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| MMWR Morb Mortal Wkly Rep, 2000 Mar 24, 49(11), 228 - 32 Adoption of perinatal group B streptococcal disease prevention recommendations by prenatal-care providers--Connecticut and Minnesota, 1998; The lack of binding ability of staphylococcal protein A and streptococcal protein G to egg yolk immunoglobulins of different fowl species (short communication); Paul-Ehrlich-Institute, Federal Agency for Sera and Vaccines, Langen, GermanyThe binding ability of staphylococcal protein A (SpA) and streptococcal protein G (SpG) to egg yolk antibodies of four fowl species (turkey, duck, moskovy duck and goose) was studied and compared with the binding ability to three serum antibodies from chicken, horse and cattle . SpA and SpG were not able to bind to any of the avian immunoglobulins. Mol Microbiol, 2000 Mar, 35(6), 1469 - 82 Antisense RNA-mediated transcriptional attenuation: an in vitro study of plasmid pT181; Brantl S et al.; Antisense RNAs regulate plasmid replication by several different mechanisms . One of these mechanisms, transcriptional attenuation, was first described for the staphylococcal plasmid pT181, and later for the streptococcal plasmids pIP501 and pAMbeta1 . Previously, we performed detailed in vitro and in vivo analyses of the pIP501 system . Here, we present an in vitro analysis of the antisense system of plasmid pT181 . The secondary structures of antisense and sense RNA species of different lengths were determined . Binding rate constants for sense/antisense RNA pairs were measured, and functional segments required for complex formation were determined . A single-round transcription assay was used for in vitro analysis of transcriptional attenuation . A comparison between pT181 and pIP501 revealed several differences; whereas a truncated derivative of pIP501 antisense RNA was sufficient for stable complex formation, both stem-loop structures of pT181-RNAI were required . In contrast to the sense RNA of pIP501, which showed an intrinsic propensity to terminate (30-50% in the absence of antisense RNA), the sense RNA of pT181 required antisense RNA for induced termination . Rate constants of formation of pT181 sense-antisense RNA complexes were similar to inhibition rate constants, in striking contrast to pIP501, in which inhibition occurred at least 10-fold faster than stable binding. Headache, 2000 Mar, 40(3), 200 - 3 Acute headache in children and adolescents presenting to the emergency department; Lewis DW et al.; OBJECTIVES: Our goals were (1) to investigate the causes of acute headache in childhood from the emergency department perspective and (2) to search for clinical clues that might distinguish headache associated with serious underlying disease . BACKGROUND: The clinical presentation of headache in children and adolescents can be separated into 5 temporal patterns: acute, acute-recurrent, chronic progressive, chronic nonprogressive, and mixed . Few data exist regarding acute headache in children . METHODS: Consecutive children who presented to our emergency department with the abrupt onset of severe headache were prospectively evaluated . The headache character, location, severity, and associated symptoms, as well as underlying causes, were recorded using a standardized survey . RESULTS: One hundred fifty children, aged from 2 to 18 years, 87 boys and 63 girls, were enrolled over a 10-month period . Upper respiratory tract infection with fever (viral upper respiratory tract infection 39%, sinusitis 9%, streptococcal pharyngitis 9%) was the most frequently identified cause of acute headache (57%) . Other causes included migraine (18%), viral meningitis (9%), posterior fossa tumors (2.6%), ventriculoperitoneal shunt malfunction (2%), epileptic seizure (postictal headache) (1.3%), concussion (postconcussive headache) (1 . 3%), intracranial hemorrhage (1.3%), and undetermined (7%) . Two clinical features were found to have statistically significant associations with serious underlying disease: occipital location of headache and an inability of the patient to describe the quality of the head pain . All children with surgically remediable conditions had clear and objective neurological signs . CONCLUSIONS: In children and adolescents, the abrupt onset of severe headache is most frequently caused by upper respiratory tract infection with fever, sinusitis, or migraine . Special attention is warranted if the acute headache is occipital in location and if the affected patient is unable to describe the quality of the pain . Serious underlying processes such as brain tumor or intracranial hemorrhage are uncommon and, when present, are accompanied by multiple neurological signs (ataxia, hemiparesis, papilledema). J Immunol Methods, 2000 Apr 21, 238(1-2), 181 - 93 Improved systems for hydrophobic tagging of recombinant immunogens for efficient iscom incorporation; Andersson C et al.; We have previously reported a strategy for production in Escherichia coli of recombinant immunogens fused to a hydrophobic tag to improve their capacity to associate with an adjuvant formulation {Andersson et al., J . Immunol . Methods 222 (1999) 171} . Here, we describe a further development of the previous strategy and present significant improvements . In the novel system, the target immunogen is produced with an N-terminal affinity tag suitable for affinity purification, and a C-terminal hydrophobic tag, which should enable association through hydrophobic interactions of the immunogen with an adjuvant system, here being immunostimulating complexes (iscoms) . Two different hydrophobic tags were evaluated: (i) a tag denoted M, derived from the membrane-spanning region of Staphylococcus aureus protein A (SpA), and (ii) a tag denoted MI consisting of the transmembrane region of hemagglutinin from influenza A virus . Furthermore, two alternative affinity tags were evaluated; the serum albumin-binding protein ABP, derived from streptococcal protein G, and the divalent IgG-binding ZZ-domains derived from SpA . A malaria peptide M5, derived from the central repeat region of the Plasmodium falciparum blood-stage antigen Pf155/RESA, served as model immunogen in this study . Four different fusion proteins, ABP-M5-M, ABP-M5-MI, ZZ-M5-M and ZZ-M5-MI, were thus produced, affinity purified and evaluated in iscom-incorporation experiments . All of the fusion proteins were found in the iscom fractions in analytical ultracentrifugation, indicating iscom incorporation . This was further supported by electron microscopy analysis showing that iscoms were formed . In addition, these iscom preparations were demonstrated to induce M5-specific antibody responses upon immunisation of mice, confirming the successful incorporation into iscoms . The novel system for hydrophobic tagging of immunogens, with optional affinity and hydrophobic tags, gave expression levels that were increased ten to fifty-fold, as compared to the earlier reported system . We believe that the presented strategy would be a convenient way to achieve efficient adjuvant association for recombinant immunogens. Brain Tumor Pathol, 1999, 16(2), 92 - 7 Primary CNS lymphoma associated with streptococcal abscess: an autopsy case; Kano M et al.; This report describes a case of streptococcal abscess in the nodules of a primary central nervous system (CNS) lymphoma . Magnetic resonance imaging (MRI) of the brain revealed multiple lesions with ringlike enhancement over the bilateral frontal, right temporal, and left parietal lobes . On admission, acute brain edema occurred following angiography, which resulted in respiratory