and this study provides the basis upon which to develop a randomized clinical trial evaluating the current GD regimen with placebo . (c) 2004 Wiley-Liss, Inc.

J Nephrol, 2004 Nov-Dec, 17(6), 747 - 8
Histopathological atlas of renal diseases: Acute post-streptococcal glomerulonephritis; Ferrario F et al.; Acute post-streptococcal glomerulonephritis, also known as "proliferative-exudative nephritis" is morphologically characterized by intense endocapillary proliferation and massive accumulation of inflammatory cells.

Psychiatry Res, 2004 Dec 15, 129(2), 119 - 125
Mycoplasma pneumoniae infection and Tourette's syndrome; Muller N et al.; An association between infection and Tourette's syndrome (TS) has been described repeatedly . A role for streptococcal infection (PANDAS) has been established for several years, but the involvement of other infectious agents such as Borrelia Burgdorferi or Mycoplasma pneumoniae has only been described in single case reports . We examined antibody titers against M . pneumoniae and various types of antibodies by immunoblot in patients and in a sex- and age-matched comparison group . Participants comprised 29 TS patients and 29 controls . Antibody titers against M . pneumoniae were determined by microparticle agglutination (MAG) assay and confirmed by immunoblot . Elevated titers were found in significantly more TS patients than controls (17 vs . 1) . Additionally, the number of IgA positive patients was significantly higher in the TS group than in the control group (9 vs . 1) . A higher proportion of increased serum titers and especially of IgA antibodies suggests a role for M . pneumoniae in a subgroup of patients with TS and supports the finding of case reports implicating an acute or chronic infection with M . pneumoniae as one etiological agent for tics . An autoimmune reaction, however, has to be taken into account . In predisposed persons, infection with various agents including M . pneumoniae should be considered as at least an aggravating factor in TS.

J Am Chem Soc, 2004 Dec 15, 126(49), 16038 - 47
Refinement of NMR structures using implicit solvent and advanced sampling techniques; Chen J et al.; NMR biomolecular structure calculations exploit simulated annealing methods for conformational sampling and require a relatively high level of redundancy in the experimental restraints to determine quality three-dimensional structures . Recent advances in generalized Born (GB) implicit solvent models should make it possible to combine information from both experimental measurements and accurate empirical force fields to improve the quality of NMR-derived structures . In this paper, we study the influence of implicit solvent on the refinement of protein NMR structures and identify an optimal protocol of utilizing these improved force fields . To do so, we carry out structure refinement experiments for model proteins with published NMR structures using full NMR restraints and subsets of them . We also investigate the application of advanced sampling techniques to NMR structure refinement . Similar to the observations of Xia et al . (J.Biomol . NMR 2002, 22, 317-331), we find that the impact of implicit solvent is rather small when there is a sufficient number of experimental restraints (such as in the final stage of NMR structure determination), whether implicit solvent is used throughout the calculation or only in the final refinement step . The application of advanced sampling techniques also seems to have minimal impact in this case . However, when the experimental data are limited, we demonstrate that refinement with implicit solvent can substantially improve the quality of the structures . In particular, when combined with an advanced sampling technique, the replica exchange (REX) method, near-native structures can be rapidly moved toward the native basin . The REX method provides both enhanced sampling and automatic selection of the most native-like (lowest energy) structures . An optimal protocol based on our studies first generates an ensemble of initial structures that maximally satisfy the available experimental data with conventional NMR software using a simplified force field and then refines these structures with implicit solvent using the REX method . We systematically examine the reliability and efficacy of this protocol using four proteins of various sizes ranging from the 56-residue B1 domain of Streptococcal protein G to the 370-residue Maltose-binding protein . Significant improvement in the structures was observed in all cases when refinement was based on low-redundancy restraint data . The proposed protocol is anticipated to be particularly useful in early stages of NMR structure determination where a reliable estimate of the native fold from limited data can significantly expedite the overall process . This refinement procedure is also expected to be useful when redundant experimental data are not readily available, such as for large multidomain biomolecules and in solid-state NMR structure determination.

Clin Infect Dis, 2004 Dec 1, 39(11), 1625 - 32 Epub 2004 Dec 1.
Prevention of peritransplantation viridans streptococcal bacteremia with early vancomycin administration: a single-center observational cohort study; Jaffe D et al.; BACKGROUND: Viridans streptococcal bacteremia (VSB) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with substantial mortality . Prevention of this serious complication is therefore a high priority . The objective of this study was to evaluate the effect of early vancomycin administration on rates and outcomes of VSB . METHODS: We analyzed the effect of early vancomycin on the incidence of VSB in a cohort of 430 consecutive HSCTs performed during the period of 1 January 1998 to 30 September 2002 . The primary end point was time to diagnosis of VSB . Early vancomycin was defined as >or=2 doses of vancomycin between days -7 through +7 after HSCT or diagnosis of VSB, whichever occurred first . Risk factors for VSB were identified in univariate and multivariate Cox proportional hazard models . RESULTS: The incidence of VSB in the cohort was 7.4% . The incidence of VSB in patients who did not receive early vancomycin was 24.8%, compared with 0.3% in patients who did (P<.001) . Additional risk factors were female sex, conditioning with total body irradiation, and diagnosis of chronic myelogenous leukemia . CONCLUSIONS: The attributable mortality rate for VSB in our cohort was 21% . Early vancomycin was associated with decreased VSB (hazard ratio, 0.02; 95% confidence interval, 0.003-0.19) after controlling for age, sex, underlying disease, and transplantation variables . The benefits of vancomycin prophylaxis for the prevention of VSB and associated mortality need to be evaluated in a prospective clinical trial.

Clin Lab, 2004, 50(11-12), 667 - 73
Evaluation of recombinant antigens for the measurement of antibodies to streptolysin O and streptococcal DNase B on the Beckman Coulter IMMAGE system and comparison with a method employing conventional antigens; Freyaldenhoven BS et al.; The performance of a newly devised method employing recombinant antigens for the determination of antibodies to streptolysin O and DNase B on the Beckman Coulter IMMAGE System was compared with a nephelometric assay using conventional antigens . Sera from 114 patients with or without evidence of streptococcal infection were analysed by the two techniques . The results obtained with the new method correlated well with those of the reference test . The sensitivity of a combination measurement of antibodies to streptolysin O and DNase B was higher than that obtained when measuring each parameter alone . Handling of the tests was easier on the Beckman Coulter IMMAGE System . In conclusion, the new test from Beckman Coulter for the measurement of antibodies to streptolysin O and DNase B performs well and equals measurements using conventional antigens on a nephelometer.

J Paediatr Child Health, 2004 Dec, 40(12), 664 - 8
Prevention of neonatal group B streptococcal disease: progress, challenges and dilemmas; Daley AJ et al.; Significant advances in the prevention of neonatal group B streptococcal (GBS) disease have occurred in the last decade . In Australia, as well as in centres overseas, intrapartum penicillin given to carrier mothers has been shown to unequivocally decrease early onset neonatal GBS sepsis . In choosing which women should receive intrapartum chemoprophylaxis, recent data suggest that screening programmes for the detection of GBS carriage may be more effective than risk-based strategies to prevent early onset neonatal GBS sepsis . Combined vaginal and rectal swabs, collected between 35 and 37 weeks gestation, either by a health care worker or by the patient herself and inoculated onto selective media after enrichment provide the optimum conditions to detect carriage . Increasingly erythromycin and clindamycin resistance is being described overseas, which may influence the choice of antibiotics used in those allergic to penicillin . Widespread antibiotic use, particularly with broad-spectrum agents, may lead to increasing neonatal sepsis with ampicillin resistant organisms . Whilst rates of non-GBS neonatal sepsis are generally stable there is evidence suggesting that Escherichia coli sepsis in premature infants is increasing . Novel vaccination strategies for GBS are being developed that may ultimately provide broader protection for mothers and babies and eliminate the need for intrapartum antibiotics.

Infect Immun, 2004 Dec, 72(12), 7055 - 62
Streptococcal pyrogenic exotoxin B-induced apoptosis in a549 cells is mediated by a receptor- and mitochondrion-dependent pathway; Tsai WH et al.; It has been shown that streptococcal pyrogenic exotoxin B (SPE B) can induce cells to undergo apoptosis . The present study is to dissect the role of SPE B protease and SPE B protein in the apoptotic process of A549 cells and to elucidate the SPE B-induced apoptotic pathway . Recombinant SPE B (rSPE B) and C192S, a mutant of SPE B without protease activity, were expressed in Escherichia coli and purified by using an affinity column . The apoptosis of A549 cells was assayed by propidium iodide staining, followed by flow cytometry analysis . Our results showed that SPE B induced apoptosis in a dose-dependent manner, whereas C192S did not . When cells were pretreated with rSPE B (2 mug/ml) for as briefly as 5 min and then incubated with C192S of 28 kDa, an apoptosis that is proportional to the period of pretreatment was observed but not with C192S of 42 kDa . These results suggest that the extracellular protease activity of rSPE B is required for the initiation of apoptosis and that the size of SPE B is important for an effective induction of apoptosis . The time course analysis revealed that molecules activated in apoptosis were in the following order: caspase-8 (1.5 h), t-Bid (2.5 h), Bax (3 h), cytochrome c release (6 h), caspase-9 (7 h), and caspase-3 (8 h) . The overexpression of Bcl-2 inhibited depolarization of mitochondrial membrane, cytochrome c release, and apoptosis . The results of the present study suggest that SPE B-induced apoptosis is mediated through a receptor-like mechanism and a mitochondrion-dependent pathway.

Eur J Pediatr, 2005 Jan, 164(1), 3 - 8 Epub 2005 Jan.
Treatment and outcome of severe and non-severe acute otitis media; Hotomi M et al.; To determine outcomes in acute otitis media (AOM) according to severity of disease and to assess different initial treatment regimens, 308 with AOM were enrolled and divided into severe ( n=277; 89.9%) and non-severe ( n=31; 10.1%) groups based on symptoms and tympanic membrane changes . Children in the severe group were initially managed with amoxicillin (AMPC) whereas children in the non-severe group were initially managed without antibiotics . Children were monitored on days 1, 5, 10, 14 and 28 . Five outcome measures were assessed: disappearance of symptoms at day 5, resolution of tympanic membrane changes by day 28, disappearance of middle ear effusions by day 28, recurrence of acute symptoms prior to day 28, and need to change treatment regimens . Children with severe disease were more often male (57% versus 36%, P<0.05) and more often colonized with pathogens (77% versus 55%, P<0.05 than children with non-severe disease . The two groups were similar with respect to age and day care attendance . Despite differences in initial treatment regimens between the two groups, symptoms improved at the same rate for severe and non-severe disease, 94% by day 5 . In contrast, tympanic membranes returned to normal in 69% of the severe and 81% of the non-severe groups by day 28; however, as early as day 5, 10% of the severe and 55% of the non-severe groups demonstrated normal tympanic membranes . Middle ear effusions similarly disappeared more slowly in the severe group, 52% versus 74% by day 14 and 76% versus 84% by day 28 . Recurrence rates of acute symptoms occurred with equal frequency in the severe, 15%, and non-severe groups, 10% . Failure of the symptoms or the tympanic membranes to improve led to antibiotic changes in 59.9% of the severe group and to the addition of antibiotics in 51.6% of the non-severe group . Children in the severe group who failed to improve with an initial course of amoxicillin were younger (40.2 months versus 45.8 months, P<0.05), had higher tympanic membrane scores (4.5 versus 4.1, P<0.05), and were more often colonized with penicillin-resistant Streptococcusp neumoniae (33.8% versus 6.5%, P<0.01) than children who responded to AMPC . In a similar manner, children with non-severe disease who failed to improve without antibiotics were younger (40.7 months versus 54.8 months, P<0.05) and more often colonized with pathogens (75.0% versus 33.4%, P<0.05) . CONCLUSION:Severe disease occurred more often among males and among children colonized with pathogens . Response to treatment was impaired in younger children and in children colonized with pathogens, especially penicillin-resistant Streptococcusp neumoniae.

Pediatrics, 2004 Dec, 114(6), e748 - 51 Epub 2004 Dec.
Echocardiographic findings in the PANDAS subgroup; Snider LA et al.; BACKGROUND: Sydenham's chorea is the neurologic manifestation of rheumatic fever and is a diagnosis of exclusion requiring only the presence of frank chorea in the absence of another neurologic disorder . Two thirds of children with Sydenham's chorea also have rheumatic carditis (pathologic mitral valve regurgitation) . Although there are similar neuropsychiatric symptoms and preceding group A beta-hemolytic streptococcal infection associated with both Sydenham's chorea and the PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) subgroup, it is unknown whether patients in the PANDAS subgroup have any cardiac involvement . METHODS: Sixty children meeting the criteria for PANDAS were entered into protocols at National Institute of Mental Health between 1993 and 2002 . Doppler and 2-dimensional echocardiograms were performed on these subjects to assess valvular heart disease . RESULTS: Of these 60 children, no echocardiographic evidence of significant mitral or aortic valve regurgitation was found . One patient was found to have mild mitral regurgitation, and all patients had normal left atrial size and normal left ventricular size and function . Follow-up echocardiograms on 20 children showed no significant valvular regurgitation . CONCLUSION: The evidence of a clear lack of rheumatic carditis in these children supports the hypothesis that PANDAS is a distinct neuropsychiatric diagnosis separate from Sydenham's chorea.

Protein Sci, 2004 Dec, 13(12), 3322 - 30 Epub 2004 Dec.
Analysis of side chain mobility among protein G B1 domain mutants with widely varying stabilities; Goehlert VA et al.; "Host-guest" studies of the B1 domain from Streptococcal protein G have been used previously to establish a thermodynamic scale for the beta-sheet-forming propensities of the 20 common amino acids . To investigate the contribution of side chain conformational entropy to the relative stabilities of B1 domain mutants, we have determined the dynamics of side chain methyl groups in 10 of the 20 mutants used in a previous study . Deuterium relaxation rates were measured using two-dimensional NMR techniques for 13CH2D groups . Analysis of the relaxation data using the Lipari-Szabo model-free formalism showed that mutations introduced at the guest position caused small but statistically significant changes in the methyl group dynamics . In addition, there was a low level of covariation of the Lipari-Szabo order parameters among the 10 mutants . The variations in conformational free energy estimated from the order parameters were comparable in magnitude to the variations in global stability of the 10 mutants but did not correlate with the global stability of the domain or with the structural properties of the guest amino acids . The data support the view that conformational entropy in the folded state is one of many factors that can influence the folding thermodynamics of proteins.

J Immunother, 2004 Nov-Dec, 27(6), 432 - 41
Anti-tumor effect of an intratumoral administration of dendritic cells in combination with TS-1, an oral fluoropyrimidine anti-cancer drug, and OK-432, a streptococcal immunopotentiator: involvement of toll-like receptor 4; Ahmed SU et al.; The authors investigated the in vivo anti-tumor effect of intratumoral administration of bone marrow-derived dendritic cells (DCs) after chemotherapy using an oral fluoropyrimidine anti-cancer drug TS-1, and followed by immunotherapeutic agent OK-432, in two syngeneic tumor-bearing mouse models . Both in Meth-A fibrosarcoma-bearing BALB/c mice and in SCCVII-bearing C3H/HeN mice, 1 week of oral administration of TS-1 effected partial eradication of established tumors . Intratumoral injection of DCs and OK-432 caused only slight inhibition of the tumor growth . However, TS-1 administration followed by DCs and OK-432 resulted in a marked inhibition in the tumor growth and also contributed to a greater prolongation of survival . By the injection of DCs and OK-432 after TS-1 administration, a significant infiltration of immune cells, especially CD8+ T cells, was observed . Furthermore, the cytotoxic activities of tumor-infiltrating lymphocytes and draining lymph node cells against inoculated tumor cells were significantly increased by the therapy, while activities against nonspecific target cells were not . Cytotoxic memory T cells were also induced; the main effectors were MHC class I-restricted, CD8+ T cells . The same therapy was also applied to SCCVII-bearing C3H/HeJ mice in which the Toll-like receptor (TLR) 4 is mutated and its function impaired; no immunotherapeutic effect was observed in the TLR4-deficient mouse model . These findings suggest that the local DC therapy in combination with TS-1 and OK-432 may be a useful strategy for the treatment of solid tumors, and that TLR4 signaling is involved in the success of this therapy.

J Vet Med B Infect Dis Vet Public Health, 2004 Sep, 51(7), 333 - 6
Epidemiological study of non-contagious intramammary infections in nine commercial dairy herds following a Staphylococcus aureus control programme; Zecconi A et al.; Changes in prevalence in intramammary infection, by pathogen type, in herds applying a stringent contagious mastitis control programme was studied . Enrollment of 1651 lactating cows and collection of milk samples was made in this ancillary study to a cohort study of the dynamics of mastitis prevalence after adoption of a strict contagious mastitis control programme that targeted the elimination of mastitis caused by Staphylococcus aureus . Nine commercial dairies in Italy were used . Aseptic collection of milk samples from all lactating cows was performed at the time of enrollment, from all cows within 7-14 days of entering the lactating herd after the date of enrollment, and from all lactating cows at 2, 4, 7, 10 and 14 months after the date of enrollment . Prevalence of intramammary infection by pathogen type was determined from culture of milk samples . Application of the strict contagious mastitis programme did not lead to an increased risk of non-contagious mastitis . The risk of coliform, environmental streptococcal and coagulase-negative staphylococcal intramammary infections decreased after adoption of the programme . The data reported herein indicate that the overall risk for any intramammary infections decreases with adoption of a strict contagious mastitis programme, and that such a programme therefore does not necessarily lead to an increase in environmental mastitis.

Int J Antimicrob Agents, 2004 Nov, 24(5), 496 - 501
General and URTI-specific antibiotic prescription rates in a Malaysian primary care setting; Teng CL et al.; Antibiotic prescribing by primary care doctors has received renewed interest due to the continuing emergence of antibiotic resistance and the attendant cost to healthcare . We examined the antibiotic prescribing rate in relation to selected socio-demographic characteristics of the prescribers at the Seremban Health Clinic, a large public primary care clinic, designated for teaching, in the state of Negeri Sembilan, Malaysia . Data were obtained from: (1) retrospective review of prescriptions for the month of June 2002 and (2) a questionnaire survey of prescribers . A total of 10667 prescriptions were reviewed . The overall antibiotic prescribing rate was 15%; the rate (16%) was higher for the general Outpatient Department (OPD) than the 3% for the Maternal & Child Health Clinic (MCH) . The antibiotic prescription rates for upper respiratory tract infection (URTI) were 26% and 16%, respectively, for the OPD and MCH . Half of all the antibiotic prescriptions were for URTI making prescribing for URTI an appropriate target for educational intervention . The URTI-specific antibiotic prescription rate did not correlate with the prescribers' intention to specialise, patient load, perceived patient's expectation for an antibiotic, or the score for knowledge of streptococcal tonsillitis . Prescribing behaviours and record-keeping practices requiring correction were identified.

Immunopharmacol Immunotoxicol, 2004 Aug, 26(3), 387 - 99
Nigerooligosaccharides augments mitogen-induced proliferation and suppresses activation-induced apoptosis of human peripheral blood mononuclear cells; Hirose Y et al.; Nigerooligosaccharides (NOS), a mixture of nigerose and nigerosylmaltooligosaccharides, consists of immunopotentiating oligosaccharides found in foodstuffs . We have previously reported that activation of peripheral blood mononuclear cells (PBMC) in response to concanavalin A (Con A) or a streptococcal preparation of OK-432 is augmented in healthy young adults and elderly subjects after the intake of NOS-supplemented syrup . A reappraisal of the data suggests that NOS augments proliferation but partly suppresses activation-induced apoptosis of PBMC in response to these mitogens . To confirm this hypothesis, PBMC from healthy male subjects were stimulated with Con A or OK-432 in the presence of nigerose at the concentrations at which it was detected in the blood of subjects who had ingested NOS-supplemented syrup . Cellular activation, specifically metabolic demand, viability and proliferation, was assessed from glucose consumption, by WST-1 colorimetry and by 5-bromo-2'-deoxy-uridine incorporation assay, respectively . The Con A-induced activation of PBMC in each measurement was significantly augmented by nigerose . OK-432-induced decreases in the viability of PBMC were significantly inhibited by nigerose . Stimulation of PBMC with Con A or OK-432 induced apoptosis, but nigerose suppressed such activation-induced cell death . These results indicated that nigerose activated PBMC in vitro in a manner similar to the process observed in vivo, providing further evidence for the effectiveness of consumption of NOS-supplemented syrup.

Anticancer Res, 2004 Sep-Oct, 24(5C), 3295 - 301
Biological effect of OK-432 (picibanil) and possible application to dendritic cell therapy; Ryoma Y et al.; OK-432 (Picibanil), a streptococcal preparation with potent biological response modifying activities, was approved in Japan as an anticancer agent in 1975 . In the ensuing 30 years, since then, a significant amount of data, including clinical as well as experimental studies, has been accumulated . OK-432 has been reported to induce various cytokines, activate immunological cells and thus augment anticancer immunity . Recently, the interrelation between innate immunity and adaptive immunity has become clear and it was reported that OK-432 acts, at least in part, via Toll-like receptor (TLR) 4-MD2 signaling pathway . In addition, dendritic cells (DCs) are considered to play a pivotal role in immunological response and it is reported that OK-432 induced maturation of DCs both in vitro and in vivo . These results suggest that OK-432 is a useful adjuvant in DC-based anticancer immunotherapy . Clinical studies of DC therapy with OK-432 are under way.

Gene Ther . 2004 Oct 28; {Epub ahead of print}
Tumor cell targeted gene delivery by adenovirus 5 vectors carrying knobless fibers with antibody-binding domains; Henning P et al.; Most human carcinoma cell lines lack the high-affinity receptors for adenovirus serotype 5 (Ad5) at their surface and are nonpermissive to Ad5 . We therefore tested the efficiency of retargeting Ad5 to alternative cellular receptors via immunoglobulin (Ig)-binding domains inserted at the extremity of short-shafted, knobless fibers . The two recombinant Ad5's constructed, Ad5/R7-Z(wt)-Z(wt) and Ad5/R7-C2-C2, carried tandem Ig-binding domains from Staphylococcal protein A (abbreviated Z(wt)) and from Streptococcal protein G (C2), respectively . Both viruses bound their specific Ig isotypes with the expected affinity . They transduced human carcinoma cells independently of the CAR pathway, via cell surface receptors targeted by specific monoclonal antibodies, that is, EGF-R on A549, HT29 and SW1116, HER-2/neu on SK-OV-3 and SK-BR-3, CA242 (epitope recognized by the monoclonal antibody C242) antigen on HT29 and SW1116, and PSMA (prostate-specific membrane antigen) expressed on HEK-293 cells, respectively . However, Colo201 and Colo205 cells were neither transduced by targeting CA242 or EGF-R nor were LNCaP cells transduced by targeting PSMA . Our results suggested that one given surface receptor could mediate transduction of certain cells but not others, indicating that factors and steps other than cell surface expression and virus-receptor interaction are additional determinants of Ad5-mediated transduction of tumor cells . Using penton base RGD mutants, we found that one of these limiting steps was virus endocytosis.Gene Therapy advance online publication, 28 October 2004; doi:10.1038/sj.gt.3302408.

Am J Pathol, 2004 Nov, 165(5), 1583 - 91
Rheumatic heart disease: proinflammatory cytokines play a role in the progression and maintenance of valvular lesions; Guilherme L et al.; Heart lesions of rheumatic heart disease (RHD) patients contain T-cell clones that recognize heart proteins and streptococcal M peptides . To functionally characterize heart-infiltrating T lymphocytes, we evaluated their cytokine profile, both directly in situ and in T-cell lines derived from the heart (HIL) . Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-10 expressions were characterized in 20 heart tissue infiltrates from 14 RHD patients by immunohistochemistry . IFN-gamma-, TNF-alpha-, and IL-10-positive cells were consistently predominant, whereas IL-4 was scarce in the valves . In agreement with these data, the in vitro experiments, in which 13 HILs derived from heart samples of eight patients were stimulated with M5 protein and the immunodominant M5 (81-96) peptide, IL-4 was detected in HIL derived from the atrium (three of six) but not from the valve (zero of seven) . IFN-gamma and IL-10 production were detected in culture supernatants in 11 of 13 and 6 of 12 HILs, respectively . The predominant IFN-gamma and TNF-alpha expression in the heart suggests that Th1-type cytokines could mediate RHD . Unlike in reversible myocardium inflammation, the significantly lower IL-4 expression in the valvular tissue (P = 0.02) may contribute to the progression of the RHD leading to permanent valvular damage (relative risk, 4.3; odds ratio, 15.8) . The lack of IL-4 in vitro production by valve-derived HIL also emphasizes the more severe tissue destruction in valves observed in RHD.

Chang Gung Med J, 2004 Jul, 27(7), 501 - 8
Neonatal group B streptococcal infection: a 7-year experience; Chung MY et al.; BACKGROUND: This retrospective study was designed to determine the trend of neonatal group B streptococcal (GBS) infection during the past 7 years at the Chang Gung Memorial Hospital of Kaohsiung, as well as to assess the risk factors, clinical features and patient outcomes . METHODS: Medical records of infants with neonatal GBS infection identified by positive results of cultures of sterile body fluid in our hospital from January 1996 through December 2002 were reviewed for demographic and clinical data . RESULTS: There were 33 infants with neonatal GBS infections during the past 7 years in our hospital . The number of patients increased from 1996 to 2001 . Sixteen infants had early onset infections and 17 infants had late onset infections . Of the nine patients with maternal risk factors in the early onset group, prolonged rupture of membranes (7, 44%) was most frequently encountered . Distressed respiratory sign (8, 50%) was the most common clinical presentation in early onset group, while fever >38 degrees C (17, 100%) was the most common presentation in late-onset group . The mortality rates were 13% and 6% in early and late onset groups, respectively . Gestational age (p = 0.05) and pneumonia (p = 0.015) were two most important factors influencing the mortality rate . CONCLUSIONS: The number of GBS-infected infants seemed to have increased during the past 7 years in our hospital . Because the incidence of neonatal GBS infection and maternal colonization in Taiwan has not been collected, we could not determine the necessity of intrapartum chemoprophylaxis . Setting a comprehensive surveillance in Taiwan should be considered.

Am Fam Physician, 2004 Oct 1, 70(7), 1279 - 87
Epstein-Barr virus infectious mononucleosis; Ebell MH; Infectious mononucleosis should be suspected in patients 10 to 30 years of age who present with sore throat and significant fatigue, palatal petechiae, posterior cervical or auricular adenopathy, marked adenopathy, or inguinal adenopathy . An atypical lymphocytosis of at least 20 percent or atypical lymphocytosis of at least 10 percent plus lymphocytosis of at least 50 percent strongly supports the diagnosis, as does a positive heterophile antibody test . False-negative results of heterophile antibody tests are relatively common early in the course of infection . Patients with negative results may have another infection, such as toxoplasmosis, streptococcal infection, cytomegalovirus infection, or another viral infection . Symptomatic treatment, the mainstay of care, includes adequate hydration, analgesics, antipyretics, and adequate rest . Bed rest should not be enforced, and the patient's energy level should guide activity . Corticosteroids, acyclovir, and antihistamines are not recommended for routine treatment of infectious mononucleosis, although corticosteroids may benefit patients with respiratory compromise or severe pharyngeal edema . Patients with infectious mononucleosis should be withdrawn from contact or collision sports for at least four weeks after the onset of symptoms . Fatigue, myalgias, and need for sleep may persist for several months after the acute infection has resolved.

Semin Arthritis Rheum, 2004 Oct, 34(2), 553 - 8
Lack of association between the HLA-DRB1 locus and post-streptococcal reactive arthritis and acute rheumatic fever in Italian children; Simonini G et al.; OBJECTIVE: Post-streptococcal reactive arthritis (PSReA) may be a variant of acute rheumatic fever (ARF), but there still is debate on the relationship between the 2 entities . Possible associations with HLA class II antigens of PSReA (DRB1*01) and ARF (DRB1*16) were described previously in white Americans . To confirm these findings, we studied DRB1 alleles in a group of Italian children with PSReA and ARF . METHODS: We performed low-resolution HLA-DRB1 typing by a sequence-specific primer polymerase chain reaction method in 33 children with PSReA and 25 children with ARF . We also compared the DRB1 genotypes of our patients with 200 normal subjects from the same geographic area and typed in the same laboratory with the same methods . RESULTS: The allele distributions at the DRB1 locus observed in PSReA patients, ARF patients, and controls were not significantly different from each other (chi-square test with small numbers, P = .65) . The positivity for each of the 13 HLA-DRB1 alleles was compared in disease groups (PSReA and ARF) and controls, and failed to show any significant association . Comparisons of the frequency of the DRB1*01 allele among PSReA, ARF, and controls did not show any statistical differences . No significant difference in the frequency of DRB1*16 was present between ARF vs the control group, between ARF vs PSReA, and in PSReA patients when compared with controls . CONCLUSIONS: Our data do not confirm in Italian patients the previously reported associations of DRB1*01 and DRB1*16 with PSReA and ARF, respectively.

J Magn Reson, 2004 Nov, 171(1), 4 - 9
A simple method to measure 13CH2 heteronuclear dipolar cross-correlation spectral densities; Idiyatullin D et al.; Here, we report a method to simultaneously determine CH2 cross-correlation spectral densities and T1 relaxation times in the laboratory and rotating frames . To accomplish this, we have employed an indirect approach that is based on measurement of differences in relaxation rates acquired with and without cross-correlation terms . The new method, which can be employed using multidimensional NMR and standard relaxation pulse sequences, is validated experimentally by investigation of a selectively 13C-enriched hexadecapeptide and the uniformly 13C-enriched immunoglobulin-binding domain of streptococcal protein G (GB1) . Use of this approach makes determination of CH2 cross-correlation spectral densities in uniformly 13C-enriched proteins now routine and provides novel information concerning their internal motions.

Cochrane Database Syst Rev . 2004 Oct 18;(4):CD004417.
Delayed antibiotics for symptoms and complications of respiratory infections; Spurling G et al.; BACKGROUND: The use of antibiotics for upper respiratory tract infections is controversial . Any benefits have to be weighed against common adverse reactions (including rash, abdominal pain, diarrhoea and vomiting), cost and antibacterial resistance . There has been interest in ways to reduce antibiotic prescribing for acute respiratory infections . One is delaying the use of prescribed antibiotics by more than 48 hours for acute upper respiratory tract infections . Such methods have been shown to reduce prescribing . This review asks what effect this practice has on the clinical course of the illness . OBJECTIVES: To evaluate the clinical effect of delayed antibiotic use in acute upper respiratory tract infections compared to immediate use of antibiotics SEARCH STRATEGY: The following electronic databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004) which includes the Acute Respiratory Infection Groups' specialised register; MEDLINE (January 1966 to January Week 1 2004), EMBASE (1990 to September 2003) and Current Contents (1998 to 2003) . The search was carried out by an expert librarian . Abstracts of identified articles were used to determine which studies were trials . SELECTION CRITERIA: Randomised controlled trials involving patients of all ages defined as having acute otitis media, acute pharyngitis, sore throat, common cold, a viral upper respiratory tract infection, acute sinusitis, and acute bronchitis were included in which delayed antibiotics are compared to antibiotics used immediately . Delayed antibiotic use was defined as the use of or advice to use antibiotics more than 48 hours after the initial consultation . 'Immediate antibiotic use' was defined as the immediate use of oral antibiotics given at the initial consultation . Clinical outcomes measured included: the presence or absence of fever, cough, pain, duration and severity of illness, complications of the disease, adverse effects from the antibiotics . Trial quality was assessed independently by two reviewers who were blinded to the author, journal and results of each study . DATA COLLECTION AND ANALYSIS: Data was collected by two reviewers who were blinded to the author and journal . Data were analysed and reported using RevMan . MAIN RESULTS: Seven trials were eligible on the basis of design and all reported patient-centred outcomes . Methodological quality of included trials was generally high . There was no difference between immediate and delayed antibiotic groups for symptoms on day one and day seven . For most symptom measures there was no significant difference between the immediate and delayed antibiotic groups . Missing data and marked heterogeneity between study outcomes prevented pooling of results as a meta-analysis . Three studies out of six reporting fever, all involving patients with sore throat, indicated that there was more fever in the delayed antibiotic group . The remaining three studies showed no difference . There was no significant symptom difference for patients with cough or the common cold between the two intervention groups . Pain and malaise severity scores at day three significantly favoured the immediate antibiotic group in children with acute otitis media (Little 2001) . In this study by Little 2001 of children with otitis media proxies for other malaise related outcomes were reported, including 'last day of crying' which favoured the immediate antibiotic group by approximately 16 hours (0.69 days; 95% CI 0.31 to 1.07) . In the same study, just over half a spoon of paracetamol a day less was used in the immediate antibiotic group (0.59; 95% CI 0.25 to 0.93) . There was no significant difference between the intervention groups for the adverse outcome of rash . Two studies reported the outcome of vomiting which was reduced in the immediate antibiotic group in children with suspected streptococcal pharyngitis in El-Daher 1991 but there was no difference in children with sore throat in Little 1997 . Diarrhoea was reported by three studies of which two showed no difference Little 1997; Arroll 2002a while Little 2001reported less diarrhoea in the delayed antibiotic group in children with otitis media . REVIEWERS' CONCLUSIONS: When considering treatment options for upper respiratory tract infections, the option of delayed antibiotics has been used in an attempt to reduce the use of antibiotic prescriptions . This review shows that for all symptom scores the evidence varies between trials . Most symptom outcomes show no difference between immediate and delayed antibiotic groups . Three of the six studies, all involving patients with sore throat, indicated that patients in the delayed antibiotic group had significantly more fever that their counterparts in the immediate antibiotic group . The other three showed no difference for the outcome of fever . There is evidence indicating that for children with otitis media, pain and malaise scores are worse in the delayed antibiotic group compared to the immediate antibiotic group . This price must be weighed up against the benefits of reduced antibiotic prescribing . Future randomised controlled trials of delaying antibiotics as an intervention should fully report symptoms as well as changes of prescription rates.

Cochrane Database Syst Rev . 2004 Oct 18;(4):CD004070.
Vaginal chlorhexidine during labour for preventing maternal and neonatal infections (excluding Group B Streptococcal and HIV); Lumbiganon P et al.; BACKGROUND: The incidence of chlorioamnionitis occurs in between 8 to 12 women for every 1000 live births and 96% of the cases of chlorioamnionitis are due to ascending infection . Following spontaneous vaginal delivery, 1% to 4% of women develop postpartum endometritis . The incidence of neonatal sepsis is 0.5% to 1% of all infants born . Maternal vaginal bacteria are the main agents for these infections . It is reasonable to speculate that prevention of maternal and neonatal infections might be possible by washing the vagina and cervix with an antibacterial agent for all women during labour . Chlorhexidine belongs to the class of compounds known as the bis-biguanides . Chlorhexidine has antibacterial action against a wide range of aerobic and anaerobic bacteria, including those implicated in peripartal infections . OBJECTIVES: To evaluate the effectiveness and side-effects of chlorhexidine vaginal douching during labour in reducing maternal and neonatal infections (excluding Group B Streptococcal and HIV) . SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (July 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002), MEDLINE (from 1966 to 2002), EMBASE (from 1980 to 2002), CINAHL (from 1982 to 2002) and LILACS (from 1982 to 2002) . SELECTION CRITERIA: Randomized or quasi-randomized trials comparing chlorhexidine vaginal douching during labour with placebo or other vaginal disinfectant to prevent (reduce) maternal and neonatal infections (excluding Group B Streptococcal and HIV) . DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and quality, extracted and entered the data into the RevMan software and interpreted the data . A third reviewer analysed and interpreted the data . The fourth reviewer also interpreted the data . MAIN RESULTS: Three studies (3012 participants) were included . There was no evidence of an effect of vaginal chlorhexidine during labour in preventing maternal and neonatal infections . Although the data suggest a trend in reducing postpartum endometritis, the difference was not statistically significant (relative risk 0.83; 95% confidence interval 0.61 to 1.13) . REVIEWERS' CONCLUSIONS: There is no evidence to support the use of vaginal chlorhexidine during labour in preventing maternal and neonatal infections . There is a need for a well-designed randomized controlled trial using appropriate concentration and volume of vaginal chlorhexidine irrigation solution and with adequate sample size.

Rev Med Liege, 2004 Jul-Aug, 59(7-8), 423 - 5
{How I prevent erysipelas and its consequences and recurrences}; Henry F et al.; Erysipelas is a serious infection of the skin . In case of delay in initiating adequate antibiotic treatment, complications, sometimes dismal, can supervene . In addition, erysipelas shows a tendancy to recurrences . The prevention of an episode of erysipelas calls for correct personal hygiene and adequate use of topical antiseptics in case of skin effraction, even when minimal . When erysipelas is established, a rapidly initiated antibiotic treatment for a prolonged period prevents streptococcal gangrene complications . Elastic contention of any leg edema from venous or lymphatic origin and prophylactic antisepsis of discrete wounds help in preventing erysipelas recurrences.

Int J Mol Med, 2004 Nov, 14(5), 801 - 6
Stable long-term induction of perforin-positive CD8+ T cells in gut by oral administration of streptococcal preparation OK-432; Mino N et al.; Perforin is known as a pore-forming cytotoxic granule released from cytotoxic T cells . Previous experiments in vitro revealed the presence of precursor cells that are capable of producing perforin in the immune system cells . The present study was undertaken to examine whether perforin-positive cells could be induced in the digestive tract and to characterize their precursor cells . Expression of perforin-positive cells in the intestine of Balb/c mice induced by OK-432 was analyzed by immunohistochemical staining and RT-PCR . Oral treatment of Balb/c mice with OK-432 resulted in the occurrence of perforin-positive cells in the inferior segment of small intestine, the superior segment of large intestine, mesenteric lymph nodes and spleen . In the small intestine, perforin-positive cells were found in the lamina propria mucosa . The presence of perforin-positive cells was also noted following long-term OK-432 treatment . Similar results were obtained following treatment with biological response modifiers such as lipopolysaccharide . In mice with GVHD (graft-versus-host disease), the presence of perforin-positive cells was noted in the small intestine and spleen . When the serial sections of the small intestinal mucosa from OK-432-treated mice were immunostained with anti-perforin, anti-CD8 and anti-asialo-GM1 antibodies, the perforin-positive cells were found to be CD8-positive . The results suggest that CD8(+) cells in lamina propria mucosa play a significant role as effectors in the mucosal immune system which is activated by various stimuli.

Lett Appl Microbiol, 2004, 39(5), 459 - 65
Effects of Magnolol and Honokiol on the activities of streptococcal glucosyltransferases both in solution and adsorbed on an experimental pellicle; Jun L et al.; AIMS: To investigate the inhibitory effects of Magnolol and Honokiol on the activity of streptococcal glucosyltransferases (Gtfs) . METHODS AND RESULTS: The effect of Magnolol and Honokiol that inhibits the activities of streptococcal GtfB, GtfC, GtfD and GtfS was explored with standard assays . The results showed that both samples can efficiently inhibit the activity of all Gtfs in solution (66.4-96.3%) and adsorbed on the surface of saliva-coated hydroxyapatite (sHA) beads (65.5-92.7%) at concentrations between 1.25 and 5.0 mg ml(-1) . Furthermore, Magnolol had a stronger inhibition of four kinds of Gtfs than Honokiol both in solution and adsorbed on the surface of sHA beads at concentrations between 0.04 and 0.63 mg ml(-1) (P < 0.05) . CONCLUSIONS: Magnolol had significant effects on the activities of streptococcal Gtfs . SIGNIFICANCE AND IMPACT OF THE STUDY: Magnolol as a natural herb can be developed into a new oral hygiene product to prevent plaque formation.

Zh Mikrobiol Epidemiol Immunobiol, 2004 Jul-Aug, (4), 17 - 20
{Experience in the prophylaxis of respiratory streptococcal infection in organized groups of children of pre-school age with the use of Tomicid}; Pneumococcal meningitis in Western Australian children: epidemiology et al.; TVW Telethon Institute for Child Health Research, University of Western Australia, Perth, Western Australia, Australia . barbara.king@health.wa.gov.au

OBJECTIVES: Pneumococcal meningitis is now vaccine-preventable but continues to cause high rates of neurological sequelae internationally . Population-based epidemiology, outcome and microbiology data are necessary to target vaccination strategies . This study outlines these key areas for Western Australian children diagnosed 1990-2000 . METHODS: The charts of all rural and metropolitan children with International Classification of Disease 9 and 10 discharge codes of pneumococcal or streptococcal meningitis from the Health Department's Hospital Morbidity Data System were reviewed . RESULTS: Over 10.5 years, 94 episodes were confirmed . The average annual incidence for children under 2 years was 13.45 per 100 000 and 0.66 per 100 000 for children 2 years or older . Indigenous children had an almost seven-fold increased risk compared to non-Indigenous (with 78.55 per 100 000 in the under two-year Indigenous group) . Eight children died and 24 of the survivors had neurological sequelae . Penicillin resistance occurred in four of 87 isolates . One quarter of the cohort qualify under the current Australian policy of vaccination of high-risk children with seven-valent conjugate (7vPCV) vaccine . Most isolates (49/58) were 7vPCV serotypes, however, Indigenous populations were less well-covered (58.3% covered vs 91.3% of isolates from non-Indigenous children) . Indigenous coverage would be improved to 75% with 11-valent conjugate vaccine . CONCLUSIONS: Indigenous children and those under 2 years are most affected by pneumococcal meningitis and remain primary vaccination targets . Three quarters of these children would not be protected by a policy of vaccination of only high-risk children with 7vPCV--improved protection requires higher valencies for Indigenous populations and universal infant vaccination.

J Paediatr Child Health, 2004 Nov, 40(11), 606 - 10
Pneumococcal meningitis: clinical course and resource use in Western Australian children; King BA et al.; OBJECTIVES: Paediatric pneumococcal meningitis causes high rates of neurological sequelae and is presenting challenges due to the emergence of antibiotic resistance . Diagnosis can be difficult and management is frequently complicated and resource intensive . This population-based study outlines the diagnosis, clinical course and initial resource use of Western Australian (WA) children diagnosed between 1990 and 2000 . METHODS: The charts of all rural and metropolitan children discharged from all WA hospitals with International Classification of Disease 9 and 10 codes of pneumococcal or streptococcal meningitis from the Health Department's Hospital Morbidity Data System were reviewed retrospectively . RESULTS: Ninety-four episodes of pneumococcal meningitis were confirmed (median age 12.4 months) . Initial diagnosis was often difficult with a suggestive prodrome in less than one quarter of cases and a median of two reviews until diagnosis (range 1-7) . The median duration of hospitalization was 11.6 days, 41.5% were admitted to the Intensive Care Unit (ICU), and 47.9% had seizures . There were eight related deaths and neurological sequelae occurred in 24 . Initial hospitalization cost on average $A 19,900 . Penicillin resistance was first noted in 1993 and occurred in 4.6% of isolates . Most cases (84.5%) were caused by serotypes contained in the currently available seven-valent conjugate vaccine . CONCLUSIONS: Pneumococcal meningitis is often difficult to diagnose, necessitates long and frequently complicated in-patient stays and has high rates of neurological sequelae . It is possible to prevent most cases with new conjugate vaccines.

Klin Med (Mosk), 2004, 82(8), 61 - 6
{Present-day classification and nomenclature of rheumatic fever}; Nasonova VA et al.; The paper presents a new classification of rheumatic fever, which has been adopted by the Plenary Session of the Association of Rheumatologists of Russia in May 2003 . This classification envisages the abandonment of the term "rheumatism" in its former interpretation . The term "acute rheumatic fever" (ARF) appears to be more justified since it makes a physician elucidate its association with Group A streptococcal infection of the throat and prescribe antibiotics for eradication of this infection in its acute period (primary prophylaxis) and for prevention of repeated attacks (secondary prophylaxis) . The current interpretation of the clinical syndromes/symptoms and laboratory parameters that enter into diagnostic criteria for ARF is presented . There are 2 types of outcome of the disease . In case of recovery, we are dealing with the complete regression of the clinical symptomatology of ARF, normalized laboratory parameters and no residual changes . Chronic rheumatic diseases of the heart are considered to mean a disease characterized by a cardiac valvular lesion as postinflammatory marginal fibrosis of valvular leaflets or cardiac abnormality (failure and/or stenosis) developed after prior ARF . Emphasis is laid on the significance of evidence of Group A streptococcal infection that precedes the development of the disease . Examples of clinical diagnosis in accordance with the terminology of the International Classification of Diseases, the 10th edition, are given in the paper.

Fam Med, 2004 Oct, 36(9), 622 - 4
A Web-based approach to teaching students about diagnostic reasoning; Smucny J et al.; BACKGROUND: Web-based curricula can decrease classroom time and provide self-paced, active learning experiences for medical students . INTERVENTION: In our family medicine clerkship, we implemented a Web-based module on applying diagnostic reasoning to determine the likelihood that a patient has Group A beta-hemolytic streptococcal pharyngitis based on the history, physical examination, and diagnostic tests . RESULTS: Students rated the module more favorably than other classroom sessions and homework assignments . Most students accurately calculated pretest and posttest probabilities in a write-up of an actual patient with a sore throat . CONCLUSIONS: This Web-based module was well received and effective.

J Dermatol, 1977 Oct, 4(5), 187 - 91
Unspecific increase of antistreptolysin-O titer in acute guttate psoriasis; Sato H et al.; An acute streptococcal infection is well-known to be a predisposing factor in acute guttate psoriasis . This study also revealed a high ASO titer in 11 of 13 patients at first examination . However, a non-specific ASO increase due to non-immunological reaction of serum lipoproteins with antistreptolysin-O, was found in 5 of these patients who visited our clinic at the evolving phase, 2 or 3 weeks after onset of the eruption but was no longer observed at 5-6 weeks and thereafter . On the other hand, specific ASO increase, which was not related to lipoproteins, was observed first in some patients at 3-4 weeks and at 7-10 weeks in all patients examined . These observations suggest the role of streptococcal lipoprotein alteration in the occurrence of this disease.

Antibiot Khimioter, 2004, 49(4), 25 - 34
{Dynamics of Streptococcos pneumoniae antibiotic resistance emergence in Moscow in 1998-2003}; Immunoglobulin E to staphylococcal and streptococcal toxins in patients with chronic sinusitis/nasal polyposis; Division of Allergy and Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 North St . Clair, Suite 15-200, Chicago, IL 60611, U.S.ABACKGROUND: The role of infectious agents and their contribution to the inflammation in chronic sinusitis/nasal polyposis (CS/NP) is not clear . Staphylococcal and streptococcal toxins have superantigen activity and have been implicated in inflammatory conditions such as atopic dermatitis, psoriasis, and asthma . OBJECTIVE: We investigated the presence of immunoglobulin (Ig)E antibodies to staphylococcal and streptococcal toxins in the serum of individuals with CS/NP . METHOD: IgE antibodies to staphylococcal exotoxins, A, B, and toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, B, and C were measured in 23 individuals with CS/NP before functional endoscopic sinus surgery and in controls (7 atopic and 6 nonatopic) individuals without chronic sinusitis . Presence of IgE to the toxins was also correlated with disease severity on sinus computed tomography (CT) scans . RESULTS: Staphylococcal and streptococcal toxin specific IgE antibodies were detected in 18 of 23 (78%) and 7 of 21 (33.3%) patients, respectively . None of the controls had IgE to the staphylococcal or streptococcal toxins (P <.0001) . There was no association between radiographic severity of sinus disease and the presence of IgE antibody to the toxins . CONCLUSION: A significantly greater proportion of CS/NP patients had IgE to staphylococcal or streptococcal toxins . Evidence of IgE antibodies directed against staphylococcal and streptococcal toxins in the sera of patients with CS/NP suggests a potential role of these toxins with established superantigen effects in the pathogenesis of CS/NP.

Microbes Infect, 2004 Oct, 6(12), 1073 - 7
Factors determining prognosis in streptococcal toxic shock-like syndrome: results of a nationwide investigation in Japan; Hasegawa T et al.; Since the first report of streptococcal toxic shock-like syndrome (TSLS) in Japan, the numbers of reported patients have been increasing . However, clinical manifestations remain somewhat unclear, and factors potentially defining prognosis remain to be identified . We conducted a retrospective nationwide postal survey of major Japanese hospitals concerning clinical manifestations of invasive streptococcal infections including necrotizing fasciitis and TSLS . We evaluated 30 patients who died and 36 survivors . The overall mortality rate was 45% . Physical and laboratory findings on admission were compared statistically between fatal cases and surviving patients . Most laboratory results from the patients who died showed greater abnormality than results from the survivors . Patients who died had significantly fewer leukocytes and platelets, although their C-reactive protein concentrations were similar to those in survivors . Creatinine was significantly higher, and temperature and blood pressure were significantly lower, in patients who died . Patients with invasive streptococcal infections should be managed aggressively when the above features are present.

Scand J Infect Dis, 2004, 36(8), 610 - 2
Fournier's gangrene after genital piercing; Ekelius L et al.; A fulminant case of streptococcal toxic shock syndrome is described . Early surgery was life saving, and the antibiotic regimen should include clindamycin . The value of secondary measures is discussed . High dose intravenous immunoglobulin (IVIG) has shown promising effects in recent publications . Hyperbaric oxygen (HBO) treatment is under evaluation . Piercing of mucosal surfaces might be associated with severe infections.

J Obstet Gynaecol Can, 2004 Sep, 26(9), 826 - 40
The prevention of early-onset neonatal group B streptococcal disease; Money DM et al.; OBJECTIVE: To review the evidence in the literature and to provide recommendations on the management of pregnant women in labour for the prevention of early-onset neonatal group B streptococcal (GBS) disease . OUTCOMES: Maternal outcomes evaluated included exposure to antibiotics in pregnancy and labour and complications related to antibiotic use . Neonatal outcomes of rates of early-onset group B streptococcal infections are evaluated . EVIDENCE: A review of the literature through MEDLINE from January 1980 to December 2003, relating to neonatal group B streptococcal infection and a review of the Centers for Disease Control and Prevention recommendations . VALUES: The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on the Periodic Health Exam . RECOMMENDATIONS: 1 . Offer all women screening for group B streptococcal disease at 35 to 37 weeks' gestation with culture done from one swab first to the vagina then to the rectal area . (II-1)2 . Treat the following women intrapartum at time of labour or rupture of membranes with IV antibiotics: -all women positive by GBS culture screening done at 35 to 37 weeks (II-2) - any women with an infant previously infected with GBS (II-3) - any women with documented GBS bacteriuria (regardless of level of colony-forming units per mL) in this pregnancy (II-2) 3 . Treat women at less than 37 weeks' gestation with IV antibiotics unless there has been a negative GBS vaginal/rectal swab culture within 5 weeks . (II-3) 4 . Treat women with intrapartum fever with IV antibiotics (i.e., chorioamnionitis must be treated, but broader spectrum antibiotics would be advised) . (II-2) 5 . If a woman is GBS-positive by culture screening or by history of bacteriuria, with prelabour rupture of membranes at term, treat with GBS antibiotic prophylaxis and initiate induction of labour with IV oxytocin (II-1) 6 . If GBS culture result is unknown and the woman has ruptured membranes at term for greater than 18 hours, treat with GBS antibiotic prophylaxis . (II-2)

Am J Orthod Dentofacial Orthop, 2004 Sep, 126(3), 325 - 30
Fluoridated elastomers: effect on the microbiology of plaque; Benson PE et al.; The objective of this study was to investigate the effect of fluoridated elastomeric ligatures on the microbiology of local dental plaque in vivo . This randomized, prospective, longitudinal, clinical trial had a split-mouth crossover design . The subjects were 30 patients at the beginning of their treatment with fixed orthodontic appliances in the orthodontic departments of the Liverpool and the Sheffield dental hospitals in the United Kingdom . The study consisted of 2 experimental periods of 6 weeks with a washout period between . Fluoridated elastomers were randomly allocated at the first visit to be placed around brackets on tooth numbers 12, 11, 33 or 22, 21, 43 . Nonfluoridated elastomers were placed on the contralateral teeth . Standard nonantibacterial fluoridated toothpaste and mouthwash were supplied . After 6 weeks (visit 2), the elastomers were removed, placed in transport media, and plated on agar within 2 hours . Nonfluoridated elastomers were placed on all brackets for 1 visit to allow for a washout period . At visit 3, fluoridated elastomers were placed on the teeth contralateral to those that received them at visit 1 . At visit 4, the procedures at visit 2 were repeated . Samples were collected on visits 2 and 4 . A logistic regression was performed, with the presence or absence of streptococcal or anaerobic growth as the dependent variable . A mixed-effects analysis of variance was carried out with the percentage of streptococcal or anaerobic bacterial count as the dependent variable . The only significant independent variables were the subject variable (P =<.001) for the percentage of streptococcal and anaerobic bacterial count and the visit variable for the percentage of streptococcal count (P =<.001) . The use of fluoridated or nonfluoridated elastomers was not significant for percentage of either streptococcal (P =.288) or anaerobic count (P =.230) . Fluoridated elastomers are not effective at reducing local streptococcal or anaerobic bacterial growth after a clinically relevant time in the mouth.

Arch Pediatr Adolesc Med, 2004 Sep, 158(9), 848 - 56
Does group A beta-hemolytic streptococcal infection increase risk for behavioral and neuropsychiatric symptoms in children?
Perrin EM, Murphy ML, Casey JR, Pichichero ME, Runyan DK, Miller WC, Snider LA, Swedo SE.
OBJECTIVE: To determine whether group A beta-hemolytic streptococcal infections increase the risk of developing symptoms characteristic of the diagnosis pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) . DESIGN: Prospective cohort study . METHODS: Children (N = 814) aged 4 to 11 years seen for sore throat or well-child care in a large pediatric practice in Rochester, NY, were enrolled from October 2001 to June 2002 (group A beta-hemolytic streptococcal {GAS} infected, n = 411; GAS uninfected, n = 403, of whom 207 had a sore throat of presumed viral etiology and 196 were well children) . Symptomatic children with GAS infection (n = 399) were treated with antibiotics . At baseline and 2 and 12 weeks following baseline, all parents completed a 20-item questionnaire about the presence/absence of recent PANDAS symptoms in their children, and capable children answered 10 items about worries, obsessions, and compulsions . The relative risk of developing a "mild PANDAS variant" (> or = 2 new PANDAS symptoms) by illness type (GAS positive, presumed viral, or well child) and by parent and child report was determined and adjusted for potential covariates . RESULTS: By parent report, ill children more frequently manifested several PANDAS symptoms at baseline than well children . However, neither new symptoms nor the risk of developing a mild PANDAS variant developed during the subsequent 12 weeks more commonly in children with GAS infection than in those with presumed viral illness or in well children by parent or child report . CONCLUSIONS: Ill children with GAS infection, treated for their GAS infection, were not at increased risk for developing PANDAS symptoms or a mild PANDAS variant compared with children with presumed viral illness or well children . The role of antibiotics in the prevention or treatment of PANDAS as well as the investigation of PANDAS in the asymptomatic, infectious host deserves future research.

J Mol Biol, 2004 Sep 24, 342(4), 1101 - 14
Complex interactions between bovine plasminogen and streptococcal plasminogen activator PauA; Ward PN et al.; The interactions between bovine plasminogen and the streptococcal plasminogen activator PauA that culminate in the generation of plasmin are not fully understood . Formation of an equimolar activation complex comprising PauA and plasminogen by non-proteolytic means is a prerequisite to the recruitment of substrate plasminogen; however the determinants that facilitate these interactions have yet to be defined . A mutagenesis strategy comprising nested deletions and random point substitutions indicated roles for both amino and carboxyl-terminal regions of PauA and identified further essential residues within the alpha domain of the plasminogen activator . A critical region within the alpha domain was identified using non-overlapping PauA peptides to block the interaction between PauA and bovine plasminogen, preventing formation of the activation complex . Homology modelling of the activation complex based upon the known structures of streptokinase complexed with human plasmin supported these findings by placing critical residues in close proximity to the plasmin component of the activation complex.

Zhonghua Er Ke Za Zhi, 2004 Aug, 42(8), 571 - 3
{Clinical significance of antiphospholipid antibody in pediatric patients and review of literature}; Xiao HJ et al.; OBJECTIVE: Antiphospholipid antibody (APL) is a particularly important laboratory diagnostic criterion for antiphospholipid syndrome (APS) . The significances of positive APL in childhood are seldom reported nor fully understood . The purpose of this study was to analyze 13 cases with positive APL seen in our hospital and to study the relationship between the positive rates of APL and various clinical diseases especially systemic lupus erythematosus (SLE) in order to improve the clinical diagnoses and treatment level of APS in children . METHODS: The clinical data collected from 2000 to 2002 of 13 hospitalized children with positive APL were retrospectively evaluated . Enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence technique were used respectively to detect APL and antineutrophil cytoplasmic autoantibodies (ANCA) of sera from those children . Other various indexes were also detected according to different characteristics of different diseases . RESULTS: Eight cases had SLE; 2 had acute post-streptococcal infections . The other 3 cases did not show any evidences of primary diseases; they probably had primary APS . SLE was the most common primary diseases to cause development of APL and the cases with SLE showed more severe cutaneous vasculitis than SLE patients who were negative for APL . There was no significant relationship between the positive rates of APL and that of ANCA . Eight APL positive cases complicated with thrombocytopenia and bleeding were treated with high dosage of immunoglobulin {400 mg/(kg.d), for 3 - 5 d} intravenously; the clinical conditions of these cases were ameliorated soon . While the 5 cases who had thrombotic vasculitis and thromboembolism were treated with anticoagulant and antithrombotic therapy with low molecular weight heparin {50 - 100 U/(kg.d)}, which led to good clinical effects . CONCLUSIONS: The clinical manifestations of children positive for APL were somehow different from those of adults . Positive APL itself may be nonspecific, it can occur from different causes of diseases . APL detection may be useful to suggest anticoagulant and/or antithrombosis therapy . Treatments for APS should be variable according to different causes and severity of diseases, in the cases of thrombocytopenia and bleeding, high dose intravenous immunoglobulin should be given as soon as possible, while in the cases of thrombotic vasculitis and thromboembolism, anticoagulant and antithrombotic therapy should be given soon.

J Bacteriol, 2004 Sep, 186(18), 6254 - 64
Transcriptional Repressor CopR: use of SELEX to study the copR operator indicates that evolution was directed at maximal binding affinity; Freede P et al.; CopR is one of the two copy number control elements of the streptococcal plasmid pIP501 . It represses transcription of the repR mRNA encoding the essential replication initiator protein about 10- to 20-fold by binding to its operator region upstream of the repR promoter pII . CopR binds at two consecutive sites in the major groove of the DNA that share the consensus motif 5'-CGTG . Previously, the minimal operator was narrowed down to 17 bp, and equilibrium dissociation constants for DNA binding and dimerization were determined to be 0.4 nM and 1.4 microM, respectively . In this work, we used a SELEX procedure to study copR operator sequences of different lengths in combination with electrophoretic mobility shift assays of mutated copR operators as well as copy number determinations to assess the sequence requirements for CopR binding . The results suggest that in vivo evolution was directed at maximal binding affinity . Three simultaneous nucleotide exchanges outside the bases directly contacted by CopR only slightly affected CopR binding in vitro or copy numbers in vivo . Furthermore, the optimal spacer sequence was found to comprise 7 bp, to be AT rich, and to need an A/T and a T at the 3' positions, whereas broad variations in the sequences flanking the minimal 17-bp operator were well tolerated.

Brain Res Mol Brain Res, 2004 Sep 10, 128(1), 95 - 102
Expression of proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1beta in the brain during experimental group B streptococcal meningitis; Kim YS et al.; We performed mRNA in situ hybridization for TNF-alpha and IL-1beta from infant rats with group B streptococcal meningitis . Induction of both cytokines was seen in the ependyma and the meninges at 4 h . Both cytokines were expressed in the brain parenchyma at 12 h . Induction of IL-1beta mRNA was seen in vessels within the brain cortex . Neutrophilic infiltrate at all time points examined was minimal and could not account for the observed cytokine expression.

Asia Pac J Clin Nutr, 2004, 13(3), 226 - 30
Immunological response to antioxidant vitamin supplementation in rural Bangladeshi school children with group A streptococcal infection; Ahmed J et al.; Group A beta haemolytic streptococcal (GABHS) infection induce an abnormal immune response in a susceptible host . Micronutrient deficiency may affect the immune response of an individual . The aim of this study was to determine whether antioxidant vitamins could improve the abnormal immune response in GABHS infected children in rural Bangladesh . A total of 516 GABHS infected school children aged 5 to 15 years were randomly assigned to two groups . Group 1 (N=258) was treated with phenoxymethyl penicillin V and group 2 (N=258) was treated with penicillin V plus antioxidant vitamins (beta carotene, alpha tocopherol and ascorbic acid) . From each group two blood samples were drawn; the first sample at the beginning of the study and another one after eight weeks . Streptococcal antibodies and immunoglobulin levels were compared between the two samples . The mean age of the study population was 10.6 years . Equal number of boys and girls were included in both groups . After treatment, antistreptolysin O (ASO) and antideoxyribonuclease B (ADNase B) titres were decreased in both groups . Serum alpha tocopherol and beta-carotene levels were increased significantly in group 2 . In group 1 immunoglobulin M and A levels decreased significantly (P =0.0001) whereas immunoglobulin G showed no change . To the contrary, concentration of three immunoglobulins decreased significantly (P=0.0001) in group 2 . Least-square means of between-group differences showed highly significant results for ASO, ADNase B, immunoglobulins M, A and G (P=0.0001) . Our data indicate that treatment by antioxidant vitamins plus penicillin is more effective in decreasing immunological abnormalities in GABHS infected children then penicillin alone.

Neuropediatrics, 2004 Aug, 35(4), 242 - 5
Are sensory phenomena present in Sydenham's Chorea? Evaluation of 13 cases; Rodopman-Arman A et al.; Sydenham's Chorea (SC) is an early complication of rheumatic fever caused by group A beta-hemolytic streptococcal infection that manifests itself with adventitious choreatic movements and behavioral problems . Sensory phenomena are the premonitory sensory experiences that are described prior to tics . Tic disorders and SC share common underlying neurobiological substrates, yet sensory phenomena have not previously been examined in SC . We aimed to explore the presence of sensory phenomena associated with choreatic movements in children with SC . Thirteen SC patients are examined on measures of sensory phenomena using a semi-structured instrument . 10 out of 13 patients described sensory phenomena . Five of the SC patients described sensory phenomena as "between physical and mental" . The patients described physical feelings of tension in joints, tingling and trembling sensations on skin . 69 % of them described movements as "completely involuntary" . Sites of choreatic movements that were consistently preceded by sensory phenomena were upper and lower extremities, and trunk . Children may have difficulty in articulating sensory phenomena due to the subjective nature of premonitory feelings in SC . We recommend exploring the sensory experiences that might accompany the choreatic movements in children with SC.

BJOG, 2004 Sep, 111(9), 1006 - 11
Early-onset neonatal group B streptococcal infection in London: 1990-1999; Mifsud AJ et al.; OBJECTIVE: To identify the incidence of early-onset group B streptococcal infection and to describe the antecedent maternal risk factors, in order to provide data to inform the design of interventional strategies that could be introduced in the UK to reduce the burden of this infection . DESIGN: A retrospective study with review of case notes of mothers and babies . SETTING: Seven maternity units in London during 1990-1999 . Population All cases of proven early-onset neonatal group B streptococcal infection . METHODS: Identification of presence of risk factors that could be used to select women for the offer of intrapartum antibiotic prophylaxis . MAIN OUTCOME MEASURES: Incidence and case-fatality rate of invasive early-onset group B infection . RESULTS: One hundred and forty cases were identified among a birth cohort of 198,388 live births, an incidence of 0.71 per 1000 live births . Twenty-two babies died, a case-fatality rate of 15.6% or 1.1 per 100,000 live births . Women of black ethnic origin, and those who had had a previously affected infant, multiple pregnancy, preterm delivery, prolonged rupture of membranes or intrapartum fever all had a significantly increased risk of delivering an infected infant . CONCLUSIONS: These data suggest that the incidence of early-onset group B streptococcal infection in these London centres is sufficiently high to warrant administration of intrapartum antibiotics to at-risk women.

J Am Chem Soc, 2004 Sep 1, 126(34), 10560 - 70
Relaxation-optimized NMR spectroscopy of methylene groups in proteins and nucleic acids; Miclet E et al.; A large fraction of hydrogens in proteins and nucleic acids is of the methylene type . Their detailed study, however, in terms of structure and dynamics by NMR spectroscopy is hampered by their fast relaxation properties, which give rise to low sensitivity and resolution . It is demonstrated that six different relaxation interference processes, involving 1H-13C and 1H-1H dipolar interactions and 1H and 13C chemical shift anisotropy, can be used simultaneously to mitigate these problems effectively . The approach is applicable to the majority of NMR experiments commonly used to study side chain and backbone conformation . For proteins, its efficiency is evaluated quantitatively for two samples: the third IgG-binding domain from Streptococcal Protein G and the protein calmodulin complexed with a 26-residue target peptide . Gains in both resolution and sensitivity by up to factors of 3.2 and 2.0, respectively, are observed for Gly residues at high magnetic field strengths, but even at much lower fields gains remain substantial . The resolution enhancement obtained for methylene groups makes possible a detailed analysis of spectral regions commonly considered inaccessible due to spectral crowding . For DNA, the high resolution now obtainable for C5' sites permits an H5'/H5''-based sequential NOE assignment procedure, complementary to the conventional base-H1'/H2'/H2'' pathway.

Int J Infect Dis, 2004 Sep, 8(5), 292 - 8
Detection of circulating superantigens in an intensive care unit population; Azuma K et al.; OBJECTIVE: Plasma concentrations of superantigens were measured in an intensive care unit (ICU) population and the relationship of superantigen positive rates with the presence of sepsis was investigated . METHODS: Plasma samples were collected at least twice a week from 78 patients whose primary diagnoses were abdominal disorders (n = 27), respiratory disorders (n = 11), trauma (n = 10), burns (n = 10), cardiovascular disorders (n = 4), neurological disorders (n = 2), and others (n = 14) . Five different species of superantigens, i.e., staphylococcal enterotoxins A, B, and C (SEA, SEB, and SEC), toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin A (SPEA), were measured using an enzyme-linked immunosorbent assay . RESULTS: Significant levels of plasma superantigens were detected in 16 patients . SEA was found in seven patients, SEB in four patients, SEC in two patients, TSST-1 in six patients, and SPEA in five patients . Superantigen detection rates were 6% (1/17) in patients without systemic inflammatory response syndrome (SIRS), 0% (0/21) in SIRS patients without infection, 31% (5/16) in septic patients without shock, and 42% (10/24) in septic shock patients . CONCLUSIONS: The presence of superantigens was confirmed in part of the ICU population . The role of superantigens in the pathogenesis of sepsis remains to be determined.

Eur J Pediatr . 2004 Aug 19; {Epub ahead of print}
Hypertension induced reversible posterior leukoencephalopathy syndrome: a report of two cases; Ozcakar ZB et al.; Reversible posterior leukoencephalopathy syndrome (RPLS) is a recently described disorder with typical radiological findings of bilateral grey and white matter abnormalities in the posterior regions of the cerebral hemispheres . The majority of patients with RPLS are adults and it is rare in children . In this report, two patients with RPLS are presented . In the first patient the primary diagnosis was acute post-streptococcal glomerulonephritis, a known cause of RPLS both in adults and in children . The second patient had Henoch Schonlein purpura . CONCLUSION:These patients are presented to highlight the importance of reversible posterior leukoencephalopathy syndrome . As the spectrum of associated diseases is diverse, paediatricians must be aware of this syndrome in order to initiate appropriate management.

Arch Neurol, 2004 Aug, 61(8), 1261 - 4
Recurrence of Sydenham chorea: implications for pathogenesis; Korn-Lubetzki I et al.; BACKGROUND: Sydenham chorea (SC), a major sign of rheumatic fever (RF), is related to systemic streptococcal infection and is treated with antibiotics . Recurrence usually occurs within a short interval following the initial event and is considered part of RF . OBJECTIVE: To evaluate the rate, nature, and course of recurrent SC during an extended follow-up period . DESIGN: Prospective assessment of a cohort of patients with SC who were admitted between 1985 and 2002 . SETTING: General community hospital . METHODS: Diagnosis of RF was based on the revised Jones criteria . Other causes of chorea were excluded . Recurrence was defined as the development of new signs, lasting more than 24 hours and separated by a minimum of 2 months from the previous episode . Patients were observed from 1 to 14 years following the initial SC episode and for at least 1 year after recurrence . At recurrence, patients were assessed for RF clinical and laboratory activity, including change in cardiac involvement . RESULTS: Twenty-four patients had SC . In 19 patients (79%), the chorea was associated with other RF signs, and 5 suffered from pure chorea . Ten patients (42%, 7 women) developed 11 recurrent episodes of chorea 3 months to 10 years after the initial episode . Association of recurrent chorea with RF could be suspected in only 6 episodes: cessation of prophylactic antibiotic treatment or poor compliance in 4 patients and rise in antistreptolysin O titers in 2 . In an 18-year-old woman, chorea recurred during her first pregnancy . At recurrence, chorea was the sole rheumatic sign in all 9 patients who had 1 recurrent episode . In the patient with 2 recurrent episodes, mitral regurgitation developed into mitral stenosis . No statistical differences in previous RF activity and rheumatic cardiac involvement between patients with recurrent SC and patients with a single episode could be found . CONCLUSIONS: In a significant subgroup of patients, SC recurrence might not be a true relapse of rheumatic fever . It might represent either a primary underlying abnormality that renders patients susceptible to developing such a movement disorder or the outcome of permanent subclinical damage to the basal ganglia following the initial SC episode.

Biochemistry, 2004 Aug 24, 43(33), 10678 - 91
Amplitudes of protein backbone dynamics and correlated motions in a small alpha/beta protein: correspondence of dipolar coupling and heteronuclear relaxation measurements; Clore GM et al.; Backbone residual dipolar coupling (N-H, Calpha-Halpha, N-C', and Calpha-C') data collected in five different media on the B3 IgG binding domain of streptococcal protein G (GB3) have been analyzed by simultaneous refinement of the coordinates and optimization of the magnitudes and orientations of the alignment tensors using single and multiple structure representations . We show, using appropriate error analysis, that agreement between observed and calculated dipolar couplings at the level of experimental uncertainty is obtained with a two-structure (N(e) = 2) ensemble representation which represents the simplest equilibrium description of anisotropic motions . The data permit one to determine the magnitude of the anisotropic motions along the four different backbone bond vectors in terms of <S(2)(jump)> order parameters . The order parameters, <S(2)NH(jump)>, for the N-H bond vectors are in qualitative agreement with the generalized order parameters, S(2)NH(relaxation), derived from (15)N relaxation measurements, with a correlation coefficient of 0.84 . S(2)NH(relaxation) can be regarded as the product of an anisotropic order parameter, corresponding to <S(2)NH(jump)> derived from the residual dipolar couplings, and an axially symmetric order parameter, S(2)NH(axial), corresponding to bond librations which are expected to be essentially uniform along the polypeptide chain . The current data indicate that the average value of S(2)NH(axial) is approximately 0.9 . The close correspondence of <S(2)NH(jump)> and S(2)NH(relaxation) indicates that any large-scale displacements from the mean coordinate positions on time scales longer than the rotational correlation time are rare and hence do not perturb the observed dipolar couplings . Analysis of a set of 100 N(e) = 2 ensembles reveals the presence of some long-range correlated motions of N-H and Calpha-Halpha vectors involving residues far apart in the sequence but close together in space . In addition, direct evidence is obtained for ubiquitous crankshaft motions along the entire length of the polypeptide backbone manifested by the anticorrelation of the backbone torsion angles phi(i) and psi(i-1).

Scand J Infect Dis, 2004, 36(6-7), 424 - 7
Erythema nodosum: an experience of 10 years; Mert A et al.; In this study, we investigated clinical features, aetiology, prospective follow-up results and also factors favouring secondary erythema nodosum (EN) in patients with EN . A total of 50 patients (mean age 38 y) with a diagnosis of EN between 1993 and 2002 in our clinic were included in the study prospectively . A biopsy was performed in 30 of the patients . Patients were considered to have secondary EN when an underlying condition was found, and to have primary (or idiopathic) EN when no such condition was found . For the diagnosis of the underlying diseases, diagnostic criteria and/or diagnostic methods were used . Categorical variables were compared by using chi2 test . The majority of the patients were female (6F/1M) and 54% of cases had a determined aetiology . The foremost aetiology was primary tuberculosis (18%) followed in decreasing order by a poststreptococcal (16%), sarcoidosis (12%), inflammatory bowel diseases (IBD) (4%), Behcet's disease (2%), and pregnancy (2%) . All the patients were followed for a mean duration of 7 y . The nodosities relapsed every y in 74% of idiopathic EN patients but in only 1 (Behcet's disease) of the secondary ones . Factors favouring secondary EN were as follows: prolonged fever, cough, sore throat, not relapsing EN, abnormal chest X-ray, leukocytosis, an erythrocyte sedimentation rate of higher than 50 mm/h and a CRP value of higher than 6 times the upper limit of normal . All the patients had bed rest and the majority was given naproxen . The outcomes were usually favourable within 7 d . The patients with an underlying disease were given specific treatment . EN has been associated with numerous diseases . In order to reduce cost and duration of diagnosis, every centre should determine its own most frequent aetiological factors . Factors favouring secondary EN should also be determined . Our study revealed primary tuberculosis, streptococcal pharyngitis, sarcoidosis, IBD, and Behcet's syndrome as the main aetiologies of EN.

Clin Infect Dis, 2004 Aug 1, 39(3), 325 - 32 Epub 2004 Jul 15.
Group A streptococcal pharyngitis serotype surveillance in North America, 2000-2002; Shulman ST et al.; Geographic and interseasonal heterogeneity of pharyngeal group A streptococcal (GAS) genotypes (emm types) is poorly characterized . We evaluated emm type and subtype distribution among pediatric pharyngitis isolates obtained from 9 sites in the United States during 2000-2001 (year 1) and from 10 sites in the United States and 1 site in Canada during 2001-2002 (year 2) . The 7 predominant types were the same in both years, although their order changed . emm 12, 1, and 28 accounted for 49.2% of year 1 isolates, and emm 1, 12, and 4 accounted for 47.1% of year 2 isolates; 6 types accounted for 72.1% in year 1 and 69.4% in year 2 . From year 1 to year 2, the proportions of emm 12 and 28 decreased and emm 1 and 6 increased . Striking intersite and interseasonal variations in the distribution of predominant emm types were observed . We conclude that the most-predominant GAS genotypes were similar for each year despite fluctuations, that intersite and intrasite variations in the distribution of emm types were apparent, and that emm type surveillance is needed as M protein vaccine development proceeds.

Pediatr Neurol, 2004 Aug, 31(2), 119 - 21
Restless legs syndrome: association with streptococcal or mycoplasma infection; Matsuo M et al.; Group A beta-hemolytic streptococcal infections have been reported to cause neuropsychiatric symptoms, such as chorea, tics, and obsessive-compulsive disorder, presumably through autoimmune damage to basal ganglia . Mycoplasma pneumoniae infections have also been reported to cause damage to the basal ganglia . Restless legs syndrome is a movement disorder with focal restlessness, an irresistible desire to move, and exacerbation by long periods of sitting or lying . We present three children with transient restless legs syndrome-like symptoms possibly associated with group A beta-hemolytic streptococcal infection or Mycoplasma pneumoniae infection . One of three patients had persistently elevated enzyme-linked immunosorbent optical density values against human caudate and putamen.

Optom Vis Sci, 2004 Aug, 81(8), 578 - 85
Choroiditis, pigment epithelial detachment, and cystoid macular edema as complications of poststreptococcal syndrome; Besada E et al.; PURPOSE: Two cases of poststreptococcal uveitis are presented . One patient developed nongranulomatous anterior uveitis (case 1) . A second patient developed nongranulomatous anterior uveitis followed by granulomatous uveitis with concurrent choroiditis, retinal pigment epithelial detachment, and cystoid macular edema (case 2) . Current concepts regarding the pathogenesis of poststreptococcal syndrome and its ocular sequelae are also discussed . CASE REPORTS: Case 1: A 31-year-old female patient presented with bilateral nongranulomatous uveitis after a recent onset of sore throat . A past diagnosis of rheumatic fever was revealed during acquisition of the patient's history . Blood chemistry analysis indicated elevated anti-streptolysin O antibody titers as the only significant elevated result . Case 2: A 33-year-old female presented initially with bilateral nongranulomatous uveitis . A history of recurrent sore throat was reported . Blood chemistry analysis revealed elevated anti-streptolysin O antibody titers only . "Mutton fat" keratic precipitates eventually developed; however, the bilateral uveitis resolved after topical cycloplegic and corticosteroid treatment . An anterior granulomatous uveitis with concurrent choroiditis, retinal pigment epithelial detachment, and cystoid macular edema ensued during a recurrent episode . Blood chemistry analysis was unremarkable at that time . CONCLUSIONS.: Anterior nongranulomatous/granulomatous and posterior uveitis should be considered clinical manifestations of poststreptococcal syndrome in patients with a clinical history and/or serological evidence indicating possible past streptococcal infection . A variation of host-genetic-predisposed immune response, the patient's human leukocyte antigen haplotype, pathogen virulence, and/or deposition location of immune circulating complexes may give rise to the diverse spectrum of clinical ocular sequelae in poststreptococcal syndrome . Poststreptococcal uveitis may comprise a similar immunologic pathogenesis to that of acute rheumatic fever, acute glomerulonephritis, and other autoimmune diseases.

Protein Sci, 2004 Sep, 13(9), 2285 - 90 Epub 2004 Aug 04.
Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1); Baker MD et al.; Streptococcal pyrogenic exotoxin A (SpeA1) is a bacterial superantigen associated with scarlet fever and streptococcal toxic shock syndrome (STSS) . SpeA1 is found in both monomeric and dimeric forms, and previous work suggested that the dimer results from an intermolecular disulfide bond between the cysteines at positions 90 of each monomer . Here, we present the crystal structure of the dimeric form of SpeA1 . The toxin crystallizes in the orthorhombic space group P212121, with two dimers in the crystallographic asymmetric unit . The final structure has a crystallographic R-factor of 21.52% for 7248 protein atoms, 136 water molecules, and 4 zinc atoms (one zinc atom per molecule) . The implications of SpeA1 dimer on MHC class II and T-cell receptor recognition are discussed.

J Biol Chem, 2004 Oct 1, 279(40), 41706 - 14 Epub 2004 Jul 29.
BBK32, a fibronectin binding MSCRAMM from Borrelia burgdorferi, contains a disordered region that undergoes a conformational change on ligand binding; Kim JH et al.; BBK32 is a fibronectin-binding lipoprotein on Borrelia burgdorferi, the causative agent of Lyme disease . Analysis using secondary structure prediction programs suggested that BBK32 is composed of two domains, an N-terminal segment lacking well defined secondary structure and a C-terminal segment composed largely of alpha-helices . Analysis of purified recombinant forms of the two domains by circular dichroism spectroscopy, gel permeation chromatography, and intrinsic viscosity determination were consistent with an N-terminal-extended, unstructured segment and a C-terminal globular domain in BBK32 . Solid phase binding experiments suggest that the unstructured N-terminal domain binds fibronectin . Analysis of changes in circular dichroism spectra of the N-terminal segment of BBK32 upon binding of the N-terminal domain of fibronectin revealed an increase in beta-sheet content in the complex . Hence, BBK32, which belongs to a different family of proteins and shows no overall sequence similarity with the fibronectin binding MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) of Gram-positive bacteria, binds fibronectin by a mechanism that is reminiscent of the "tandem beta-zipper" previously demonstrated for the fibronectin binding of streptococcal adhesins.

J Comput Biol, 2004, 11(2-3), 277 - 98
A polynomial-time nuclear vector replacement algorithm for automated NMR resonance assignments; Langmead CJ et al.; High-throughput NMR structural biology can play an important role in structural genomics . We report an automated procedure for high-throughput NMR resonance assignment for a protein of known structure, or of a homologous structure . These assignments are a prerequisite for probing protein-protein interactions, protein-ligand binding, and dynamics by NMR . Assignments are also the starting point for structure determination and refinement . A new algorithm, called Nuclear Vector Replacement (NVR) is introduced to compute assignments that optimally correlate experimentally measured NH residual dipolar couplings (RDCs) to a given a priori whole-protein 3D structural model . The algorithm requires only uniform( 15)N-labeling of the protein and processes unassigned H(N)-(15)N HSQC spectra, H(N)-(15)N RDCs, and sparse H(N)-H(N) NOE's (d(NN)s), all of which can be acquired in a fraction of the time needed to record the traditional suite of experiments used to perform resonance assignments . NVR runs in minutes and efficiently assigns the (H(N),(15)N) backbone resonances as well as the d(NN)s of the 3D (15)N-NOESY spectrum, in O(n(3)) time . The algorithm is demonstrated on NMR data from a 76-residue protein, human ubiquitin, matched to four structures, including one mutant (homolog), determined either by x-ray crystallography or by different NMR experiments (without RDCs) . NVR achieves an assignment accuracy of 92-100% . We further demonstrate the feasibility of our algorithm for different and larger proteins, using NMR data for hen lysozyme (129 residues, 97-100% accuracy) and streptococcal protein G (56 residues, 100% accuracy), matched to a variety of 3D structural models . Finally, we extend NVR to a second application, 3D structural homology detection, and demonstrate that NVR is able to identify structural homologies between proteins with remote amino acid sequences using a database of structural models.