arrest . Autopsy findings showed that the ringlike enhanced lesions on MRI were streptococcal abscesses localized in the lymphoma nodules . The lymphoma was classified as non-Hodgkin, diffuse large cells of B-cell lineage . No other lymphoma mass was found extracranially . An immunohistochemical study showed that the lymphoma cells were positive for leukocyte common antigen, Epstein-Barr virus, bax . and bcl-XL, and negative for L-26 and bcl-2 . This case demonstrated that an opportunistic streptococcal abscess developed in primary CNS lymphoma in a patient without acquired immunodeficiency syndrome (AIDS), though a few similar cases have been reported in patients with AIDS. Pediatrics, 2000 Apr, 105(4 Pt 1), 753 - 9 Outcomes after judicious antibiotic use for respiratory tract infections seen in a private pediatric practice; Pichichero ME et al.; BACKGROUND: Most respiratory tract infections (RTIs) in children have a viral cause, they resolve on their own, and antibiotics need not be prescribed . OBJECTIVE: We sought to provide evidence that judicious antibiotic use can be accomplished in private pediatric practice without observing an increase in return office visits or in the rate of bacterial infections that may follow . STUDY DESIGN: This was a prospective 12-month study from July 1, 1996 through June 30, 1997 . On the same 1 day each week, a representative convenience sample of acute respiratory tract illness patients was enrolled, and laboratory studies performed as appropriate, including viral cultures on all . Children were then followed for 30 days to ascertain the outcomes of not prescribing antibiotics except when specific bacterial infections were present at the initial visit . RESULTS: Three hundred eighty-three children were enrolled; 293 (77%) did not receive antibiotics at the enrollment visit . Ninety children (23%) received antibiotics based on a diagnosis of acute otitis media (n = 53), acute streptococcal tonsillopharyngitis (n = 18), or other presumed or documented bacterial infections (n = 19) . An unscheduled return visit related to the initial visit occurred for 86 (29%) of the 293 children not receiving antibiotics initially and in 40 (44%) of 90 children receiving antibiotics initially . Eighty-seven children (23%) had positive viral culture results . The most frequently isolated viruses were adenovirus, enterovirus, parainfluenzae virus, and influenza virus . CONCLUSION: Children with RTIs without a concomitant presumed or proven bacterial infection do not require antibiotics . In this busy office practice, >75% of the children presenting with an RTI did not have a presumed or proven bacterial infection . These children did not have a higher rate of return office visits or an increase in bacterial infections . This reinforces the judicious use of antibiotics in managing children with RTIs.outcomes, antibiotic, respiratory infections. Nat Med, 2000 Apr, 6(4), 414 - 21 Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activation; Arad G et al.; Superantigens trigger an excessive cellular immune response, leading to toxic shock . We have designed a peptide antagonist that inhibits superantigen-induced expression of human genes for interleukin-2, gamma interferon and tumor necrosis factor-b, which are cytokines that mediate shock . The peptide shows homology to a b-strand-hinge-a-helix domain that is structurally conserved in superantigens, yet is remote from known binding sites for the major histocompatibility class II molecule and T-cell receptor . Superantigens depend on this domain for T-cell activation . The peptide protected mice against lethal challenge with staphylococcal and streptococcal superantigens . Moreover, it rescued mice undergoing toxic shock . Surviving mice rapidly developed protective antibodies against superantigen that rendered them resistant to further lethal challenges, even with different superantigens . Thus, the lethal effect of superantigens can be blocked with a peptide antagonist that inhibits their action at the beginning of the toxicity cascade, before activation of T cells takes place. Med Educ, 2000 Apr, 34(4), 269 - 74 Differences in teaching about the acute sore throat within one medical faculty; Brooker C et al.; OBJECTIVES: To examine the consistency of teaching about the acute sore throat in four departments in one medical faculty, and to determine whether there is agreement between what is taught and the evidence-based literature . DESIGN: Cross-sectional study . SUBJECTS: 71 undergraduates and 15 postgraduate general practice registrars and four lecturers . RESULTS: Differences were identified in teaching about the diagnostic value of a throat swab, a full blood count and clinical scoring, as well as on the use of penicillin in suspected streptococcal pharyngitis . Only one department based their teaching on the evidence-based literature . No department discussed issues of cost-effectiveness . Half of the students identified discrepancies in the teaching about the sore throat and were initially confused by them . CONCLUSION: One method of resolving disagreement between teachers from different disciplines is to rely on the evidence-based literature . This type of study can be useful in curricular development and in correcting teaching inconsistencies within a faculty. Obstet Gynecol, 2000 Apr, 95(4), 496 - 501 Effect of a screening-based prevention policy on prevalence of early-onset group B streptococcal sepsis; Brozanski BS et al.; OBJECTIVE: To assess the effectiveness and feasibility of implementing the Centers for Disease Control and Prevention (CDC) screening-based guidelines for preventing early-onset group B streptococcal sepsis . METHODS: We compared prevalence of early-onset group B streptococcal sepsis after institution of the CDC screening-based protocol (October 1, 1995 through August 31, 1999) with that of historical controls (January 1, 1992 through June 30, 1995) . We reviewed medical records for a cohort of deliveries of at least 23 weeks' gestation (January 1, 1996 through December 31, 1996) for group B streptococcal colonization status, risk factors, and intrapartum antibiotic prophylaxis . RESULTS: The prevalence of early-onset group B streptococcal sepsis was 1.16 per 1000 (36 of 31, 133) live births before and 0.14 per 1000 (four of 28,733) live births after institution of the CDC protocol (P <.001) . Maternal colonization was known for 95.3% of the 7168 women who delivered (January 1, 1996 through December 31, 1996) at or after 37 weeks' gestation . Of 2174 women who qualified for intrapartum antibiotic prophylaxis, 1871 (86.1%) received it before delivery . There was 93 . 8% compliance with intrapartum antibiotic prophylaxis for women who delivered vaginally and 53.2% compliance for women who delivered by cesarean . CONCLUSION: Institution of the CDC screening-based protocol was accomplished at a specialty women's hospital, staffed by full-time faculty and community physicians, with 93.8% compliance for vaginal deliveries, and was associated with an 88% reduction in early-onset group B streptococcal sepsis. Can J Physiol Pharmacol, 2000 Mar, 78(3), 217 - 27 Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis; Mertineit C et al.; Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS damage during neonatal meningitis . We tested (i) the hypothesis that cerebrovascular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive mediators such as prostaglandins and (or) nitric oxide (NO), and (iii) whether this impairment is preventable by specific and (or) nonspecific inhibitors: dexamethasone, ibuprofen, and Nomega-nitro-L-arginine, a NO inhibitor . Sterile saline or 10(9) colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets . CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon-tipped catheters placed in the aorta . GBS produced a narrow range of CBF autoregulation due to an impairment at the upper limit of CPP . We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GBS impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen, dexamethasone, and Nomega-nitro-L-arginine not only prevent this GBS-induced autoregulatory impairment but improve the range of cerebrovascular autoregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the induction of NO synthase gene expression . Thus, acute early onset GBS-induced impairment of the upper limit of CBF autoregulation can be correlated with increases of NO synthase production, suggesting that NO is a vasoactive mediator of CBF. Pediatr Dermatol, 2000 Jan-Feb, 17(1), 1 - 6 Vulvar disease in children: a clinical audit of 130 cases; Fischer G et al.; We evaluated 130 prepubertal girls presenting with a vulvar complaint to determine the spectrum and frequency of conditions seen in this age group . Of the patients, 41 (33%) had atopic or irritant dermatitis, 23 (18%) had lichen sclerosus, 21 (17%) had psoriasis, 15 (12%) had vulvar lesions, most often hemangiomas and nevi, and 13 (10%) had streptococcal vulvovaginitis . Diagnoses less frequently seen were staphylococcal folliculitis (four patients), labial fusion (three patients), genital warts (two patients), molluscum contagiosum of the vulva only (one patient), vulvar bullous pemphigoid (two patients), scabies nodules (one patient), erythema annulare centrifugum (one patient), tinea (two patients), and vitiligo (one patient) . We also encountered vulvar presentations of systemic diseases (varicella, staphylococcal scalded skin syndrome, and Henoch-Schonlein purpura, all one patient each) . We did not see candidal vulvovaginitis in this age group nor did we encounter bacterial infection with pathogens other than Staphylococcus aureus and S . pyogenes. Inflammation, 2000 Apr, 24(2), 157 - 73 Integrin expression on neutrophils in a rabbit model of Group B Streptococcal meningitis; Rowin ME et al.; Products released by polymorphonuclear cells (PMNs) during an acute inflammatory response can result in diffuse tissue injury . Integrins are cell surface adhesion proteins that play a pivotal role in inflammation by allowing PMNs to adhere to the endothelium and migrate through the extracellular matrix . We examined the expression of beta1 and beta2 integrins on neutrophils from blood and cerebrospinal fluid (CSF) in an animal model of Group B Streptococcal meningitis . We further evaluated whether integrin expression correlates with pathophysiologic markers of central nervous system inflammation . Our data demonstrate that beta3 and beta2 integrin expression on circulating neutrophils does not significantly increase as a consequence of meningitis . In extravesated CSF neutrophils, a significant increase in expression of both beta1 and beta2 integrins is noted . Furthermore, a majority of the beta1 integrins on extravesated neutrophils have undergone affinity modulation . Using regression analysis, we demonstrated that increasing beta1 integrin expression correlates with decreasing CSF glucose concentration and serum/CSF glucose ratio . Regression analysis approached significance when CSF protein was compared to PMN beta1 integrin expression . Polymorphonuclear leukocytes beta1 integrin expression also showed a direct correlation to myeloperoxidase activity in brain tissue . Beta2 expression on CSF PMNs did not correlate with these markers of inflammation/sequestration . These data demonstrate integrin expression on extravesated neutrophils markedly increases during meningitis and support a role for beta1 integrins on neutrophils in the pathophysiologic consequences of meningitis. Ann Trop Paediatr, 1999 Sep, 19(3), 253 - 5 Henoch-Schonlein purpura and streptococcal infection: a prospective case-control study; al-Sheyyab M et al.; A prospective, matched, case-control study conducted over a period of 3 years was designed to examine the association of group A beta-haemolytic streptococcal infections and Henoch-Schonlein purpura . Demographic and clinical data were collected as well as measurement of antistreptolysin O titres and throat swab culture on all children admitted with Henoch-Schonlein purpura, as well as their matched controls . Antistreptolysin O titre positivity was associated with a 10-fold increase in the risk of Henoch-Schonlein purpura . Renal involvement was common among cases with positive antistreptolysin O titres (27%) compared with cases with a negative titre (8%) but this difference has no statistical significance. J Lab Clin Med, 2000 Mar, 135(3), 287 - 93 Further observations and characterization of monoclonal antibodies reacting with B cell alloantigens associated with rheumatic fever and rheumatic heart disease; Kumar D et al.; Elevated levels of B lymphocytes with a unique surface alloantigen have been reported to be characteristic of patients with acute rheumatic fever or rheumatic heart disease . Mouse monoclonal antibodies (mAbs) to this alloantigen have been proposed as being useful in identifying individuals at risk for the development of these sequelae of group A streptococcal infection . However, previous studies have suggested that the discriminating ability of the mAbs was highest when the mAbs were made by using lymphocytes from the same ethnic population . To confirm and extend this observation, additional mouse mAbs were developed and their properties defined . These three mAbs-PG-12A, PG-13A, and PG-20A-reacted with B cells from more than 90% of North Indian patients with acute rheumatic fever or rheumatic heart disease . Each of these three new mAbs identified the highest levels of reactive B cells in patients with active acute rheumatic fever . Lower levels of positive reacting lymphocytes were found in individuals with quiescent chronic rheumatic heart disease, and markedly reduced percentages of reactive cells were observed in normal control subjects . The proportion of reactive lymphocytes in individual patients varied according to which of the three was tested, suggesting the possibility of a spectrum of "rheumatic" epitopes in susceptible individuals . The data further suggested that enhanced discriminatory ability for identifying "at-risk" susceptible patients could be obtained by testing with a combination of mAbs . If reduction in the incidence of acute rheumatic fever can be facilitated by early identification of susceptible individuals, accurate and sensitive detection of a marker antigen would result in more cost-effective public health measures . Additional population studies are required to more precisely define and confirm these detection techniques. J Nutr, 2000 Mar, 130(3), 559 - 65 The eicosapentaenoic to docosahexaenoic acid ratio of diets affects the pathogenesis of arthritis in Lew/SSN rats; Volker DH et al.; Dietary-induced changes in tissue levels of polyunsaturated fatty acids modify inflammatory reactions through changes in the synthesis of lipid and peptide mediators of inflammation . Four semipurified 20% fat diets, based on beef tallow (BT), safflower oil (SFO), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were provided . The DHA and EPA ratios of the (n-3) fatty acid-based diets were 1.1 and 3.4, respectively . The effect of prefeeding diets differing in EPA to DHA ratios prior to the induction of streptococcal cell wall (SCW) arthritis