Indian J Pediatr, 2004 Jul, 71(7), 601 - 5
Pediatric tonsillopharyngitis--an evaluation of cefprozil in Indian patients; Gupta N et al.; OBJECTIVE: The emergence of penicillin resistant strains and the presence of co-pathogens have made the treatment of bacterial infections in children a challenge . Streptococcal tonsillopharyngitis, which is a common infection has been well treated with cefprozil, a novel third generation cephalosporin . The aim of the present study was to evaluate cefprozil in pediatric tonsillopharyngitis . An assessment of the clinical cure and bacteriological eradication rates and an overall tolerability was made . METHODS: It was a prospective, open, non-comparative multicentric study . 316 children (mean age 6.61 years) with tonsillopharyngitis were included . Patients were given cefprozil susp 15 mg/kg/day in two divided doses a day for 10 days . RESULTS: A clinical cure of 96.6% and bacteriological eradication of 94.29% was achieved with cefprozil . Overall tolerability of cefprozil was assessed by physicians and 46% rated tolerability of cefprozil as excellent, 38% as very good, 10% as good, 6% as fair and none as poor . CONCLUSION: Cefprozil has been found to be an excellent drug of superior microbiological and clinical activity in the treatment of pediatric patients with tonsillopharyngitis . The drug also has an expanded spectrum.

Am J Med Genet, 2004 Aug 15, 129B(1), 64 - 8
Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive-compulsive disorder; Zai G et al.; Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes . Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections . Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system . Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband . We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT) . A biased transmission of the 459-bp allele (allele 2: chi2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles . The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (chi2 = 6.426, P = 0.011) was also significant . Quantitative analysis using the family-based association test (FBAT) was significant for MOG4 in total Yale-Brown Obsessive-Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020) . Further investigations combining genetic, pathological, and pharmacological strategies, are warranted .

J Med Chem, 2004 Jul 29, 47(16), 4100 - 4
Toward the development of a synthetic group a streptococcal vaccine of high purity and broad protective coverage; Horvath A et al.; Using native chemical ligation, we synthesized a group A streptococcal (GAS) vaccine that contained three different GAS M protein peptide epitopes in a chemically well-characterized construct in high purity . Two of the peptide epitopes represented variable amino terminal serotype determinants, and the third represented a carboxyl terminal conserved region determinant of the GAS M protein . We also synthesized a lipid core peptide (LCP) construct containing the same three peptides . Upon immunization of mice, the non-LCP construct only elicited antibody responses to all three epitopes with the use of adjuvant . The LCP construct, however, elicited excellent antibody responses to all three epitopes without the need for any additional adjuvant or carrier . We have synthesized the LCP synthetic vaccine system with good reproducibility.

Cochrane Database Syst Rev . 2004;(3):CD003667.
Intramuscular penicillin for the prevention of early onset group B streptococcal infection in newborn infants; Woodgate P et al.; BACKGROUND: Early-onset group B streptococcal disease (EOGBSD) is the most frequent cause of serious infection in the newborn period . Current strategies used to prevent EOGBSD are focused upon maternal antibiotic prophylaxis to reduce transmission of GBS to the infant . Observational studies have suggested that the administration of intramuscular penicillin to the newborn immediately following delivery may be an effective strategy to reduce the incidence of EOGBSD . OBJECTIVES: To determine if the administration of intramuscular penicillin to newborns at birth is a safe and effective method to prevent morbidity and mortality from EOGBSD . SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group was used . This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 1, 2004), and MEDLINE (1966 - Dec 2003); and previous reviews including cross references, expert informants and journal hand searching in the English language as well as conference and symposia proceedings published in Pediatric Research . SELECTION CRITERIA: Randomised trials in which intramuscular penicillin was administered as prophylaxis for EOGBSD within four hours of birth.Outcomes considered were EOGBSD, neonatal mortality, late-onset GBSD, neonatal sepsis, and other secondary outcomes such as neurodevelopmental status and length of hospital stay . DATA COLLECTION AND ANALYSIS: The search for and assessment of trials for inclusion, quality assessment and data extraction were undertaken independently by the reviewers . Meta-analysis was not undertaken as data from only one trial is included in this review . Data were analysed using relative risk (RR) with 95% confidence intervals (CI) . MAIN RESULTS: One randomised controlled trial was included in this review . In this trial of 1187 infants of birthweight 501 to 2000 grams, there were no significant differences found for the outcomes of EOGBSD (RR 0.73; 95%CI 0.32, 1.62), or neonatal mortality (RR 0.78; 95% CI 0.55, 1.11) . No other outcomes were able to be assessed . REVIEWERS' CONCLUSIONS: This review does not support the routine use of intramuscular penicillin to prevent EOGBSD in newborn infants . There is a discrepancy between this finding and the results of a number of larger non-randomised trials . Explanations for this are proposed . There is a need for this intervention to be tested as a component of the existing prevention strategies in widespread use.

Eur J Paediatr Neurol, 2004, 8(4), 211 - 6
Distinguishing PANDAS from Sydenham's chorea: case report and review of the literature; van Toorn R et al.; Children with Sydenham's chorea and PANDAS (Pediatric autoimmune neuropsychiatric disorders associated with streptococcal throat infections) share an array of neuropsychiatric symptoms and distinguishing one from the other, especially at onset can prove challenging . It is, however, important to distinguish between these two post-streptococcal disorders since their response to therapy differs . Children with Sydenham's chorea require long-term benzathine penicillin prophylaxis to reduce the risk of rheumatic heart disease . In contrast, the efficacy of penicillin prophylaxis in preventing tic or obsessive-compulsive symptom exacerbations in children with PANDAS remains doubtful . Immunomodulatory therapies such as plasma exchange and intravenous immunoglobulin have shown to reduce neuropsychiatric symptom severity in children with PANDAS . Tonsillectomy may also represent an effective treatment option in children severely affected by PANDAS . We present this case to demonstrate the pitfalls in differentiating between these two closely associated conditions in a developing country where the prevalence of rheumatic fever is high.

Commun Dis Public Health, 2004 Jun, 7(2), 123 - 7
Group A streptococcal bacteraemia in Yorkshire and the Humber: evidence of another problematic infection among injecting drug users; Engler KH et al.; It has been estimated that in England and Wales, in 2002, 15% of all invasive group A streptococcal (GAS) cases were amongst injecting drug users (IDUs) . This study sought to clarify the extent of this problem in the Yorkshire and Humber region by asking laboratories for further information on reported cases . In our region we found that there was a near doubling of cases, from 64 reports of GAS bacteraemia in the first six months of 2001, to 121 reports in the same period of 2003 . We estimated that 34% of all GAS cases, more than twice the previous national estimate, occurred in IDUs and that the proportion of cases occurring in IDUs nearly doubled from 2001 to 2002 . Our findings should be viewed within the context of the increasing reports of several other problematic infections in IDUs.

Clin Microbiol Rev, 2004 Jul, 17(3), 638 - 80, table of contents
Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants; Kaufman D et al.; Twenty percent of very-low-birth-weight (<1500 g) preterm infants experience a serious systemic infection, and despite advances in neonatal intensive care and antimicrobials, mortality is as much as threefold higher for these infants who develop sepsis than their counterparts without sepsis during their hospitalization . Outcomes may be improved by preventative strategies, earlier and accurate diagnosis, and adjunct therapies to combat infection and protect the vulnerable preterm infant during an infection . Earlier diagnosis on the basis of factors such as abnormal heart rate characteristics may offer the ability to initiate treatment prior to the onset of clinical symptoms . Molecular and adjunctive diagnostics may also aid in diagnosing invasive infection when clinical symptoms indicate infection but no organisms are isolated in culture . Due to the high morbidity and mortality, preventative and adjunctive therapies are needed . Prophylaxis has been effective in preventing early-onset group B streptococcal sepsis and late-onset Candida sepsis . Future research in prophylaxis using active and passive immunization strategies offers prevention without the risk of resistance to antimicrobials . Identification of the differences in neonatal intensive care units with low and high infection rates and implementation of infection control measures remain paramount in each neonatal intensive care unit caring for preterm infants.

Pediatr Infect Dis J, 2004 Jul, 23(7), 677 - 9
Characterization of a community cluster of group a streptococcal invasive disease in Maui, Hawaii; Erdem G et al.; A community cluster of severe group A streptococcal skin infections occurred in Maui, Hawaii with 3 fatal cases of necrotizing fasciitis in 2002 . emm types 1, 12, 58, 74, 85 and 109 were identified from 8 patients . emm types 74 and 109 have not been previously described in the United States according to the Centers for Disease Control and Prevention database . The identification of uncommon emm types suggested that group A streptococcal sero-types in Hawaii are different from those in the continental United States and can result in serious disease.

Pediatr Infect Dis J, 2004 Jul, 23(7), 630 - 4
Ten-year study on the effect of intrapartum antibiotic prophylaxis on early onset group B streptococcal and Escherichia coli neonatal sepsis in Australasia; Daley AJ et al.; BACKGROUND: Intrapartum antibiotics have reduced the incidence of neonatal early onset (EO) group B streptococcal (GBS) disease . Some surveillance data suggest that this success may be at the cost of increasing rates of non-GBS infection, especially in premature neonates . OBJECTIVE: To examine rates of EOGBS infection and EO Escherichia coli neonatal sepsis in Australasia . METHODOLOGY: Analysis of trends in EO (<48 h age) GBS and E . coli sepsis from longitudinal prospective surveillance data collected from representative tertiary obstetric hospitals in each state of Australia and selected centers in New Zealand during a 10-year period from 1992 through 2001 . Statistical analysis used Poisson regression . RESULTS: 206 GBS and 96 E . coli cases occurred in 298,319 live births during the study period . The EOGBS sepsis rate fell from a peak of 1.43/1000 live births in 1993 to 0.25/1000 in 2001 (P < 0.001) . The overall EO E . coli sepsis rate was 0.32/1000 . In babies with birth weight <1500 g, it was 6.20/1000 . There was an overall trend to decreasing EO E . coli sepsis (P = 0.07), and there was no significant change in E . coli sepsis in babies <1500 g (P = 0.60) . Sixty-nine percent of E . coli cases occurred in the <1500 g cohort; the case fatality rate in this group was 50% . The overall case fatality rate from E . coli sepsis was 36%, and this rate remained stable during the study period (P = 0.47) . CONCLUSIONS: The increasing use of intrapartum antibiotics produced a steady decline in EOGBS disease in Australasia . There was also a trend to decreasing EO E . coli sepsis in all babies, and the rate in very low birth weight infants remained stable.

Curr Opin Neurol, 2004 Aug, 17(4), 425 - 32
Antibasal ganglia antibodies and their relevance to movement disorders; Martino D et al.; PURPOSE OF REVIEW: Recently, autoaggressive immunological responses were included among the causative agents of basal ganglia dysfunction . Autoaggressive immune-mediated illnesses secondary to group A beta-haemolytic streptococcal infections present with motor and psychiatric symptoms, due to basal ganglia involvement . These disorders have been associated with serum antineuronal antibodies, relatively specific to human basal ganglia tissue . This review summarizes the most recent studies concerning antibasal ganglia antibodies, focusing on the associated phenotypes and the hypotheses concerning their pathogenicity . RECENT FINDINGS: The spectrum of post-streptococcal neuropsychiatric disorders associated with antibasal ganglia antibodies seems broader than previously recognized . Other than chorea, tics and obsessive-compulsive disorder, which constituted the bulk of previously described disorders associated with antibasal ganglia antibodies, post-streptococcal neuropsychiatric disturbances include a wider range of motor and behavioural abnormalities, in keeping with the multifunctional role of the basal ganglia . An encephalitis lethargica-like illness following streptococcal infection was reported, and unusual adult-onset movement disorders associated with antibasal ganglia antibodies were documented . Moreover, investigators provided preliminary evidence for a pathogenic role of autoantibodies in Sydenham's chorea, the prototypic post-streptococcal neuropsychiatric disorder . SUMMARY: Antibasal ganglia antibodies are relatively specific in identifying post-streptococcal neuropsychiatric disorders, which constitute a wider spectrum of movement disorders than previously recognized . Although their sensitivity in diagnosing Sydenham's chorea seems excellent, it is not yet possible to extrapolate this sensitivity to all the recently identified post-streptococcal neuropsychiatric disorders . The antigens targeted by these autoantibodies and their pathogenic importance are currently under investigation . Preliminary evidence suggests that antibasal ganglia antibodies may be pathogenic.

Vaccine, 2004 Jul 29, 22(21-22), 2737 - 42
Development of antibodies against pneumococcal proteins alpha-enolase, immunoglobulin A1 protease, streptococcal lipoprotein rotamase A, and putative proteinase maturation protein A in relation to pneumococcal carriage and Otitis Media; Adrian PV et al.; Surface associated pneumococcal proteins alpha-enolase (Eno), immunoglobulin A1 protease (Iga), streptococcal lipoprotein rotamase A (SlrA), and putative proteinase maturation protein A (PpmA) have potential as candidates for future protein-based anti-pneumococcal vaccines . The immunogenicity of these proteins were studied in a cohort of 329 children during their first two years of life . During the first recorded episode of otitis media, acute and convalescent phase sera were available from 151 children . Concentrations of antibodies against Eno, Iga, SlrA and PpmA were measured by EIA and detected in 99% (300/302), 95% (288/302), 95% (288/302), and 83% (251/302) of the sera, respectively . There were no statistically significant differences between the groups of children with and without a history of pneumococcal contact or with respect to the type of pneumococcal contact . Despite a mean overall decrease in the antibody titers in the convalescent sera following AOM, several children were able to respond with a more than twofold increase in antibody titer in response to AOM . The majority of the children with increased antibody concentrations appeared in the groups, which were colonized with pneumococci at the time of serum collection, but were recorded as having no prior contact with pneumococci . In conclusion, SlrA, PpmA, Eno and Iga are immunogenic proteins that elicit antibody responses early in life . No significant correlation between antibody titers to these proteins and pneumococcal carriage or infection was found . Presumably, this results from the presence of cross-reactive epitopes on commensal bacteria.

J Infect Dis, 2004 Aug 1, 190(3), 558 - 64 Epub 2004 Jun 30.
Use of type V group B streptococcal conjugate vaccine in adults 65-85 years old; Palazzi DL et al.; One-third of the cases of invasive group B streptococcal (GBS) disease now occur in adults >or=65 years old . Serotype V is most frequent among these invasive isolates . The safety and immunogenicity of type V GBS capsular polysaccharide (CPS)-tetanus toxoid (V-TT) conjugate vaccine (CV) were assessed in 32 healthy adults 65-85 years old who were randomized to receive a single intramuscular dose of V-TT CV (n=22) or licensed tetanus-diphtheria toxoid vaccine (Td) (n=10; double-masked design) . V-TT CV elicited significant increases in type V CPS-specific immunoglobulin (Ig) G, IgM, and IgA serum concentrations 4, 8, 26, and 52 weeks after immunization . V-TT-induced type V CPS-specific antibodies promoted the opsonophagocytic killing of type V GBS in vitro . Both vaccines elicited similar concentrations of TT-specific IgG in 4-week postimmunization serum samples . These results suggest the potential for prevention of invasive type V GBS infections in healthy elderly adults through immunization.

J Biomol NMR, 2004 Aug, 29(4), 505 - 16
NMR spectroscopic filtration of polypeptides and proteins in complex mixtures; Rajagopalan S et al.; Due to the inherent complexity of the natural biological environment, most studies on polypeptides, proteins and nucleic acids have so far been performed in vitro, away from physiologically relevant conditions . Nuclear magnetic resonance is an ideal technique to extend the in vitro analysis of simple model systems to the more complex biological context . This work shows how diffusion-based spectroscopic selection can be combined with isotopic labeling to tackle and optimize the NMR analysis of specific macromolecules in multicomponent mixtures . Typical media include cell-free systems containing overexpressed proteins, lysates and proteolytic mixtures . We present a few variants of diffusion-edited HSQC pulse sequences for the selective spectroscopic detection of protein and polypeptide resonances within complex mixtures containing undesired species of smaller molecular weight . Due to diffusion-based filtering, peak intensities of fast diffusing small molecules are attenuated more than peaks due to large molecules . The basic sequence, denoted as PFGSTE-HSQC, combines translational diffusion-ordering with two dimensional heteronuclear single quantum correlation spectroscopy . The GCSTE-HSQC and BPPSTE-HSQC sequences include bipolar gradients and are therefore suitable for both diffusion-based filtering and determination of diffusion coefficients of individual mixture components . Practical applications range from protein stability/folding investigations in physiologically relevant contexts to prescreening of tertiary fold and resonance assignments in structural genomics studies . A few applications of diffusion-edited HSQC to an E . coli cell lysate containing the (15)N-labeled B domain of streptococcal protein G (GB1), and to a (15)N-labeled N-acetylglycine/apomyoglobin mixture are presented . In addition, we provide specific guidelines for experimental setup and parameter optimization.

Arch Phys Med Rehabil, 2004 Jul, 85(7), 1205 - 9
Streptococcal infection and necrotizing fasciitis--implications for rehabilitation: a report of 5 cases and review of the literature; Balbierz JM et al.; Five cases are presented of patients who were diagnosed with necrotizing fasciitis secondary to (1) hip disarticulation (in a paraplegic patient); (2) tooth abscess with extensive neck dissection, complicated by sepsis and hypotension with resultant dysphagia and ischemic encephalopathy; (3) below-knee amputation, anoxia, and severe debility; (4) emergent above-knee amputation; and (5) percutaneous endoscopic gastrostomy placement . The latter patient developed abdominal and chest wall necrotizing fasciitis that required skin grafting . Four patients were treated in an acute rehabilitation setting and returned home, and the fifth was rehabilitated in a subacute facility . This report emphasizes the importance of carefully monitoring rehabilitation patients, especially those with impaired sensation.

Mol Psychiatry, 2004 Oct, 9(10), 900 - 7
PANDAS: current status and directions for research; Snider LA et al.; The recognition of the five criteria for PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) by Swedo et al established a homogenous subgroup of children with childhood onset obsessive-compulsive disorder (OCD) and/or tic disorders . The five clinical characteristics that define the PANDAS subgroup are the presence of OCD and/or tic disorder, prepubertal age of onset, abrupt onset and relapsing-remitting symptom course, association with neurological abnormalities during exacerbations (adventitious movements or motoric hyperactivity), and a temporal association between symptom exacerbations and a Group-A beta-hemolytic streptococcal (GAS) infection . These five criteria have been used for the purpose of systematic research on the phenomenology and unique therapies for the PANDAS subgroup as well as studies of the pathophysiology of post-streptococcal OCD and tic disorders . The etiology of OCD and tics in the PANDAS subgroup is unknown, but is theorized to occur as a result of post-streptococcal autoimmunity in a manner similar to that of Sydenham's chorea . The working hypothesis for the pathophysiology begins with a GAS infection in a susceptible host that incites the production of antibodies to GAS that crossreact with the cellular components of the basal ganglia, particularly in the caudate nucleus and putamen . The obsessions, compulsions, tics, and other neuropsychiatric symptoms seen in these children are postulated to arise from an interaction of these antibodies with neurons of the basal ganglia.

J Crit Care, 2004 Jun, 19(2), 75 - 81
Intravenous immunoglobulin for severe infections: a survey of Canadian specialists; Laupland KB et al.; PURPOSE: To survey the opinions of Canadian critical care medicine and infectious disease specialists about the use of intravenous immunoglobulin (IVIG) for the treatment of severe infections . MATERIALS AND METHODS: A scenario-based, cross-sectional survey of Canadian critical care medicine and infectious disease specialists was conducted from March to June 2003 . RESULTS: The response rate was 291/487 (60%) . Respondents were primarily medically trained and most (241/291; 83%) were practicing in large academic referral centers . Physicians reported that they would use IVIG in patients with streptococcal toxic shock syndrome (STSS; 218/288; 76%), streptococcal necrotizing fasciitis without STSS (143/286; 50%), staphylococcal toxic shock syndrome (75/288; 26%), streptococcal soft tissue infection without NF or STSS (31/286; 11%), and septic shock due to intra-abdominal focus (9/283; 3%) . The majority (> or =67%) of respondents believed that it would be ethical to randomize patients to IVIG or placebo in a clinical trial in each of the five scenarios . One third (192/286) reported that it would not be ethical to randomize patients with STSS . Canadian specialists commonly report favoring the use of IVIG to treat STSS and necrotizing fasciitis but less commonly endorse this treatment for other infections . CONCLUSION: Specialist's beliefs surrounding the efficacy of IVIG would challenge but not preclude the conduct of future placebo controlled trials of severe streptococcal infections in Canada.

Indian J Med Res, 2004 May, 119 Suppl, 228 - 32
Construction of recombinant polypeptides based on beta antigen C (Bac) protein & their usage for protection against group B streptococcal infection; Suvorov A et al.; BACKGROUND & OBJECTIVES: immunocompromized adults . Approximately 50 per cent of the GBS strains carry and express the gene of BAC antigen which is capable to bind IgA . Gene encoding for the BAC antigen has been cloned and sequenced but actual IgA binding region on the protein has not been detected . The aim of the present work was to localize the region of IgA binding on Bac protein, to evaluate the role of one of the Bac protein regions MLKKIE in IgA binding, and to investigate the ability of Bac based recombinant proteins to generate protective antibodies against GBS infection . METHODS: Recombinant proteins based on beta antigen C were generated after PCR amplification of the fractions of bac gene with the following cloning of the PCR products into expression plasmids . Recombinant peptides were tested for IgA binding by immunoprecipitation and Western blot . One of the recombinant proteins expressing IgA binding was used as an antigen for immunization of mice and for GBS protection studies . RESULTS: Several bac gene constructs were generated . Their ability to bind IgA varied dramatically depending on the size of the construct and location of the fragment on the bac gene map . The smallest peptide expressing IgA binding was 14 kD in size . Amino acid substitutions in MLKKIE region facilitated IgA binding ability . Immunization of mice with recombinant Bac based peptide induced the appearance of anti-GBS antibody with high affinity level providing protection against GBS infection . INTERPRETATION & CONCLUSION: Size dependence of Bac based recombinant peptides proved that the effective IgA binding required specific folding of the protein binding IgA . Region MLKKIE could not be considered as region, responsible for IgA binding . Generation of antibodies against Bac based recombinant peptides with high titre and affinity makes these proteins a potent candidates for generating a vaccine against GBS infection.

Indian J Med Res, 2004 May, 119 Suppl, 191 - 6
Diversity of surface protein expression in group B streptococcal colonizing & invasive isolates; Ferrieri P et al.; BACKGROUND & OBJECTIVES: The classification of group B streptococcal (GBS) isolates is based on the capsular polysaccharides (Ia-VIII), and antigenic characterization of clinical isolates is augmented by the detection of various surface-localized protein antigens . In our laboratory, all GBS isolates are routinely analysed for the alpha trypsin-resistant and the beta trypsin-sensitive c protein antigens, as well as other trypsin-resistant proteins R1, R3, and R4, as well as BPS . The purpose of this work was to study diversity of protein expression in colonizing isolates (vaginal and rectal sites) from nonpregnant women and from invasive isolates (blood or CSF) from mothers and their less than seven day old newborn infants . METHODS: A total of 289 invasive isolates and 2660 colonizing isolates were collected between 1993-2002 . All isolates were tested for polysaccharide serotype and cell surface-expressed protein profile by double immunoprecipation in agarose using monospecific antisera . RESULTS: Among the 289 invasive isolates, 89.6 per cent expressed one or more trypsin-resistant proteins; 93 per cent of the colonizing isolates expressed one or more of these proteins . Overall, the most common surface protein expression profile by GBS serotype was: alpha in type Ia; alpha plus beta in type Ib; alpha and R4 in type II; R4 in type III; and co-expression of R1 plus R4 in isolates of type V . BPS was found in five (1.7%) invasive isolates, alone in two isolates and with other proteins in three isolates . Among 2660 colonizing isolates, BPS was found alone in 15 (0.6%) and in 57 additional isolates with other proteins . Among the total isolates, BPS was found predominantly in serotype Ia isolates, also expressing R1 . Uncommon protein profiles of known serotypes included 11 type III isolates expressing alpha plus beta . Among 72 nontypable colonizing isolates, expression of R1 plus R4 was the commonest (33.3%) profile . INTERPRETATION & CONCLUSION: The GBS surface proteins and the common serotypes were distributed comparably in colonizing and invasive isolates . Trypsin-resistant, alpha and alpha-like proteins, R1 and R4 were the most prevalent . The phenotypic diversity of the surface-localized protein antigens of GBS is intriguing, and genotypic analysis will permit consensus in nomenclature from laboratory to laboratory.

Indian J Med Res, 2004 May, 119 Suppl, 186 - 90
Colour Doppler echocardiography in children with group A streptococcal infection related tic disorders; Cardona F et al.; BACKGROUND & OBJECTIVES: A possible relationship has been suggested between tic disorders and streptococcal infections . To understand the complex relationship between streptococcal infections and neuropsychiatric disorders in children the present study was done on colour Doppler echocardiography of patients with possible post-streptococcal tic disorders . METHODS: The patients were 23 children (22 males, 1 female) affected by tic disorders, who at the time of the observation presented (or had presented in the past) signs of streptococcal infections temporally related to the onset or recrudescence of tic disorders . Echocardiographic examination and laboratory tests were performed on these children . RESULTS: In 4 cases a mild mitral insufficiency and in 8 cases a minimal mitral insufficiency was seen, all haemodynamically not significant . Follow up studies (up to 1 yr) showed the consistency and persistence of these findings . Of the 12 patients with echocardiographic abnormalities, 10 displayed very high anti streptolysin O (ASO) titres, 5 showed positive cultures for GAS and 9 had abnormal ESR, even if no significant differences were found in respect to patients with tics and normal echocardiography . INTERPRETATION & CONCLUSION: With the caution due to the design of study and to low number of patients, our data seem to indicate that the pathophysiology of GAS-infection related tic disorders is similar to that SC, at least in some cases.

Indian J Med Res, 2004 May, 119 Suppl, 174 - 8
Characterisation of group A streptococcal (GAS) isolates from children with tic disorders; Creti R et al.; BACKGROUND & OBJECTIVES: An association between the onset or recrudescence of some neuropsychiatric disorders in children such as tic disorders and group A streptococcal (GAS) infections has been suggested . No information is available on the characterization of GAS strains associated with such disorders . The present study was undertaken to characterize the GAS strains isolated from children with tic disorders and to determine and correlate the antistreptolysin O (ASO) titre with the presence of GAS . METHODS: During 1996-2001, 368 children with tic disorders were investigated for possible exposition to streptococcal antigens . All children, at the time of the first visit and during the follow up visits were apparently healthy and showed no clinical evidence of streptococcal infections or post streptococcal sequelae . Blood and throat swab samples were collected and serological and bacteriological tests done . The isolates obtained were investigated for T pattern, M protein and emm type, as well as for the production of protease . RESULTS: Of the 800 throat swabs studied 100, corresponding to 67 patients, were positive for GAS; 49 children were found positive for GAS only once during the study, 18 had more than one sample positive for different serotypes, 8 were positive twice or more for the same type . ASO titres of these children were, in general, elevated . Five types, namely type M12, 3, 13, 11, 1, accounted for 39 per cent of the isolates, M12 being the most common, but a large number of different types were also found . A large number of isolates (62%) showed an elevated prodution of protease in the casein plate assay . INTERPRETATION & CONCLUSION: Despite the high level of ASO titres found, the results were not in favour of a particular virulence or invasivity of the isolates . Only a few colonies per sample were found indicating that factors different from the microbial virulence play a role in this type of disease.

Indian J Med Res, 2004 May, 119 Suppl, 144 - 7
The burden of group A streptococcal pharyngitis in Melbourne families; Danchin MH et al.; BACKGROUND & OBJECTIVES: There are no recent data from industrialised countries documenting the incidence and costs of group A streptococcal (GAS) pharyngitis . Such data are important in developing policy regarding management (e.g., whether or not to use antibiotics to treat sore throat) and in planning preventive strategies, including preparing for the arrival of GAS vaccines . The present study was undertaken to estimate the incidence and costs of GAS pharyngitis in school aged children in Melbourne, Australia . We report here the results after initial 11 months of surveillance . METHODS: A total of 202 families (852 individuals) with at least one child aged 3 to 12 yr were enrolled across Melbourne in a family-based cohort study, and are being followed prospectively for 24 months . Surveillance data for acute GAS pharyngitis (including serology), throat carriage, and costs of the disease were collected . Additional cases of GAS pharyngitis have been ascertained to improve the precision of costing estimates . RESULTS: Cohort retention was 97 per cent . The spring, summer and winter carriage rates for children were 13.0, 8.0 and 16.0 per cent respectively . The incidence of GAS pharyngitis was 14 per 100 person-years for children . For every primary case there were 0.7 secondary cases and 24 per cent of families experienced at least one episode of GAS pharyngitis per year . Preliminary costing data suggest that 46 per cent of cases lead to school absenteeism and a high rate of antibiotic use . INTERPRETATION & CONCLUSION: The present data suggest that GAS pharyngitis remains very common in childhood, and that it has further implications in terms of secondary cases and costs.

Indian J Med Res, 2004 May, 119 Suppl, 121 - 5
Prospecting for new group A streptococcal vaccine candidates; McMillan DJ et al.; BACKGROUND & OBJECTIVES: Most group A streptococcal (GAS) vaccine strategies focused on the surface M protein of the GAS . However, vaccine based on M protein have some drawbacks . In the present study, we used two approaches to identify new proteins and peptides that may have utility as vaccine candidates . METHODS: A whole gel elution procedure was used to separate GAS surface antigens into 9 size fractionated pools . Mice were vaccinated with each pool and antibody titre, opsonic ability and protective capacity measured . In an alternative approach BioInformatics was used to identify putative GAS surface proteins . Peptides from within these proteins were then selected on the basis of predicted antigenicity or location . These peptides were conjugated to keyhole lymphocyanin (KLH) and immunogenicity measured in a mouse model . RESULTS: One pool of GAS surface proteins (approximately 29kDa) induced antibodies that were both opsonic and potentially protective . Immunoflourescent microscopy demonstrated that these antibodies bound to the surface of M1 GAS . Amino acid sequencing subsequently identified superoxide dismutase as the major antigen in this pool . A BioInformatic search of the M1 GAS genome and subsequent analysis identified several peptides that fulfilled criteria as potential vaccine candidates . Each peptide when conjugated to KLH was able to induce a strong antibody response . INTERPRETATION & CONCLUSION: Several new antigens were identified that may have potential as vaccine targets . A future GAS vaccine may have multiple peptide epitopes, providing protection against multiple GAS strains.

Indian J Med Res, 2004 May, 119 Suppl, 88 - 94
Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct; Olive C et al.; BACKGROUND & OBJECTIVES: To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved Cregion . These approaches, however, have relied on the use of adjuvants that are toxic for human application . The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines . In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach . METHODS: An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein . B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies . RESULTS: Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant . In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins . INTERPRETATION & CONCLUSION: These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases.

Indian J Med Res, 2004 May, 119 Suppl, 26 - 8
Evaluation & revaluation of upper limits of normal values of anti-streptolysin O & anti-deoxyribonuclease B in Mumbai; Karmarkar MG et al.; BACKGROUND & OBJECTIVES: For the serodiagnosis of group A streptococcal (GAS) infections and their late sequelae, a battery of tests have been suggested . However, anti-streptolysin O (ASO) and antideoxyribonuclease B (ADNase B) are the most widely accepted tests for the same . It is essential to evaluate the upper limits of ASO and ADNase B levels in age and sex matched normal population before using them for the detection of patients . For this study, these values were determined in the past and were revaluated again in 2001-2002, in normal subjects . METHODS: A total of 200 healthy individuals were included in the study in 1991-1992 and same number of age and sex matched healthy individuals were included in 2001-2002 . The methodology used for determination of ASO and ADNase B levels were as per the techniques recommended by the WHO . RESULTS: The findings show that the upper limits of normal ASO titers are 195 IU and 305 IU for adults and children respectively while the said levels for ADNase B for both adults and children were found to be 200 IU . INTERPRETATION & CONCLUSION: The findings of the present study will be helpful in the follow-up, better diagnosis and prognosis of group A streptococcal infections.

Pediatrics, 2004 Jul, 114(1), 182 - 6
Spectrum bias of a rapid antigen detection test for group A beta-hemolytic streptococcal pharyngitis in a pediatric population; Hall MC et al.; BACKGROUND: Rapid antigen detection testing (RADT) is often performed for diagnosis of group A beta-hemolytic streptococcal (GABHS) pharyngitis among children . Among adults, the sensitivity of this test varies on the basis of disease severity (spectrum bias) . A similar phenomenon may occur when this test is used in a pediatric population, which may affect the need for culture confirmation of all negative RADT results . OBJECTIVES: To assess the performance of a clinical scoring system and to determine whether RADT spectrum bias is present among children who are evaluated for GABHS pharyngitis . METHODS: Laboratory and clinical records for a consecutive series of pediatric patients who underwent RADT at the Marshfield Clinic between January 2002 and March 2002 were reviewed retrospectively . Patients were stratified according to the number of clinical features present by using modified Centor criteria, ie, history of fever, absence of cough, presence of pharyngeal exudates, and cervical lymphadenopathy . The sensitivity of the RADT was defined as the number of patients with positive RADT results divided by the number of patients with either positive RADT results or negative RADT results but positive throat culture results . RESULTS: RADT results were positive for 117 of 561 children (21%), and culture results were positive for 35 of 444 children (8%) with negative RADT results . The overall prevalence of GABHS pharyngitis was 27% (95% confidence interval: 23-31%) . The prevalence of GABHS pharyngitis was 18% among patients with 0 Centor criteria, 16% among those with 1 criterion, 32% among those with 2 criteria, and 50% among those with 3 or 4 criteria . Spectrum bias was present, inasmuch as RADT sensitivity increased with Centor scores, ie, 47% sensitivity among children with 0 Centor criteria, 65% among those with 1 criterion, 82% among those with 2 criteria, and 90% among those with 3 or 4 criteria . CONCLUSIONS: The sensitivity of RADT for GABHS pharyngitis is not a fixed value but varies with the severity of disease . However, even among pediatric patients with > or =3 Centor criteria for GABHS pharyngitis, the sensitivity of RADT is still too low to support the use of RADT without culture confirmation of negative results.

Ter Arkh, 2004, 76(5), 45 - 51
{In Process Citation}; Bacteriocin production and sensitivity; Institute of Animal Physiology, Slovak Academy of Sciences, 040 01 Kosice, Slovakia . kecerova@saske.sk

Using an overlay test the production of bacteriocin-like activity and resistance was found in 6 of the total of 7 isolates (5 enterococcal and 2 streptococcal) . The majority of strains were sensitive to all bacteriocin producers tested . After acetone precipitation, bacteriocin precipitates were tested for thermal stability . They exhibited high stability at 37 degrees C and some of them were active even after a treatment at 95 degrees C.

J Child Neurol, 2004 May, 19(5), 387 - 90
Functional brain imaging in Sydenham's chorea and streptococcal tic disorders; Citak EC et al.; Group A streptococcal infections cause a wide range of neuropsychiatric disorders, such as Sydenham's chorea, tics, obsessive-compulsive disorders, and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) . Structural (computed tomography and magnetic resonance imaging) and functional (positron emission tomography, single-photon emission computed tomography) imaging studies in patients with Sydenham's chorea have suggested reversible striatal abnormalities . The objective of this study was to investigate the cerebral perfusion patterns of the subcortical structures by using hexamethylpropylenamine oxime single-photon emission computed tomography (HMPAO-SPECT) in seven cases of Sydenham's chorea and two cases of streptococcal tic disorder . HMPAO-SPECT studies revealed a hyperperfusion pattern in two and a hypoperfusion pattern in five of the chorea patients and in two patients with tic disorder . The results are discussed in relation to the duration and severity of the symptoms and the response to therapy . Functional imaging findings can be variable in Sydenham's chorea, and hyperperfusion of the striatum and thalamus could be an indicator of the response to therapy and the severity of symptoms . However, the number of cases so far investigated by either SPECT or positron emission tomography is still too limited to draw any firm conclusions.

Infect Immun, 2004 Jul, 72(7), 4261 - 70
Structural relationships and cellular tropism of staphylococcal superantigen-like proteins; Al-Shangiti AM et al.; The staphylococcal superantigen-like proteins (SSLs) are a family of polymorphic paralogs encoded in the Staphylococcus aureus genome whose function is unknown . The crystal structure of SSL7 was determined and compared to that of SSL5 and that of a classical superantigen, streptococcal pyrogenic exotoxin . Although the overall architecture of the superantigen family is retained in both SSL7 and SSL5, there are significant differences in the structures which suggest that the characteristic major histocompatibility complex binding site of superantigens has been lost . To complement these data, the abilities of SSL7 and a closely related paralog, SSL9, to interact with cells of the immune system were investigated . In populations of human white blood cells, both SSLs interacted selectively with monocytes via specific saturable but separate binding sites, which led to rapid uptake of the SSLs . In addition, SSLs were rapidly taken up by dendritic cells, but not by macrophages, into the same endosomal compartment as dextran . The ability of these secreted proteins to target antigen-presenting cells may enhance a misplaced antibody response against the proteins, which may facilitate bacterial colonization rather than contribute to host protection . Like classical superantigens, therefore, SSLs may distract the host's immune system, but they may do so via entirely different molecular mechanisms.

Arch Dis Child, 2004 Jul, 89(7), 611 - 4
Anti-basal ganglia antibodies: a possible diagnostic utility in idiopathic movement disorders?
Church AJ, Dale RC, Giovannoni G.
BACKGROUND: The spectrum of post-streptococcal brain disorders includes chorea, tics, and dystonia . The proposed mediators of disease are anti-basal ganglia (neuronal) antibodies (ABGA) . AIM: To evaluate ABGA as a potential diagnostic marker in a cohort of UK post-streptococcal movement disorders . METHODS: Forty UK children presenting with movement disorders associated with streptococcal infection were recruited . ABGA was measured using ELISA and Western immunoblotting . To determine ABGA specificity and sensitivity, children with neurological diseases (n = 100), children with uncomplicated streptococcal infection (n = 40), and children with autoimmune disease (n = 50) were enrolled as controls . RESULTS: The mean ELISA result was increased in the post-streptococcal movement disorder group compared to all controls and derived a sensitivity of 82.4% and specificity of 79% . The Western immunoblotting method to detect ABGA derived a sensitivity and specificity of 92.5% and 94.7% respectively . There was common binding to basal ganglia antigens of 40, 45, and 60 kDa . Immunofluorescence localised the antibody binding to basal ganglia neurones . CONCLUSION: ABGA appears to be a potentially useful diagnostic marker in post-streptococcal neurological disorders . Western immunoblotting appears to be the preferred method due to good sensitivity and specificity and the ability to test several samples at once.

J Mol Biol, 2004 Jul 9, 340(3), 615 - 25
A captured folding intermediate involved in dimerization and domain-swapping of GB1; Byeon IJ et al.; Immunoglobulin binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single domain protein, is one of the most extensively used model systems in the area of protein folding and design . The recently determined NMR structure of a quadruple mutant (HS#124F26A, L5V/F30V/Y33F/A34F) revealed a domain-swapped dimer that dissociated into a partially folded, monomeric species at low micromolar protein concentrations . Here, we have characterized this monomeric, partially folded species by NMR and show that extensive conformational heterogeneity for a substantial portion of the polypeptide chain exists . Exchange between the conformers within the monomer ensemble on the microsecond to millisecond timescale renders the majority of backbone amide resonances broadened beyond detection . Despite these extensive temporal and spatial fluctuations, the overall architecture of the monomeric mutant protein resembles that of wild-type GB1 and not the monomer unit of the domain-swapped dimer .

MMWR Morb Mortal Wkly Rep, 2004 Jun 18, 53(23), 502 - 5
Diminishing racial disparities in early-onset neonatal group B streptococcal disease--United States, 2000-2003; Centers for Disease Control and Prevention (CDC); Increased use of intrapartum antibiotics to prevent perinatal group B streptococcal (GBS) disease during the 1990s led to substantial declines in the incidence of GBS disease in newborns . Despite this success, at the end of the 1990s, early-onset GBS disease (in infants aged <7 days) continued to be a leading infectious cause of neonatal mortality in the United States, and black infants remained at higher risk than white infants . In 2002, CDC and the American College of Obstetricians and Gynecologists (ACOG) revised guidelines for prevention of early-onset GBS disease to recommend late prenatal screening of all pregnant women and intrapartum antibiotic prophylaxis (IAP) for GBS carriers . These guidelines were expected to result in further declines in early-onset disease . This report updates early-onset incidence trends since 1999 analyzed by using population-based, multistate data from the Active Bacterial Core surveillance (ABCs)/Emerging Infections Program Network . The results of the analysis indicated that 1) after a plateau in early-onset disease incidence during 1999-2002, rates declined 34% in 2003 and 2) although racial disparities in incidence persist, rates for blacks now approach the 2010 national health objective of 0.5 cases per 1,000 live births . Continued implementation of screening and prophylaxis guidelines by clinicians and public health practitioners should lead to further declines in racial disparities.