in female Lew/SSN rats was examined . Weanling rats were fed diets for 5 wk before arthritis induction and 5 wk post-arthritis induction . Footpad thickness, hock circumference, plasma and macrophage fatty acids and histological assessment were compared . There were no differences in food intake and final body weights among the groups . Footpad inflammation, reported as percentage change (adjusted for growth) was greatest for rats fed the BT-based diet, intermediate in those fed the SFO-based diet and least for the rats fed the EPA- and DHA-based diets (P < 0.05) . Macrophage phospholipids revealed cellular incorporation of EPA and DHA from the fish-oil based diets which modified lipid and peptide mediators of inflammation . Histological sections of rat hocks ranked by severity of arthritis-related changes suggested that the SFO- and EPA-based diets were more successful in ameliorating the destructive arthritic phase in hock joints than the BT- and DHA-based diets (P = 0.09) in this model of arthritis . The course of SCW-induced arthritis can be altered by diet-induced changes in macrophage fatty acid composition . The EPA-based diet is more effective in suppression of inflammation than the DHA-based diet. Arch Pediatr, 2000 Feb, 7(2), 168 - 72 {Ureaplasma urealyticum respiratory infection in newborn infants}; Prajs-Philippe N et al.; The neonatal respiratory infection by Ureaplasma urealyticum is rare, but it could represent a major risk for the newborn infants . CASE REPORTS: A term newborn infant presented an early respiratory distress with persistent pulmonary hypertension, requiring artificial ventilation and inhaled nitric oxide therapy . Tracheal aspirates were positive for Ureaplasma urealyticum, although his mother was not contamined . A preterm newborn infant (gestational age: 33 weeks) presented a severe respiratory distress, requiring mechanical ventilation . The tracheal aspirates we positive for Ureaplasma urealyticum, as well as his mother's cervico-vaginal swab . Both recovered thanks to antibiotics (intravenous macrolid during ten days) . The outcome was favorable for both babies . CONCLUSION: Neonatal infection due to Ureaplasma is serious . The clinical diagnosis is difficult, recalling group B streptococcal infection . Clinical aggravation, despite antibiotics associated with negative bacteriological standard detection, leads one to evoke this diagnosis and perform specific bacteriological cultures. Ann Rheum Dis, 2000 Mar, 59(3), 196 - 205 Blockade of endogenous interleukin 12 results in suppression of murine streptococcal cell wall arthritis by enhancement of interleukin 10 and interleukin 1Ra; Joosten LA et al.; OBJECTIVE: The goal of this study was to investigate the role of endogenous interleukin 12 (IL12) in acute murine streptococcal cell wall (SCW) arthritis . METHODS: C57black/6 mice were injected intraperitoneally with rat anti-murine IL12 (C17.8), shortly before induction of arthritis by intra-articular injection of 25 microg SCW fragments into the right knee joint . Joint swelling and chondrocyte synthetic function was analysed several days after induction of SCW arthritis . Local cytokine profile was determined, protein by using ELISA and mRNA by RT-PCR technology . To confirm the findings at later time points, tissue chamber model of inflammation was used . Histology was performed to examine cell influx and cartilage damage . RESULTS: Suppression of joint swelling was noted at days 2 and 4, whereas no suppressive effect of anti-IL12 was found at day 1 . Severe inhibition of chondrocyte proteoglycan synthesis was seen at day 1 in both arthritic control and anti-IL12 treated mice . However, chondrocyte function was restored at day 4 of arthritis in the anti-IL12 injected animals, but not in the arthritic controls . Moreover, cell influx in synovial tissue and joint cavity was reduced by anti-IL12 treatment . Neutralisation of IL12 reduced the local levels of IL1beta, IL12 and interferon gamma, when examined shortly after induction of SCW arthritis, whereas tumour necrosis factor alpha levels were not affected . In contrast, IL10 and IL1Ra protein and mRNA levels were strongly up regulated in synovial tissues after IL12 blockade . Enhancement of IL10 and IL1Ra by anti-IL12 was confirmed in a tissue chamber model with SCW induced inflammation . CONCLUSIONS: This study indicates that IL12 is a pro-inflammatory cytokine during onset of acute SCW arthritis . Balances of proinflammatory and anti-inflammatory cytokines were strongly improved by anti-IL12 treatment. J Invest Dermatol, 2000 Mar, 114(3), 576 - 80 Skin CD4+ T cells produce interferon-gamma in vitro in response to streptococcal antigens in chronic plaque psoriasis; Brown DW et al.; Recently, we have demonstrated that group A streptococcal antigen reactive T cells are present in the skin lesions of chronic plaque psoriasis . To determine the cytokine profile (interferon-gamma, interleukin-4 and interleukin-10) of these T cells in response to streptococcal antigens, T cell lines were cultured from untreated lesional skin of 13 patients with chronic plaque psoriasis and 12 patients with other inflammatory skin diseases . T cell lines were incubated with or without a sonicated heat-killed mixture of group A streptococcal isolates for 18 h in the presence of a transport inhibitor, stained for surface CD4 or CD8 and intracellular cytokine expression, and analyzed by flow cytometry . Psoriatic T cell lines were grown from 10 of 13 patients and were predominately CD4+ (64%-85%) with 10%-32% CD8+ T cells . Variable numbers of CD4+ T cells produced interferon-gamma (0.8%-35%, median 13.9) in eight of 10 T cell lines (p < 0.02) . In contrast, CD4+ T cells in five of 12 T cell lines obtained from disease controls did not produce or produced minimal interferon-gamma in response to group A streptococcal isolates; this was significantly different from the psoriatic T cell lines (p < 0.05) . Small numbers of interleukin-10 positive (0.8%-1.3%) and interleukin-4 positive (2.1%-2.5%) CD4+ T cells induced by group A streptococcal isolates were also present in two out of five and three out of five psoriatic T cell lines, respectively . This was significantly less in each case than the numbers of CD4+/interferon-gamma+ T cells (p < 0.05) . Cytokine-positive CD8+ T cells were rarely observed . These findings demonstrate that a subpopulation of CD4+ T cells in chronic plaque psoriasis skin lesions produces interferon-gamma in response to streptococcal antigens and may be relevant to the pathogenesis of psoriasis. J Immunother, 2000 Jan, 23(1), 94 - 103 Cytokine-inducing activity and antitumor effect of a liposome-incorporated interferon-gamma-inducing molecule derived from OK-432, a streptococcal preparation; Okamoto M et al.; An interferon-gamma (IFN-gamma)-inducing molecule (OK-PSA) has been purified from OK-432 by an affinity chromatographic technique performed on cyanogen bromide-activated Sepharose 4B-bound TS-2 monoclonal antibody, which neutralizes IFN-gamma-inducing activity of OK-432 . OK-PSA has striking anti-tumor activity in vivo and in vitro . In the current study, the liposomes were used to improve the delivery of the agent (OK-PSA) to effector cells and to increase the therapeutic effect . Significantly less OK-PSA encapsulated into liposomes (Lipo-OK-PSA) than OK-PSA alone (1/100 or less of OK-PSA alone) was required to induce IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, interleukin-1 beta (IL-1 beta), natural killer, and lymphokine-activated killer activities by human peripheral blood mononuclear cells