Therapie, 2004 Jan-Feb, 59(1), 155 - 62
{Software modeling for better understanding of pharmacokinetic-pharmacodynamic relationships: application to azithromycin in the treatment of streptococcal tonsillitis and in acute exacerbation fo chronic bronchitis}}; le Normand Y et al.; In order to illustrate the significance of pharmacokinetic/pharmacodynamic (PK/PD) parameters of azithromycin (AZM) in tonsillar and respiratory tract infections, we developed original simulation software . As area under the curve over 24 hours divided by the minimum inhibitory concentration (AUC24/MIC) and time over a 24-hour period that the drug concentration exceeds the MIC (t > MIC) are important predictors of the clinical efficacy of macrolides, our software calculates these indices for plasma, tonsil, epithelial lining fluid (ELF), lung tissue (LT) and alveolar macrophages (AM) . For an MIC of 0.5 microgram.mL-1, after administration of AZM 500 mg daily for 3 days (tonsillitis) or AZM 500 mg on day 1 and 250 mg daily for the next 4 days (respiratory tract infections) to a 70 kg subject, PK/PD parameters are as follows: AUC24/MIC (h): 9.5 (plasma); 439 (tonsil); 57.5 (ELF); 439 (LT); 1354 (AM); t > MIC is 24 hours in all tissues . Our simulation model illustrates the following: (i) AUC24/MIC values are above the 25-30-hour threshold in S . pneumoniae infection; and (ii) tissue concentrations exceed the MIC for 6 days after the last dose in ELF and for more than 2 weeks in tonsils, LT and AM.

J Leukoc Biol, 2004 Sep, 76(3), 709 - 18 Epub 2004 Jun 14.
Distinct and overlapping roles of CXCR5 and CCR7 in B-1 cell homing and early immunity against bacterial pathogens; Hopken UE et al.; CXC chemokine receptor (CXCR)5 and CC chemokine receptor (CCR)7 are the major chemokine receptors required for B cell homing and microenvironmental localization during antigen-independent and -dependent B cell differentiation . Here, we show markedly decreased B-1 B cell numbers in the peritoneal cavity of CXCR5-/- and CXCR5-/-CCR7-/- double-deficient mice paralleled by reduced antigen-induced phosphorylcholine-specific immunoglobulin (Ig)M responses after intraperitoneal (i.p.) administration of streptococcal antigen . CCR7-/- mice also revealed a partial reduction in peritoneal B-1 cell numbers combined with a reduced humoral response to i.p . injected bacterial antigen . However, opposite roles of CXCR5 and CCR7 were observed when the frequency of peritoneal B-2 cells was analyzed . CXCR5-/- mice almost completely lacked B-2 cells, whereas CCR7 deficiency engendered an increase in peritoneal B-2 cells . In addition, CCR7-/- mice had enhanced, splenic IgM+ plasma cell responses, whereas the extrafollicular B cell response of the CXCR5-/- mice was not significantly altered compared with wild-type controls . Thus, the two chemokine receptors exert divergent forces at multiple levels of the innate immune response . CXCR5 plays a dominant role in peritoneal B-1 B cell homing and body cavity immunity, but both chemokine receptors are needed for a proportional peritoneal B-2 cell homing and balanced development of an early splenic B cell response.

Clin Exp Immunol, 2004 Jul, 137(1), 65 - 73
Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment; Rioja I et al.; Biomarker quantification in disease tissues from animal models of rheumatoid arthritis (RA) can help to provide insights into the mechanisms of action of novel therapeutic agents . In this study we validated the kinetics of IL-1beta, TNF-alpha and IL-6 mRNA and protein expression levels in joints from DBA/1OlaHsd murine collagen-induced arthritis (CIA) and Lewis rat Streptococcal cell wall (SCW)-induced arthritis by real-time polymerase chain reaction (PCR) TaqMan and Enzyme-linked immunosorbent assay (ELISA) . Prednisolone was used as a reference to investigate any correlation between clinical response and cytokine levels at selected time-points . To our knowledge this is the first report showing a close pattern of expression between mRNA and protein for IL-1beta and IL-6, but not for TNF-alpha, in these two models of RA . The kinetics of expression for these biomarkers suggested that the optimal sampling time-points to study the effect of compounds on both inflammation and cytokine levels were day 4 postonset in CIA and day 3 after i.v challenge in SCW-induced arthritis . Prednisolone reduced joint swelling through a mechanism associated with a reduction in IL-1beta and IL-6 protein and mRNA expression levels . At the investigated time points, protein levels for TNF-alpha in arthritic joints were lower than the lower limit of detection of the ELISA, whereas mRNA levels for this cytokine were reliably detected . These observations suggest that RT-PCR TaqMan is a sensitive technique that can be successfully applied to the quantification of mRNA levels in rodent joints from experimental arthritis models providing insights into mechanisms of action of novel anti-inflammatory drugs.

Arch Pediatr Adolesc Med, 2004 Jun, 158(6), 556 - 60
Risk factors associated with ampicillin-resistant infection in newborns in the era of group B streptococcal prophylaxis; Rentz AC et al.; OBJECTIVES: To document the trend of ampicillin-resistant infections in newborns weighing at least 1500 g and to determine factors associated with ampicillin-resistant neonatal early-onset infection in the era of routine group B streptococcal prophylaxis . DESIGN: Case-control study . SETTING: Referral hospital with level I through level III nurseries.Patients Newborns aged 0 to 7 days with cultures positive for bacterial infection, born from January 1994 to August 2002 (n = 53) . Random controls were matched to admission year and nursery level (n = 159) . MAIN OUTCOME MEASURES: Trends of and factors associated with ampicillin-resistant infections . RESULTS: Trends in our institution were the same as those found in some recent reports, a decrease in group B streptococcal early-onset infections without a concomitant increase in gram-negative early-onset infections . Specifically, when stratified by birth weight, newborns weighing at least 1500 g had no increase in gram-negative pathogens in the eras both before and after group B streptococcal prophylaxis (0.8 per 1000 live births to 0.3 per 1000 live births; incidence ratio, 2.3 {95% confidence interval, 0.5-10.9}) . No increase in ampicillin resistance was seen during the same 3 periods (50%, 60%, and 50%, respectively; P =.97) . Independent risk factors associated with ampicillin-resistant early-onset infection were intrapartum antibiotics for a 24-hour duration or longer (odds ratio, 4.8 {95% confidence interval, 1.0-23.3}) and clinical chorioamnionitis (odds ratio, 9.2 {95% confidence interval, 2.6-32.9}) . CONCLUSIONS: No increase in early-onset infections with gram-negative or ampicillin-resistant pathogens was detected . Ampicillin-resistant early-onset infection was associated with intrapartum antibiotics given for 24 hours or longer prior to delivery and with clinical chorioamnionitis . Ampicillin sodium and gentamicin sulfate remain appropriate initial antibiotic therapies for early-onset infection in newborns weighing at least 1500 g and without these risk factors.

Ophthalmology, 2004 Jun, 111(6), 1191 - 5
Aqueous and vitreous penetration of linezolid (Zyvox) after oral administration; Fiscella RG et al.; OBJECTIVE: To investigate the penetration of linezolid, a synthetic oxazolidinone antibiotic, into the aqueous and vitreous humor after oral administration . DESIGN: Noncomparative interventional, prospective case series study, randomized into group 1 (dose, one 600-mg tablet) or group 2 (2 doses of 600 mg given 12 hours apart) . PARTICIPANTS: Patients undergoing pars plana vitrectomy between March 2001 and August 2002 at the University of Illinois at Chicago Eye Center who had not had prior vitrectomy surgery . METHODS: Aqueous, vitreous, and plasma samples were obtained and analyzed from 29 patients after oral administration of 1 dose (group 1A, 13 patients {13 eyes} sampled less than 2 hours after administration; group 1B, 9 patients {9 eyes} sampled more than 2 hours after administration) or 2 doses 12 hours apart (group 2, 7 patients {7 eyes}) before surgery . MAIN OUTCOME MEASURES: Aqueous, vitreous, and plasma concentrations of linezolid (micrograms per milliliter) . RESULTS: Group 1A achieved mean aqueous, vitreous, and plasma levels of 0.77+/-0.6 microg/mL, 0.3+/-0.3 microg/mL, and 5.0+/-3.3 microg/mL, respectively . Group 1B achieved mean aqueous, vitreous, and plasma levels of 3.8+/-1.2 microg/mL, 2.3+/-1.4 microg/mL, and 7.6+/-2.7 microg/mL, respectively . Group 2 achieved mean aqueous, vitreous, and plasma levels of 6.6+/-2.7 microg/mL, 5.7+/-2.7 microg/mL, and 10.3+/-4.1 microg/mL, respectively . CONCLUSIONS: Mean inhibitory aqueous and vitreous minimum inhibitory concentrations for 90% of isolates (MIC(90)) were achieved against all gram-positive bacteria, including vancomycin-resistant enterococcus, methicillin-resistant Staphylococcus aureus, and streptococcal species after 2 doses given 12 hours apart . Mean MIC(90) were achieved for many gram-positive pathogens after only one dose in many patients after approximately 4 hours.

New Microbiol, 2004 Apr, 27(2), 203 - 6
Toxic scarlet fever complicating cellulitis: early clinical diagnosis is crucial to prevent a fatal outcome; Lau SK et al.; We describe a case of toxic scarlet fever in a healthy adult with streptococcal cellulitis of the right elbow as a result of skin abrasion . The clinical picture mimicked that of drug eruption after treatment of cellulitis with antibiotics . Among the five cases of scarlet fever complicating cellulitis, including the present one, reported in the English literature, four had severe systemic complications and two died . As a result of re-emergence of invasive streptococcal infections, clinicians should be aware of the differential diagnosis of scarlet fever in patients presenting with cellulitis and skin rash . Early clinical diagnosis is crucial to exclude drug eruptions, prompt initiation of antibiotic treatment, and prevention of the potentially fatal outcome.

Eur J Clin Microbiol Infect Dis, 2004 Jun, 23(6), 434 - 44 Epub 2004 May 26.
Epidemiological features of invasive and noninvasive group A streptococcal disease in the Netherlands, 1992-1996; Vlaminckx B et al.; A prospective, nationwide, laboratory-based surveillance of invasive group A streptococcal infections was conducted in the Netherlands from 1992 through 1996 . Clinical and demographic data were obtained and all isolates were T/M typed . All noninvasive group A streptococcal isolates were registered from 1994 through 1996 . A total of 880 patients with invasive streptococcal disease were identified . The annual incidence was found to be 2.2 per 100,000 . Predominant M types were M1 (21%), M3 (11%), M6 (5%), M12 (5%), and M28 (8%) . Particular age and M-type distributions were observed in different clinical entities . The case-fatality rate was 18% overall, but it reached 59% among cases of toxic shock-like syndrome . Older age, necrotizing fasciitis, sepsis without focus, pneumonia, infection with type M1 or M3 strains, and underlying cardiopulmonary disease were associated with fatality . A total of 10,105 patients with noninvasive group A streptococcal disease were registered . These patients differed significantly from patients with invasive disease with regard to age distribution and primary foci of infection.

Pharmacotherapy, 2004 May, 24(5), 558 - 63
Inhibition of streptokinase-induced, antibody-mediated platelet aggregation with tirofiban after exposure to streptokinase or streptococcal infection; Courval M et al.; STUDY OBJECTIVE: To evaluate the effect of tirofiban (a glycoprotein IIb-IIIa inhibitor) in preventing streptokinase-induced, antibody-mediated platelet aggregation after administration of streptokinase or development of a streptococcal infection . DESIGN: Prospective analysis . SETTING: Research center of a Canadian hospital . PARTICIPANTS: Forty-five healthy volunteers, 45 patients who had received streptokinase within the past 3 years, and 13 patients who had a severe streptococcal infection also within the past 3 years . INTERVENTION: Blood samples were drawn to measure the extent of inhibition of streptokinase-induced, antibody-mediated platelet activation and aggregation by tirofiban . MEASUREMENTS AND MAIN RESULTS: Platelet aggregation was measured by using a turbidimetric method . The extent of inhibition by tirofiban was measured by incubating tirofiban for 2 minutes before adding streptokinase 5000 U/ml . Also, tirofiban was added 2 minutes before adding adenosine 5'-diphosphate (ADP) 2 microM/L into the last tube as a comparison . Strepto-kinase-induced, antibody-mediated platelet aggregation was observed in 10 (22%) of the 45 patients treated with streptokinase, in 3 (23%) of the 13 patients with streptococcal infection, and in none of the 45 healthy volunteers . Tirofiban inhibited streptokinase-induced, antibody-mediated platelet aggregation by 89 +/- 14% (p<0.001) . Similarly, ADP-induced platelet aggregation was inhibited by 92 +/- 6% (p<0.001) with tirofiban . CONCLUSION: Streptokinase-induced, antibody-mediated platelet aggregation occurred in 13 (22%) of 58 patients who received streptokinase or were exposed to a streptococcal infection in the past 3 years . Such patients may not benefit from streptokinase therapy . In these patients, tirofiban significantly decreased the extent of antistreptokinase antibody-mediated platelet aggregation . Hence, patients undergoing streptokinase therapy may benefit from tirofiban as adjunctive therapy.

Clin Infect Dis, 2004 Jun 1, 38(11), 1526 - 34 Epub 2004 May 11.
Meta-analysis of cephalosporins versus penicillin for treatment of group A streptococcal tonsillopharyngitis in adults; Casey JR et al.; We conducted a meta-analysis of 9 randomized controlled trials (involving 2113 patients) comparing cephalosporins with penicillin for treatment of group A beta -hemolytic streptococcal (GABHS) tonsillopharyngitis in adults . The summary odds ratio (OR) for bacteriologic cure rate significantly favored cephalosporins, compared with penicillin (OR,1.83; 95% confidence interval {CI}, 1.37-2.44); the bacteriologic failure rate was nearly 2 times higher for penicillin therapy than it was for cephalosporin therapy (P=.00004) . The summary OR for clinical cure rate was 2.29 (95% CI, 1.61-3.28), significantly favoring cephalosporins (P<.00001) . Sensitivity analyses for bacterial cure significantly favored cephalosporins over penicillin in trials that were double-blinded and of high quality, trials that had a well-defined clinical status, trials that performed GABHS serotyping, trials that eliminated carriers from analysis, and trials that had a test-of-cure culture performed 3-14 days after treatment . This meta-analysis indicates that the likelihood of bacteriologic and clinical failure in the treatment of GABHS tonsillopharyngitis is 2 times higher for oral penicillin than for oral cephalosporins.

Rheumatology (Oxford), 2004 Aug, 43(8), 949 - 54 Epub 2004 May 18.
Poststreptococcal reactive arthritis: what is it and how do we know?
Mackie SL, Keat A.
OBJECTIVE: To find out whether poststreptococcal reactive arthritis (PSRA) is a discrete, homogeneous clinical syndrome . METHOD: Literature review from case reports and case series . RESULTS: One hundred and eighty-eight cases were identified . The age distribution was bimodal, with one peak in childhood and one peak in adulthood . Eighty-three percent of streptococcal isolates were group A . The clinical presentation was heterogeneous but appeared different both from that of acute rheumatic fever (ARF) and from that of HLA B27-associated reactive arthritis . Carditis was rare . CONCLUSIONS: The term PSRA encompasses significant heterogeneity . The link between the arthritis and the streptococcal infection is unproven.

Biomaterials, 2004 Nov, 25(24), 5467 - 72
Effect of composite resin biodegradation products on oral streptococcal growth; Khalichi P et al.; Hydrolytic degradation by-products associated with the constitutive monomers 2,2-bis {4-(2-hydroxy-3-methacryloxypropoxy) phenyl} propane (bis-GMA), bisphenol A polyethylene glycol diether dimethacrylate (bis-EMA), and triethylene glycol dimethacrylate (TEDGMA) used in dental restorative composites include bis-hydroxy-propoxyphenyl propane (bis-HPPP), ethoxylated bisphenol A (E-bisPA), methacrylic acid (MA), and triethylene glycol (TEG) . These products are generated from the interaction of human salivary esterases with the composites . Recent findings have indicated that TEGDMA has the ability to modulate oral bacteria but it is unclear which components of TEGDMA are related to the observed effects . The objective of the current study was to investigate the influence of TEGDMA derived degradation products MA and TEG on the growth of three strains of oral bacteria: S . mutans strains NG8 and JH1005, and S . salivarius AT2 . Bacterial growth rates were measured at 37 degrees C, and pH values of 5.5 (representative of cariogenic state) or 7.0 at concentrations of 0-50mmol/l for MA (Sigma, US) and 0-100mmol/l for TEG (Sigma, US) . It was found that at pH 5.5 TEG significantly stimulated the growth of both S . mutans strains ( p<0.05 ) in the concentration range of 0.5-10.0mmol/l and stimulated the growth of S . salivarius AT2 for the entire concentration range tested (p<0.05) . TEG (above 50mmol/1) did not significantly affect the doubling times of S . salivarius at pH of 7.0 and it inhibited the growth of both S . mutans strains above 50mmol/l at the same pH value . At pH 5.5 MA inhibited the growth of all three strains with increasing concentration . At neutral pH, the growth of S . mutans NG8 strain was significantly reduced by MA ( p<0.05 ) above 10mmol/l . In summary, these results indicate that TEG and MA modulate the growth rate of important oral bacteria in a concentration and pH dependent manner.

Curr Infect Dis Rep, 2004 Jun, 6(3), 181 - 186
Rapid Detection and Diagnosis of Group A Streptococcal Pharyngitis; Corneli HM; This article reviews techniques of rapid testing and the effective diagnosis of streptococcal pharyngitis . Despite 50 years' study of streptococcal pharyngitis and 20 years' experience with rapid tests for its diagnosis, the subject continues to evolve . Rapid diagnostic tests have become more sensitive . Experts now consider not if but when they may replace throat cultures . Highly accurate rapid tests will still challenge clinicians to screen the right patients . The improvement of clinical diagnosis will require an understanding of the clinical spectrum of pharyngitis and questions relating to disease prevalence, test performance, and medical decision making . Implications for diagnostic strategies are discussed.

Lung, 2004, 182(2), 61 - 72
Lipid peroxidation of lung surfactant in experimental neonatal group B streptococcal pneumonia; Bouhafs RK et al.; Group B streptococcal (GBS) pneumonia, with neutrophilic granulocytes immigrating into the lungs, may occur in neonates . The incidence is particularly high among preterm infants, who often are treated with exogenous surfactant . We have previously demonstrated in vitro that neutrophils stimulated by GBS cause lipid peroxidation (LPO) and functional impairment of lung surfactant . The present study aimed at evaluating LPO of exogenous lung surfactant (Curosurf) and the protective effect of the natural antioxidant, vitamin E in immature ventilated newborn rabbits with experimental neonatal GBS pneumonia . There was a prominent proliferation of GBS in the lungs of animals treated with surfactant and ventilated for 5 h . GBS-infected rabbits had a higher LPO of lung lavage fluid than non-infected ones . The LPO could be diminished using vitamin E, which, however, did not affect bacterial proliferation . During the 5-h incubation period, mean lung-thorax compliance values were significantly lower in GBS-infected than in noninfected animals . We speculate that addition of vitamin E to exogenous surfactant preparations may improve their resistance to LPO and make them more suitable for treatment of neonates with pneumonia.

Hautarzt, 2004 Jun, 55(6), 512 - 8
{Special emergencies in dermatology}; Neumann NJ et al.; Emergency cases in dermatology are rare but potentially life-threatening conditions . They comprise a broad spectrum of diseases which require immediate hospitalization or even intensive care . A rapid diagnosis and appropriate therapy is necessary since some of these emergency cases are associated with a high mortality and with severe disabling complications . Typical examples are: the bacterial infections Waterhouse-Friderichsen syndrome, necrotizing erysipelas and necrotizing fasciitis, as well as staphylococcal and streptococcal toxic shock syndromes . Another special emergency situation is venomous snake bites.

J Clin Psychiatry, 2004 Apr, 65(4), 537 - 42
Lack of effect of intravenous immunoglobulins on tics: a double-blind placebo-controlled study; Hoekstra PJ et al.; BACKGROUND: Case studies and a placebo-controlled study previously suggested the effectiveness of immunomodulatory therapy in patients with tic or related disorders whose symptoms show a relationship with streptococcal infections . No data are available on the effectiveness of intravenous immunoglobulins (IVIG) on tic severity in unselected tic disorder patients . METHOD: Thirty patients with a DSM-IV tic disorder were randomly assigned to IVIG (1 g/kg on 2 consecutive days; mean age = 28.71 years; range, 14-53 years) or placebo (mean age = 30.73 years; range, 14-63 years) . Symptoms were rated with the Yale Global Tic Severity Scale, the Yale-Brown Obsessive Compulsive Scale, and the Clinical Global Impressions scale of symptom change with regard to tic severity . These were used at baseline and on weeks 2, 4, 6, 10, and 14 posttreatment, after which blinding was broken . The study was conducted from March through August 2002 . RESULTS: We observed no significant differences between both treatment groups regarding posttreatment changes in tic severity . Severity of obsessions and compulsions, which was in the subclinical range, decreased significantly in the IVIG group compared with the placebo group at week 6 (p =.02) . Then, there was a 32.3% improvement in the IVIG group compared with baseline . Though this improvement was maintained over the following 8 weeks, no statistically significant differences between the IVIG and the placebo group with regard to improvements in obsessions and compulsions were detected at subsequent assessments . IVIG treatment was associated with significantly more side effects than placebo, most notably headache . CONCLUSION: Based on the present results, IVIG cannot be recommended in tic disorders.

Kardiol Pol, 2004 Feb, 60(2), 138 - 40; discussion 141
{Pericarditis as a consequence and first symptom of microcellular lung carcinoma--case report}; Skalik R et al.; A case of a patient suffering from Streptococcal suppurative pericarditis with cardiac tamponade and acute renal failure as a first symptom of disseminated lung cancer is presented . The examination of pericardial fluid only confirmed Streptococcal infection as a cause of exudative pericarditis . The neoplasmatic cells were not found in the examined fluid . Next, chest CT and bronchoscopy were performed due to the lack of clinical improvement, recurrence of severe pericardial effusion and enlargement of the upper mediastinum found on chest radiogram . CT and bronchoscopy allowed to establish the final diagnosis - disseminated lung cancer.

Int J Clin Oncol, 2004 Apr, 9(2), 98 - 106
Randomized controlled trial of the efficacy of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil and uracil/tegafur; Watanabe M et al.; BACKGROUND: We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT) . METHODS: Patients with stage II, III, or IV (Dukes' B, C) colorectal cancer were enrolled and randomly assigned to one of three groups: an immunochemotherapy group (mitomycin C {MMC} + 5-fluorouracil {5-FU} + HCFU + OK-432), a chemotherapy group (MMC + 5-FU + HCFU), and a control group (surgery alone) for those with colon cancer (study 1); and an immunochemotherapy group (MMC + 5-FU + UFT + OK-432), a chemotherapy group (MMC + 5-FU + UFT), and a control group (surgery alone) for those with rectal cancer (study 2) . RESULTS: A total of 760 patients with colon cancer and 669 patients with rectal cancer were entered into this randomized clinical trial (RCT) . The incidence of side-effects was in the order of: immunochemotherapy group >> chemotherapy group >> control group in both the cohort of patients with colon cancer and the cohort with rectal cancer . In particular, the frequency of leucopenia and skin disorders was significantly higher than control groups . There were no severe adverse events such as death related to the adjuvant therapy . In both the colon cancer and rectal cancer cohorts, no significant difference in the 5-year survival rate and disease-free survival rate was noted among the three groups . CONCLUSION: The results of an RCT demonstrated that the combination of MMC + 5-FU + HCFU + OK-432 for colon cancer and that of MMC + 5-FU + UFT + OK-432 for rectal cancer could not prolong the survival of patients with surgically resected colorectal cancer, but that both combinations were well tolerated as adjuvant therapy.We investigated the efficacy and safety of adjuvant immunochemotherapy and adjuvant chemotherapy for colorectal cancer, using different combinations of the intracutaneous streptococcal preparation OK-432 and the oral pyrimidines 1-hexylcarbamoyl-5-fluorouracil (carmofur, HCFU) and uracil/tegafur (UFT).

CNS Spectr, 2002 Jun, 7(6), 432 - 4
Neuroanatomical correlates and somatosensorial disturbances in body dysmorphic disorder; Yaryura-Tobias JA et al.; Body dysmorphic disorder (BDD) is a condition characterized by an intense preoccupation with an imagined or slight defect in physical appearance . Although there is a general consensus that psychosocial factors play a major role in the development of BDD, there is some evidence suggesting that an organic somatosensorial disturbance may also exist in this condition . Several psychiatric and neurological disorders, including the interparietal syndrome, Gertsman's syndrome, inferoparietal syndrome, phantom limb syndrome, genital retraction syndrome, panencephalitis, cerebrovascular syndromes, and pharyngeal streptococcia affecting the basal ganglia, can present with somatosensorial disturbances similar to BDD . The cerebral pathology in all these disorders appears to be localized in the parietal-occipital region, indicating that cerebral involvement may also be associated with BDD . An interdependence exists between cerebral regions through integrated neural networks that enable efficient processing of information . Disturbances in these association pathways can lead to an imbalance in the extensive cerebral loops . Therefore, it is possible that a defect in information-processing may play a role in the pathogenesis of BDD.

Indian J Pediatr, 2004 Apr, 71(4), 357 - 8
Perforated acute appendicitis in a term neonate; Managoli S et al.; Acute appendicitis is rare in term neonates . In most of the reported cases, it is seen as a complication of necrotizing enterocolitis, Hirschsprung's disease, cystic fibrosis, meconium plug, inguinal hernia, umbilical hernia, Group B Streptococcal septicemia and chorioamnionitis . A surviving term male newborn with isolated acute appendicitis with perforation is reported . A high index of suspicion of acute appendicitis, early surgery and the importance of a thorough search for a perforation in cases of neonatal acute abdominal distention is stressed . Literature of this rare condition is reviewed briefly.

Clin Immunol, 2004 Apr, 111(1), 119 - 25
Differential effects of interleukin 12 and interleukin 10 on superantigen-induced expression of cutaneous lymphocyte-associated antigen (CLA) and alphaEbeta7 integrin (CD103) by CD8+ T cells; Sigmundsdottir H et al.; At both cutaneous and mucosal sites, interleukin (IL)-10, IL-12 and transforming growth factor (TGF)-beta are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and alphaE integrin (CD103) may be expressed . Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells . While adding IL-12 augmented the expression of CLA, superantigen-induced expression of CD103 was markedly suppressed by IL-12, which could be reversed by TGF-beta . Antibodies against TGF-beta inhibited, and a combination of anti-TGF-beta and IL-12 completely abrogated the induced CD103 expression . IL-10 strongly decreased the frequency of CLA+ and although not increasing the frequency of CD103+CD8+ T cells, the amount of CD103 expressed per cell was markedly increased . Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12 and the balance between these cytokines could influence the T cell migration of inflammatory cells into epithelial tissues.

Int J Antimicrob Agents, 2004 Apr, 23(4), 394 - 7
Is the MIC useful in deciding to treat endocarditis surgically?
Walton BI, Wallace SM, Kukreja N, Kharbanda R, Varey-Tyburczy E, Wilson AP, Swanton RH.
The infecting pathogen and its susceptibility to antibiotics is used to suggest prognosis in endocarditis . A case study was performed in a tertiary referral cardiology centre to assess the contribution of the measurement of minimum inhibitory concentration (MIC) to the decision to treat endocarditis surgically . The records were examined of 125 patients admitted between 1981 and 1999 in whom the minimum inhibitory concentration for the pathogen had been measured . The measures of outcome were mortality at time of hospital discharge and at 6 months, surgical referral and cure by medical treatment . Endocarditis caused by Staphylococcus aureus with a raised MIC of flucloxacillin (methicillin) was associated with higher mortality even if glycopeptides were used in treatment (< or = 35 mg/l 0/7 versus MIC 1-2 mg/l 4/13, P = 0.01) . Elevated MICs of flucloxacillin in S . aureus infection or of gentamicin in streptococcal disease were associated with surgical intervention . There were no significant differences between bacterial pathogens in mortality, surgical referral or cure by medical treatment . The measurement of MIC appears prognostically important in deciding the surgical management of endocarditis.

Mov Disord, 2004 Apr, 19(4), 406 - 15
Anti-basal ganglia antibodies in PANDAS; Singer HS et al.; An autoimmune-mediated mechanism involving molecular mimicry has been proposed for a variety of pediatric movement disorders that occur after a streptococcal infection . In this study, anti-basal ganglia antibodies (ABGA) were measured in 15 children with the diagnosis of pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and compared with those in 15 controls . ELISA and Western immunoblotting (WB) methods were used to detect ABGA against supernatant (S1), pellet (P2), and synaptosomal preparations from adult postmortem caudate, putamen, and globus pallidus . ELISA optical density values did not differ between PANDAS patients and controls across all preparations . Immunoblotting identified multiple bands in all subjects with no differences in the number of bands or their total density . Discriminant analysis, used to assess mean binding patterns, showed that PANDAS patients differed from controls only for the caudate S1 fraction (Wilks' lambda = 0.0236, P < 0.0002), with PANDAS-primarily tic subjects providing the greatest discrimination . Among the epitopes contributing to differences between PANDAS and control in the caudate S1 fraction, mean binding to the epitope at 183 kDa was the most different between groups . In conclusion, ELISA measurements do not differentiate between PANDAS and controls, suggesting a lack of major antibody changes in this disorder . Further immunoblot analyses using a caudate supernatant fraction are required to completely exclude the possibility of minor antibody repertoire differences in PANDAS subjects, especially in those who primarily have tics .

Mov Disord, 2004 Apr, 19(4), 390 - 6
Striatal microinfusion of Tourette syndrome and PANDAS sera: failure to induce behavioral changes; Loiselle CR et al.; Rodent striatal microinfusions have been suggested as a model for assessing the behavioral effects induced by antineuronal antibodies . We used this approach to evaluate the proposed autoimmune etiology for Tourette syndrome (TS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) . Sera were assessed from patients with TS (n = 9) preselected based on the presence of elevated enzyme-linked immunosorbent assay optical densities against putamen homogenate and sera from patients with PANDAS (n = 8), selected from a larger group assayed for antibodies against a putamen synaptosomal preparation . The effect of antibodies against the streptococcal M5 protein were also studied . A total of 44 Fischer rats received bilateral infusion of sera: 23 ventral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 8 control); 21 ventrolateral striatum (5 PANDAS, 5 TS, 5 anti-M5 protein, and 6 controls) . Cannulas were placed bilaterally and symmetrically by stereotactic techniques . After animals were allowed to recover for 1 week, sera were microinfused for 3 days . Animal behavior was then simultaneously quantified by daily observation and monitoring using automated activity boxes for 10 days after infusion . No significant alterations in stereotypic behavior or movement were observed between the PANDAS, TS, or anti-M5 protein and control groups . Our findings are in contrast to previous reports, and suggest the need for further investigations to determine the validity of the model and of autoimmune-mediated hypotheses for pediatric movement disorders .

J Comput Chem, 2004 Jun, 25(8), 1015 - 29
A semi-implicit solvent model for the simulation of peptides and proteins; Basdevant N et al.; We present a new model of biomolecules hydration based on macroscopic electrostatic theory, that can both describe the microscopic details of solvent-solute interactions and allow for an efficient evaluation of the electrostatic hydration free energy . This semi-implicit model considers the solvent as an ensemble of polarizable pseudoparticles whose induced dipole describe both the electronic and orientational solvent polarization . In the presented version of the model, there is no mutual dipolar interaction between the particles, and they only interact through short-ranged Lennard-Jones interactions . The model has been integrated into a molecular dynamics code, and offers the possibility to simulate efficiently the conformational evolution of biomolecules . It is able to provide estimations of the electrostatic solvation free energy within short time windows during the simulation . It has been applied to the study of two small peptides, the octaalanine and the N-terminal helix of ribonuclease A, and two proteins, the bovine pancreatic trypsin inhibitor and the B1 immunoglobin-binding domain of streptococcal protein G . Molecular dynamics simulations of these biomolecules, using a slightly modified Amber force field, provide stable and meaningful trajectories in overall agreement with experiments and all-atom simulations . Correlations with respect to Poisson-Boltzmann electrostatic solvation free energies are also presented to discuss the parameterization of the model and its consequences .

Biochem Biophys Res Commun, 2004 Apr 30, 317(2), 401 - 5
An efficient system for small protein expression and refolding; Cheng Y et al.; The low expression yield and poor refolding efficiency of small recombinant proteins expressed in Escherichia coli have continued to hinder the large-scale purification of such proteins for structural and biological investigations . A system based on a small fusion partner, the B1 domain of Streptococcal protein G (GB1), was utilized to overcome this problem . We have tested this system on a small cysteine-rich toxin, mutant myotoxin alpha (MyoP20G) . The highly expressed fusion protein was refolded using an unfolding/refolding protocol . Due to the small size of GB1, we were able to monitor the unfolding/refolding status by heteronuclear single quantum coherence (HSQC) NMR spectroscopy . The final product yielded well-resolved NMR spectra, with a topology corresponding to the natural product . We conclude that GB1 not only increases the expression level but also enhances the refolding of small proteins.

Pediatrics, 2004 Apr, 113(4), 866 - 82
Meta-analysis of cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis in children; Casey JR et al.; OBJECTIVE: To conduct a meta-analysis of randomized, controlled trials of cephalosporin versus penicillin treatment of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis in children . METHODOLOGY: Medline, Embase, reference lists, and abstract searches were conducted to identify randomized, controlled trials of cephalosporin versus penicillin treatment of GABHS tonsillopharyngitis in children . Trials were included if they met the following criteria: patients <18 years old, bacteriologic confirmation of GABHS tonsillopharyngitis, random assignment to antibiotic therapy of an orally administered cephalosporin or penicillin for 10 days of treatment, and assessment of bacteriologic outcome using a throat culture after therapy . Primary outcomes of interest were bacteriologic and clinical cure rates . Sensitivity analyses were performed to assess the impact of careful clinical illness descriptions, compliance monitoring, GABHS serotyping, exclusion of GABHS carriers, and timing of the test-of-cure visit . RESULTS: Thirty-five trials involving 7125 patients were included in the meta-analysis . The overall summary odds ratio (OR) for the bacteriologic cure rate significantly favored cephalosporins compared with penicillin (OR: 3.02; 95% confidence interval {CI}: 2.49-3.67, with the individual cephalosporins {cephalexin, cefadroxil, cefuroxime, cefpodoxime, cefprozil, cefixime, ceftibuten, and cefdinir} showing superior bacteriologic cure rates) . The overall summary OR for clinical cure rate was 2.33 (95% CI: 1.84-2.97), significantly favoring the same individual cephalosporins . There was a trend for diminishing bacterial cure with penicillin over time, comparing the trials published in the 1970s, 1980s, and 1990s . Sensitivity analyses for bacterial cure significantly favored cephalosporin treatment over penicillin treatment when trials were grouped as double-blind (OR: 2.31; 95% CI: 1.39-3.85), high-quality (OR: 2.50; 95% CI: 1.85-3.36) trials with well-defined clinical status (OR: 2.12; 95% CI: 1.54-2.90), with detailed compliance monitoring (OR: 2.85; 95% CI: 2.33-3.47), with GABHS serotyping (OR: 3.10; 95% CI: 2.42-3.98), with carriers eliminated (OR: 2.51; 95% CI: 1.55-4.08), and with test of cure 3 to 14 days posttreatment (OR: 3.53; 95% CI: 2.75-4.54) . Analysis of comparative bacteriologic cure rates for the 3 generations of cephalosporins did not show a difference . CONCLUSIONS: This meta-analysis indicates that the likelihood of bacteriologic and clinical failure of GABHS tonsillopharyngitis is significantly less if an oral cephalosporin is prescribed, compared with oral penicillin.

Am Fam Physician, 2004 Mar 15, 69(6), 1465 - 70
Pharyngitis; Vincent MT et al.; Sore throat is one of the most common reasons for visits to family physicians . While most patients with sore throat have an infectious cause (pharyngitis), fewer than 20 percent have a clear indication for antibiotic therapy (i.e., group A beta-hemolytic streptococcal infection) . Useful, well-validated clinical decision rules are available to help family physicians care for patients who present with pharyngitis . Because of recent improvements in rapid streptococcal antigen tests, throat culture can be reserved for patients whose symptoms do not improve over time or who do not respond to antibiotics.

J Clin Oncol, 2004 Apr 1, 22(7), 1222 - 7
Predictors of viridans streptococcal shock syndrome in bacteremic children with cancer and stem-cell transplant recipients; Gassas A et al.; PURPOSE: To describe episodes of viridans streptococcal bacteremia (VSB) in a cohort of children with cancer and stem-cell transplant (SCT) recipients and to determine predictors of viridans streptococcal shock syndrome (VSSS) in this group of children . PATIENTS AND METHODS: For this retrospective review, we included episodes of VSB isolated between March 1997 and September 2002, in children (<or= 18 years) with a diagnosis of cancer or SCT patients . The primary outcome was VSSS, defined as hypotension requiring intravascular volume expansion or inotropic support and/or respiratory insufficiency necessitating assisted ventilation . RESULTS: Eighty-eight episodes of VSB occurred in 79 children . The mean age of the children was 6.7 years (range, 0.6 to 18.0 years) . The most common underlying diagnosis was acute myelogenous leukemia (AML) in 31 (35%) of 88 episodes, and 38 (43%) of 88 had undergone SCT . VSSS occurred in 16 (18%) of 88 episodes, and two children died from VSSS . Two variables were predictive of VSSS, namely peak temperature at presentation (odds ratio {OR}, 6.3; 95% CI, 2.1 to 19.0; P =.001) and inpatient status (OR, 5.9; 95% CI, 1.3 to 28.0; P =.02) . Diagnosis of AML (OR, 1.1; 95% CI, 0.4 to 3.5; P =.8), receipt of SCT (OR, 1.9; 95% CI, 0.6 to 5.7; P =.2), high-dose cytarabine (OR, 0.6; 95% CI, 0.1 to 3.2; P =.6), and mucositis (OR, 0.8; 95% CI, 0.3 to 2.6; P =.7) were not predictive of VSSS . CONCLUSION: VSSS occurred in 18% of episodes of VSB in children with cancer or SCT recipients . Peak temperature before antibiotic therapy and inpatient status were predictive of VSSS.

An Med Interna, 2004 Mar, 21(3), 108 - 12
{Subcutaneous panniculitis at a third level hospital retrospective study of 113 cases}; Aviles Izquierdo JA et al.; INTRODUCTION: The panniculitides or hypodermitis are a wide and heterogeneous group of diseases characterized by the presence of subcutaneous inflammatory nodules located generally in low limbs . OBJETIVES: Show the clinicopathologic characteristics of the cases diagnosed as panniculitis for a 5 years period; their epidemiology, etiopathogenic factors, evolution and treatment . MATERIAL AND METHODS: A retrospective study of 113 patients diagnosed as panniculitis by histopathologic report of cutaneous biopsy since 1997 to 2001 were performed . RESULTS: The sex proportion was of 4.65 women to every man . The mean age of these patients was 49 +/- 20 years old . 100% had legs affectation, 7.1% in arms, 5.9% in trunk and 0.9% in face . 9.7% presented fever and arthromyialgias, especially in young people (p < 0.05) . The etiopathogenic factors implied were tuberculosis, streptococcic pharyngoamygdalitis, sarcoidosis and different drugs . The most frequent histological pattern was septal panniculitis without vasculitis . 24.8% did not realize any treatment; 32.5% took nonsteroideal anti-inflammatory drugs; 31.6% potassium iodide; 16% systemic corticosteroids and 7.1% tuberculostatic drugs . Evolution of the patients was good and independently from the treatment performed . CONCLUSIONS: Panniculitides are a group of diseases with similar clinic, but very heterogeneous in their etiology and histopathologic findings . They are more frequent in women and with more expressive clinic in young people . Up to in the 59.3% of the studied cases a causal etiologic agent was identified . These factors are compatible with the published ones in other previous panniculitis series . When a paniculitis is suspected, the most efficient tool is the clinical diagnosis . Histological confirmation by cutaneous biopsy it must be done when it is possible.

Psychiatr Pol, 2004 Jan-Feb, 38(1), 105 - 23
{Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) . A report of two cases}; Brynska A et al.; AIM: To critically review the past years of research on paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections in children and adolescents . METHOD: Literature on PANDAS published from 1995 onward was systematically reviewed . The review focuses on definition and diagnostic consideration aetiological and therapeutical issues . To illustrate the clinical characteristic of PANDAS authors present two cases of children with a severe course of obsessive-compulsive disorder and Tourette's syndrome . RESULTS: Post-streptococcal autoimmunity has been postulated as an aetiologic factor in the development of childhood-onset obsessive-compulsive disorder, tic disorders including Tourette's disorder . This hypothesis arose from a series of clinical observations including the documentation of obsessive-compulsive symptoms of children affected by Sydenham's chorea, a variant of rheumatic fever characterised by neurological dysfunction and also by concomitant investigations of childhood-onset OCD and Tourette's syndrome . CONCLUSION: Results of these studies led to the identification of children whose clinical course is characterised by abrupt and dramatic symptom exacerbations which are temporally related to group A beta-hemolytic streptococcal infections . The identification of such a subgroup will allow for testing of the model of pathogenesis as well as development of novel treatment and prevention strategies . Future research are needed to explore the nature of PANDAS and their relationship with different psychiatric disorders in children and adolescents.

Eur J Clin Pharmacol, 2004 Apr, 60(2), 75 - 82 Epub 2004 Mar 20.
Comparison of rational pharmacotherapy decision-making competence of general practitioners with intern doctors; Akici A et al.; OBJECTIVE: The aim of this study was to compare rational pharmacotherapy decision-making competency of interns (final-year medical students) who had received rational pharmacotherapy education (RPE), with their classmates at another medical school and general practitioners (GPs) who had not been exposed to RPE . DESIGN: A written, objective, structured clinical examination (OSCE), consisting of open and structured questions, was given to all participants . The participants were expected to make a treatment plan and prescribe for simple, uncomplicated beta-hemolytic streptococcal tonsillitis and mild-to-moderate essential hypertension patients, explain their proposed treatment plans and reasons affecting their drug choice . After the OSCE, a questionnaire to assess knowledge of the rational use of drugs was given to the participants . RESULTS: Fifty RPE(+) interns, 54 RPE(-) interns and 53 GPs participated in the study . Mean scores of RPE(+) interns were higher than those of GPs, which were in turn found to be higher than those of RPE(-) interns for all cases . The RPE(+) interns scored the highest regarding all components of rational pharmacotherapy process for all cases of both indications . However, participants in all groups had higher scores for the structured questions compared with the corresponding open ones for both diseases . Prescription analysis also revealed better results for RPE(+) interns regarding the number of drugs/prescription and treatment costs . CONCLUSION: The present study demonstrated that the final-year medical students (interns) markedly benefited from undergraduate RPE at the medical school in developing rational prescribing skills compared with their classmates from a medical school with traditional pharmacology education . Interestingly, they got higher scores than not only RPE(-) interns, but also than the GPs participating in this study, indicating the urgent need for continuous medical education programs in this field throughout the country for practicing GPs.

Mol Immunol, 2004 Feb, 40(14-15), 1129 - 35
Heart infiltrating T cell clones from a rheumatic heart disease patient display a common TCR usage and a degenerate antigen recognition pattern; Fae K et al.; CD4+ T cells are most likely the ultimate effectors of chronic heart lesions in rheumatic heart disease (RHD) . We have demonstrated that infiltrating CD4+ T cell clones were able to recognize several heart tissue and streptococcal antigens by molecular mimicry . Clonality analysis of the mitral valve and myocardium infiltrating T cell lines showed several oligoclonal expansions, some of which were found in both sites of the lesions . The results presented in this study showed a degenerate pattern of reactivity of intralesional T cell clones from one RHD patient . Four mitral valve and one papillar muscle-derived T cell clones, presenting the same TCR-BV13 BJ2S7 with same sequences of the CDR3 region recognized different antigens . They expressed two alpha chains at the RNA level and the AV AJ segments were the same for mitral valve T cell clones, but not for the papillar muscle-derived T cell clone . Two other intralesional T cell clones using the same TCR-BV3 JB2S1 segments with identical CDR3 sequences also recognized different antigens . These results indicate that intralesional T cell clones with common TCR usage can recognize several epitopes that probably amplify the deleterious immune reaction . These data, allow us to hypothesize that degenerate T cell recognition may lead to intramolecular degenerate reactivity against epitopes with low homology . This can be a novel mechanism of epitope spreading, of relevance in the increase of epitopes targets that can activate cross-reactive autoimmune T cells.

Mol Immunol, 2004 Feb, 40(14-15), 1121 - 7
T cell mimicry in inflammatory heart disease; Cunningham MW; Inflammatory heart diseases such as myocarditis and rheumatic heart disease result from the infiltration of the myocardium or valve with T cells and macrophages that result in scarring of the myocardium or valve and alteration in cardiac function . Our studies of T cells from these diseases have identified cardiac myosin in both rheumatic carditis and myocarditis as an important autoantigen . In rheumatic heart disease, streptococcal M protein specific T cells migrate to valves . By investigating streptococcal M protein and cardiac myosin in the Lewis rat model of myocarditis and valvulitis, T cell mimicry is supported as a potential mechanism in disease . Structural and immunological mimicry between the streptococcal M protein and cardiac myosin is shown directly in the Lewis rat model . Rat T cell lines demonstrate mimicry between cardiac myosin and M protein, and T cells isolated directly from inflammatory lesions in myocarditis respond to streptococcal M protein peptides . Studies in BALB/c mice also support the immunological crossreactivity of T cells primed against cardiac myosin with streptococcal M protein peptides containing cardiac myosin homologies . T cell lines produced from the Lewis rat specific to the cardiac myosin like sequences of streptococcal M protein migrated to the valves after passive transfer of the M protein specific T cell lines . In coxsackieviral myocarditis in the MRL mouse strain, cardiac myosin mimicking M protein peptide NT4 was found to induce tolerance and prevent coxsackieviral induced myocarditis, suggesting T cell mimicry between coxsackievirus and streptococcal M protein, both of which are associated with inflammatory heart disease . T cell mimicry between cardiac myosin and microbial antigens such as the streptococcal M protein may prime the immune system for inflammatory heart disease.

J Formos Med Assoc, 2004 Jan, 103(1), 67 - 70
Use of extracorporeal membrane oxygenation to rescue a newborn with early-onset group B streptococcal sepsis and cardiopulmonary failure; Lin YC et al.; Group B streptococcal (GBS) infection is an important cause of perinatal morbidity and mortality . We report the use of extracorporeal membrane oxygenation (ECMO) to rescue a newborn with refractory GBS sepsis and meningitis who developed cardiopulmonary failure . This 2-day-old infant weighed 2640 g and was born to a healthy mother at full term . Respiratory distress, hypotension, and persistent pulmonary hypertension developed on the second day of life . The clinical condition deteriorated rapidly despite conventional treatment, and venoarterial ECMO was established to rescue this moribund newborn . During ECMO, the patient regained stable hemodynamics and good oxygenation, and infection was controlled . ECMO was used for 90 hours and the baby was weaned smoothly . Neurologic assessment after ECMO revealed hydrocephalus, abnormal electroencephalogram, and increased brain auditory evoked potential threshold . This report emphasizes that ECMO may be considered to rescue neonatal patients with cardiopulmonary failure due to GBS sepsis . Possible neurologic complications after ECMO should be carefully monitored.

Bull Soc Pathol Exot, 2003 Jan, 96(5), 351 - 6
{Public health and dermatology in developing countries}; Mahe A et al.; Recently some common skin diseases (SD) (i.e . pyoderma, scabies, and superficial mycosis) received special interest in terms of public health assessing their significance in developing countries (DC) . The importance of this problem has been established through several kinds of studies: studies from specialized dermatology centres, where the main reasons for consulting were common infectious skin diseases; prevalence studies in the general population pointing out very high prevalence rates for common infectious SD; and studies conducted in non-specialized health centres, where those SD represented about 10% of the total number of consultations . Classical complications of common infectious SD, such as post-streptococcic nephritis, appear rather unusual . However, the costs related to SD have been established as significant; this is partly due to the low efficiency of the health agents when trying to manage SD, and to their usual lack of training . So far, SD have been considered as having a very low priority level, due to their low lethality rate, and therefore have been ignored by health authorities . However, it seems unwise to ignore a health problem for which such a demand of the populations is expressed . Health policies aiming at the improvement of this situation have to be aware of the economic and health system context in DC, and should take into account every step of the health system . The following actions have been proposed: definition of SD priorities; training of non-specialized health agents to a basic management of SD priorities; promotion of use and availability of low-cost "essential dermatologic drugs"; education of the populations regarding measures to prevent certain SD . The feasibility and the impact of such a "public health dermatology" program remain to be evaluated.

J Biomol NMR, 2004 Jun, 29(2), 111 - 38
An expectation/maximization nuclear vector replacement algorithm for automated NMR resonance assignments; Langmead CJ et al.; We report an automated procedure for high-throughput NMR resonance assignment for a protein of known structure, or of an homologous structure . Our algorithm performs Nuclear Vector Replacement (NVR) by Expectation/Maximization (EM) to compute assignments . NVR correlates experimentally-measured NH residual dipolar couplings (RDCs) and chemical shifts to a given a priori whole-protein 3D structural model . The algorithm requires only uniform (15)N-labelling of the protein, and processes unassigned H(N)-(15)N HSQC spectra, H(N)-(15)N RDCs, and sparse H(N)-H(N) NOE's (d(NN)s) . NVR runs in minutes and efficiently assigns the (H(N),(15)N) backbone resonances as well as the sparse d(NN)s from the 3D (15)N-NOESY spectrum, in O (n(3)) time . The algorithm is demonstrated on NMR data from a 76-residue protein, human ubiquitin, matched to four structures, including one mutant (homolog), determined either by X-ray crystallography or by different NMR experiments (without RDCs) . NVR achieves an average assignment accuracy of over 99% . We further demonstrate the feasibility of our algorithm for different and larger proteins, using different combinations of real and simulated NMR data for hen lysozyme (129 residues) and streptococcal protein G (56 residues), matched to a variety of 3D structural models.

Int J Oncol, 2004 Apr, 24(4), 959 - 66
Locoregional immunotherapy of malignant ascites from gastric cancer using DTH-oriented doses of the streptococcal preparation OK-432: Treatment of Th1 dysfunction in the ascites microenvironment; Yamaguchi Y et al.; Locoregional administration of the streptococcal preparation OK-432 is effective in treating malignant ascites from gastric cancer . In order to enhance the efficacy, we conducted a pilot study of locoregional immunotherapy for malignant ascites using host-oriented doses of OK-432 . Moreover, action mechanisms of OK-432 were further explored in view of the T-helper type 1 (Th1)-Th2 concept . Gastric cancer patients with cytologically determined malignant ascites were locoregionally administered with OK-432 . The dose of OK-432 was selected according to the delayed-type hypersensitivity (DTH) reaction levels to OK-432 . Cytokine production profiles of ascites cells were determined using whole ascites assay by stimulation with OK-432 . IL-10 mRNA expression was analyzed using RT-PCR . It was found that a positive clinical response was observed in 37 of the 51 (73%) patients with the DTH-oriented approach, showing a significantly higher efficacy than traditional dosage methods using empirical doses (31/58, 53%) (p=0.0487) . The DTH-oriented administration of OK-432 produced adverse effects such as fever elevation (p<0.0001) and abdominal pain (p=0.0013) to a significantly lesser extent compared with the traditional treatment . Analysis of the action mechanism of OK-432 revealed that the DTH reaction in responders (19+/-6 mm) was stronger than that in non-responders (6+/-4 mm) (p<0.0001) . Tumor necrosis factor (TNF)-alpha production of ascites cells was also higher in responders (3943+/-1247 pg/ml) than in non-responders (1217+/-939 pg/ml) (p=0.0002) . There was a significant positive correlation (p=0.0085) between the levels of DTH reaction and TNF-alpha production of ascites cells, but not of blood cells . Responders appeared to polarize on the Th1 axis when clinical responses were plotted on Th1-Th2 dimensions according to the cytokine production profiles of TNF-alpha, IFN-gamma, IL-4 and IL-6 of ascites cells . In vitro culture with IL-2 of ascites cells after OK-432 administration demonstrated an almost clonal expansion of CD4+ lymphocytes, which produced TNF-alpha and IFN-gamma, but did not produce IL-4 or IL-6 . IL-10 mRNA expression was detectable in ascites cells from non-responders before treatment . These results suggest that the DTH-oriented locoregional administration of OK-432 may be both effective and less toxic in treating malignant ascites from gastric cancer, showing a possibility of the tailored immunotherapy for malignant ascites . Th1 dysfunction exists in the microenvironment of malignant ascites from gastric cancer, in which IL-10 may, in part, play a role . The up-regulation of Th1 responses by OK-432 may result in positive clinical responses . The DTH reaction to OK-432 may be a useful tool not only for predicting clinical response but also for selecting the optimal dose of OK-432.

Exp Mol Pathol, 2004 Apr, 76(2), 117 - 21
Antibodies to highly conserved peptide sequence of staphylococcal and streptococcal superantigens in Kawasaki disease; Gupta-Malhotra M et al.; Superantigen-mediated disease such as toxic shock syndrome is seen in patients who have a weak antibody response to the antigen toxic shock syndrome toxin 1 (TSST-1) . We hypothesized that there may be deficiency in antibody production to staphylococcal and streptococcal toxins in Kawasaki disease (KD) children . A peptide was constructed from the homologous portion of the staphylococcal enterotoxins (SE) and streptococcal pyrogenic enterotoxins (SPE), and antibodies to the peptide were made . The anti-peptide antibody immunoblotted several of the SE toxins and SPE toxins . Presence of the peptide antibodies was investigated via ELISA in the sera of acute KD (n = 30), convalescent KD (n = 12), control adults (n = 10), and children (n = 19) . The mean anti-peptide antibodies were indistinguishable between control children and KD before treatment with immunoglobulin (P = 0.7) but rose significantly after therapy (P < 0.01) . The adults had significantly higher antibodies than the KD, both acute and late (P < 0.0001) and the control children (P < 0.0001) . Thus, KD patients do not have a defective serological response against toxins such as SPE/SE/TSST-1 . Normal children have significantly lower antitoxin antibody levels to the toxins compared to the adults.

J Oral Rehabil, 2004 Feb, 31(2), 140 - 8
In vitro streptococcal adherence on prosthetic and implant materials . Interactions with physicochemical surface properties; Sardin S et al.; The aim of this study was to evaluate streptococcal adherence to eight currently used prosthetic and implant materials, and enamel samples, after a salivary coating and to investigate the influence of substrata surface free energy (SFE) and its polar and non-polar components, as well as bacterial surface characteristics, on bacterial adherence . Our results indicate a moderate hydrophobic character of saliva-coated surfaces and a pronounced basic character of the polar component of SFE values, except for one substrata . The lowest colonization was observed with enamel samples and the lowest values of adherent bacteria on the different substrata were observed with the hydrophilic bacterial strain . Both the nature of the substrata and the nature of the bacterial strains could have an effect on the extent of bacterial adhesion . When the interrelationship between the number of adherent bacteria and the surface properties of bacteria and substrata were analysed, bacterial adherence correlated with the non-polar component of substrata SFE (r = 0.8, P = 0.02) and with the adhesion to the solvents (r = 0.8, P < 0.0001) . These results are consistent with the thermodynamic theory and underline the importance of acid-base characteristics of the cell surface when one is studying bacterial adherence on dental casting alloys and implant materials.

Bioorg Med Chem Lett, 2004 Mar 22, 14(6), 1599 - 602
Elimination of antibacterial activities of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A; Randolph JT et al.; Antibacterial SAR for a series of macrolides derived from erythromycin A that are potent LHRH antagonists was developed in an attempt to eliminate the antibiotic activities of these compounds . Increasing the size of the alkyl substituents on the desosamine 3'-amine resulted in potent LHRH antagonists that were inactive against staphylococcal bacteria strains, and were significantly (>10-fold) less active against streptococcal bacteria strains . Complete elimination of antibacterial activities could be achieved by replacement of one or both methyl groups on the 3'-amine with a large alkyl substituent.

J Can Dent Assoc, 2004 Mar, 70(3), 170 - 4
Exposure to the dental environment and prevalence of respiratory illness in dental student populations; Scannapieco FA et al.; OBJECTIVE: To determine if the prevalence of respiratory disease among dental students and dental residents varies with their exposure to the clinical dental environment . METHODS: A detailed questionnaire was administered to 817 students at 3 dental schools . The questionnaire sought information concerning demographic characteristics, school year, exposure to the dental environment and dental procedures, and history of respiratory disease . The data obtained were subjected to bivariate and multiple logistic regression analysis . RESULTS: Respondents reported experiencing the following respiratory conditions during the previous year: asthma (26 cases), bronchitis (11 cases), chronic lung disease (6 cases), pneumonia (5 cases) and streptococcal pharyngitis (50 cases) . Bivariate statistical analyses indicated no significant associations between the prevalence of any of the respiratory conditions and year in dental school, except for asthma, for which there was a significantly higher prevalence at 1 school compared to the other 2 schools . When all cases of respiratory disease were combined as a composite variable and subjected to multivariate logistic regression analysis controlling for age, sex, race, dental school, smoking history and alcohol consumption, no statistically significant association was observed between respiratory condition and year in dental school or exposure to the dental environment as a dental patient . CONCLUSION: No association was found between the prevalence of respiratory disease and a student's year in dental school or previous exposure to the dental environment as a patient . These results suggest that exposure to the dental environment does not increase the risk for respiratory infection in healthy dental health care workers.

J Infect Dis, 2004 Mar 15, 189(6), 1103 - 12 Epub 2004 Mar 01.
Immune response of healthy women to 2 different group B streptococcal type V capsular polysaccharide-protein conjugate vaccines; Baker CJ et al.; BACKGROUND: Infections caused by group B streptococcal (GBS) type V are increasingly common . Capsular polysaccharide (CPS)-protein conjugate GBS vaccines are immunogenic in healthy adults, but type V vaccines have not previously been tested . METHODS: Thirty-five healthy, nonpregnant women were randomized to receive an intramuscular dose of GBS type V CPS-tetanus toxoid (TT) vaccine (n=15), GBS type V CPS-cross-reactive material (CRM(197)) conjugate vaccine (n=15), or placebo (n=5) (double-masked design) . Levels of serum antibodies to type V CPS were measured by ELISA, and functional activity was measured by opsonophagocytosis . RESULTS: The vaccines were well tolerated . Significant increases in type V CPS-specific immunoglobulin G (IgG) were elicited by both vaccines, peaking at 4-8 weeks and persisting for 26 weeks . Four-fold or greater increases in type V CPS-specific IgG concentrations were noted in postimmunization serum samples obtained from 93% of subjects in each vaccine group . These concentrations persisted in > or =85% of conjugate-vaccine recipients 104 weeks later . Type V CPS-specific immunoglobulin M was a dominant isotype of immune response to each conjugate . Postimmunization serum samples promoted opsonophagocytic killing of GBS type V in vitro, whereas those from placebo recipients did not . CONCLUSION: GBS type V conjugate vaccines are safe and immunogenic and would be appropriate for inclusion in a candidate multivalent GBS vaccine.

J Int Med Res, 2004 Jan-Feb, 32(1), 1 - 13
Acute streptococcal tonsillopharyngitis: a review of clinical efficacy and bacteriological eradication; Schaad UB; This review evaluates studies published between January 1997 and August 2003 comparing clinical outcome and bacteriological eradication rates for patients with acute streptococcal tonsillopharyngitis treated with penicillin or other antimicrobial agents . Studies were identified using MEDLINE, and clinical outcome and bacteriological eradication at end of treatment and 2 weeks after end of treatment were ascertained . Any longer-term follow-up was also noted, along with treatment-related adverse events and compliance . Clinical efficacy rates between penicillin and comparator antibiotics were generally high and similar . Bacterial eradication rates were more variable and, 2 weeks after treatment, ranged from 64% to 93% for penicillin and 31% to 98% for comparators . Simpler dosing schedules and shorter therapy durations produced higher compliance rates . This review highlights the similarities and differences between treatment with penicillin and a wide range of comparator antibiotics . Therapy for acute group A streptococcal pharyngitis should combine excellent clinical efficacy, high bacteriological eradication rates, good tolerance and a simple, convenient dosing regimen.

Adv Neonatal Care, 2004 Feb, 4(1), 20 - 5
Facial submandibular cellulitis associated with late-onset group B streptococcal infection; Pickett KC et al.; A complete history and systematic physical examination are important first steps in assessing any infant . In some instances these steps may provide immediate clues to a potentially life-threatening illness . This article presents the case of a former 26-week male infant, who presented on day of life 42, 32 weeks gestation corrected, with increased respiratory distress and an evolving lesion on the left lower cheek . The classic location and progressive erythema, warmth, induration, and tenderness in the submandibular region strongly suggested the diagnosis of group B streptococcal (GBS) cellulitis . Despite the presence of concurrent GBS septicemia, the infant had complete resolution of focal and systemic symptoms with 10 days of treatment . One month later, the infant developed pneumonia with respiratory failure, shock, culture-positive septicemia, and presumed meningitis and was again treated with broad-spectrum antibiotics . Diagnosis at that time was late-onset group B streptococcal infection . Serotypes were not available to aid in distinguishing between recurrent or persistent GBS versus a new occurrence of late-onset disease . A brief overview of late-onset GBS infections and their cutaneous manifestations, along with a step-by-step guide to physical examination, is provided . The differential diagnosis for facial cellulitis is reviewed with an emphasis on early recognition and treatment in light of the escalated risks for persistent or recurrent GBS infection in infants with GBS cellulitis.

Eur J Clin Microbiol Infect Dis, 2004 Mar, 23(3), 168 - 73 Epub 2004 Feb 25.
Group B streptococcal disease in nonpregnant adults: incidence, clinical characteristics, and outcome; Blancas D et al.; A retrospective review of 150 cases of group B streptococcal disease in nonpregnant adults over an 8-year period was performed in a single tertiary-care teaching hospital to determine the incidence, clinical spectrum, and outcome of the disease . Incidence increased from 0.53 cases per 1,000 admissions in the 1993-1994 period to 0.96 cases per 1,000 admissions in 1999-2000 (P=0.013, chi-square test for trend) . Bacteremia also increased from 0.15 to 0.42 cases per 1,000 admissions over the same period of time (P=0.005, chi-square test for trend) . The mean age of the patients was 61.4 years, and 92% had at least one underlying disease . Bacteremia was detected in 60.9% of patients in whom blood cultures were performed . Fourteen (9.3%) patients died . Factors independently associated with an increased risk of dying were shock at diagnosis (OR, 23.96; 95%CI, 3.44-166.57; P=0.001) and cancer (OR, 4.96; 95%CI, 1.43-17.20; P=0.012) . Group B streptococcal disease in nonpregnant adults is on the rise in the hospital investigated, particularly in persons with underlying conditions . The clinical spectrum of the disease ranges from localized to severe bacteremic infections . Shock at diagnosis and cancer are factors independently associated with a higher fatality rate.

J Antimicrob Chemother, 2004 Apr, 53(4), 669 - 74 Epub 2004 Feb 25.
Daptomycin activity and spectrum: a worldwide sample of 6737 clinical Gram-positive organisms; Streit JM et al.; BACKGROUND: Increasing antimicrobial resistance among bacterial pathogens has prompted attempts to develop new antimicrobial agents active against multidrug-resistant Gram-positive pathogens . OBJECTIVES: To evaluate the in vitro activity of daptomycin against a worldwide collection of clinical bacterial isolates . METHODS: Daptomycin is a novel cyclic lipopeptide recently approved by the United States Food and Drug Administration . Daptomycin and selected comparators were tested against 6737 clinical Gram-positive strains from more than 70 centres located in Europe, North America and South America . RESULTS: The overall distribution of daptomycin MIC values were in the range < or = 0.12-8 mg/L and 99.4% of all strains were inhibited at < or = 2 mg/L . Despite resistances to other antimicrobial agents, >99.9% of staphylococcal isolates were inhibited at < or = 1 mg/L of daptomycin (MIC90 0.5 mg/L for staphylococci) . Streptococcal isolates were very susceptible to daptomycin independent of their susceptibility to penicillin . MIC50/90 values were < or = 0.12 and 0.25 mg/L, respectively . Enterococci showed the highest daptomycin MIC values, but all isolates tested were inhibited at < or = 4 mg/L (except for one Enterococcus faecium isolate which showed a daptomycin MIC of 8 mg/L) . CONCLUSIONS: Daptomycin exhibited excellent in vitro activity against a wide spectrum of Gram-positive organisms and may represent a therapeutic option for infections caused by multidrug-resistant pathogens worldwide.

Protein Eng, 2003 Dec, 16(12), 1147 - 52
Evaluation of different linker regions for multimerization and coupling chemistry for immobilization of a proteinaceous affinity ligand; Linhult M et al.; Alkaline conditions are generally preferred for sanitization of chromatography media by cleaning-in-place (CIP) protocols in industrial biopharmaceutical processes . The use of such rigorous conditions places stringent demands on the stability of ligands intended for use in affinity chromatography . Here, we describe efforts to meet these requirements for a divalent proteinaceous human serum albumin (HSA) binding ligand, denoted ABD*dimer . The ABD*dimer ligand was constructed by genetic head-to-tail linkage of two copies of the ABD* moiety, which is a monovalent and alkali-stabilized variant of one of the serum albumin-binding motifs of streptococcal protein G . Dimerization was performed to investigate whether a higher HSA-binding capacity could be obtained by ligand multimerization . We also investigated the influence on alkaline stability and HSA-binding capacity of three variants (VDANS, VDADS and GGGSG) of the inter-domain linker . Biosensor binding studies showed that divalent ligands coupled using non-directed chemistry demonstrate an increased molar HSA-binding capacity compared with monovalent ligands . In contrast, equal molar binding capacities were observed for both types of ligands when using directed ligand coupling chemistry involving the introduction and recruitment of a unique C-terminal cysteine residue . Significantly higher molar binding capacities were also detected when using the directed coupling chemistry . These results were confirmed in affinity chromatography binding capacity experiments, using resins containing thiol-coupled ligands . Interestingly, column sanitization studies involving exposure to 0.1 M NaOH solution (pH 13) showed that of all the tested constructs, including the monovalent ligand, the divalent ligand construct containing the VDADS linker sequence was the most stable, retaining 95% of its binding capacity after 7 h of alkaline treatment.

Antimicrob Agents Chemother, 2004 Mar, 48(3), 739 - 46
Comparative in vitro activities of AC98-6446, a novel semisynthetic glycopeptide derivative of the natural product mannopeptimycin alpha, and other antimicrobial agents against gram-positive clinical isolates; Petersen PJ et al.; AC98-6446 is a novel semisynthetic cyclic glycopeptide antibiotic related to the natural product mannopeptimycin alpha (AC98-1) . In the present study the activity of AC98-6446 was evaluated against a variety of recent clinical gram-positive pathogens including multiply resistant strains . AC98-6446 demonstrated similar potent activities against methicillin-susceptible and methicillin-resistant staphylococci and glycopeptide-intermediate staphylococcal isolates (MICs at which 90% of isolates are inhibited {MIC(90)s}, 0.03 to 0.06 microg/ml) . AC98-6446 also demonstrated good activities against both vancomycin-resistant and -susceptible strains of enterococci (MIC(90)s, 0.12 and 0.25 microg/ml, respectively) as well as against streptococcal strains (MIC(90)s, <or= 0.008 to 0.03 microg/ml) . AC98-6446 demonstrated bactericidal activity in terms of the reduction in the viable counts (>3 log(10) CFU/ml) of staphylococcal and streptococcal isolates and a marked decrease in the viable counts of most enterococcal strains (from 0.2 to 2.5 log(10) CFU/ml) . Unlike vancomycin, which demonstrates time-dependent killing, AC98-6446 demonstrated concentration-dependent killing . The potent activity, novel structure, and bactericidal activity demonstrated by AC98-6446 make it an attractive candidate for further development.

Paediatr Respir Rev, 2004, 5 Suppl A, S289 - 97
Surfactant use for neonatal lung injury: beyond respiratory distress syndrome; Finer NN; Surfactant has led to a significant reduction in neonatal mortality for premature infants with lung immaturity and respiratory distress . However, surfactant therapy has been shown to be effective in the treatment of a number of other neonatal respiratory disorders and the evidence for surfactant use in such circumstances is presented . Meconium aspiration is characterised by severe atelectasis, the influx of neutrophils, edema, and hyaline membranes, with decreased levels of SP-A and SP-B and the large aggregate fraction of lung surfactant, and altered surfactant surface morphology . Meconium contains cholesterol, free fatty acids and bilirubin all of which can interfere with surfactant function in a dose-dependent fashion . Providing larger amounts of surfactant can overcome some of this inhibition . Animal models of meconium aspiration treated with surfactant have improved histology, lung mechanics and gas exchange . Studies in human infants with meconium aspiration have found elevated concentrations of total protein, albumin, and membrane-derived phospholipid in lung lavage fluid, and haemorrhagic pulmonary edema . Clinical studies in such neonates have reported improved gas exchange and clinical outcomes following surfactant treatment . More recently surfactant lavage has been shown to be a potentially efficacious therapy for such infants . The inflammatory exudate containing plasma proteins and cytokines which accompanies neonatal pneumonia may inactivate surfactant . Surfactant treatment given to animals following the tracheal instillation of group B Streptococcal resulted in significantly less bacterial growth and improved lung function . Small clinical experiences have demonstrated the benefit of surfactant to infants with pneumonia/sepsis . Pulmonary haemorrhage, which some consider a complication of surfactant therapy, has also been effectively managed using surfactant instillation . The hemoglobin and red blood cell lipids may act to inhibit natural surfactant and treatment with surfactant has been shown to improve outcome for infants with pulmonary haemorrhage . Animal models of congenital diaphragmatic hernia (CDH) have hypoplastic lungs with evidence of decreased lamellar bodies in their type II pneumocytes and resultant surfactant deficiency, and respond to surfactant replacement with improved gas exchange and lung mechanics . The lungs of human infants with CDH contain less phospholipids and phosphatidylcholine per milligram of DNA than control infants . Case reports have reported a benefit of surfactant for infants with CDH . In the near-term infants with severe respiratory distress, surfactant is one of the therapies along with inhaled nitric oxide and high frequency ventilations, that have resulted in improved outcomes . Surfactant treatment may be of significant benefit in newborn infants with respiratory compromise secondary to a number of insults, and further prospective evidence of its efficacy in such disorders is needed.

Infez Med, 1996, 4(3), 153 - 61
{Beta-haemolytic group A streptococcal acute pharyngo-tonsillitis in pediatric patients: a clinical and epidemiological study}; Esposito S et al.; Authors compared the efficacy and safety of 10-day regimen of Cefaclor (CEC), oral suspension, at the dose of 25 mg/kg BID, and Amoxicillin/clavulanic acid (AMC), and Erythromycin (E) both given TID at the dose of 15 mg/kg in the treatment of proven group A beta hemolytic streptococcal pharyngo-tonsillitis . Of the 673 enrolled pediatric patients, 245 were selected and assigned to three groups of treatment (85 received CEC, 78 received AMC and 82 received E) and 217 were evaluated for efficacy . Clinical evaluations were performed on days 5 and 10 of treatment and 20 days after its completion (follow up) . Before treatment, on treatment day 10 and at follow up throat swab cultures were performed . In evaluable patients the post-therapy clinical success and bacteriological eradication rate for CEC was 91.8% (68 of 74 evaluable patients); the rate for AMC and E were 90.5% (67/74) and 76.8% (53/69) respectively . At follow up bacteriological eradication was observed in 63 of 68 clinically cured patients (92.6%) in the CEC treatment group; in 64 of 67 (95.5%) in the AMC treatment group and in 49 of 53 (92.4%) in the E treatment group . Adverse events occurred in 24 of 217 (11.05%) treated patients and the incidence of side effects was lower in CEC group . In vitro sensitivity tests showed 37.9% of isolated SBEGA strains resistant to macrolides and 32% of SBEGA strains resistant to tetracycline . In our experience Cefaclor administered BID is as effective and more safe than Amoxicillin/clavulanic acid and more effective than Erythromycin both given TID.

Gene Ther, 2004 Apr, 11(7), 581 - 90
An inflammation-inducible adenoviral expression system for local treatment of the arthritic joint; van de Loo FA et al.; To achieve a disease-regulated transgene expression for physiologically responsive gene therapy of arthritis, a hybrid promoter was constructed . The human IL-1 beta enhancer region (-3690 to -2720) upstream of the human IL-6 promoter region (-163 to +12) was essential in mounting a robust response in HIG-82 synovial fibroblasts and in RAW 264,7 macrophages . A replication-deficient adenovirus was engineered with luciferase (Luc) controlled by the IL-1/IL-6 promoter (Ad5.IL-1/IL-6-Luc) . LPS caused a 23- and 4.6-fold induction of Luc . activity in RAW cells infected with Ad5.IL-1/IL-6-Luc or the conventional Ad5.CMV-Luc construct, respectively . Next, adenoviruses (10(6) ffu) were injected into the knees of C57Bl/6 mice . An intra-articular injection of zymosan, 3 days after Ad5.IL-1/IL-6-Luc, increased Luc . activity by 39-fold but had no effect in the Ad5.CMV-Luc joints . The constitutive CMV promoter was rapidly silenced and could not be reactivated in vivo . In contrast, the IL-1/IL-6 promoter could be reactivated by Streptococcal cell wall (SCW)-induced arthritis up to 21 days after infection . Next the IL-1/IL-6 promoter was compared to the C3-Tat/HIV-LTR two-component system in wild-type, IL-6(-/-) and IL-1(-/-) gene knockout mice . Both systems responded well to LPS-, zymosan- and SCW-induced arthritis . However, the basal activity of the IL-1/IL-6 promoter was lower and IL-6 independent . This study showed that the IL-1/IL-6 promoter is feasible to achieve disease-regulated transgene expression for treatment of arthritis.

J Neurosci, 2004 Feb 18, 24(7), 1780 - 91
A murine model for neuropsychiatric disorders associated with group A beta-hemolytic streptococcal infection; Hoffman KL et al.; A syndrome of motoric and neuropsychiatric symptoms comprising various elements, including chorea, hyperactivity, tics, emotional lability, and obsessive-compulsive symptoms, can occur in association with group A beta-hemolytic streptococcal (GABHS) infection . We tested the hypothesis that an immune response to GABHS can result in behavioral abnormalities . Female SJL/J mice were immunized and boosted with a GABHS homogenate in Freund's adjuvant, whereas controls received Freund's adjuvant alone . When sera from GABHS-immunized mice were tested for immunoreactivity to mouse brain, a subset was found to be immunoreactive to several brain regions, including deep cerebellar nuclei (DCN), globus pallidus, and thalamus . GABHS-immunized mice having serum immunoreactivity to DCN also had increased IgG deposits in DCN and exhibited increased rearing behavior in open-field and hole-board tests compared with controls and with GABHS-immunized mice lacking serum anti-DCN antibodies . Rearing and ambulatory behavior were correlated with IgG deposits in the DCN and with serum immunoreactivity to GABHS proteins in Western blot . In addition, serum from a GABHS mouse reacted with normal mouse cerebellum in nondenaturing Western blots and immunoprecipitated C4 complement protein and alpha-2-macroglobulin . These results are consistent with the hypothesis that immune response to GABHS can result in motoric and behavioral disturbances and suggest that anti-GABHS antibodies cross-reactive with brain components may play a role in their pathophysiology.

Pediatr Infect Dis J, 2004 Feb, 23(2), 172 - 3
Neonatal group B streptococcal infection: incidence and strategies for prevention in Europe; Trijbels-Smeulders MA et al.; We sent a questionnaire to all members of the European Society for Paediatric Infectious Diseases and to all delegates of the European Association of Perinatal Medicine to determine existing policies for prevention of neonatal group B streptococcal (GBS) infection in Europe . The incidence of GBS colonization in pregnant women and of neonatal GBS infection varies . Policies for prevention of GBS infection are not well-developed.

Pediatr Infect Dis J, 2004 Feb, 23(2), 161 - 5
Neonatal invasive group A streptococcal disease: case report and review of the literature; Miyairi I et al.; We present a fatal case of neonatal invasive group A streptococcal disease and review of the literature . Twenty-four cases were early onset disease and were associated with concurrent maternal infection, respiratory distress, pneumonia, toxic shock-like syndrome and serotype M1 . Fifteen cases were late onset disease associated with soft tissue infections and meningitis . Maternal carriage was identified as an important factor in neonatal group A streptococcal disease.

Rev Med Chir Soc Med Nat Iasi, 2003 Jul-Sep, 107(3), 565 - 9
{Cutaneous and oral manifestations in HIV-infected children and adults--169 cases}; Mihalache D et al.; The aim of the study was to evaluate cutaneous and oral manifestations in infected HIV patients . MATERIALS AND METHODS: We retrospectively analyzed 169 cases admitted in Infectiouse Disease Department of Iasi in 2001-2002 period . RESULTS: Cutaneous and oral manifestations were: candidiasis (99 cases), herpes virus infectious (36 cases), scabies and straphylococcal/streptococcal skin disease (26 cases), prurigo nodularis, psoriasis and verruca vulgaris (9 cases) . Children of 0-13 year old group was 75.73 percent . Classification of HIV infection was related with CD4 count for 166 cases . Twelve cases with oral pharyngitis candidiasis, scabies and streptococcal skin diseases was 2-3 recurrent episodes of manifestations . Etiotrop treatment was associated with HAART therapy . CONCLUSIONS: Cutaneous and oral manifestations are occurred frequently in HIV infected patients, with a various etiology, but the severity, persistence and its evolution did not evaluate.

MLO Med Lab Obs, 2004 Jan, 36(1), 10 - 5; quiz 16-7
Direct nucleic acid diagnostic tests for bacterial infectious diseases: streptococcal pharyngitis, pulmonary tuberculosis, vaginitis, chlamydial and gonococcal infections; Paillard F et al.; Partnering with a reference lab can actually help grow a referring lab's own business . The reference lab provides a hospital's physicians with access to unique tests and clinical information and broadens the scope and depth of the referring lab's menu . As medicine moves toward prescribed treatments based on a patient's individual genotype or phenotype, the reference lab will play an even bigger role in helping the hospital to educate physicians and their patients to the most efficient testing strategies consistent with good patient management.

Lancet, 2004 Jan 24, 363(9405), 292 - 4
Group B streptococcal disease in UK and Irish infants younger than 90 days; Heath PT et al.; The incidence, morbidity, and mortality of group B streptococcal disease in the UK and Republic of Ireland are largely unknown . Between Feb 1, 2000, and Feb 28, 2001, we identified cases of invasive group B streptococcal disease in infants younger than 90 days through surveillance involving paediatricians, microbiologists, and parents . 568 cases were identified, equivalent to a total incidence of 0.72 per 1000 live-births (95% CI 0.66-0.78); the incidence for early-onset disease (n=377) was 0.48 per 1000 (0.43-0.53), and for late-onset disease (n=191) was 0.24 per 1000 (0.21-0.28) . Risk factors were identifiable for 218 (58%) cases of early-onset disease . 53 infants died (overall 9.7%) . We have established the minimum current burden of group B streptococcal disease in UK and Irish infants . This information will assist in the formulation of guidelines for prevention of this disease.

J Immunol, 2004 Feb 1, 172(3), 1719 - 26
HLA class II polymorphisms determine responses to bacterial superantigens; Llewelyn M et al.; The excessive immunological response triggered by microbial superantigens has been implicated in the etiology of a wide range of human diseases but has been most clearly defined for the staphylococcal and streptococcal toxic shock syndromes . Because MHC class II presentation of superantigens to T cells is not MHC-restricted, the possibility that HLA polymorphisms could influence superantigenicity, and thus clinical susceptibility to the toxicity of individual superantigens, has received little attention . In this study, we demonstrate that binding of streptococcal and staphylococcal superantigens to HLA class II is influenced by allelic differences in class II . For the superantigen streptococcal pyrogenic exotoxin A, class II binding is dependent on DQ alpha-chain polymorphisms such that HLA-DQA1*01 alpha-chains show greater binding than DQA1*03/05 alpha-chains . The functional implications of differential binding on T cell activation were investigated in various experimental systems using human T cells and murine Vbeta8.2 transgenic cells as responders . These studies showed quantitative and qualitative differences resulting from differential HLA-DQ binding . We observed changes in T cell proliferation and cytokine production, and in the Vbeta specific changes in T cell repertoire that have hitherto been regarded as a defining feature of an individual superantigen . Our observations reveal a mechanism for the different outcomes seen following infection by toxigenic bacteria.

Structure (Camb), 2004 Jan, 12(1), 145 - 56
Crystal and solution structures of a superantigen from Yersinia pseudotuberculosis reveal a jelly-roll fold; Donadini R et al.; Superantigens are a class of microbial proteins with the ability to excessively activate T cells by binding to the T cell receptor . The staphylococcal and streptococcal superantigens are closely related in structure and possess an N-terminal domain that resembles an OB fold and a C-terminal domain similar to a beta-grasp fold . Yersinia pseudotuberculosis produces superantigens, YPMa, YPMb, and YPMc, which have no significant amino acid similarity to other proteins . We have determined the crystal and solution structures of YPMa, which show that the protein has a jelly-roll fold . The closest structural neighbors to YPMa are viral capsid proteins and members of the tumor necrosis factor superfamily . In the crystal structure, YPMa packs as a trimer, another feature shared with viral capsid proteins and TNF superfamily proteins . However, in solution YPMa behaves as a monomer, and any functional relevance of the trimer observed in the crystals is yet to be established.

J Trop Pediatr, 2003 Dec, 49(6), 377 - 9
The validity of diagnostic criteria for streptococcal pharyngitis in Integrated Management of Childhood Illness (IMCI) guidelines; Sahin F et al.; The WHO's Integrated Management of Childhood Illness (IMCI) programme is being implemented in Turkey with an additional section relating to throat problems for our country's adaptation . The aim of this study is to evaluate the validity of this additional part and suggest new combinations for the diagnosis of streptococcal pharyngitis to improve the guidelines . Throat swabs were obtained from 245 children between 0 and 17 years of age with signs and symptoms of upper respiratory tract infections . Considering the throat culture based diagnosis as the gold standard, the validity of the symptoms alone and in combinations were calculated . The combination in Turkey's IMCI guideline was found to be 36.9 per cent sensitive and 68.3 per cent specific . Sensitivities of combinations including at least two of the following three symptoms, namely sore throat, pharyngeal erythema, and pharyngeal exudates or sore throat, pharyngeal erythema, and fever, were 76.9 and 87.7 per cent, respectively . Specificities of the same combinations were 49.4 and 30.6 per cent . We concluded that new combinations with a higher sensitivity may be considered as a criterion for antibiotic treatment.