and mouse spleen cells . Furthermore, higher levels of these activities were detected in peripheral blood mononuclear cells and mouse spleen cells treated with Lipo-OK-PSA than in those treated with OK-PSA . All of these activities induced by Lipo-OK-PSA were almost completely neutralized by anti-asialo-GM1 antibody and complement (p < 0.001) . In in vivo experiments, Lipo-OK-PSA elicited striking anti-tumor activity on syngeneic Meth-A tumor-bearing and colon 26-bearing BALB/c mice and on salivary gland tumor-bearing nude mice far better than did OK-PSA . Furthermore, high levels of natural killer and lymphokine-activated killer activities and a significant increase in the number of cells positive for asialo-GM1, IFN-gamma, TNF-alpha, or IL-1 beta were detected in the spleen cells derived from the animals given Lipo-OK-PSA compared with those given saline . These findings clearly indicate that OK-PSA plays an important role in the anti-tumor efficiency of OK-432, and that, for the most part, liposome encapsulation of this molecule markedly accelerates its effect mediated by asialo-GM1-positive cells (mainly natural killer cells). Mayo Clin Proc, 2000 Feb, 75(2), 144 - 7 Poststreptococcal reactive arthritis in adults: a case series; Aviles RJ et al.; OBJECTIVE: To guide primary care physicians regarding the diagnosis and treatment of poststreptococcal reactive arthritis (PSReA) in adults . PATIENTS AND METHODS: We retrospectively reviewed an indexed database of all patients evaluated or hospitalized between 1976 and 1998 at Mayo Clinic Rochester and identified 35 patients with the diagnosis of reactive streptococcal arthritis, arthralgia, or arthritides . Twenty-nine patients with the diagnosis of acute rheumatic fever (ARF), septic streptococcal arthritis, or nonspecific reactive arthritis were excluded . RESULTS: PSReA was confirmed in 6 adults (3 women, 3 men; age range, 25-66 years) . All patients were symptomatic with polyarthritis and oligoarthritis disproportionate to the objective findings on physical examination . Although all patients had negative throat cultures at the onset of arthritis, increased titers of anti-DNase B and antistreptolysin O confirmed recent streptococcal infection . Antecedent events included pharyngitis in 3 patients (who had received a minimum of a 10-day course of penicillin) and toxic shock syndrome in 1 patient . The latency of onset of arthritis ranged from 4 days to 6 weeks . The arthritic symptoms had a protracted course beyond the typical maximum of 3 weeks described for ARF . Treatment with aspirin did not provide symptomatic relief in any of the patients, whereas the response to therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) was at least partial in all cases . Symptomatic relief occurred in 1 patient who received indomethacin and in 1 patient treated with prednisone . Penicillin prophylaxis was recommended in 1 patient . CONCLUSION: PSReA should be included in the differential diagnosis of all adult patients presenting with arthritis . Treatment strategies include aspirin, other NSAIDs, and corticosteroids . In adult patients with PSReA, there is no evidence to support the use of penicillin prophylaxis at this time. Scand J Infect Dis, 1999, 31(6), 523 - 37 Pathogenic mechanism of acute post-streptococcal glomerulonephritis; Nordstrand A et al.; Considerable knowledge has been accumulated regarding the characteristics of acute post-streptococcal glomerulonephritis (APSGN), and many attempts have been made to identify a streptococcal factor or factors responsible for triggering this disease . However, the pathogenic mechanism behind APSGN remains largely unknown . As glomerular deposition of C3 is generally demonstrated before that of IgG in the disease process, it is likely that the inflammatory response is initiated by renal deposition of a streptococcal product, rather than by deposition of antibodies or pre-formed immune complexes . During recent years, a number of streptococcal products have been suggested to be involved in the pathogenic process . In this review, possible roles of these factors are discussed in the context of the clinical and renal findings most often demonstrated in patients with APSGN . Streptokinase was observed to be required in order to induce signs of APSGN in mice, and a number of findings suggest that the initiation of the disease may occur as a result of renal binding by certain nephritis-associated variants of this protein . However, additional factors may be required for the development of the disease. Rev Hosp Clin Fac Med Sao Paulo, 1999 May-Jun, 54(3), 85 - 90 Rheumatic fever: a multicenter study in the state of São Paulo . Pediatric Committee--São Paulo Pediatric Rheumatology Society; da Silva CH; Rheumatic fever is still the most commonly seen rheumatic disease in Brazilian pediatric rheumatology clinics . It remains a significant health problem since subsequent cardiac sequelae represent one of the most important causes of chronic heart disease in children . We reviewed the clinical manifestations of rheumatic fever in 786 patients followed at seven pediatric rheumatology clinics in the state of Sao Paulo, Brazil . All patients were diagnosed according to revised Jones' criteria . Regarding major criteria, 396 (50.4%) children exhibited carditis, 453 (57.6%) polyarthritis, 274 (34.8%) chorea, 13 (1.6%) erythema marginatum, and 12 (1.5%) subcutaneous nodules . Valvular lesions documented by echocardiography in the absence of accompanying auscultatory findings were found in 144 (18.3%) patients . Migratory polyarthritis was observed in 290 (64.0%) patients with articular involvement . Documented previous streptococcal infection assessed by serum antistreptolysin (ASO) titers occurred in 531 (67.5%) patients . Even though prophylaxis with benzathine penicillin was recommended to all patients, recurrent attacks were observed in 147 (18.7%) . We emphasize the high frequency of chorea, silent carditis and recurrences in our series as well as the variable clinical presentation of arthritis in rheumatic fever . Multicenter studies should be encouraged to improve our understanding of the clinical features of rheumatic diseases in children and adolescents. Pediatrics . 2000 Feb;105(2):E19. The impact of dosing frequency on the efficacy of 10-day penicillin or amoxicillin therapy for streptococcal tonsillopharyngitis: A meta-analysis; Lan AJ et al.; OBJECTIVE: The recommended dosing frequency of oral penicillin for the treatment of acute streptococcal tonsillopharyngitis has long been 3 to 4 times daily . In 1994, treatment guidelines included twice-daily (BID) dosing for the first time, a recommendation that could significantly increase the ease of compliance . This meta-analysis was performed to determine whether overall cure rates differed between BID or once-daily (QD) versus more frequent dosing schedules in the treatment of streptococcal tonsillopharyngitis . DATA SOURCES: Candidate studies for this meta-analysis included all clinical trials of therapy for streptococcal tonsillopharyngitis published through August 1998 and identified using Medline, Dissertation Abstracts, conference proceedings, and bibliographies of all retrieved articles . STUDY SELECTION: A study was eligible for inclusion if it was a randomized clinical trial that compared the efficacies of different dosing frequencies of 10-day penicillin or amoxicillin in the treatment of streptococcal tonsillopharyngitis . Of the 30 articles initially identified, 6 studies met eligibility criteria . OUTCOME MEASURE: The measure of interest was the difference