Am J Respir Med, 2003, 2(2), 175 - 201
Clarithromycin extended-release tablet: a review of its use in the management of respiratory tract infections; Darkes MJ et al.; Clarithromycin is an orally active, advanced-generation macrolide that has been reformulated as an extended-release tablet (Biaxin) XL Filmtab allowing convenient once-daily administration . The reformulation is intended to improve patient compliance and the tolerability of the drug.Although maximum plasma clarithromycin concentrations are lower and reached later with the extended-release tablets than with the immediate-release tablets, the two formulations are bioequivalent with respect to the area under the plasma concentration-time curve . Bioequivalence is also achieved between the formulations for the microbiologically active metabolite, 14-hydroxy-clarithromycin . Two randomized trials in patients with acute exacerbations of chronic bronchitis (AECB) showed that a 7-day course of clarithromycin extended-release 1000 mg once daily produced clinical cure rates of 83% and 85% and bacteriologic cure rates of 86% and 92% at the test-of-cure study visit . Similar rates of cure were achieved with a 7-day course of twice-daily clarithromycin immediate-release and with a 10-day course of twice-daily amoxicillin/clavulanic acid.A 7-day course of clarithromycin extended-release 1000 mg once daily produced clinical and bacteriologic cure rates of 88% and 86%, respectively, in patients with community-acquired pneumonia (CAP) . Similar cure rates were achieved in recipients of once-daily levofloxacin in the same trial . In patients with acute maxillary sinusitis, a 14-day course of either once-daily clarithromycin extended-release or twice-daily clarithromycin immediate-release produced statistically equivalent clinical cure rates of 85% and 79%, respectively . Both treatment groups achieved similar rates of radiographic success and resolution of sinusitis . Recent results indicate that clarithromycin extended-release 500 mg once daily for 5 days is also effective in the treatment of patients with streptococcal pharyngitis/tonsillitis and in the treatment of AECB.The most frequently reported drug-related events with clarithromycin extended-release were abnormal taste (7% incidence), diarrhea (6%) and nausea (3%) . Most adverse drug reactions were of a mild and transient nature . In comparative clinical trials, clarithromycin extended-release had an improved gastrointestinal tolerability profile compared with the immediate-release formulation . In addition, clarithromycin extended-release was better tolerated than amoxicillin/clavulanic acid and as well tolerated as levofloxacin . Further studies are required to assess the cost-effectiveness ratio of clarithromycin relative to comparator antibacterial agents . CONCLUSION: Clarithromycin extended-release is an effective treatment for AECB, CAP, acute maxillary sinusitis, and pharyngitis (although not approved for the latter in the US), and is administered in a convenient dosage regimen that has the potential to encourage good compliance . The reformulation modulates clarithromycin absorption kinetics thereby improving tolerability . Therefore, clarithromycin extended-release provides a useful option for the treatment of specific respiratory tract infections.

Bone Marrow Transplant, 2004 Jan, 33(1), 79 - 85
Viridans streptococcal septicaemia in neutropenic patients: role of proinflammatory cytokines; Ihendyane N et al.; The immunostimulatory activity of viridans streptococcal strains isolated from neutropenic patients with severe sepsis (n=9) or uncomplicated bacteraemia (n=10) was compared . Peripheral blood mononuclear cells from healthy individuals were stimulated with heat-killed bacteria or culture supernatants, and cytokine production assessed . All strains were potent inducers of IL1beta, IL8, and TNFalpha production . Heat-killed bacteria induced consistently higher IL1beta and TNFalpha production than did the cell-free bacterial supernatants (P<0.01) . The strains did not induce any proliferative response, nor any significant TNFbeta or IFNgamma production . No difference in cytokine-inducing capacity could be detected between the cohorts of severe and nonsevere isolates . Comparison of strains causing severe and nonsevere episodes in the same patient (n=2) revealed a significantly higher induction of IL1beta by the severe episodes associated isolates as compared to the nonsevere (P<0.04) . The study underscores the importance of the host-pathogen interplay in determining the level of inflammation, and hence the severity of disease.

Rev Esp Quimioter, 2003 Sep, 16(3), 313 - 24
{Meta-analysis of clarithromycin compared with other antimicrobial drugs in the treatment of upper respiratory tract infections}; Abad-Santos F et al.; The goal of this meta-analysis was to evaluate the effectiveness of clarithromycin versus most commonly used treatments for upper respiratory infections . We performed a systematic review of comparative clinical trials found in the literature . Regarding effectiveness, no significant differences were found in comparisons between clarithromycin and amoxicillin-clavulanic acid for upper respiratory infections, nor for cephalosporins, amoxicillin or amoxicillin-clavulanic acid for otitis media, nor oral penicillin for classic streptococcal tonsillitis . Clarithromycin was more effective than betalactam antibiotics for sinusitis (OR: 1.27, 95% CI: 1.01-1.61 in intent-to-treat analysis) . The effectiveness of clarithromycin was better than that for azithromycin, but only reached statistical significance in the per-protocol analysis . The global analysis including all 33 clinical trials showed a small benefit for clarithromycin reaching statistical significance in the fixed-effects model (OR: 1.12, 95% CI: 1.01-1.25) . Regarding safety, the incidence of adverse events was significantly lower for clarithromycin compared to amoxicillin and amoxicillin-clavulanic acid . No differences were found when comparing adverse events due to cephalosporins, azithromycin and betalactam antibiotics, but the incidence of adverse events for clarithromycin was higher compared to that of oral penicillin for streptococcal tonsillitis treatment . Overall, all the compared drugs were well tolerated; discontinuations due to adverse events were very low: 2.2% for clarithromycin treatment and 2.5% for the other antibiotics . It was concluded that clarithromycin is an effective and safe treatment for upper respiratory infection, and its new formulation in a single daily dose may improve therapeutic compliance.

Thromb Res, 2003, 111(4-5), 243 - 9
Platelet activity and antibody titers after exposure to streptokinase or streptococcal infection; Courval M et al.; INTRODUCTION: Streptokinase use, in acute myocardial infarction, is hindered by failure to reperfuse (60%) and early reocclusion (16%) . This phenomenon may, among other causes, be due to systemic inactivation of streptokinase, as well as streptokinase-induced platelet aggregation and clot propagation from antibodies to streptokinase produced after streptokinase administration or streptococcal infections . The purpose of this study was to determine the incidence of streptokinase-induced, antibody-mediated, platelet activation and aggregation after administration of SK or development of a streptococcal infection . MATERIALS AND METHODS: We included 45 normal volunteers (Control group), as well as 45 patients who had received streptokinase (Streptokinase group) and 13 who had suffered a severe streptococcal infection (Streptococcal infection group) within the past 3 years . Extent of streptokinase-induced, antibody-mediated, platelet activation and aggregation, as well as anti-streptokinase antibody and streptokinase resistance titers (lowest streptokinase concentration to cause clot lysis within 10 min) were measured . RESULTS: Whereas streptokinase-induced, antibody-mediated, platelet activation was observed in 49% of streptokinase patients and in only 17% and 15% of streptococcal infection patients and normal volunteers (p<0.05 Streptokinase vs . Control and Streptokinase vs . Streptococcal infection), streptokinase-induced platelet aggregation was observed in 23% of streptokinase patients and streptococcal infection patients, and in none of the control patients (p<0.05) . CONCLUSIONS: Streptokinase-induced, antibody-mediated, platelet activation and aggregation occur in patients with high titers of anti-streptokinase antibody and may play a role in failure of streptokinase therapy . Streptococcal infection patients behave like streptokinase patients in terms of the reactivity of their platelets to subsequent streptokinase dose in vitro.

Infect Immun, 2004 Jan, 72(1), 364 - 70
Plasminogen binding by group A streptococcal isolates from a region of hyperendemicity for streptococcal skin infection and a high incidence of invasive infection; McKay FC et al.; Reports of resurgence in invasive group A streptococcal (GAS) infections come mainly from affluent populations with infrequent exposure to GAS . In the Northern Territory (NT) of Australia, high incidence of invasive GAS disease is secondary to endemic skin infection, serotype M1 clones are rare in invasive infection, the diversity and level of exposure to GAS strains are high, and no particular strains dominate . Expression of a plasminogen-binding GAS M-like protein (PAM) has been associated with skin infection in isolates elsewhere (D . Bessen, C . M . Sotir, T . M . Readdy, and S . K . Hollingshead, J . Infect . Dis . 173:896-900, 1996), and subversion of the host plasminogen system by GAS is thought to contribute to invasion in animal models . Here, we describe the relationship between plasminogen-binding capacity of GAS isolates, PAM genotype, and invasive capacity in 29 GAS isolates belonging to 25 distinct strains from the NT . In the presence of fibrinogen and streptokinase, invasive isolates bound more plasminogen than isolates from uncomplicated infections (P < or = 0.004) . Only PAM-positive isolates bound substantial levels of plasminogen by a fibrinogen-streptokinase-independent pathway (direct binding) . Despite considerable amino acid sequence variation within the A1 repeat region of PAM where the plasminogen-binding domain maps, the critical lysine residue was conserved.

J Mol Biol, 2004 Jan 16, 335(3), 733 - 43
Features of the plasmid pMV158-encoded MobM, a protein involved in its mobilization; de Antonio C et al.; The streptococcal promiscuous plasmid pMV158 can be mobilized between a number of bacterial species by means of three elements: (i) the plasmid-encoded nicking-closing protein MobM, involved in the initiation and termination of the conjugative transfer; (ii) the DNA sequence where the MobM-mediated nick takes place (the oriT(pMV158)); and (iii) the function(s) provided by auxiliary plasmids . MobM belongs to the Pre/Mob family of plasmid-encoded DNA-relaxing proteins (relaxases) . Purified MobM protein has been used to assay cleavage conditions on plasmid supercoiled DNA . Some structural features of MobM have been addressed by analytical ultracentrifugation, circular dichroism, thermal denaturation, and fluorescence emission . The protein behaved as a dimer of identical subunits with an ellipsoidal shape . MobM showed a high (about 60%) alpha-helical content and a midpoint denaturation of about 40 degrees C . Cell fractionation assays showed that MobM was associated to the cell membrane . This association was abolished when a great alteration was introduced within a putative coiled-coil located at the C-terminal region of the protein . Emission fluorescence suggested that the three Trp residues of MobM are located within a hydrophobic environment . A molecular model of MobM on the known structure of colicin Ia has been built.

J Pediatr (Rio J), 1999 Nov, 75(Suppl 2), S207 - 13
{Hypertensive crisis}; Sapolnik R; OBJECTIVE: Based on the review of the principal aspects of physiopathology, clinical presentation, and differential diagnosis, the article outlines the principles for the treatment of hypertensive crises in children, supporting early and systematic approach, with better short and long term prognoses . METHODS: Electronic research of the medical literature from the last twenty years (1979-1999) and protocols from intensive care and emergency services from USA and Canada were reviewed.RESULTS: Hypertensive crises in children can occur as primary presentation or in a child known as hypertensive . The differential diagnosis of the most common causes is based on the clinical history, physical examination and laboratory and bioimage studies . Renal (post-streptococcal glomerulonephritis, acute and chronic renal insufficiency, renal arterial stenosis) and cardiac (aortic stenosis) diseases are the most common causes in children . The treatment is directed by the clinical presentation: urgency or emergency crisis . The most used drugs are presented, together with clinical indications and pharmacological characteristics (route of administration, half-life, side effects) . The general principles of treatment are described, improving the care of affected children.CONCLUSIONS: The treatment of hypertensive crises in children is based on the rational use of antihypertensive drugs for the different causes and clinical presentations, and on basic and advanced support of the systemic repercussions of the crises.

Am J Med Genet B Neuropsychiatr Genet, 2004 Jan 1, 124(1), 76 - 80
Linkage disequilibrium analysis of polymorphisms in the gene for myelin oligodendrocyte glycoprotein in Tourette's syndrome patients from a Chinese sample; Huang Y et al.; Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder characterised by multiple motor and phonic tics, which wax and wane . Recently, evidence has accumulated supporting the role of autoimmune mechanisms in the aetiology of GTS, suggesting that it is within the paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) spectrum of childhood neurobehavioural disorders . An immunopathogenic role of antibodies against myelin oligodendrocyte glycoprotein (MOG) has been suggested in this syndrome . In this study, we investigate the association of three microsatellite polymorphisms (MOGa, MOGb, MOGc) in the gene for MOG with GTS in 197 family trios collected from southwest China . Linkage disequilibrium between these three markers was observed with the strongest between MOGa and MOGc (D' = 0.541, P = 0.000) . We did not find overall significant evidence for distorted transmission of any of these three markers of MOG gene in GTS, although we observed a weak preferential transmission of the 148 bp allele of MOGc (chi(2) = 4.000, P = 0.046) which did not survive correction for multiple testing . Our results suggest that there is no association between the MOG gene polymorphisms we tested and GTS .

Child Care Health Dev, 2004 Jan, 30(1), 1 - 3
Neonatal Group B streptococcal infection at the Mount Hope Women's Hospital, Trinidad; Ali Z; OBJECTIVE: To determine the incidence of early onset Group B streptococcal (GBS) infection in neonates at the Mount Hope Women's Hospital, Trinidad over the period 1996-97 . DESIGN AND METHODS: This retrospective study included all babies with a positive blood culture for GBS during the study period . RESULTS: There were 9866 live births (LB) of whom 29 were diagnosed as early onset GBS disease . The incidence was 2.9/1000 LB . 37.9% of babies were preterm and 65.5% were delivered to primiparous women . Rupture of amniotic membranes occurred within 12 h of delivery in 55% of infected babies . Four of the 29 infected babies died and all were preterm . CONCLUSION: The incidence of early onset neonatal GBS sepsis was five to six times higher in this series than that reported in the USA and UK . An intervention policy to control this preventable disease is urgently needed.

Am J Transplant, 2004 Jan, 4(1), 132 - 6
Acute post-bacterial glomerulonephritis in renal transplant patients: description of three cases and review of the literature; Moroni G et al.; Only a few cases of acute post-infectious glomerulonephritis have been described in renal transplant patients . We report here three cases of acute post-bacterial glomerulonephritis in renal transplants . In contrast to the classic cases of post-streptococcal glomerulonephritis the type of infection was heterogeneous: respectively, Escherichia coli bacteremia, a skin abscess, and cholangitis . The clinical presentation was characterized by a deterioration of graft function in two of our three patients . Acute renal dysfunction recovered in both patients, but in the long term the outcome was severe; two of the three patients lost their graft function . It is difficult to ascertain whether progression was due to chronic allograft nephropathy, to glomerulonephritis, or both . It may be concluded that acute post-infectious glomerulonephritis is a possible, although rare, complication in renal transplant recipients . It has an unusual presentation and may have a poor outcome in the long term . The role of therapy, if any, is still undefined.

Arthritis Rheum, 2003 Dec, 48(12), 3557 - 67
Splenectomy attenuates streptococcal cell wall-induced arthritis and alters leukocyte activation; Kimpel D et al.; OBJECTIVE: To investigate the role of the spleen in the pathogenesis of streptococcal cell wall (SCW)-induced arthritis and determine the impact of splenectomy on monocytes and T cells involved in the arthritis . METHODS: Female Lewis rats were separated into 4 groups: 1) saline-injected, sham-operated; 2) saline-injected, splenectomized; 3) peptidoglycan-polysaccharide (PG-PS)-injected, sham-operated; and 4) PG-PS-injected, splenectomized . After a 10-day recovery period, rats received a single intraperitoneal injection of saline or PG-PS (25 microg rhamnose/gm body weight) . We evaluated the effect of splenectomy on joint inflammation, histopathology, leukocyte subtypes in blood and lymph nodes, cytokines, and cell surface expression of CD44 and CD45RC in the chronic phase of the disease (day 28) . RESULTS: Splenectomy dramatically decreased chronic joint inflammation and histopathologic damage as well as altered cell types in lymph nodes and peripheral blood, as analyzed by flow cytometry . Nitric oxide (NO) production, levels of interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha, and a biomarker of Th1 cell predominance correlated with the level of joint inflammation . Surprisingly, in splenectomized animals, increased expression of adhesion molecules thought to track T cells to inflamed tissue were observed in lymph nodes . CONCLUSION: The result of splenectomy was attenuation of SCW-induced arthritis and changes in mediators of inflammation, including T cell subsets, proinflammatory cytokines, and NO production . Splenectomy may remove an important antigen reservoir and alter immune cell activation in the SCW-induced arthritis model.

Anticancer Res, 2003 Nov-Dec, 23(6a), 4459 - 65
Combined immunotherapy with intracavital injection of activated lymphocytes, monocyte-derived dendritic cells and low-dose OK-432 in patients with malignant effusion; Morisaki T et al.; We have conducted a pilot study with combined immunotherapy using autologous lymphocytes activated ex vivo and monocyte-derived dendritic cells in combination with low-dose OK-432, a streptococcal preparation, in five patients with peritoneal or pleural carcinomatosis who were resistant to standard chemotherapy . All patients were given 3 to 10 courses of the combined immunotherapy . No severe adverse reactions occurred . Effusion production was decreased in all of the patients . Significant decreases in tumor markers of both effusions and sera as well as effusion volume occurred in all of the patients . Cytological examinations revealed a marked decrease or disappearance of cancer cells in those effusions . Three patients showed increase in IFN-gamma levels in the effusions . The overall prognosis of the patients was acceptable and the mean survival time was more than 9 months . The locoregional immunotherapy seems to be encouraging in view of therapeutic modality in patients who are resistant to standard chemotherapy . Our study provides a new protocol for immunotherapy and warrants further phase I/II clinical study for chemo-resistant patients with malignant effusion.

Anticancer Res, 2003 Nov-Dec, 23(6a), 4443 - 9
Combination of adoptive immunotherapy with Herceptin for patients with HER2-expressing breast cancer; Kubo M et al.; Clinical use of Herceptin (trastuzumab), which is a humanized monoclonal antibody against HER2, started for patients with HER2-overexpressing breast cancer . To potentiate the efficacy of the Herceptin therapy, this study focused on the combination of Herceptin with activated immune lymphocytes . We used peripheral blood mononuclear cells (PBMCs) as effector cells and used HER2-unexpressing K562 cells, HER2-weakly-expressing breast carcinoma cells (Breast-M), or HER2-strongly-expressing breast carcinoma cells (BT-474) as target cells . Interleukin-2 (IL-2)-activated PBMCs, IL-2/OKT-3-activated PBMCs and a streptococcal preparation OK-432-activated PBMCs were generated and used as effector cells . Cytotoxic activity was determined with 4-hour 51Cr release assay . Both fresh PBMCs and activated PBMCs exhibited Herceptin-dependent cytotoxicity . Importantly, Herceptin-dependent cytotoxicity was found even at a lower effector to target cell ratio (E/T ratio) than that of Herceptin-independent cytotoxicity . In addition, Herceptin-dependent cytotoxicity by these activated PBMCs was observed even in HER2-weakly-expressing Breast-M cells . Since gamma-globulin or anti-CD16 antibody abrogated Herceptin-dependent cytotoxicity, it seems likely that antibody-dependent cellular cytotoxicity (ADCC) plays an important role in the Herceptin-dependent cytotoxicity . We present a recurrent breast cancer patient with malignant pleural effusion, in which HER2-strongly-expressing tumor cells were present, who was undergoing Herceptin therapy . Cluster formation between tumor cells and intrapleural mononuclear cells was induced 24 hours after intravenous injection of Herceptin (4 mg/kg) . Mononuclear cells bound specifically to HER2-strongly-expressing tumor cells but not to other cells, such as mesothelial cells, suggested a Herceptin-mediated binding like ADCC in vivo . Taken together, these findings suggest that the combination of Herceptin with various types of activated lymphocytes may be a new therapeutic strategy, not only for HER2-strongly-expressing breast cancer but also for HER2-weakly-expressing cancer.

J Immunol Methods, 2003 Dec, 283(1-2), 9 - 15
Rapid analysis of the Vbeta repertoire of CD4 and CD8 T lymphocytes in whole blood; MacIsaac C et al.; Determination of the T cell receptor Vbeta repertoire of human CD4 and CD8 populations is a useful immunological tool, particularly in the investigation of superantigen involvement in various disease states . We describe the optimisation of a rapid technique for the simultaneous evaluation of 24 Vbeta families of the T cell receptor of CD4 and CD8 positive lymphocytes in whole blood by flow cytometry adapting a commercially available monoclonal antibody kit . The technique described is reliable and reproducible, and we describe its use as a potential diagnostic tool in patients with staphylococcal and streptococcal toxic shock syndromes.

J Pediatr (Rio J), 2001 Mar-Apr, 77(2), 105 - 11
{Antistreptolysin O titer profile in acute rheumatic fever diagnosis}; Machado CS et al.; OBJECTIVE: To determine ASO titer profile by establishing ARF differential diagnoses of other diseases with high levels of ASO antibodies . METHODS: We investigated 78 patients with ARF at onset and follow-up, 22 with isolated chorea at onset, 45 with recurrent oropharyngeal tonsillitis, and 23 with recent flare of juvenile idiopathic arthritis . We tested ASO with automated particle-enhanced immunonephelometric assay (Behring(R)-Germany) . The ASO (IU/ml) titers were assessed at the following time intervals: 0-7 days, 1-2 weeks, 2-4 weeks, 1-2 months, 2-4 months, 4-6 months, 6-12 months, 1-2 years, 2-3 years, 3-4 years, and 4-5 years after onset of ARF . RESULTS: ASO titers in patients diagnosed with ARF had a significant increase up to the 2-4-month time interval (P<0.0001) . Baseline levels were observed afterwards in patients under regular penicillin prophylaxis . The levels of ASO in ARF were also significantly higher than in patients with isolated chorea, recurrent oropharyngeal infections or juvenile idiopathic arthritis (P=0.0025), when age-matched samples of these groups were compared . The testacute;s sensitivity was 73.3% and the specificity was 57.6%, and it was calculated taking into account the upper limit of normality at 320 IU/ml, as well as the established diagnosis of ARF . The testacute;s specificity and positive predictive value increased with rising or higher titers, being higher with titers above 960 UI/ml . CONCLUSION: This reappraisal of ASO profile in ARF patients indicates a remarkable response during the acute phase, and that points to the extent to which ASO levels may differentiate ARF from other diseases with high levels of ASO antibodies, as coincidental but unrelated streptococcal infection or chronic arthritis flareup.

Clin Orthop, 2003 Nov, (416), 129 - 34
Open debridement of acute gram-positive infections after total knee arthroplasty; Deirmengian C et al.; Open debridement and retention of components is an attractive, but often ineffective strategy for the treatment of a total knee arthroplasty (TKA) with acute infection . Few studies have stratified the outcomes of debridement specifically according to bacterial species . Thirty-one TKAs with acute gram-positive infections, seen at our institution during the past 10 years, were treated with open debridement, component retention, and antibiotics . The average duration of symptoms before debridement was 9 days (range, 1-40 days), and 78% of debridements were done within 10 days of the onset of symptoms . Eleven (35%) of the 31 patients successfully retained their components at most recent followup, without ongoing infection (mean, 4 years; range, 2-10 years) . Only one (8%) of the 13 who had an infection with Staphylococcus aureus was treated successfully, compared with 10 (56%) of 18 patients who had infections, with either Staphylococcus epidermidis or a streptococcal species . The difference between these groups is statistically significant . The success rate of debridement of acute infections in TKA varies significantly depending on the involved pathogen . A high failure rate suggests that immediate component removal should be considered in the presence of acute Staphylococcus aureus infection in TKA . Debridement for acute streptococcal or Staphylococcus epidermidis species has better success, but likely should be done within 2 to 3 days from the onset of symptoms.

Apoptosis, 1997, 2(2), 227 - 38
Therapy for oral squamous cell carcinoma by tegafur and streptococcal agent OK-432 in combination with radiotherapy: association of the therapeutic effect with differentiation and apoptosis in the cancer cells; Sato M et al.; Twenty patients with oral squamous cell carcinoma having mainly stage II or III lesions without distant metastasis, were treated with tegafur and streptococcal agent, OK-432, in combination with radiotherapy . As a consequence, 16 cases among the treated 20 cases showed complete remission by this therapy alone . Especially, we have found that the squamous cell carcinoma arising in non-keratinizing oral epithelium rather than in keratinizing oral epithelium has better response to this therapy . Among the 16 cases with complete remission (CR) by the current therapy, 10 cases were histopathologically diagnosed as well-differentiated squamous cell carcinoma and six cases as moderately differentiated squamous cell carcinoma . When we examined immunohistochemically the expression of various antigens such as proliferating cell nuclear antigen (PCNA), p53 and LeY or the presence of DNA fragmentation by nick-end labelling in the biopsy materials taken at the first visit to our clinic from 20 patients treated with the current therapy, the CR group showed a significantly increased LeY expres-sion level ( p< 0.05) and DNA fragmentation rate (p< 0.05) as compared with the partial response (PR, n= 3) + no change (NC, n= 1) group . On the other hand, the CR group with respect to PCNA expression level was significantly decreased as compared with the PR + NC group ( p< 0.05) . From these findings, it can be considered that the therapy for oral squamous cell carcinoma by UFT and OK-432 in combination with radiotherapy is very effective, which may be associated with differentiation or apoptosis in oral squamous carcinoma cells . In addition, we present the clinical findings and results of immunohistochemical staining for the biopsy materials obtained from four CR cases treated with the current therapeutic method.

J Obstet Gynaecol Res, 2003 Dec, 29(6), 364 - 73
Post-partum endomyometritis diagnosis and treatment: a review; Ledger WJ; Over the past 80 years, obstetrical treatment strategies devised to control current problems have resulted in the emergence of new types of infection . These, in turn, have caused modifications in diagnostic techniques and treatment specifics . Currently, the two most obvious changes influencing post-partum infection care are shortened post-partum hospital care, and the widespread use of intra-partum antibiotics to prevent early onset Group B streptococcal sepsis in the newborn . In the present review, risk factors for post-partum infection are delineated and strategies for prophylaxis and treatment are given.

J Immunol, 2003 Dec 1, 171(11), 6145 - 53
Toll-like receptor 2 pathway drives streptococcal cell wall-induced joint inflammation: critical role of myeloid differentiation factor 88; Joosten LA et al.; The IL-1R/Toll-like receptor (TLR) superfamily of receptors has a key role in innate immunity and inflammation . In this study, we report that streptococcal cell wall (SCW)-induced joint inflammation is predominantly dependent on TLR-2 signaling, since TLR-2-deficient mice were unable to develop either joint swelling or inhibition of cartilage matrix synthesis . Myeloid differentiation factor 88 (MyD88) is a Toll/IL-1R domain containing adaptor molecule known to have a central role in both IL-1R/IL-18R and TLR signaling . Mice deficient for MyD88 did not develop SCW-induced arthritis; both joint swelling and disturbance of cartilage chondrocyte anabolic function was completely abolished . Local levels of proinflammatory cytokines and chemokines in synovial tissue washouts were strongly reduced in MyD88-deficient mice . Histology confirmed the pivotal role of MyD88 in acute joint inflammation . TLR-2-deficient mice still allow influx of inflammatory cells into the joint cavity, although the number of cells was markedly reduced . No influx of inflammatory cells was seen in joints of MyD88-deficient mice . In addition, cartilage matrix proteoglycan loss was completely absent in MyD88 knockout mice . These findings clearly demonstrated that MyD88 is a key component in SCW-induced joint inflammation . Since agonists of the Toll-like pathway are abundantly involved in both septic and rheumatoid arthritis, targeting of MyD88 may be a novel therapy in inflammatory joint diseases.

Infect Dis Obstet Gynecol, 2003, 11(2), 109 - 15
Group B streptococcal endocarditis in obstetric and gynecologic practice; Crespo A et al.; BACKGROUND: We describe a case and review ten other instances of group B streptococcal endocarditis in the setting of obstetric and gynecologic practice reported since the last review in 1985 . CASE: Abortion remains a common antecedent event, but in contrast to earlier reports, most patients did not have underlying valvular disease, the tricuspid valve was most often involved, and mortality was low . Patients with tricuspid valve infection tended to have a subacute course, whereas those with aortic or mitral involvement typically had a more acute, fulminant course . CONCLUSION: Despite an improvement in mortality, morbidity remains high, with 8 of 11 patients having clinically significant emboli.

Cancer Immunol Immunother, 2003 Sep, 52(9), 561 - 8
Streptococcal preparation OK-432: a new maturation factor of monocyte-derived dendritic cells for clinical use; Kuroki H et al.; For vaccinations based on dendritic cells (DCs), maturation of DCs is critical to the induction of T-cell responses . We tested the efficacy of streptococcal preparation OK-432 as a Good Manufacturing Practice (GMP)-grade maturation agent . OK-432 is currently used in Japan as a cancer immunotherapy drug . Immature monocyte-derived dendritic cells (imMo-DCs) isolated from human peripheral blood monocytes stimulated with granulocyte-macrophage colony stimulating factor and interleukin-4 were exposed to maturation factors, i.e., lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha) plus prostaglandin E2 (PGE2), and OK-432 for 2 days . OK-432 increased expression of activation- and maturation-related molecules such as HLA-DR, CD80, CD83, and CD86 in imMo-DCs at levels similar to that of TNF-alpha plus PGE2, and higher than that of LPS . All agents examined induced allogeneic T-cell proliferation at a similar level . Only OK-432 caused significant production of interleukin-12 (IL-12) p70 and interferon gamma (IFN-gamma) at both the mRNA and protein levels in imMo-DCs . Neutralizing antibody against IL-12 p70 blocked IFN-gamma secretion from OK-432-stimulated Mo-DCs . IL-12 p70 produced by OK-432-stimulated imMo-DCs induced secretion of IFN-gamma by CD4+ T cells . OK-432 and LPS activated nuclear factor kappa B (NF-kappaB) in imMo-DCs . Both secretion of IL-12 p70 and IFN-gamma and activation of NF-kappaB induced by OK-432 were suppressed when imMo-DCs were pretreated with cytochalasin B . These results indicate that uptake of OK-432 by imMo-DCs is an early critical event for IL-12 p70 production and that NF-kappaB activation induced by OK-432 also contributes partially to IL-12 p70 production . In conclusion, OK-432 is a GMP-grade maturation agent and may be a potential tool for DC-based vaccine therapies.

J Infect Dis, 2003 Nov 15, 188(10), 1578 - 86 Epub 2003 Nov 05.
Toxin-gene profile heterogeneity among endemic invasive European group A streptococcal isolates; Schmitz FJ et al.; We determined the toxin-gene profiles of 239 endemic, invasive group A streptococcal (GAS) isolates that circulated, within a 5-year period, in European university hospitals . Profiling was performed by use of multiplex polymerase chain reaction that screened for 9 streptococcal pyrogenic exotoxins (speA, speB, speC, speF, speG, speH, speJ, ssa, and smeZ) . Analysis revealed that invasive GAS isolates do not share a common toxin-gene profile . Although all emm types were characterized by several different toxin-gene profiles, a predominance of 1 or 2 toxin-gene profiles could be observed, reflecting that a few invasive clones have spread successfully throughout the world . Remarkably, statistical pair-wise analysis of individual toxin genes revealed that strains that did not share the predominant profile still showed a nonrandom distribution of key toxin genes characteristic of the specific emm type . This could indicate that M proteins function, directly or indirectly, as barriers for horizontal gene exchange.

Gan To Kagaku Ryoho, 2003 Oct, 30(11), 1559 - 61
{Analysis of 5-year survival among breast cancer patients with malignant pleural effusion receiving intrapleural OK-432 followed by adoptive transfer with cultured effusion lymphocytes}; Kan N; Since 1984, we have had 151 breast cancer patients with cytologically-confirmed malignant pleural effusions by local transfer of autologous effusion lymphocytes cultured with a conditioned medium containing T-cell growth factor after intrapleural preadministration of a streptococcal preparation, OK-432 . Among the 81 patients given this therapy more than 5 years ago, 12 patients have survived 5 or more years, and 4 of these 12 have survived 10 (<) years . Patients surviving 5 (<) years had longer (32-204 months) disease-free periods, except for one patient with stage IV disease . Estrogen receptor was positive in 5 patients, negative in 1 patient, and unknown in 6 patients . Moreover, preceding or concomitant metastases in these patients were not life-threatening (6 chest-wall, 2 lymph-node, 4 lung, 3 bone metastases) . In conclusion, effective therapy (effusion disappeared in all patients) and good control of concomitant metastases resulted in long-term survival of patients who had intrinsically better prognostic factors.

J Clin Oncol, 2003 Nov 15, 21(22), 4127 - 37
Reappraisal with meta-analysis of the addition of Gram-positive prophylaxis to fluoroquinolone in neutropenic patients; Cruciani M et al.; PURPOSE: Past reports and meta-analyses indicate that fluoroquinolones are highly effective in preventing Gram-negative infections in neutropenic cancer patients, but offer inadequate coverage for Gram-positive infections . We evaluated by meta-analysis the efficacy of the addition of antimicrobial agents with enhanced Gram-positive activity to prophylaxis with quinolones.Materials and METHODS: Randomized trials comparing fluoroquinolones alone (ciprofloxacin, ofloxacin, pefloxacin, or norfloxacin) with fluoroquinolone in combination with Gram-positive prophylaxis (rifampin, vancomycin, amoxicillin, roxithromycin, or penicillin) were retrieved . We pooled relative risks (RRs) using a fixed-effects model . RESULTS: Nine trials (1,202 patients) published between 1993 and 2000 meet inclusion criteria . Compared with fluoroquinolone alone, Gram-positive prophylaxis reduced total bacteremic episodes (RR, 1.54; 95% CI, 1.26 to 1.88), streptococcal infections (RR, 2.20; 95% CI, 1.44 to 3.37), coagulase-negative staphylococcal infections (RR, 1.46; 95% CI, 1.04 to 2.04), and rate of febrile patients (RR 1.08; 95% CI, 1.00 to 1.16) . Occurrence of clinically documented infections, unexplained fever, and infectious mortality was similar in the two groups . The addition of Gram-positive prophylaxis, however, significantly increased side effects (RR, 0.46; 95% CI, 0.28 to 0.76) . Rifampin use resulted in a higher incidence of undesirable effects . CONCLUSION: Considering the lack of cut-clear benefit on some parameters of morbidity and mortality, routine use of Gram-positive prophylaxis is not advisable . This strategy, however, should be particularly valuable in subgroups of patients at high risk of streptococcal infection (eg, those with severe and prolonged neutropenia or mucositis, and those receiving cytarabine) . Problems of tolerability and the potential for the emergence of resistant microorganisms should be considered when prescribing prophylaxis with enhanced Gram-positive activity to neutropenic patients.

Br J Cancer, 2003 Nov 17, 89(10), 1876 - 84
Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK-432 plus interleukin-2: induction of autologous tumor-reactive CD4+ Th1 killer lymphocytes; Yamaguchi Y et al.; In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied . A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2 . Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells) . The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6 . The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells . This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody . The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells . TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells . Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced . The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in effusion lymphocytes from the other patients . Taken together, it is suggested that locoregional administration of OK-432 plus IL-2 is highly effective for the management of malignant effusion from colorectal cancer . OK-432 plus IL-2 induces autologous tumour-reactive CD4+ Th1 killer lymphocytes, which recognise tumour antigen(s) presented with HLA class II molecules on effusion tumour cells by means of preferential usage of TCRVbeta20 . The clonotypic PCR using the TCRVbeta20-CDR3 sequences may be informative for treating malignant effusion from colorectal cancer using OK-432 plus IL-2.

Arch Dis Child, 2003 Nov, 88(11), 1019 - 20
Late onset group B streptococcal disease manifested by isolated cervical lymphadenitis; Fluegge K et al.; Sepsis and meningitis are the major clinical manifestations of group B streptococcal (GBS) infections in neonates, but GBS can cause a wide spectrum of presentations ranging from asymtomatic bacteraemia to fulminate septicaemia and shock . To our knowledge this is the first report of isolated neonatal lymphadenitis as a manifestation of late onset GBS disease.

Minerva Pediatr, 2003 Oct, 55(5), 385 - 93
Colonization with antibiotic-resistant Gram-negative bacilli in the neonatal intensive care unit; Toltzis P; Infections with Gram-negative bacilli have affected critically ill newborns throughout the era of modern neonatal intensive care . Selected topics regarding the acquisition of Gram-negative bacteria, particularly those expressing antibiotic resistance, in the neonatal intensive care unit (NICU) are reviewed . Some data suggest that the recent introduction of intrapartum antibiotic prophylaxis programs, through which selected women are administered penicillin or ampicillin during labor to prevent vertically transmitted Group B streptococcal disease, has increased the incidence and resistance of early onset Gram-negative bacillary infection in the newborn over the past 5 years . Additional data suggest that late onset, nosocomially-acquired Gram-negative bacillary infections also are increasing among critically-ill newborns . The seminal event in Gram-negative bacterial infection in the hospitalized infant is colonization of the gastrointestinal tract and nasopharynx . Newborns admitted to the intensive care unit acquire hospital-associated Gram-negative bacterial colonization throughout their NICU stay, presumably transmitted from the environmental flora via the hands of caregivers . Colonization specifically by antibiotic-resistant bacilli follows a similar pattern, suggesting that such bacteria make up part of the modern NICU ecology and are acquired by infants similar to susceptible microorganisms . Althou-gh some clinically-undetected cross-transmission of resistant bacilli occurs during non-outbreak periods, most colonizing antibiotic-resistant bacilli are unique to each infant . The role of antibiotic exposure on the acquisition of antibiotic resistant bacilli in the intensive care nursery is difficult to calculate given the covariance of such exposure to other markers of severe disease . Experience has demonstrated, however, that use of the aminoglycosides is infrequently associated with emergence of resistance in the newborn, whereas the use of higher-generation cephalosporins may be associated with the rapid appearance of bacilli resistant to betha-lactams.

Pediatr Res, 2004 Jan, 55(1), 163 - 76 Epub 2003 Nov 06.
The history of Pediatric Infectious Diseases; Shulman ST; The history of Pediatric Infectious Diseases closely parallels the history of Pediatrics at least until the last century, because historically infections comprised the major causes of childhood morbidity and mortality, as they still do in the developing world . This history reviews developments in the field through the centuries and is written so that it does not overlap the contribution to this series by Baker and Katz entitled 'Childhood Vaccine Development in the United States.' Remarkable descriptions of selected pediatric infections existed long before the invention of printing, and early pediatric texts included many chapters devoted to various infections . Coincident with the establishment of pediatric organizations in America in the late 19th and early 20th Centuries, major attention was focused on diphtheria, infant diarrheal illnesses, tuberculosis, streptococcal infections and their complications, and other pediatric infections, and substantial progress was made . The American Pediatric Society (1888), the American Academy of Pediatrics (1930), the Society for Pediatric Research (1931), and the American Board of Pediatrics (1933) all contributed to the evolution of the discipline of Pediatric Infectious Disease, and numerous leaders of these organizations had significant infectious diseases interests . The establishment of the Pediatric Infectious Diseases Society, the Pediatric Infectious Diseases sub-board, and an accreditation process for training programs, as well as sub-specialty textbooks and journal, further validated the development of this specialty, particularly in North America . The many remaining challenges related to infectious diseases in children (including HIV, emerging infections, antimicrobial resistance, opportunistic infections, and infections in the developing world) insure the future of the specialty . The genomic era of medicine and the tools of molecular biology will lead to new insights into pathogenesis, diagnosis, and treatment of infections . Pediatric Infectious Diseases physicians can celebrate the past triumphs of the discipline and future achievements, all contributing to improved health for children.

Clin Ther, 2003 Sep, 25(9), 2419 - 30
Association between antibiotic prescribing and visit duration in adults with upper respiratory tract infections; Linder JA et al.; BACKGROUND: Upper respiratory tract infections (URTIs) are the most common reason for individuals to seek health care in the United States . Inappropriate antibiotic use exposes patients unnecessarily to potential adverse events and increases the prevalence of antibiotic-resistant bacteria . One of the reasons physicians may prescribe an antibiotic inappropriately is to save time . OBJECTIVE: The aim of this study was to determine whether there is an association between antibiotic use and a shorter visit duration in adults with URTIs . METHODS: Visits to office-based primary care physicians made by adults aged 18 to 60 years from 1995 through 2000 were extracted from the National Ambulatory Medical Care Survey . Visits that resulted in a primary diagnosis of acute URTI; acute nasopharyngitis; acute bronchitis; sinusitis; streptococcal sore throat, acute pharyngitis, or acute tonsillitis; or otitis media were included in the study . Visits associated with >1 diagnosis were included in a separate category Visit duration was defined as the face-to-face time between the patient and physician . RESULTS: There were 3764 visits that met the criteria for inclusion in this study, representing an estimated 27 million annual visits to office-based primary care physicians by adults with URTIs . Antibiotics were prescribed in 67% of visits . The mean visit duration associated with prescription of an antibiotic was 14.2 minutes, compared with 15.2 minutes without prescription of an antibiotic (P = 0.007) . In multivariable modeling, independent predictors of visit duration were calendar year (additional 0.3 minute per year; 95% CI, 0.1 to 0.6), internal medicine specialty (additional 2.2 minutes vs family practice; 95% CI, 1.3 to 3.1), covisit with a nurse-practitioner or physician assistant (6.6 minutes shorter; 95% CI, -2.7 to -10.6), and Midwestern location of practice (1.1 minutes shorter vs Northeast; 95% CI, -0.1 to -2.2) . Antibiotic use was marginally associated with a shorter visit duration (0.7 minute shorter; 95% CI, 0.0 to -1.3; P = NS) . CONCLUSIONS: In the present study, antibiotic use was marginally associated with a shorter visit duration for adults with URTIs . Any potential efficiencies gained by physicians through prescribing antibiotics for adults with URTIs are likely to be outweighed by increases in antimicrobial resistance and exposure of patients to unneeded medication.

Int J Cardiol, 2003 Nov, 92(1), 49 - 54
MHC class II alleles in Mexican patients with rheumatic heart disease; Hernandez-Pacheco G et al.; BACKGROUND: Rheumatic heart disease (RHD) is an autoimmune sequel of group A streptococcal infection that has been associated with the presence of some major histocompatibility complex (MHC) genes . Thus, the aim of the present study was to investigate the role of class II alleles in the genetic susceptibility to RHD in Mexican patients and establish the relationship of these alleles with the pattern of valve damage . METHODS: HLA-DR, -DQA1 and -DQB1 allele frequencies were determined by PCR-SSO reverse dot blot and PCR-SSP in 98 Mexican Mestizo patients with RHD and 99 healthy controls . Patients were divided into mitral valve damage (n=46), multivalvular lesion (n=49) and aortic damage (n=3) . RESULTS: RHD patients presented an HLA-DR16 increased frequency (pC=0.009, OR=3.9) and a decreased HLA-DR11 frequency (pC=0.018) when compared to healthy controls . HLA-DR16 subtyping showed that DRB1*1602 was the DR16 allele increased in patients (pC=0.007, OR=5.3) . Haplotype analysis showed increased frequency of DR16-DQA1*0501-DQB1*0301 in RHD patients when compared to healthy controls (pC=0.011) . HLA-DR16 frequency remained significantly increased on patients with multivalvular lesion (pC=0.004, OR=4.8) . CONCLUSIONS: Our data suggest an important participation of Amerindian autochthonous HLA-DR16 (DRB1*1602) allele and DR16-DQA1*0501-DQB1*0301 haplotype as markers for RHD genetic susceptibility in the Mexican Mestizo population . HLA-DR16 allele could also play an important role in determining the pattern of valve damage on these patients.

Pediatr Infect Dis J, 2003 Oct, 22(10), 929 - 31
Invasive group A streptococcal infection after tonsillectomy; Timmers-Raaijmaakers BC et al.; Tonsillectomy is a very common procedure in childhood . Infectious complications after tonsillectomy are infrequently reported . We describe two children with severe group A beta-hemolytic streptococcal infection after tonsillectomy, and we review the literature about bacteremia and infectious complications after tonsillectomy.

Clin Rheumatol, 2003 Oct, 22(4-5), 350 - 2
Post-streptococcal reactive arthritis and glomerulonephritis in an adult; Niewold TB et al.; We report the case of an adult who developed severe post-streptococcal reactive arthritis (PSRA) and poststreptococcal glomerulonephritis (PSGN) after a subclinical streptococcal infection . Antistreptococcal antibody titres, renal biopsy and the clinical course confirmed the diagnosis . Coincidence of PSRA and PSGN is rare in the adult population and the potential for misdiagnosis exists, particularly when prior streptococcal infection is not apparent . The clinical manifestations of poststreptococcal syndromes are highly variable, and the diagnosis of concomitant PSRA and PSGN should be considered when patients present with glomerulonephritis and inflammatory arthritis . Factors from both the host and the pathogen are probably important in determining disease expression in poststreptococcal syndromes.

Protein Sci, 2003 Nov, 12(11), 2482 - 91
Soluble mimics of a chemokine receptor: chemokine binding by receptor elements juxtaposed on a soluble scaffold; Datta A et al.; Despite the broad biological importance of G protein-coupled receptors (GPCRs), ligand recognition by GPCRs remains poorly understood . To explore the roles of GPCR extracellular elements in ligand binding and to provide a tractable system for structural analyses of GPCR/ligand interactions, we have developed a soluble protein that mimics ligand recognition by a GPCR . This receptor analog, dubbed CROSS5, consists of the N-terminal and third extracellular loop regions of CC chemokine receptor 3 (CCR3) displayed on the surface of a small soluble protein, the B1 domain of Streptococcal protein G . CROSS5 binds to the CCR3 ligand eotaxin with a dissociation equilibrium constant of 2.9 +/- 0.8 microM and competes with CCR3 for eotaxin binding . Control proteins indicate that juxtaposition of both CCR3 elements is required for optimal binding to eotaxin . Moreover, the affinities of CROSS5 for a series of eotaxin mutants are highly correlated with the apparent affinities of CCR3 for the same mutants, demonstrating that CROSS5 uses many of the same interactions as does the native receptor . The strategy used to develop CROSS5 could be applied to many other GPCRs, with a variety of potential applications.

South Med J, 2003 Oct, 96(10), 968 - 73
Invasive group A streptococcal infections in Florida; Mulla ZD et al.; BACKGROUND: Several previous studies of invasive Group A streptococcal (GAS) disease have been hindered by small sample sizes (< or = 100 patients) and limited generalizability . METHODS: We conducted a population-based study of invasive GAS disease . The objectives of the study were to describe the clinical features of individuals who were hospitalized for invasive GAS disease and to identify risk factors for hospital mortality . The cases were 257 patients who were hospitalized throughout Florida during a 4-year period and reported to the Florida Department of Health . Logistic regression was used to calculate adjusted odds ratios (OR) for mortality and 95% confidence intervals (CI) . RESULTS: The overall mortality was 18% (41 of 228) . Admission into an intensive care unit was a strong predictor of mortality (OR, 20.41; 95% CI, 6.41-64.96) . Treatment with clindamycin reduced mortality in patients who had necrotizing fasciitis (OR, 0.11; 95% CI, 0.01-0.89) but not in patients who did not have necrotizing fasciitis (OR, 1.01; 95% CI, 0.31-3.33) . CONCLUSION: Clindamycin reduces mortality in patients with invasive GAS disease who have necrotizing fasciitis.

Curr Opin Rheumatol, 2003 Nov, 15(6), 691 - 7
Cytokines in juvenile dermatomyositis pathophysiology: potential and challenge; Uzel G et al.; PURPOSE OF REVIEW: Cytokines are criticalmediators of the immune response . This review focuses on cytokine-specific information from children with juvenile dermatomyositis, and includes pertinent data from adults with polymyositis and dermatomyositis . RECENT FINDINGS: Much of the new data concern the role of possible antigens and the definition of genetic control of the immune response in juvenile dermatomyositis . Gene expression profile data of DQA1*0501 (present in 85% of patients) compared with age-matched control subjects show that the initial immune response is an interferon-alpha/beta-induced cascade with secondary stimulation of interferon-gamma . Specific epitopes of group A beta-hemolytic streptococcal M protein, with sequence homology for myosin, elicit both cell-mediated cytotoxicity and tumor necrosis factor-alpha production when incubated with mononuclear cells from children with active juvenile dermatomyositis . Tumor necrosis factor-alpha synthesis is increased in juvenile dermatomyositis patients with the tumor necrosis factor-alpha-308A allele, and is associated with increased thrombospondin-1 (an antiangiogenic agent) production and small vessel occlusion in untreated juvenile dermatomyositis . Studies in adults with polymyositis and dermatomyositis implicate interleukin-1alpha, transforming growth factor-beta, and endothelial cell perturbation early in the disease course . Cultured myoblasts were found to produce interleukin-15, which impacts local T-cell activation and proliferation . SUMMARY: The limited data suggest that a possible viral/microbial antigen may elicit an interferon-alpha/beta-induced response, and that antigenic epitopes may be shared . Increased synthesis of tumor necrosis factor-alpha, more common in juvenile dermatomyositis with the tumor necrosis factor-alpha-308A polymorphism, may augment this response and is associated with a wide range of pathologic consequences, as well as disease chronicity and calcifications . The muscle fibers themselves can regulate local inflammation by production of tumor necrosis factor-alpha, interleukin-15 and interleukin-1alpha, and transforming growth factor-beta.

Jpn J Antibiot, 2003 Aug, 56(4), 281 - 8
{Clinical efficacy and bacteriological studies of clarithromycin and cefdinir against group A beta-hemolytic streptococcal tonsillopharyngitis}; Nishimura T et al.; The clinical efficacy and safety of clarithromycin (CAM) and cefdinir (CFDN) were evaluated in 65 pediatric outpatients with group A beta-hemolytic streptococcal tonsillopharyngitis . Treatment was "effective" or better in 26 (78.8%) children receiving CAM and in 27 (87.1%) receiving CFDN based on antigen clearance and the "Criteria for Evaluation in Clinical Trials of Antibacterial Agents in Children" proposed by Japan Society of Chemotherapy (p = NS) . The causative organisms were eradicated in 94.7% and 93.8% of subjects in the CAM and CFDN groups, respectively (p = NS) . Adverse drug reactions were limited to moderate diarrhea in one patient in each group, and subsided during treatment . Causative organisms exhibited good susceptibility to CAM and CFDN . These results suggest excellent efficacy, safety and usefulness of CAM and CFDN in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitsis in children.

J Foot Ankle Surg, 2003 Sep-Oct, 42(5), 305 - 8
Aeromonas hydrophilia infections after penetrating foot trauma; Larka UB et al.; The bacterium Aeromonas hydrophila is an anaerobic gram-negative bacillus commonly found in natural bodies of water and can cause infection in patients who suffer water-associated trauma or in immunocompromised hosts . The authors present 5 cases of penetrating wound trauma that did not involve any aquatic environment and developed rapidly forming infections . All patients presented with severe pain, cellulitis, ascending lymphangitis, fever, and pain on range of motion of the joint near the traumatic site . Presentation of clinical symptoms mimicked that of a septic joint or of severe streptococcal infection . All patients required surgical incision and drainage, intravenous and oral antibiotics using levofloxacin or bactrim, and local wound care . Results from cultures taken intraoperatively showed only A hydrophilia in every case . Resolution of symptoms occurred rapidly after surgery, and clinical resolution was seen within 72 hours . Each patient healed uneventfully and returned to preinjury status.

J Arthroplasty, 2003 Oct, 18(7 Suppl 1), 22 - 6
Limited success with open debridement and retention of components in the treatment of acute Staphylococcus aureus infections after total knee arthroplasty; Deirmengian C et al.; The purpose of this study was to review our experience in treating acute gram-positive infections after total knee arthroplasty with debridement, component retention, and intravenous antibiotics . Thirty-one total knee arthroplasties with acute gram-positive infections, seen at our institution over a 10-year period, were treated with open debridement and component retention . Eleven (35%) of 31 patients successfully retained their components at most recent follow-up, without ongoing infection (mean, 4 years; range, 2-10 years) . Only one (8%) of the 13 patients infected with Staphylococcus aureus was successfully treated, compared with 10 (56%) of 18 patients with either Staphylococcus epidermidis or a streptococcal species . The difference between these groups is statistically significant (P=.007) . The high failure rate of debridement and component retention suggests that immediate component removal should be considered in the presence of acute S . aureus infection in total knee arthroplasty.

Eur J Clin Microbiol Infect Dis, 2003 Nov, 22(11), 670 - 4 Epub 2003 Oct 14.
External quality control of direct antigen tests to detect group A streptococcal antigen; Morandi PA et al.; Presented here are the results of an external quality control survey organized by the Swiss Center for Quality Control (CSCQ) to evaluate the performance of direct antigen tests (DATs) widely used in Swiss medical practices and laboratories for the diagnosis of group A streptococcal pharyngitis . Twice yearly over a 4-year period, just over 100 participants were requested to analyze positive, weakly positive and negative samples provided to them by the CSCQ with their routinely used DATs and to send the results to the CSCQ . For 1,620 samples distributed, the CSCQ received 1,484 (91.6%) results obtained with 17 different DATs . The specificity of all DATs for negative samples was >91% . For samples containing abundant group A streptococcal antigen, sensitivities ranged from 59.1% to 95.5%; however, for samples containing low levels of antigen, the sensitivity was much lower for all DATs, ranging from 8.7% to 69.8% . Therefore, negative DAT results should be verified with well-performed cultures in order to assure the optimal care of patients with pharyngitis.

Arch Virol, 2003 Oct, 148(10), 1885 - 97
Detection of antibody for the serodiagnosis of hantavirus infection in different rodent species; Lee BH et al.; Peroxidase-labeled staphylococcal protein A, streptococcal protein G, and antibodies directed against Mus musculus (mouse), Rattus norvegicus (rat), Mesocretus auratus (hamster), and Peromyscus leucopus were examined for their reactivity with immunoglobulin G (IgG) from various rodent species . The purpose of this study was to identify the optimal secondary antibodies or reagents for specific serodiagnosis of hantavirus infection in various rodent species . Using ELISA, a total of 65 sera from 29 rodent species of the family Muridae and one serum sample from family Octodontidae were compared for IgG reactivity with the six different reagents . The results demonstrate that the reactivities of the secondary antibodies and reagents to the sera varied, even among sera from rodents of the same genus . Hantavirus-specific antibody ELISA revealed that hantavirus-infected rodent sera obtained from M . musculus, R . norvegicus, Apodemus agrarius, A . peninsulae, and Bandicota indica bound to the six different conjugates in a similar pattern as that detected in IgG ELISA . These results indicate that the applicability of secondary antibodies and protein A and G should be carefully evaluated before use for serodiagnosis in different rodent species.

Pediatr Infect Dis J, 2003 Oct, 22(10), 853 - 7
Impact of intrapartum antibiotics on the care and evaluation of the neonate; Balter S et al.; BACKGROUND: Management of infants whose mothers receive intrapartum antibiotic prophylaxis (IAP) is controversial . In 1996 consensus guidelines for prevention of neonatal Group B streptococcal disease included an algorithm for management of infants whose mothers received IAP . To assess practices for testing and treatment of infants, we evaluated a population-based sample of deliveries to see whether excessive evaluation and treatment occurs after IAP . METHODS: Medical records for 869 deliveries in Connecticut during 1996 were sampled . IAP was administered in 96 full term deliveries . We excluded infants <37 weeks and those with intrapartum fever . We reviewed hospital records for infants born after IAP (n = 81) and a random sample of those not exposed (n = 180) . Analyses were conducted with sample weights to account for unequal probability of selection . RESULTS: Infants whose mothers received IAP were more likely to have complete blood counts, (26% vs . 9% P = 0.05) but were no more likely to receive antibiotics in the first week of life (P = 0.48), have an intravenous catheter placed (P = 0.83), or to have other invasive procedures . Mean length of hospital stay was 6 h longer for infants born by vaginal delivery to mothers who had IAP (47.0 h) than for those without IAP (41.3 h) (P = 0.06) . CONCLUSION: Despite concerns that IAP guidelines would result in excessive neonatal evaluations, infants sampled whose mothers received IAP were not more likely to undergo invasive procedures or to receive antibiotics . Consistent with the guidelines, collection of complete blood counts was more common among such infants.

Rev Neurol, 2003 Aug 16-31, 37(4), 322 - 6
{The efficiency of carbamazepine in a case of post-streptococcal hemichorea}; Hernandez-Latorre MA et al.; INTRODUCTION: Chorea is an infrequent disorder at the paediatric age which has a number of both hereditary and acquired causes . Post-streptococcal or Sydenham's chorea (SC) is still the main cause of chorea in children, in spite of the drop in prevalence of rheumatic fever in the last few years . SC is a benign, self-limiting disorder, but may last for several months and can be highly disabling . Several different types of symptomatic treatment have been proposed, for example corticoids, haloperidol, valproic acid, and carbamazepine . In each case, both the speed with which the clinical improvement is brought about, and the degree to which they are tolerated and the absence of side effects must be evaluated . CASE REPORT: We present a new case of SC that had been developing for three months . Carbamazepine was effective from the tenth day onwards and total remission of the symptoms was achieved in six weeks . Total follow-up time was nine months, and in this time no relapses or side effects were observed . CONCLUSIONS: This contribution offers new evidence supporting carbamazepine as another first choice medication in the treatment of this type of chorea.

Structure (Camb), 2003 Oct, 11(10), 1239 - 49
Structural basis for selective recognition of pneumococcal cell wall by modular endolysin from phage Cp-1; Hermoso JA et al.; Pneumococcal bacteriophage-encoded lysins are modular choline binding proteins that have been shown to act as enzymatic antimicrobial agents (enzybiotics) against streptococcal infections . Here we present the crystal structures of the free and choline bound states of the Cpl-1 lysin, encoded by the pneumococcal phage Cp-1 . While the catalytic module displays an irregular (beta/alpha)(5)beta(3) barrel, the cell wall-anchoring module is formed by six similar choline binding repeats (ChBrs), arranged into two different structural regions: a left-handed superhelical domain configuring two choline binding sites, and a beta sheet domain that contributes in bringing together the whole structure . Crystallographic and site-directed mutagenesis studies allow us to propose a general catalytic mechanism for the whole glycoside hydrolase family 25 . Our work provides the first complete structure of a member of the large family of choline binding proteins and reveals that ChBrs are versatile elements able to tune the evolution and specificity of the pneumococcal surface proteins.

Nature, 2003 Oct 2, 425(6957), 535 - 9
Staphylocoagulase is a prototype for the mechanism of cofactor-induced zymogen activation; Friedrich R et al.; Many bacterial pathogens secrete proteins that activate host trypsinogen-like enzyme precursors, most notably the proenzymes of the blood coagulation and fibrinolysis systems . Staphylococcus aureus, an important human pathogen implicated in sepsis and endocarditis, secretes the cofactor staphylocoagulase, which activates prothrombin, without the usual proteolytic cleavages, to directly initiate blood clotting . Here we present the 2.2 A crystal structures of human alpha-thrombin and prethrombin-2 bound to a fully active staphylocoagulase variant . The cofactor consists of two domains, each with three-helix bundles; this is a novel fold that is distinct from known serine proteinase activators, particularly the streptococcal plasminogen activator streptokinase . The staphylocoagulase fold is conserved in other bacterial plasma-protein-binding factors and extracellular-matrix-binding factors . Kinetic studies confirm the importance of isoleucine 1 and valine 2 at the amino terminus of staphylocoagulase for zymogen activation . In addition to making contacts with the 148 loop and (pro)exosite I of prethrombin-2, staphylocoagulase inserts its N-terminal peptide into the activation pocket of bound prethrombin-2, allosterically inducing functional catalytic machinery . These investigations demonstrate unambiguously the validity of the zymogen-activation mechanism known as 'molecular sexuality'.

J Gen Intern Med, 2003 Oct, 18(10), 802 - 7
Health-related quality of life of adults with upper respiratory tract infections; Linder JA et al.; OBJECTIVE: To determine the impact that upper respiratory tract infections have on patients' physical, social, and emotional functioning, we measured the health-related quality of life (HRQL) of adults with upper respiratory tract infections . SETTING: Acute care clinic from November 2001 to February 2002 . DESIGN: Prospectively administered survey . To measure HRQL, we used the Acute Form of the Short Form-36, version 2 (SF-36) . For all 8 SF-36 subscales, we used norm-based scoring, in which the general U.S . population has a mean of 50 . PATIENTS: Adults who had symptoms for fewer than 30 days completed the SF-36; and were diagnosed with nonspecific upper respiratory infection, viral syndrome, otitis media, sinusitis, nonstreptococcal pharyngitis, streptococcal pharyngitis, or acute bronchitis . MEASUREMENTS AND MAIN RESULTS: The sample of 318 patients was 63% female, 81% white, and had a mean age of 35 years . The primary diagnoses were nonspecific upper respiratory infection (42%), acute bronchitis (16%), sinusitis (12%), viral syndrome (9%), nonstreptococcal pharyngitis (8%), otitis media (7%), and streptococcal pharyngitis (6%) . Patients had a mean general health subscale score of 50.9, which is not significantly different from the mean population value of 50 (P =.09) . However, there were significant decrements in the remaining 7 subscales of the SF-36: physical functioning (45.5), role-physical (38.5), bodily pain (42.6), vitality (40.8), social functioning (37.8), role-emotional (46.8), and mental health (46.8; P <.0001 for all 7 subscales compared with normative values) . Results were similar for the subset of patients with no comorbid illnesses (P <.001 for the same 7 subscales) and patients diagnosed with nonspecific upper respiratory infection (P <.001 for the same 7 subscales) . These decrements were similar in magnitude, but somewhat different in subscale pattern, to those of adults with chronic lung disease, osteoarthritis, and depression . CONCLUSIONS: Physicians should remember that adults who seek care for upper respiratory tract infections have measurable, significant decrements in HRQL . For researchers, HRQL is an attractive, potential measure of outcome in future trials of established and novel therapies for upper respiratory tract infections.

J Mol Biol, 2003 Oct 10, 333(1), 141 - 52
A protein contortionist: core mutations of GB1 that induce dimerization and domain swapping; Byeon IJ et al.; Immunoglobulin-binding domain B1 of streptococcal protein G (GB1), a small (56 residues), stable, single-domain protein, is one of the most extensively used model systems in the area of protein folding and design . Recently, NMR and X-ray structures of a quintuple GB1 core mutant (L5V/A26F/F30V/Y33F/A34F) that showed an unexpected, intertwined tetrameric architecture were determined . Here, we report the NMR structure of another mutant, derived from the tetramer by reverting the single amino acid position F26 back to the wild-type sequence A26 . The structure reveals a domain-swapped dimer that involves exchange of the second beta-hairpin . The resulting overall structure comprises an eight-stranded beta-sheet whose concave side is covered by two alpha helices . The dimer dissociates into a partially folded, monomeric species with a dissociation constant of 93(+/-10)microM.

Semin Perinatol, 2003 Aug, 27(4), 293 - 301
Infections in VLBW infants: studies from the NICHD Neonatal Research Network; Stoll BJ et al.; Infection is a serious complication among very low birth weight (VLBW) preterm infants hospitalized in neonatal intensive care units . This article reviews studies from the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network including infection data from observational studies and randomized controlled trials . Blood culture-proven early-onset sepsis (< or = 72 hours) was found in less than 2% of VLBW infants, but was associated with substantial morbidity and mortality . A change in pathogens causing early-onset sepsis among Network patients has been observed over the past decade, with a significant reduction in early-onset group B streptococcal infections, but also a significant increase in early-onset Escherichia coli infections . This change is particularly worrisome, because of the high death rate associated with gram-negative infections, including E coli . Late-onset (> 72 hours) sepsis developed in almost a quarter of infants . The vast majority of infections were caused by gram-positive agents, especially coagulase-negative staphylococci . The risk of late-onset sepsis was inversely related to birth weight and gestational age . Infants with late-onset sepsis were at increased risk for a number of neonatal morbidities, for prolonged hospitalization, and for death . The percentage of deaths attributed to infection increased with increasing postnatal age . The increasing survival of extremely immature infants has resulted in a cohort of infants at prolonged risk for acquired infection . Successful strategies to reduce infections among VLBW infants would improve survival, reduce neonatal morbidity, and reduce the high medical and social costs of VLBW infant care.

J Pediatr (Rio J), 2003 May, 79 Suppl 1, S77 - 86
{Acute upper respiratory tract infections: outpatient diagnosis and treatment}; Pitrez PM et al.; OBJECTIVE: To present an updated review of the most common upper respiratory infections (URI) in children seen by the pediatrician in outpatient clinics, for better diagnostic and therapeutic decisions . SOURCES: References from Medline database were reviewed . The most relevant articles were selected . SUMMARY OF THE FINDINGS: Acute rhinopharyngitis, sinusitis, streptococcal tonsillitis and viral croup are presented in a concise and critical view . Differential and etiological diagnosis limitations and the abusive use of antimicrobials in these illnesses are also discussed . CONCLUSIONS: URI are the most common cause of visits to pediatrician clinics . Therefore, update and critical concepts, as well as references are essential for a proper management of these illnesses, decreasing the indication of unnecessary diagnostic tests and avoiding non-effective and harmful treatments.

Pediatr Infect Dis J, 2003 Sep, 22(9), 794 - 8
Possible relationship between streptococcal pyrogenic exotoxin A and Kawasaki syndrome in patients older than six months of age; Nomura Y et al.; BACKGROUND: We previously investigated antibody titers against four kinds of superantigens {streptococcal pyrogenic exotoxin A (SPEA), streptococcal pyrogenic exotoxin C, toxic shock syndrome toxin-1 and staphylococcal enterotoxin B} in patients with Kawasaki syndrome (KS) younger than 6 months of age and reported a relationship between toxic shock syndrome toxin-1 and KS patients . In this study we have investigated antibody titers in KS patients older than 6 months of age . METHODS: Serum of 81 patients with KS older than 6 months of age, before intravenous gamma-globulin therapy, and 88 normal age-matched children were used in this study . The IgG antibody titers against four kinds of superantigens were measured with an enzyme-linked immunosorbent assay . RESULTS: The KS patients showed significantly elevated mean SPEA titer (P = 0.006) and significantly higher incidence of high SPEA (P = 0.0024) compared with the controls . The SPEA titer in KS patients showed a significant positive correlation with the number of days from onset of illness (P = 0.0002) . CONCLUSIONS: The elevated antibody titer against superantigens of KS patients older than 6 months of age was different from that of KS patients younger than 6 months of age . Our results suggest that KS patients' exposure to SPEA occurred a few weeks before the onset of KS . SPEA may be one of the possible etiologic agents of KS among patients older than 6 months of age in Kagoshima, Japan.

Drugs, 2003, 63(20), 2169 - 84
Short-course antimicrobial therapy of respiratory tract infections; Guay D; Accumulating evidence suggests that short-course (</=5 days, </=3 days for azithromycin) antimicrobial therapy may be at least as effective as and, in some cases, may be more effective than traditional longer (10- to 14-day) therapies.In group A beta-haemolytic streptococcal tonsillopharyngitis, short-course therapy with 6 days of amoxicillin, 4-5 days of a variety of cephalosporins and 5 days of clarithromycin modified-release and telithromycin are all reasonable alternatives to traditional 10-day penicillin therapy . Short-course (i.e . 3-day) azithromycin therapy is not recommended because of suboptimal clinical and bacteriological results compared with penicillin therapy, unless the dosage is doubled from 10 to 20 mg/kg/day for all 3 days.In uncomplicated acute suppurative otitis media, single-dose intramuscular ceftriaxone or 3- to 5-day short-course oral antimicrobial therapy should be effective in the majority (>/=80%) of patients . However, more research is clearly needed in the subpopulations of children <2 years of age and in those with unresponsive/recurrent disease, since short-course therapy may not be successful in the majority of these patients.In sinusitis, most short-course therapy data have involved maxillary disease in adult patients . Regimens have included 3 days of azithromycin or cotrimoxazole (trimethoprim/sulfamethoxazole) or 5 days of cefpodoxime, telithromycin, gatifloxacin, gemifloxacin or amoxicillin/clavulanic acid . Preliminary results are encouraging but more study is clearly needed, especially in the paediatric population.In acute bacterial exacerbations of chronic bronchitis, short-course therapy with a variety of cephalosporins, second-generation fluoroquinolones and advanced generation macrolides/azalides/ketolides are all reasonable alternatives to traditional 7- to 14-day therapies.Cost containment in antimicrobial therapy should involve consideration of short-course therapy in the management of the most common types of respiratory tract infections.

Curr Infect Dis Rep, 2003 Oct, 5(5), 379 - 386
Group A Streptococcal Sepsis; Stevens DL; The fulminant nature of group A streptococcal sepsis poses impressive challenges from diagnostic and therapeutic perspectives . Most patients are seen early in the course of infection by primary care providers or emergency department physicians and sent home, only to return in 12 to 24 hours with fully developed group A streptococcal sepsis . Early diagnosis is imperative, but the clinician must have a high index of suspicion . Often, the diagnosis is established only after aggressive interventional management has begun . This review emphasizes salient clinical features and provides general recommendations for critical care management.

Arthritis Rheum, 2003 Sep, 48(9), 2489 - 500
Citrullination of synovial proteins in murine models of rheumatoid arthritis; Vossenaar ER et al.; OBJECTIVE: Antibodies directed to citrulline-containing proteins are highly specific for rheumatoid arthritis (RA) and can be detected in up to 80% of patients with RA . Citrulline is a nonstandard amino acid that can be incorporated into proteins only by posttranslational modification of arginine by peptidylarginine deiminase (PAD) enzymes . The objective of this study was to investigate the presence of anticitrulline antibodies, PAD enzymes, and citrullinated antigens in mouse models of both acute and chronic destructive arthritis: streptococcal cell wall (SCW)-induced arthritis and collagen-induced arthritis (CIA), respectively . METHODS: Synovial tissue biopsy specimens were obtained from naive mice, mice with CIA, and mice with SCW-induced arthritis . The expression of messenger RNA (mRNA) for PAD enzymes was analyzed by reverse transcriptase-polymerase chain reaction; the presence of PAD proteins and their products (citrullinated proteins) was analyzed by Western blotting and by immunolocalization . The presence of anticitrullinated protein antibodies was investigated by an anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay (ELISA) and an ELISA using in vitro citrullinated fibrinogen . RESULTS: In both mouse models, PAD type 2 (PAD2) mRNA was present in the synovium but was not translated into PAD2 protein . In contrast, PAD4 mRNA, although absent from healthy synovium, was readily transcribed and translated by polymorphonuclear neutrophils infiltrating the synovial tissue during inflammation . As a consequence, several synovial proteins were subjected to citrullination . One of these proteins was identified as fibrin, which has been reported to be citrullinated also in synovium of patients with RA . Although generation of citrullinated antigens during synovial inflammation in the mice was eminent, no anti-CCP antibodies could be detected . CONCLUSION: Citrullination of synovial antigens is an active process during joint inflammation in both mice and humans, but the induction of autoantibodies directed to these proteins is a more specific phenomenon, detectable only in human RA patients.

J Pediatr, 2003 Aug, 143(2), 267 - 9
Parkinsonian features after streptococcal pharyngitis; Ben-Pazi H et al.; Bradykinesia and rigidity developed in a 10-year-old girl during an episode of Sydenham chorea . These parkinsonian features improved over 6 months . Serum analysis demonstrated elevated anti-streptolysin-O and anti-basal ganglia antibodies . We suggest that autoimmune antibodies may cause remitting parkinsonian signs subsequent to streptococcal tonsillitis as part of the spectrum of poststreptococcal CNS disease.

Haematologica, 2003 Sep, 88(9), 1044 - 52
A low body mass index is correlated with poor survival after allogeneic stem cell transplantation; Le Blanc K et al.; BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether body mass index (BMI, kg body weight/height (in m2) is related to survival in recipients of allogeneic stem cell transplantation (ASCT) . DESIGN AND METHODS: Since 1977, 544 adult patients (age ranging from 18 to 64 years) diagnosed with hematologic malignancies; 172 acute myeloid leukemia, 83 acute lymphocytic leukemia, 190 chronic myeloid leukemia and 99 others, underwent myeloablative conditioning and ASCT . Low BMI (<20) was seen in 88 patients, normal BMI (20-25) in 290 and high BMI (>25) in 166 patients . The donors were 348 HLA-identical siblings, 157 matched unrelated donors and 39 HLA major mismatched donors . We assessed BMI as a risk-factor controlling for other risk-factors regarding transplant-related mortality, survival and relapse-free survival using the Cox regression model . RESULTS: Patients with a low BMI more often had ALL, were younger, were more often conditioned with total body irradiation and more often received monotherapy as immunosuppression against graft-versus-host disease . BMI had no effect on engraftment, transfusions and acute or chronic GVHD . Patients with BMI <20 had a higher incidence of a-streptococcal septicemia (p=0.005) than did patients with BMI > or = 20, but both groups had a similar incidence of overall bacteremia . Five-year survival was 36% in those with low BMI, 47% in those with normal BMI and 55% in those with high BMI . In multivariate analysis, death was associated with BMI <20 (p=0.023) . Other significant factors adjusted for were: diagnosis of acute lymphoblastic leukemia, donors other than HLA-identical siblings, disease stage beyond first complete remission or 1st chronic phase, transplantation before 1993 and total body irradiation vs . busulfan conditioning . INTERPRETATION AND CONCLUSIONS: A low BMI (<20) was significantly correlated with an increased transplant-related mortality, a decreased survival and relapse-free survival after ASCT . BMI should be considered when analyzing outcome after ASCT.

Int J Neurosci, 2003 Sep, 113(9), 1287 - 303
Endogenous hypodigoxinemia-related immune deficiency syndrome; Kurup RK et al.; The isoprenoid pathway produces three key metabolites--digoxin (membrane Na+-K+ ATPase inhibitor, regulator of neurotransmitter transport, and an immunomodulatory agent), dolichol (a regulator of N-glycosylation of proteins), and ubiquinone (a free radical scavenger) . The pathway was assessed in acute rheumatic fever patients with recurrent streptococcal infections, and who were also studied for differences in right and left hemispheric dominance . The isoprenoid pathway was downregulated with decreased digoxin synthesis in these patients and in those with left hemispheric chemical dominance . The tryptophan catabolites were decreased and the tyrosine catabolites increased . In these groups of patients the dolichol and glycoconjugate levels were reduced and lysosomal stability was increased . The ubiquinone levels were elevated and free radical levels decreased in these patients . The membrane cholesterol:phospholipid ratios were decreased and membrane glycoconjugates increased . On the other hand in right hemispheric chemical dominance the reverse patterns and hyperdigoxinemia with an upregulated isoprenoid pathway were noticed . The role of the isoprenoid pathway in the pathogenesis of acute rheumatic fever and recurrent streptococcal infections and its relation to hemispheric chemical dominance is discussed.

Conn Med, 2003 Jun-Jul, 67(6), 323 - 6
Group B streptococcal antibiotic resistance patterns in pregnant women; Stiller RJ et al.; Group B Streptococcal (GBS) antibiotic susceptibility studies were performed in 95 pregnant women in Bridgeport, Connecticut . Testing for penicillin, ampicillin, cefazolin, and clindamycin sensitivity was performed . Resistance to clindamycin was seen in 5% of isolates . All isolates were susceptible to penicillin, ampicillin, and cefazolin . Clindamycin sensitivity testing should be performed in patients who are allergic to penicillin . GBS remained uniformly susceptible to penicillin and first generation cephalosporins during this study period.

Singapore Med J, 2003 Mar, 44(3), 138 - 40
A study on early onset peritonitis in CAPD patients; Gan HC et al.; OBJECTIVE: To study the incidence of peritonitis in CAPD patients in their first six months on CAPD . PATIENTS AND METHODS: All patients who started on CAPD between 1 January 1999 and 31 December 1999 were included in the study . All of them were followed for six months for development of peritonitis . RESULTS: Four episodes of CAPD related peritonitis occurred in four different patients during this period . Patient One was an elderly man with diabetes mellitus who had Streptococcal peritonitis two months after he started on CAPD . Patient Two was an elderly woman with diabetes who developed Streptococcal peritonitis four months after she was on CAPD . Patient Three was a 51-year-old lady with diabetes who suffered Pseudomonas peritonitis at four months on CAPD . Patient Four was a young man without diabetes . He had peritonitis after he was on CAPD for four months . The culture showed no bacteria growth . For the first six months of CAPD the peritonitis rate was calculated as one episode for every 51 patient months . The average peritonitis rate of all patients on CAPD at the National University Hospital in 1999 was calculated as one episode for every 27 patient months . The CAPD related peritonitis involving new CAPD patients was lower.

Scand J Clin Lab Invest, 2003, 63(4), 267 - 72
Correlations between serum amyloid A protein and C-reactive protein in infectious diseases; Lannergard A et al.; Serum amyloid A (SAA) protein is an acute phase reactant that has recently become of increasing interest as a marker for disease and treatment monitoring . We have correlated SAA levels to those of C-reactive protein (CRP) in sera from 98 patients admitted to an infectious diseases clinic because of viral and bacterial infections, including hepatitis A and B, cytomegalovirus infection, varicellae-zoster, infectious mononucleosis, influenza A, bacterial pneumonia, streptococcal pharyngitis, bacterial sepsis and severe bacterial sepsis . The study population was chosen from the clinical setting as representatives of these frequently encountered patient groups . SAA levels correlated significantly with CRP levels (r2=0.757, p<0.001) for the entire studied population . Furthermore, positive correlations were found in viral (r2=0.572, p<0.001) and bacterial (r2=0.666, p<0.001) infections . Positive correlations were also observed when the values were compared in accordance with CRP levels higher and lower than 100 mg/L (r2=0.689, p<0.001; CRP>100; r2=0.397, p<0.001; CRP<100) . Because SAA is more sensitive than CRP for the detection of minor inflammatory stimuli, as in the viral and low CRP groups, we conclude that SAA can be of use in several viral infections, as well as in non-invasive and early invasive bacterial infections.

Rev Neurol, 2003 Aug 1-15, 37(3), 224 - 7
{Posterior reversible encephalopathy syndrome: some case reports}; Casali-Rey JI et al.; INTRODUCTION: In 1996, Hinchey et al described a clinico-radiological picture they called posterior reversible leukoencephalopathy syndrome (PRLS), which is characterized by visual disorders, seizures, altered mental states and changes in the subcortical white matter of the temporoparietooccipital lobes that are shown up in the neuroimages . These clinical manifestations are associated with arterial hypertension . Later, other triggering elements, such as cytostatic drugs, were described without being linked to hypertension . Other authors have suggested the name of posterior reversible encephalopathy, since magnetic resonance imaging (MRI) reveals a high percentage of cortical compromise . CASE REPORTS: We present three cases of posterior reversible encephalopathy with different origins . Two of the cases involved females, one of whom was a 19-year-old hypertensive with lupus nephropathy and the other was a 33-year-old with eclampsia . The third case was an 11-year-old male child with post streptococcal glomerulonephritis and hypertension . The most relevant signs and symptoms included seizures, visual disorders, arterial hypertension and sensory deterioration . MR played a decisive role in diagnosis and it revealed an alteration of the signal in the supra and infratentorial white matter of the cortex and the subcortex, which was predominant in the posterior areas of the encephalon . The three cases presented a significant radiological and clinical improvement in a short time . CONCLUSION: Failure of the self regulation of cerebral vascular circulation, with development of oedema, is the most widely accepted hypothesis to explain the pathophysiological mechanism at work in this entity.

Drug News Perspect, 2000 Oct, 13(8), 488 - 97
Potential of p38 inhibitors in the treatment of rheumatoid arthritis; Foster ML et al.; Rheumatoid arthritis (RA) is a chronic debilitating disease estimated to afflict 13% of the world population . Although palliative treatments (nonsteroidal antiinflammatory drugs or NSAIDs) are widely prescribed, there are currently only a few treatments that can modify the insidious progression of the disease (disease-modifying antirheumatic drugs or DMARDs), which frequently leads to physical incapacitation and, on occasion, death . Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) are implicated in the disease onset and in the progression of bone and joint destruction that characterizes chronic RA . p38 is an intracellular mitogen/stress-activated protein kinase (MAPK/SAPK) that regulates both the release and the actions of TNF-alpha and IL-1 beta . Inhibition of p38 kinase is thus an important potential target for novel DMARDs . Following the pioneering work conducted at SmithKline Beecham and elucidation of the roles of p38 with potent and selective inhibitors such as SB-203580, many pharmaceutical companies have embarked upon p38 synthetic programs, as indicated by the ever-increasing number of patents in this domain . At Aventis, a rapid parallel synthesis project led to the identification of RPR-200765A, a potent and selective p38 inhibitor of the lipopolysaccharide-induced release of TNF-alpha in vitro in mononuclear phagocytes and in vivo in the rat . It also reduces disease incidence and progression in the rat streptococcal cell wall arthritis model when administered orally in either a prophylactic or a therapeutic dosing regimen . Development of p38 inhibitors has been slow, probably because of toxicological problems, which might explain why only two oral p38 inhibitors, SB-242235 and VX-745, have advanced into clinical development . In the present article, the preclinical data exemplified in studies on RPR-200765A indicating why p38 inhibitors are attracting so much attention as potential novel anti-RA drugs are reviewed . Current information on the different structural classes of p38 inhibitors is presented and possible reasons for the delays in their development are critically discussed.

Antimicrob Agents Chemother, 2003 Sep, 47(9), 3025 - 9
In vitro activities of a new lipopeptide, HMR 1043, against susceptible and resistant gram-positive isolates; Bemer P et al.; The purpose of this study was to compare the activity of HMR 1043 with those of daptomycin and teicoplanin against gram-positive isolates . Susceptibility tests were performed for 52 strains, 26 parental strains, including staphylococcal, streptococcal, enterococcal, and listerial strains, and 26 HMR 1043-resistant mutants obtained from parental strains by using the Szybalski method . Agar dilution and disk diffusion susceptibility tests were performed by the procedures outlined by the NCCLS . HMR 1043 demonstrated good activity against susceptible and resistant gram-positive bacteria . The activity of HMR 1043 in vitro was less influenced by the presence of calcium ions than that of daptomycin . Susceptibility test breakpoints were not defined because of the poor correlation coefficients obtained with the different disks tested.