in proportion cured between the BID or QD dosing group and the comparison group with more frequent dosing . RESULTS: The results of this analysis suggest that BID dosing of 10-day penicillin is as efficacious as more frequent dosing regimens in the treatment of streptococcal tonsillopharyngitis . This result also holds true in a subgroup analysis confined to pediatric cases and does not vary with total daily dose of the regimen . QD dosing of penicillin is associated with a cure rate that is 12 percentage points lower than more frequent dosing (95% confidence interval: 3-21) . In contrast, this decreased efficacy is not found with QD dosing of amoxicillin . CONCLUSIONS: This meta-analysis supports current recommendations for BID dosing of penicillin in treating streptococcal tonsillopharyngitis . QD penicillin is associated with decreased efficacy and should not be used . Simplified regimens of amoxicillin of shorter duration or of less frequent dosing should be further investigated. Am J Ophthalmol, 2000 Jan, 129(1), 101 - 2 Anterior uveitis as the initial sign of adult Kawasaki syndrome (mucocutaneous lymph node syndrome); Bachmeyer C et al.; PURPOSE: To report anterior uveitis as the initial sign of adult Kawasaki syndrome (mucocutaneous lymph node syndrome) . METHODS: Case report . RESULTS: Kawasaki syndrome was diagnosed in an 18-year-old woman with reduction of vision caused by anterior uveitis, fever, erythemateous cutaneous rash, conjunctival injection, and cervical lymph adenopathy, after medical examination including serologic tests . Aspirin and intravenous immunoglobulin were given, resulting in improvement of the condition . CONCLUSION: Slit-lamp examination should be useful in the evaluation of patients with suspected Kawasaki syndrome, differentiating this condition from streptococcal and staphylococcal toxin-mediated diseases, viral infections, and drug reactions, not commonly associated with anterior uveitis. Ann Intern Med, 2000 Jan 18, 132(2), 105 - 11 45-year follow-up of hepatitis C virus infection in healthy young adults; Seeff LB et al.; BACKGROUND: The sequelae during the first two decades after acute hepatitis C virus (HCV) infection have been well studied, but the outcome thereafter is unknown . OBJECTIVE: To conduct an extended study of the natural history of HCV infection by using archived serum specimens originally collected between 1948 and 1954 . DESIGN: Retrospective cohort study . SETTING: A university, a Veterans Affairs medical center, and a medical follow-up agency that had access to the serum specimens and accompanying demographic and medical records . PARTICIPANTS: 8568 military recruits who were evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954 . Blood samples were taken from the recruits and, after testing, were stored frozen for almost 45 years . MEASUREMENTS: The presence of antibodies to HCV was determined by enzyme-linked immunoassay, supplementary recombinant immunoblot assay, and polymerase chain reaction for HCV RNA . Morbidity and mortality were also assessed . RESULTS: Of 8568 persons, 17 (0.2%) had positive results on enzyme-linked immunosorbent assay and recombinant immunoblot assay . The rate was 1.8% among the African-American persons and 0.1% among the white persons in the total sample (relative risk, 25.9 {95% CI, 8.4 to 80.0}) . During the 45-year follow-up, liver disease occurred in 2 of the 17 HCV-positive persons (11.8%) and 205 of the 8551 HCV-negative persons (2.4%) (ethnicity-adjusted relative risk, 3.56 {CI, 0.94 to 13.52}) . Seven of the 17 HCV-positive persons (41 %) and 2226 of the 8551 HCV-negative persons (26%) had died by December 1996 (ethnicity-adjusted relative risk, 1.48 {CI, 0.8 to 2.6}) . Of persons who were HCV-positive, 1 (5.9%) died of liver disease 42 years after the original phlebotomy, 5 (29%) died of non-liver-related disease a median of 37 years after the original phlebotomy, and 1 (5.9%) died of unknown causes . One hundred nineteen HCV-negative persons (1.4%) died of liver disease . CONCLUSIONS: The rate of HCV infection from 1948 to 1954 among a sample of military recruits parallels that among present-day military recruits and volunteer blood donors . During 45 years of follow-up, HCV-positive persons had low liver-related morbidity and mortality rates . This suggests that healthy HCV-positive persons may be at less risk for progressive liver disease than is currently thought. Arthritis Rheum, 2000 Jan, 43(1), 226 - 31 Subacute bacterial endocarditis with positive cytoplasmic antineutrophil cytoplasmic antibodies and anti-proteinase 3 antibodies; Choi HK et al.; OBJECTIVE: To report a potentially important limitation of antineutrophil cytoplasmic antibody (ANCA) testing: positive results in patients with subacute bacterial endocarditis (SBE) . METHODS: We describe 3 patients with SBE who presented with features mimicking ANCA-associated vasculitis (AAV) and positive findings on tests for cytoplasmic ANCA (cANCA) by indirect immunofluorescence and for anti-proteinase 3 (anti-PR3)antibodies by antigen-specific enzyme-linked immunosorbent assay (ELISA) . We also reviewed the published literature describing infectious diseases with (misinterpreted) positive ANCA results through a Medline search of English-language articles published between 1966 and January 1999 . These previously reported cases were reinterpreted using an ANCA scoring system that combines the findings of immunofluorescence and antigen-specific ELISA testing . RESULTS: We are now aware of a total of 7 cases of SBE with positive cANCA and anti-PR3 antibodies . We are not aware of any cases of SBE associated with antimyeloperoxidase/perinuclear ANCA . Clinical manifestations mimicking AAV included glomerulonephritis, purpura, epistaxis, or sinus symptoms in 6 of the patients . Streptococcal species were identified in 5 patients, and cardiac valvular abnormalities were demonstrated in 6 . All patients except 1, who died of a complication of SBE, recovered with antibiotic therapy . CONCLUSION: Findings of tests for anti-PR3/ cANCA antibodies may be positive in patients with SBE . When encountering ANCA positivity in patients suspected of having systemic vasculitis, physicians should take appropriate steps to rule out infectious diseases, including SBE, before committing the patient to long-term, aggressive immunosuppressive therapy. J Am Acad Dermatol, 2000 Feb, 42(2 Pt 2), 381 - 3 Relapsing Henoch-Schönlein purpura associated with Pseudomonas aeruginosa pyelonephritis; Egan CA et al.; Henoch-Schonlein purpura is a systemic vasculitis of unknown cause . It is frequently triggered by a streptococcal upper respiratory tract infection . Other bacteria have been implicated as triggering agents . We report a recurring case of Henoch-Schonlein purpura in a patient with Pseudomonas pyelonephritis . The Henoch-Schonlein purpura remitted only when the infection was eradicated . Pseudomonas infection should be added to the list of bacteria that can trigger Henoch-Schonlein purpura. Infect Immun, 2000 Feb, 68(2), 994 - 8 Human monocyte receptors involved in tumor necrosis factor responses to group B streptococcal products; Cuzzola M et al.; Several group B streptococcal products have been previously found to stimulate human monocytes to produce tumor necrosis factor alpha . In order to identify the receptors involved in these responses, monocytes were stimulated with purified group- or type-specific carbohydrates or lipoteichoic acid in the presence of anti-receptor monoclonal antibodies, soluble CD14, or lipopolysaccharide-binding protein . Results indicate that CD14 plays an important role in tumor necrosis factor alpha responses to all of the stimuli tested . Moreover, both CD14 and complement receptor type 3 may be involved in responses to the group-antigen. Clin Rheumatol, 1999, 18(6), 446 - 9 Familial Mediterranean fever and acute rheumatic fever: a pathogenetic relationship? Tekin M, Yalcinkaya F, Tumer N, Cakar N, Kocak H. The frequency of acute rheumatic fever (ARF) in patients with familial Mediterranean fever (FMF) was documented and the effects of preceding streptococcal infections on the exacerbation of FMF were determined . In the first part of the study, 162 individuals with FMF were investigated for a history of ARF in a retrospective study . In the second part of the study, antistreptolysin-O (ASO) titres were measured in 130 individuals with FMF . Thirty-six patients had an arthritic attack (group A1), 55 patients had a typical FMF attack without arthritis (group A2) and 39 patients were in the attack-free interval (group B) during the investigation . Nine patients with FMF (5.5%) were considered to have ARF and three of them (1.85%) also had rheumatic heart disease . This prevalence of rheumatic heart disease in FMF is higher than that of the normal population (0.65%) reported in Turkey . Elevated ASO titres were found in 75%, 42% and 38% of the patients in groups A1, A2 and B, respectively . These percentages were found to be significantly higher in group A1 than in both groups A2 (p<0.01) and B (p<0.01) . We concluded that patients with FMF might be more prone to the late complications of streptococcal infections. J Paediatr Child Health, 1999 Dec, 35(6), 588 - 90 Group A streptococcal myositis; Daley AJ et al.; Myositis is a relatively uncommon presentation of group A streptococcal infection . We present a case of a 3-year-old girl with group A streptococcal myositis primarily involving the soleus muscle . Magnetic resonance imaging was valuable in localizing the affected muscle and avoiding surgical exploration. Protein Sci, 1999 Dec, 8(12), 2773 - 83 Synthesis, folding, and structure of the beta-turn mimic modified B1 domain of streptococcal protein G; Odaert B et al.; The mechanism of beta-sheet formation remains a fundamental issue in our understanding of the protein folding process, but is hampered by the often encountered kinetic competition between folding and aggregation . The role of local versus nonlocal interactions has been probed traditionally by mutagenesis of both turn and strand residues . Recently, rigid organic molecules that impose a correct chain reversal have been introduced in several small peptides to isolate the importance of the long-range interactions . Here, we present the incorporation of a well-studied beta-turn mimic, designated as the dibenzofuran-based (DBF) amino acid, in the B1 domain of streptococcal protein G (B1G), and compare our results with those obtained upon insertion of the same mimic into the N-terminal beta-hairpin of B1G (O Melnyk et al., 1998, Lett Pept Sci 5:147-150) . The DBF-B1G domain conserves the structure and the functional and thermodynamical properties of the native protein, whereas the modified peptide does not adopt a native-like conformation . The nature of the DBF flanking residues in the modified B1G domain prevents the beta-turn mimic from acting as a strong beta-sheet nucleator, which reinforces the idea that the native beta-hairpin formation is not driven by the beta-turn formation, but by tertiary interactions. Diagn Microbiol Infect Dis, 1999 Nov, 35(3), 169 - 76 Two-year survey of Alberta laboratories processing of antenatal group B streptococcal (GBS) screening specimens: implications for GBS screening programs; Davies HD et al.; We evaluated specimen types received and methods used by laboratories to process screening GBS specimens from pregnant women . Surveys during 1995 and 1997 of all laboratories in the province of Alberta, Canada that culture GBS from screening genital specimens were completed . Between surveys, there was dissemination of information about appropriate culture techniques . Survey completion rates were 100% in both years (38/38 in 1995 and 20/20 in 1997) . During 1995 as compared to 1997, laboratories were less likely to a) have a specific written protocol for identification of genital GBS screening specimens (1995: 78.2% versus 1997: 100%, p = 0.08) b) be receiving combined vaginal-anorectal swabs (1995: 18% of all swabs received versus 1997: 60.4%, p < 0.001), and c) be using selective GBS culture media (1995: 45.5% versus 1997: 86.7%, p = 0.01) . Regions using screening based approaches for GBS prevention need to ensure that their laboratories are using adequate techniques for GBS detection. J Mol Biol, 2000 Jan 14, 295(2), 269 - 78 Thermodynamics of a beta-hairpin structure: evidence for cooperative formation of folding nucleus; Honda S et al.; To elucidate early nucleation stages in protein folding, multi-probed thermodynamic characterization was applied to the beta-hairpin structural formation of G-peptide, which is a C-terminal fragment of the B1 domain of streptococcal protein G . The segment corresponding to the sequence of G-peptide is believed to act as a nucleus during the folding process of the B1 domain . In spite of the broad thermal transition of G-peptide, nuclear magnetic resonance (NMR) melting measurements combined with our original analytical theory enabled us to obtain the thermodynamic properties of the beta-hairpin formation with considerable accuracy . Additionally, all the thermodynamic properties determined by every NMR probe on both the main-chain and the side-chains were quite similar, and also comparable to the values that were independently determined by calorimetric analysis of G-peptide . These results demonstrate that G-peptide folds cooperatively throughout the molecule . In other words, the formation of the beta-hairpin is interpreted as the fashion of a first-order phase transition between two states without any distinguishable intermediates . This cooperative formation of the short linear peptide consisting of only 16 residues provides insight into not only the first folding events of the B1 domain, but also the general principles of proteins in terms of structural hierarchy, stability and folding mechanism . Cytokine, 1999 Dec, 11(12), 1046 - 56 Immune complexes, but not streptococcal cell walls or zymosan, cause chronic arthritis in mouse strains susceptible for collagen type II auto-immune arthritis; Blom AB et al.; In this study we investigated mechanisms involved in the chronic character of experimental collagen type II induced arthritis (CIA) . We compared the knee joints of mouse strains which are prone to develop this autoimmune disease (DBA/1,B10RIII) with other nonsusceptible mouse strains (C57Bl/6,BALB/c) in their reaction to different stimuli: immune complexes (IC), zymosan and streptococcal cell walls (SCW) . Inflammation was evaluated by(99m)Tc uptake measurements and in haematoxylin- and eosin-stained knee-joint sections . Passively induced immune complex mediated arthritis (ICA) in knee joints of C57Bl/6 and BALB/c mice, showed moderate cell influx at day 3, whereas at day 7 only minor amounts of inflammatory cells were observed . In contrast, in arthritic DBA/1 and, to a lesser extent, in B10.RIII joints, a tremendous cell influx was observed at day 3 and even at day 14 there was still significant synovitis . In contrast, if arthritis was elicited by intra-articular injection of zymosan or SCW in C57Bl/6 and DBA/1, the course of inflammation was similar in both strains and no chronic