Vestn Ross Akad Med Nauk, 2003, (7), 39 - 41
{Acute rheumatic fever: problems and outlooks}; Belov BS; The issue related with acute rheumatic fever still remains to be topical at the present stage, which is accentuated by a high prevalence of rheumatic heart diseases . The results of multiple studies point out at the presence of "rheumatogenetic" A-streptococcal strains possessing certain biological properties . Although there were no changes in the disease semiotics, the intensity degree of clinical signs went down, due to which an early diagnosis of the disease became more complicated . The issues related with the nosological classification of post-streptococcal reactive arthritis and with PANDAS syndrome need to be solved . There is also an urgent necessity in creating high-technological domestic benzathine-penicillins intended for secondary prevention of the disease.

Clin Pediatr (Phila), 2003 Jul-Aug, 42(6), 519 - 26
Efficacy of cephalexin two vs . three times daily vs . cefadroxil once daily for streptococcal tonsillopharyngitis; Curtin CD et al.; The purpose of this study was to compare the bacteriologic and clinical efficacy of oral cephalexin twice vs . three times daily vs . cefadroxil once daily as therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis . A prospective open-label, observational cohort study was conducted over 18 months (January 2000-June 2001) . Children enrolled had an acute onset of symptoms and signs of a tonsillopharyngeal illness and a laboratory-documented GABHS infection . Follow-up examination and laboratory testing occurred 21 +/- 4 days following enrollment . Two hundred seventy-one patients were enrolled (intent to treat group): 63 received cephalexin twice daily, 124 received cephalexin three times daily, and 84 received cefadroxil once daily . Fifty-three children did not return for the follow-up visit, leaving 218 patients in the per-protocol group: 54 cephalexin twice-daily treated, 94 cephalexin 3-times daily treated, and 70 cefadroxil once-daily treated . In the per-protocol group, bacteriologic cure for those treated with cephalexin twice daily was 87%, for cephalexin 3 times daily, it was 81% and for cefadroxil once daily it was 81% (p = 0.61) . The clinical cure rate for cephalexin twice-daily treatment was 91%; for three-times daily, it was 86%; and for cefadroxil once daily, it was 84% (p = 0.56) . Because treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences . Younger age of patient was significantly associated with bacteriologic (p = 0.04) and clinical (p = 0.01) failure independent of treatment group but in the adjusted logistic model no differences were found among the 3 treatment regimens . Cephalexin dosed twice daily or three times daily and cefadroxil dosed once daily appear equivalent in bacteriologic and clinical cure of GABHS tonsillopharyngitis.

J Fr Ophtalmol, 2003 Jun, 26(6), 609 - 13
{Uveitis in children: about 20 cases}; Laghmari M et al.; INTRODUCTION: Uveitis in children is rare: 3%-8% of all cases . It requires the same diagnostic and etiological processes as uveitis in adults, with additional difficulties at examination and a sometimes insidious progression . MATERIAL AND METHODS: Retrospective study of 20 cases of childhood uveitis from 1995 to 2000 . All patients received an ophthalmologic examination and an etiological search, with specific and/or symptomatic treatment and follow-up lasting from 6 months to 5 years . RESULTS: The 20 children presenting uveitis were 4-16 years old, with etiologies as follows: 8 cases of Behcet's disease, 2 cases of Vogt-Koyanagi-Harada's disease, 1 case of sarcoidosis, 1 case of uveitis associated with coeliac disease, 1 case of toxoplasmosis, 1 case of sympathetic ophthalmia, 1 case of uveitis with streptococcal infection, 3 cases of ocular toxocarosis, and 2 cases with unknown etiology . Treatment based on the etiological findings was started in the cases of toxoplasmosis and uveitis from streptococcal infection . The others were treated with high- and then digressive-doses of corticosteroids . ANALYSIS: We have noted the high incidence of Behcet's disease in our series . Progression was marked by frequent recurrence for one case of Vogt-Koyanagi-Harada's syndrome and one case of toxoplasmosis . This study also revealed a few cases of complicated cataract . DISCUSSION: Clinical characteristics, diagnosis, and treatment of uveitis in children are discussed.

Biol Neonate, 2003, 84(1), 24 - 30
Effects of antenatal antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis . A retrospective study over five years; Laugel V et al.; BACKGROUND: Recommendations for the use of antenatal antibiotics have been widely implemented in the past few years, notably to prevent group B streptococcal disease or to prolong pregnancy in the case of preterm premature rupture of the membranes . OBJECTIVES: We designed a retrospective study to assess the potential effects of this increasing use of antibiotics on the incidence and bacteriological profile of early-onset neonatal sepsis (EONS) . METHODS: All neonates referred to our department for suspected EONS from January 1 1995 through December 31 1999 were included . Antenatal antibiotic exposure together with clinical and microbiological data from the neonatal period were gathered and analyzed on a yearly basis . RESULTS: Of the 485 newborns who met the inclusion criteria, there were 101 cases of culture-confirmed sepsis; 339 cases of suspected sepsis and 69 cases of confirmed sepsis involved children born in the hospital, among a total of 16,627 live births registered in our center over the study period . The overall incidence of EONS dropped from 6.8 to 0.6/1,000 births between 1995 and 1999 (p < 0.001), but the rate of group B streptococcal infection decreased much more rapidly than that of non-group B streptococcal infection . We observed a trend towards the emergence of ampicillin-resistant Escherichia coli strains, which were isolated in seven cases . Among E . COLI infections, ampicillin resistance was statistically linked with antenatal antibiotic use (p = 0.025) . We also delineated several risk factors associated with these infections . CONCLUSION: In our center, antenatal antibiotic treatment was effective in reducing the incidence of EONS, but this benefit may come at the cost of favoring the emergence of ampicillin-resistant organisms causing severe neonatal infections . Antenatal and postnatal antibiotic treatment strategies should take this adverse effect into account .

Emerg Infect Dis, 2003 Jul, 9(7), 781 - 7
Disease surveillance and the academic, clinical, and public health communities; Pinner RW et al.; The Emerging Infections Programs (EIPs), a population-based network involving 10 state health departments and the Centers for Disease Control and Prevention, complement and support local, regional, and national surveillance and research efforts . EIPs depend on collaboration between public health agencies and clinical and academic institutions to perform active, population-based surveillance for infectious diseases; conduct applied epidemiologic and laboratory research; implement and evaluate pilot prevention and intervention projects; and provide capacity for flexible public health response . Recent EIP work has included monitoring the impact of a new conjugate vaccine on the epidemiology of invasive pneumococcal disease, providing the evidence base used to derive new recommendations to prevent neonatal group B streptococcal disease, measuring the impact of foodborne diseases in the United States, and developing a systematic, integrated laboratory and epidemiologic method for syndrome-based surveillance.

J Child Neurol, 2003 Jun, 18(6), 434 - 6
Multifocal myoclonus following group A streptococcal infection; Smyth P et al.; Movement disorders as postinfectious manifestation of group A streptococcal infections have been reported and are thought to occur on an autoimmune basis . We describe an unusual case of multifocal myoclonus following strep throat infection . Clinical description and chart review were the method used . A 10-year-old boy developed focal myoclonus involving his right arm and shoulder 1 week after streptococcal throat infection treated with penicillin . His magnetic resonance image was normal, and he initially responded to clonazepam but did not sustain a response . The myoclonus spread to involve all limbs and the trunk becoming multifocal over the next few weeks . He did not have choreoathetosis of Syndenham's chorea . He was given one course of intravenous immunoglobulin and became asymptomatic after treatment . He remained symptom free for 8 months following intravenous immunoglobulin treatment . Various symptoms have been reported following group A streptococcal infections in children . These neurobehavioral abnormalities may be mediated through antineuronal antibodies . Our case demonstrates multifocal myoclonus as a poststreptococcal autoimmune phenomenon . To our knowledge, only two other cases of poststreptococcal myoclonus have been reported in the literature . Recognition of this unusual condition as a manifestation of autoimmune poststreptococcal disease in children is essential to avoid overinvestigation and to ensure early treatment.

J Dent Res, 2003 Aug, 82(8), 636 - 40
Novel OK-432-conjugated tumor vaccines induce tumor-specific immunity against murine tongue cancer; Li X et al.; Priming with tumor antigens is one of the most important strategies in cancer immunotherapy . To enhance tumor antigenicity, OK-432, a streptococcal preparation, was coupled to squamous cell carcinoma (KLN-205) by means of a 0.2% glutaraldehyde method . The purpose of this study was to investigate whether OK-432-conjugated tumor vaccines could induce tumor-specific immunity . Our originally developed mouse tongue cancer model was used throughout this work for the analysis of antitumor effects . Prepared OK-432-conjugated KLN-205 vaccines were immunized 3 times to DBA/2 mice . The results showed that the KLN-205 vaccines induced cytolytic activity and strongly suppressed both KLN-205 tumor incidence and growth, and survival of the mice was improved . Moreover, the histological results showed that a greater number of lymphocytes had infiltrated around tumor cells by 24 hours after tumor inoculation in the vaccine group . These results suggest that immunizations with KLN-205 vaccines increase the antitumor effects against tongue cancer.

Biochemistry, 2003 Aug 5, 42(30), 8999 - 9006
Structural and dynamic properties of the HIV-1 tat transduction domain in the free and heparin-bound states; Hakansson S et al.; An 11-residue basic domain of the HIV-1 tat protein, termed the tat transduction domain (TTD), has been shown to mediate transfer of biomolecules across biological membranes . The mechanism of TTD-mediated membrane translocation is currently unknown but thought to involve binding to heparan sulfate, which is found in proteoglycans that are ubiquitously present on cell surfaces . To study the mechanism of TTD-mediated membrane translocation, the TTD was fused to the C-terminus of a model cargo protein, the IgG binding domain of streptococcal protein G (PG) to form PG-TTD . NMR studies of PG-TTD in the free state indicated that the structure of the PG moiety of PG-TTD was not perturbed by the presence of the TTD and that the TTD moiety is in an extended conformation . Heteronuclear relaxation measurements of PG-TTD in the free state show that the TTD moiety of PG-TTD is relatively mobile (e.g., the average S(2) value of the TTD and PG core are approximately 0.54 and approximately 0.84, respectively) . PG-TTD has been shown to bind to heparin by isothermal titration calorimetry (K(D) = 0.37 microM, Delta H = -12 kcal/mol, Delta S = -11 cal/mol/T) . NMR spectroscopy demonstrated that heparin binds to the TTD moiety of PG-TTD . The heteronuclear relaxation measurements of PG-TTD in complex with heparin show that the TTD becomes less dynamic when bound to heparin (average S(2) value of the TTD is 0.69 in the presence of heparin) . A model for the first step of TTD-mediated entry into cells is presented.

Clin Infect Dis, 2003 Aug 1, 37(3), 333 - 40 Epub 2003 Jul 17.
Intravenous immunoglobulin G therapy in streptococcal toxic shock syndrome: a European randomized, double-blind, placebo-controlled trial; Darenberg J et al.; The efficacy and safety of high-dose intravenous polyspecific immunoglobulin G (IVIG) as adjunctive therapy in streptococcal toxic shock syndrome (STSS) were evaluated in a multicenter, randomized, double-blind, placebo-controlled trial . The trial was prematurely terminated because of slow patient recruitment, and results were obtained from 21 enrolled patients (10 IVIG recipients and 11 placebo recipients) . The primary end point was mortality at 28 days, and a 3.6-fold higher mortality rate was found in the placebo group . A significant decrease in the sepsis-related organ failure assessment score at days 2 (P=.02) and 3 (P=.04) was noted in the IVIG group . Furthermore, a significant increase in plasma neutralizing activity against superantigens expressed by autologous isolates was noted in the IVIG group after treatment (P=.03) . Although statistical significance was not reached in the primary end point, the trial provides further support for IVIG as an efficacious adjunctive therapy in STSS.

Int J Pediatr Otorhinolaryngol, 2003 Aug, 67(8), 837 - 40
PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections--an uncommon, but important indication for tonsillectomy; Heubi C et al.; Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, also know as "PANDAS," is well described in the neurologic and psychiatric literature . PANDAS is associated with obsessive compulsive disorders (OCD) and tic disorders . The streptococcal infections may trigger an autoimmune reaction that exacerbates these conditions . Recurrent streptococcal tonsillitis is one of the recurrent infections associated with PANDAS . This paper reviews the case reports of two brothers, one with OCD and the other with a tic disorder, both of whom improved significantly after undergoing adenotonsillectomy for treatment of their recurrent tonsillitis . A review of the pathophysiology and current understanding of PANDAS is presented.

J Child Adolesc Psychopharmacol, 2003, 13 Suppl 1, S89 - 92
Risperidone-induced obsessive-compulsive symptoms in two children; Diler RS et al.; OBJECTIVE: To present two cases of rapid-onset obsessive-compulsive symptoms in children treated with risperidone . Cases: "A" was an 8-year-old boy with attention deficit and chronic tic disorder who developed obsessive-compulsive symptoms within 2 weeks of starting risperidone . When the dose of 0.5 mg tid was discontinued, the obsessive-compulsive symptoms resolved with no return over 8 months of follow-up . "B" was an 11-year-old girl with mild mental retardation and aggression who was treated with risperidone 1 mg per day . Obsessive-compulsive symptoms suddenly emerged 10 days after starting risperidone and resolved within 3 days of discontinuation . In both cases, streptococcal pharyngitis was ruled out . CONCLUSION: Although the mechanism is not clear, these cases add to several other reports concerning the sudden emergence of obsessive-compulsive symptoms and anxiety symptoms in children treated with atypical antipsychotics . Clinicians should be alert to the possibility of these adverse effects in children treated with these drugs.

Anaesth Intensive Care, 2003 Jun, 31(3), 320 - 3
Immunoglobulin therapy in non-menstrual streptococcal toxic shock syndrome; Murthy BV et al.; We describe a case of non-menstrual streptococcal toxic shock syndrome requiring high doses of noradrenaline . The intravenous administration of pooled immunoglobulin was associated with improved haemodynamics and weaning of vasoconstrictors.

Scand J Infect Dis, 2003, 35(5), 302 - 5
Six day antimicrobial therapy for early-onset group B streptococcal infection in near-term and term neonates; Poschl JM et al.; Antibiotics for the treatment of group B streptococcal (GBS) infection are usually given for 7-10 d . The aim of this prospective investigation was to study whether antibiotic treatment for 6 d is sufficient to treat early-onset GBS infection in term and near-term neonates . During a 2 y period 67 neonates of GBS-positive mothers developed GBS infection and were admitted to the neonatal intensive care unit . All neonates showed clinical signs of infection, C-reactive protein levels > 20 mg/l and/or elevated immature to total neutrophil ratio > 0.25 . Two groups were differentiated: 10 neonates with proven sepsis with GBS-positive blood cultures (15%) and 57 neonates with presumed GBS infection with negative blood cultures but with GBS-positive surface swab cultures of ear (68%), nasopharyngeal (21%) or gastric aspirate (16%) . All patients were GBS positive in 1 or more cultures . Antimicrobial therapy with ampicillin and cefotaxime was discontinued after 6 d . At that time all neonates were asymptomatic and laboratory results were normal . No relapse or death within 4 weeks after therapy was detected . In conclusion, antibiotic therapy for 6 d was sufficient to treat 10 neonates with proven and 57 neonates with presumed early-onset GBS infection . Owing to the small sample size, further studies are needed to show significant differences to longer therapy regimens.

Clin Immunol, 2003 Jul, 108(1), 60 - 8
Mutational effects on protein folding stability and antigenicity: the case of streptococcal pyrogenic exotoxin A; Carra JH et al.; The influence of mutationally induced changes in protein folding on development of effective neutralizing antibodies during vaccination remains largely unexplored . In this study, we probed how mutational substitutions of streptococcal pyrogenic exotoxin A (SPEA), a model bacterial superantigen, affect native conformational stability and antigenicity . Stability changes for the toxin variants were determined using circular dichroism and fluorescence measurements, and scanning calorimetry . Self-association was assayed by dynamic light scattering . Inactivated SPEA proteins containing particular combinations of mutations elicited antibodies in HLA-DQ8 transgenic mice that neutralized SPEA superantigenicity in vitro, and protected animals from lethal toxin challenge . However, a highly destabilized cysteine-free mutant of SPEA did not provide effective immunity, nor did an irreversibly denatured version of an otherwise effective mutant protein . These results suggest that protein conformation plays a significant role in generating effective neutralizing antibodies to this toxin, and may be an important factor to consider in vaccine design.

Kidney Int Suppl, 2003 Feb, (83), S22 - 6
End-stage renal disease and acute glomerulonephritis in Goajiro Indians; Herrera J et al.; BACKGROUND: Goajiro Indians are a semi-nomad tribe that live on the Goajiro peninsula, in the northwestern part of Venezuela . We investigated the incidence of end-stage renal disease (ESRD) and post-streptococcal glomerulonephritis (PSGN) among Goajiros and to determine if it was increased and whether congenital endowment of low number of nephrons (as indicated by low birth weight) was a contributing factor in their predisposition to chronic renal failure (CRF) . METHODS: The incidence of ESRD and the attack rate of poststreptococcal glomerulonephritis (PSGN) among Goajiros during the period December 1991 through December 1998 were evaluated from the records of the University Hospital, in Maracaibo, which is the referral center for Goajiro Indians . Demographic characteristics and birth weight were obtained from the records of the Regional Public Health Service . Subclinical reduction in renal functioning mass was investigated in 11 healthy Goajiros with a standardized tubular stress test that determines the increment in tubular secretion of creatinine (TSCr) resulting from the intravenous administration of a bolus of creatinine . RESULTS: The incidence of ESRD among Goajiros was 220 patients per million inhabitants per year, 1.7 times higher than the incidence for the country . The attack rate of post-streptococcal glomerulonephritis is nearly double among Goajiro Indians (2.9 +/- 1.3 cases/100,000 inhabitants/year) than in the general population in the neighboring Maracaibo city (1.5 +/- 0.3, P < 0.02) . Low weight birth was common among Goajiros; as many as 23% of newborns weigh less than 1000 g . The stimulated TSCr in healthy Goajiros was 30% lower than in controls (P < 0.001) . CONCLUSIONS: Goajiro Indians have a high incidence of ESRD . A high attack rate of PSGN and low nephron endowment in combination may be responsible, at least in part, for the increased risk of ESRD in this population.

Clin Pediatr (Phila), 2003 Jun, 42(5), 417 - 20
Occurrence of Epstein-Barr virus illness in children diagnosed with group A streptococcal pharyngitis; Rush MC et al.; Epstein-Barr virus mononucleosis and group A streptococcal pharyngitis are acute infectious processes similar in both their clinical manifestations . Coinfections may occur and be a direct result of a synergistic effect on inflamed pharyngeal and tonsillar tissue . It was our observation that a population of children diagnosed with group A streptococcal pharyngitis and not responding to appropriate antimicrobial therapy had Epstein-Barr virus illness.

J Infect, 2003 Aug, 47(2), 185 - 7
Impetigo neonatorum associated with late onset group B streptococcal meningitis; Guha A et al.; We present a case of nonbullous impetigo neonatorum associated with late onset group B streptococcal meningitis in a 12-day-old infant . Both skin lesions and meningitis resolved with antibiotic therapy . This is the first reported case of meningitis during the course of this skin disease.

Ann Acad Med Singapore, 2003 May, 32(3), 311 - 7
Neonatology in Singapore: the way we were, the way forward; Ho NK; Singapore has a maternity hospital since 1924, but for many decades the newborns could only receive basic care . Neonatal and perinatal mortality rates were high . Marked improvement in neonatal care began from the 1980s when many neonatal departments were set up to provide intensive care . Improved socioeconomic status, better healthcare facilities, effective infection control, immunisation programmes and availability of potent antibiotics contributed to the decline of perinatal and neonatal mortality . Following the implementation of the glucose-6-phosphate dehydrogenase (G6PD) deficiency screening programme, severe neonatal jaundice and kernicterus were largely reduced . Exchange blood transfusions initiated in the 1960s and phototherapy in the 1970s had saved many babies . Kernicterus is almost not seen now . With more neonatal-trained staff, organised resuscitation teams, advances in respiratory management and better monitoring equipment, more babies have survived . Closer cooperation between obstetricians and neonatologists was a great leap forward towards perinatal medicine . Physicians should endeavour to reduce the incidence and prevalence of birth defects and metabolic errors . Perinatal asphyxia should be promptly detected and managed effectively, including neuroprotective strategies . There should be markers to predict the outcome of asphyxiated babies for decision-making . Neonatologists should be mindful of safe introduction of new technologies and rapid diagnostic techniques for infections, including group B streptococcal screening and chemoprophylaxis when required . Other current issues include prevention of major morbidities, preservation of brain function, improved neurodevelopmental outcome of premature babies, use of blood substitutes, optimal nutrition, fetal surgery, evidence-based medicine, better information systems, avoidance of medication errors, adequate sedation and pain relief of the baby, and the use of nitric oxide . One should bear in mind the need to enhance the neonatal intensive care environment, improve non-invasive monitoring and minimise invasive procedures . Physicians should prioritise neonatal care for their country and utilise less costly neonatal care . Ethical issues in neonatology that arise following advancement in neonatal care deserve attention . Advances in life sciences, such as the completion of the human genome project, cloning of tissues and organs, human stem cell research and technology, gene therapy, deoxyribonucleic acid vaccines and nanomedicine, should benefit neonatology.

Vaccine, 2003 Jul 28, 21(24), 3468 - 72
Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine; Baker CJ et al.; AIM: To determine the safety and immunogenicity of group B streptococcal (GBS) type III CPS-TT conjugate vaccine in pregnant women . METHODS: Prospective, randomized (2:1, vaccine:placebo), double-blind, placebo-controlled trial in women at 30-32 weeks' gestation and their infants . Immune responses were measured with IgG-specific ELISA assays; killing of III GBS by 1- and 2-month infant sera was assessed by opsonophagocytosis . RESULTS: Immunization was well-tolerated; maternal and infant outcomes were similar in vaccine and placebo groups . III-TT conjugate elicited good levels of IgG to III CPS that were functionally active against type III GBS through age 2 months . CONCLUSION: Maternal immunization with GBS CPS-TT conjugates could prevent maternal, neonatal and young infant GBS disease.

Autoimmun Rev, 2002 Oct, 1(5), 261 - 6
Rheumatic fever: the T cell response leading to autoimmune aggression in the heart; Guilherme L et al.; Molecular mimicry between streptococcal and heart components has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD) . CD4+ T cells apparently are the ultimate effectors of chronic heart lesions . In this review we summarize the studies on the T cell response of peripheral blood mononuclear cells and T cell clones infiltrating heart lesions from RHD patients against streptococcal M protein peptides and human heart tissue proteins . The T cell receptor usage and the cytokine profile of intralesional mononuclear cells are also presented.

J Psychosom Res, 2003 Jul, 55(1), 31 - 9
PANDAS: a commentary; Singer HS et al.; PANDAS is an acronym for Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection . As defined, the criteria include prepubertal children with either a tic or obsessive-compulsive disorder in whom a Group A beta-hemolytic streptococcal infection (GABHS) triggers the abrupt onset or exacerbation of tics/obsessive-compulsive behaviors . Pathophysiologically, it is proposed that antibodies produced against GABHS cross-react with neuronal cells, in a process involving molecular mimicry . Although PANDAS has received widespread notoriety, the existence of this condition has been questioned . This commentary reviews clinical and laboratory issues pertinent to the diagnosis of this entity . We conclude that PANDAS is an intriguing hypothesis that requires further confirmation.

Infect Dis Obstet Gynecol, 2003, 11(1), 1 - 9
Compliance with protocols for prevention of neonatal group B streptococcal sepsis: practicalities and limitations; Gilbert GL et al.; OBJECTIVE: To compare two protocols for intrapartum antibiotic prophylaxis (IAP) against neonatal group B streptococcal (GBS) sepsis, with respect to staff compliance, in a prospective cohort study in the obstetric units of a community hospital (A) and a university teaching hospital (B) . METHODS: Cohorts comprised about 500 women attending antenatal clinics at each hospital (total 1096) . Women identified as GBS carriers at 26-32 weeks' gestation and those who had intrapartum clinical risk factors (CRF) were eligible for IAP . Compliance was defined as the proportion of women eligible for IAP who received it according to protocol - as determined by audit of case records - and compared between hospitals and according to indication . RESULTS: Overall, 39% of women were eligible for IAP . Indications were GBS carriage alone (21%), CRF alone (13%) and both (5%) . Compliance was similar for GBS carriers at both hospitals: 78% at Hospital A and 76% at Hospital B . However, because of the poor predictive value of screening before 32 weeks, only 65% of intrapartum GBS carriers actually received IAP . For women with CRF only, compliance was significantly lower at Hospital B than Hospital A (56 vs . 75%; p = 0.03) . CONCLUSIONS: According to currently recommended protocols, about one-third of healthy women are eligible for intrapartum antibiotics to prevent neonatal GBS sepsis . In practice, antibiotics are often used inefficiently because of poor compliance with protocols and poor predictive values of selection criteria . Better implementation strategies should improve compliance, but GBS vaccines are needed to replace prophylactic antibiotic use, with its associated disadvantages.

Curr Opin Infect Dis, 2003 Jun, 16(3), 279 - 83
Descriptive and molecular epidemiology of Gram-negative bacilli infections in the neonatal intensive care unit; Dent A et al.; PURPOSE OF REVIEW: The critically ill neonate is particularly prone to life threatening bacterial infections compared with other patient populations . Current patterns of neonatal sepsis caused by Gram-negative bacilli are reviewed to enable the clinician to better anticipate and effectively respond to neonatal infection by these serious pathogens . RECENT FINDINGS: With increasing use of intrapartum antibiotics for prophylaxis against early-onset group B streptococcal infection, there is growing concern that the incidence of neonatal sepsis by Gram-negative pathogens may rise . Although several surveys indicate no such increase to date, studies in selected neonatal intensive care unit populations have suggested a recent elevation in newborn infection caused by Escherichia coli and other bacillary pathogens . Most recent investigations reveal growing antibiotic resistance in those Gram-negative bacilli causing neonatal infection . Modern molecular genotyping methods have been applied to Gram-negative bacilli in the neonatal intensive care unit in order to understand their epidemiology in greater detail . In most instances these techniques have been used to identify the sources and prevalence of an outbreak strain, and to devise rational interventions to control the epidemic . Studies utilizing molecular genotyping during non-outbreak periods indicate that Gram-negative bacilli, even those expressing antibiotic resistance, may be acquired very early in the intensive care unit course, and that different clones are introduced and lost in the infants' indigenous flora throughout their stay . These studies further indicate that cross-transmission of bacillary pathogens occurs regularly even in the absence of a recognized epidemic . SUMMARY: Gram-negative bacilli are prominent causes of infection in the neonatal intensive care unit . Their incidence, antibiotic susceptibility pattern, and modes of acquisition continue to evolve in the modern intensive care unit setting.

Fam Med, 2003 Jun, 35(6), 411 - 3
Maximizing neonatal early onset group B streptococcal disease prevention with universal culture screening at 35 to 37 weeks gestation: a comparison of GBS detection rates between LIM broth and CNA culture media; Orsello C et al.; BACKGROUND AND OBJECTIVES: Group B streptococcal (GBS) disease is the most common cause of early onset neonatal sepsis . The Centers for Disease Control (CDC) recommends performing recto-vaginal cultures on pregnant woman to detect GBS, followed by treatment of women with positive cultures . Our facility adopted selective culture screening in 1997 using a colistin-naladixic acid (CNA) plate media instead of the more expensive LIM broth media . CNA plate cultures cost one third that of LIM broth and allow for final results in 24 hours, versus 48-72 hours with LIM broth . We hypothesized that CNA media saves time, money, and detects GBS as effectively as LIM broth . This study determined which media is superior at detecting recto-vaginal GBS . METHODS: This was a case-control study involving 152 consecutive pregnant patients at 35-37 weeks from August 1 to October 1, 2001, at Naval Hospital Bremerton, Wash . We obtained two recto-vaginal swabs from each patient . One was cultured in LIM broth and the other on CNA medium . We then compared differences in the rates of positive cultures with LIM broth versus CNA medium using chi-square statistics and calculation of odds ratios (OR) . RESULTS: LIM broth detected GBS in 35 of 145 (24.19%) women versus 21 of 145 (14.5%) using CNA . CNA failed to detect GBS in 15 cases in which LIM broth succeeded (OR=1.88; 95% CI=1.03-3.4) . CONCLUSIONS: LIM broth is superior at detecting maternal GBS colonization and is recommended over CNA plate to maximize prevention of early onset neonatal GBS disease.

Nucleic Acids Res, 2003 Jun 15, 31(12), 3038 - 49
The C-terminal domain of Escherichia coli MutY is involved in DNA binding and glycosylase activities; Li L et al.; Escherichia coli MutY is an adenine and a weak guanine DNA glycosylase involved in reducing mutagenic effects of 7,8-dihydro-8-oxo-guanine (8-oxoG) . The C-terminal domain of MutY is required for 8-oxoG recognition and is critical for mutation avoidance of oxidative damage . To determine which residues of this domain are involved in 8-oxoG recognition, we constructed four MutY mutants based on similarities to MutT, which hydrolyzes specifically 8-oxo-dGTP to 8-oxo-dGMP . F294A-MutY has a slightly reduced binding affinity to A/G mismatch but has a severe defect in A/8-oxoG binding at 20 degrees C . The catalytic activity of F294A-MutY is much weaker than that of the wild-type MutY . The DNA binding activity of R249A-MutY is comparable to that of the wild-type enzyme but the catalytic activity is reduced with both A/G and A/8-oxoG mismatches . The biochemical activities of F261A-MutY are nearly similar to those of the wild-type enzyme . The solubility of P262A-MutY was improved as a fusion protein containing streptococcal protein G (GB1 domain) at its N-terminus . The binding of GB1-P262A-MutY with both A/G and A/8-oxoG mismatches are slightly weaker than those of the wild-type protein . The catalytic activity of GB1-P262A-MutY is weaker than that of the wild-type enzyme at lower enzyme concentrations . Importantly, all four mutants can complement mutY mutants in vivo when expressed at high levels; however, F294A, R249A and P262A, but not F261A, are partially defective in vivo when they are expressed at low levels . These results strongly support that the C-terminal domain of MutY is involved not only in 8-oxoG recognition, but also affects the binding and catalytic activities toward A/G mismatches.

Inflammation, 2003 Apr, 27(2), 59 - 70
Streptococcal cell wall induced arthritis: leukocyte activation in extra-articular lymphoid tissue; Kimpel D et al.; Rheumatoid arthritis (RA) is a common systemic inflammatory disease thought to be T-helper-1 cell driven, though current controversy involves the relative role of T cells versus other leukocytes . Thus, there is a need for better understanding of the role of various leukocytes and their subsets in RA . Using the streptococcal cell wall (SCW) induced arthritis model, we examined leukocytes isolated from peripheral blood, spleen, and lymph nodes using monoclonal antibodies directed against lineage specific cell surface markers . Activation status of these cells was assessed using CD44 and CD71 as markers . T cells in general, and CD4+ T cells in particular were found to be activated in spleen and lymph nodes . B cells and monocytes in spleen demonstrated increased activation as well . The activation of cells in the myeloid and lymphoid lineages in the chronic phase of arthritis indicates ongoing involvement of innate and cognate immunity . This study quantitates specific changes in B and T lymphocytes, and myeloid cells and is consistent with findings in human RA in which specific antibodies, T cells, and myeloid cells are all implicated in the pathogenesis of RA.

Arthritis Rheum, 2003 Jun, 48(6), 1721 - 31
Blockade of parathyroid hormone-related protein prevents joint destruction and granuloma formation in streptococcal cell wall-induced arthritis; Funk JL et al.; OBJECTIVE: To determine whether parathyroid hormone-related protein (PTHrP), an interleukin-1beta-inducible, bone-resorbing peptide that is produced in increasing amounts by the synovium in rheumatoid arthritis (RA), may play a role in the pathophysiology of joint destruction in RA . METHODS: PTHrP expression and the effect of PTHrP 1-34 neutralizing antibody on disease progression were tested in streptococcal cell wall (SCW)-induced arthritis, an animal model of RA . RESULTS: As has been reported in RA, while serum levels of PTHrP did not change during SCW-induced arthritis, PTHrP expression dramatically increased in the arthritic synovium . Treatment with PTHrP neutralizing antibody (versus control antibody) did not affect joint swelling in SCW-treated animals . However, PTHrP antibody significantly inhibited SCW-induced joint destruction, as measured by its ability to block increases in serum pyridinoline (a marker of cartilage and bone destruction), erosion of articular cartilage, decreases in femoral bone mineral density, and increases in the numbers of osteoclasts in eroded bone . Unexpectedly, granuloma formation at sites of SCW deposition in the liver and spleen was also inhibited by PTHrP antibody, an effect associated with significant decreases in the tissue influx of PTH/PTHrP receptor-positive neutrophils and in SCW-induced neutrophilia . In vitro, neutrophil chemotaxis was stimulated by PTHrP 1-34 . CONCLUSION: These findings suggest that PTHrP, consistent with its previously described osteolytic effects in metastatic bone disease, can also be an important mediator of joint destruction in inflammatory bone disorders, such as RA . Moreover, this study reveals heretofore unknown effects of PTHrP peptides on neutrophil function that could have important implications in the pathogenesis of inflammatory granulomatous disorders.

Intern Med, 2003 May, 42(5), 421 - 3
Streptococcal toxic shock syndrome presenting with spontaneous hypoglycemia in a chronic hemodialysis patient: pathophysiological mechanisms; Igaki N et al.; Hypoglycemia is fatal if associated with sepsis in end-stage renal disease (ESRD) patients . We report a hemodialysis patient of streptococcal toxic shock syndrome presenting with hypoglycemia . She was found to be severely hypoglycemic with a plasma glucose level of 16 mg/dl . Immunoreactive insulin levels were undetectable throughout the clinical course . Several factors including reduced renal gluconeogenesis, reduced hepatic glucose output and excessive peripheral glucose utilization may account for the hypoglycemia in this patient . In conclusion, we would like to draw attention to the fact that septic ESRD patients without diabetes are prone to develop profound hypoglycemia with serious consequences.

Pediatr Infect Dis J, 2003 May, 22(5), 430 - 4
Utility of complete blood count and blood culture screening to diagnose neonatal sepsis in the asymptomatic at risk newborn; Ottolini MC et al.; BACKGROUND: In May 1996, the CDC recommended obtaining a complete blood count and blood culture (BC) from all asymptomatic "at risk" newborns; those > or =35 weeks gestation born to mothers with group B streptococcal vaginal colonization or those with maternal fever, premature rupture of membranes or previous infant with group B streptococcal disease; who did not receive adequate intrapartum antibiotic prophylaxis . DESIGN/METHODS: During the study period (May 1996 to July 1999), a complete blood count and BC were obtained within 4 h from all asymptomatic at risk newborns of > or =35 weeks gestation . White blood cell count (WBC) and BC results and prevalence of clinical or culture-proven sepsis were obtained by chart review . We determined the sensitivity/specificity and likelihood ratios of an abnormal WBC (total >30 000 or <5000/mm3; absolute neutrophil count <1500/mm3, or a band form-polymorphonuclear cell ratio of >0.2) to distinguish between clinically septic vs . nonseptic term at risk newborns . RESULTS: Of 20 554 deliveries 1665 were initially asymptomatic at risk newborns; 17 (1.0%) developed early onset sepsis, all within 48 h . WBC was abnormal in 7 of 17 (41%) and in 447 of 1648 (27%) who remained nonseptic . None of the 1665 term at risk newborns had a positive BC . The sensitivity and specificity of an abnormal WBC in predicting which at risk newborns would develop sepsis were 41 and 73%, respectively . The positive likelihood ratio was 1.52, whereas the negative likelihood ratio was 0.81, with an odds ratio of 1.88 . CONCLUSIONS: Since the implementation of the CDC guidelines for maternal intrapartum antibiotic prophylaxis, culture-proved sepsis has become rare at our institution . Although BC did not aid in the diagnosis of sepsis among asymptomatic at risk newborns, close observation in the first 24 h remained critically important.

Br J Dermatol, 2003 May, 148(5), 996 - 1000
The effects of ultraviolet B treatment on the expression of adhesion molecules by circulating T lymphocytes in psoriasis; Sigmundsdottir H et al.; BACKGROUND: T lymphocytes are believed to play a role in the pathogenesis of psoriasis; > 80% of T lymphocytes that infiltrate psoriatic lesions express the surface glycoprotein cutaneous lymphocyte-associated antigen (CLA), compared with < 20% in the blood . Exposure to ultraviolet (UV) B is an effective treatment for psoriasis . OBJECTIVES: To compare the effects of UVB treatment of psoriasis on the expression of CLA and several other surface markers expressed by circulating T lymphocytes . METHODS: Peripheral blood mononuclear cells from psoriatic patients were stained for adhesion molecules and stimulated with streptococcal antigens before and once weekly during 3 weeks of UVB treatment . RESULTS: A marked and progressive decrease was observed during the treatment in expression of the CLA and the very late antigen-4alpha by T cells; this decrease correlated closely with clinical improvement (Psoriasis Area and Severity Index) . T-cell expression of intercellular adhesion molecule-1 was not significantly affected during the treatment and no change was observed in the activation markers CD25 and CD69 or lymphocyte proliferation after stimulation with streptococcal antigens or superantigens . CONCLUSIONS: UVB treatment is associated with a marked reduction in the expression of skin-homing molecules by circulating T cells . This may be relevant to the therapeutic effect of UVB in psoriasis.

Semin Pediatr Neurol, 2003 Mar, 10(1), 11 - 9
Sydenham's chorea: not gone and not forgotten; Bonthius DJ et al.; Sydenham's chorea is an ancient disease that continues to afflict large numbers of children throughout the world . A major manifestation of rheumatic fever, Sydenham's chorea is commonly manifested by movement disorder and psychiatric problems, and also may be a marker for a life-threatening carditis . Because Sydenham's chorea is triggered by streptococcal pharyngitis, the most important component of its therapy is antibiotic prophylaxis against further streptococcal infections . Because the pathogenesis of Sydenham's chorea includes the production of anti-basal ganglia antibodies, therapies that modulate immune function or that restore neurotransmitter balance within the basal ganglia may be effective for Sydenham's chorea . Recent reports have suggested that Sydenham's chorea may be part of a spectrum of neuropsychiatric syndromes induced by streptococcal infection.

Cells Tissues Organs, 2003, 174(1-2), 26 - 33
Nitric oxide in experimental joint inflammation . Benefit or detriment?
Wahl SM, McCartney-Francis N, Chan J, Dionne R, Ta L, Orenstein JM.
The host response to infection or injury initiates a cascade of events involving recruitment of leukocytes and the release of multiple inflammatory mediators . One of these mediators, nitric oxide (NO), not only represents an important microbicidal agent in host defense, but also functions as a biological signaling and effector molecule in inflammation and immunity . However, overproduction of NO can be autotoxic and contribute to tissue damage and has been implicated in pathogenesis of tumors, and infectious, autoimmune and chronic degenerative diseases . NO is generated via constitutive and inducible nitric oxide synthases (iNOS) which catalyze the oxidation of a guanidino nitrogen associated with L-arginine . Whereas endothelial NOS (eNOS) and neuronal NOS (nNOS) are constitutively expressed, iNOS is transcriptionally induced by bacterial constituents and inflammatory mediators, including TNF alpha and IL-1 . In an experimental model of bacterial component-induced joint inflammation and tissue degradation, functionally distinct roles of the constitutive NOS and iNOS were demonstrated . Following systemic delivery of an arthritogenic dose of streptococcal cell walls (SCW), these bacterial peptidoglycan-polysaccharide complexes disseminate and target the peripheral joints, liver and spleen of the treated animals . Following deposition of the SCW in the peripheral joints, an initial innate inflammatory response to the bacterial components progresses into an adaptive immune response with the recruitment and activation of mononuclear phagocytes and T lymphocytes . With the release of cytokines and inflammatory mediators, there is an upregulation of gene expression for iNOS, but not the constitutive nNOS or eNOS . Nonetheless, the constitutive NOS isoforms, regulated by calcium fluxes and interaction with calmodulin, may also enhance NO production . Increased release of NO was detected not only in the synovium, but also in the circulation, and plasma levels of nitrate plus nitrite, the stable products of NO reactions, correlated with disease progression . Following inhibition of NO production with nonspecific NOS inhibitors, such as N(G)-monomethyl-L-arginine, which target all three isoforms, there is a striking therapeutic benefit with reduced signs and symptoms of erosive arthritis . In contrast, selective targeting of iNOS with N-iminoethyl-L-lysine resulted in exacerbation of the synovial inflammation and degradation of joint structures . Based on these data, it appears that the constitutive isoforms of NOS contribute to the pathophysiology of the arthropathy, and that induced NOS and NO may function, in part, in a protective pathway . Moreover, the suppression of NO following treatment with TNF alpha antagonists results in reduced inflammation and the associated synovial pathology . Collectively, these data implicate discrete roles for the NOS isoforms in the emergence of local tissue pathology and underscore the need to define the specific pathways that are being targeted for interventional strategies .

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