inflammation developed . In line with severe arthritis, chemotactic factor production was dramatically enhanced in ICA in DBA/1 mice, and a prolonged production of IL-1 was evident . When IL-1 was neutralized before or during the ICA using specific anti-IL-1alpha,beta antibodies, inflammation could be blocked completely . Single or multiple injection of IL-1 in the knee joint of C57Bl/6 or DBA/1 showed comparable inflammation, indicating that the chemotactic response per se is comparable in both strains . No prolonged production of IL-1 was found during zymosan or SCW arthritis . Selective removal of macrophages from the synovial intima prior to ICA induction (using clodronate-containing liposomes) prevented the onset of inflammation in C57Bl/6 and DBA/1 mice . It can be concluded that immune complexes, but not zymosan or SCW, cause a more severe and chronic arthritis in mouse strains which are susceptible for collagen type II autoimmune arthritis . This is due to higher and prolonged expression of IL-1 and chemotactic factors, caused by stimulation with immune complexes . The interaction of IC with lining macrophages probably plays a dominant role in development of chronicity . Pediatrics, 2000 Jan, 105(1 Pt 1), 21 - 6 Risk factors and opportunities for prevention of early-onset neonatal sepsis: a multicenter case-control study; Schuchat A et al.; BACKGROUND: Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear . METHODS: Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52 406 births; matched case-control study of risk factors for GBS and other sepsis . RESULTS: Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births) . GBS (1.4 cases per 1000 births) and Escherichia coli (0.6 cases per 1000 births) caused most infections . GBS sepsis less often occurred in preterm deliveries compared with other sepsis . Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2-13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1-8 . 0) . An obstetric risk factor-preterm delivery, intrapartum fever, or membrane rupture >/=18 hours-was found in 49% of GBS cases and 79% of other sepsis . IAP had an adjusted efficacy of 68.2% against any early-onset sepsis . Ampicillin resistance was evident in 69% of E coli infections . No deaths occurred among susceptible E coli infections, whereas 41% of ampicillin-resistant E coli infections were fatal . Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP . CONCLUSIONS: Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases . Sepsis caused by other organisms is more often a disease of prematurity . IAP seemed efficacious against early-onset sepsis . However, the severity of ampicillin-resistant E coli sepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis. J Infect Dis, 2000 Jan, 181(1), 230 - 4 Lack of benefit of intravenous immune globulin in a murine model of group A streptococcal necrotizing fasciitis; Patel R et al.; Penicillin, clindamycin, and intravenous immune globulin (Venoglobulin-S; IVIG) alone and in combination were studied in a murine model of group A streptococcal necrotizing fasciitis . As assessed by bacterial clearance, treatment with IVIG was not significantly different from no treatment . All treatment regimens that contained penicillin or clindamycin were more effective (P<.05) than no treatment or treatment with IVIG alone . No significant differences were detected among results of treatment with penicillin, penicillin/clindamycin, penicillin/IVIG, clindamycin/IVIG, or all agents combined . Clindamycin alone was less effective than penicillin/IVIG (P=.02), penicillin/clindamycin (P=.009), clindamycin/IVIG (P=.04), or all agents combined (P=.02) . No antagonism was observed with the addition of clindamycin or IVIG to penicillin. Enferm Infecc Microbiol Clin, 1999, 17 Suppl 2, 95 - 102 {Application of the concepts of evidence-based medicine to the evidence on the treatment of febrile neutropenia}; Jarque I et al.; BACKGROUND: Infectious complications are an important cause of morbidity and mortality in cancer patients, especially those receiving chemotherapy . Early empirical administration of broad-spectrum antibiotics at the onset of fever has become common practice, but the specific empirical regimen remains controversial . Over the last two decades, a marked shift in the spectrum of causative organisms towards a gram-positive predominance has been the main factor influencing therapeutic approaches . METHODS: A MEDLINE search (January 1966-March 1999) for studies evaluating the treatment of adult patients with febrile neutropenia was carried out . Reference lists from identified articles also served as literature sources . All studies were critically evaluated for an evidence-based discussion . RESULTS: Most clinical studies have advocated the use of combination therapy, including a beta-lactam plus an aminoglycoside . However, recent trials comparing combination therapy versus monotherapy with the newer extended-spectrum agents such as carbapenems and third-generation cephalosporins could not prove relevant differences in outcome . Empirical therapy has evolved towards a planned-progressive modification in patients with persistent fever, especially aiming at early antifungal coverage . Although overwhelming streptococcal sepsis has raised particular concern, the role of glycopeptide antibiotics remains another controversial issue especially because of increasing reports of infections caused by resistant grampositive cocci (enterococci and recently S . aureus) . Likewise routine antibacterial and antifungal chemoprophylaxis is being questioned due to its association with emergence of resistant organisms (particularly fluoroquinolone-resistant Escherichia coli and fluconazole-resistant non-albicans Candida species) . CONCLUSIONS: Empirical therapy has dramatically reduced mortality rates in febrile neutropenic patients . Monotherapy with extended-spectrum antibiotics is a feasible alternative to combination therapy . The indiscriminate use of empirical glycopeptides should be discouraged . Early antifungal therapy with amphotericin B is essential in case of persistent fever . Prompt recognition of institutional resistance trends is of paramount importance for an optimal antibiotic selection . Further studies of larger size designed to confirm low-risk patient characteristics are necessary. Infect Dis Obstet Gynecol, 1999, 7(6), 276 - 82 Puerperal and intrapartum group A streptococcal infection; Anteby EY et al.; OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection . METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt . Scopus, Jerusalem were reviewed . Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records . Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock . RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM . Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash . Three patients (6%) developed a septic shock . Two of these patients presented with symptoms more than 14 days after delivery . CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection . Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection. J Microbiol Immunol Infect, 1998 Jun, 31(2), 107 - 12 Group B streptococcal infections in children: the changing spectrum of infections in infants; Yang YJ et al.; During a 9-year period from January 1988 to December 1996, 36 patients less than 18 years of age with Lancefield group B streptococcal infections were seen in the National Cheng Kung University Hospital . Among 33 infants with invasive group B streptococcal infections, 3 (9%) were early onset disease (EOD), 27 (82%) late onset disease (LOD) and 3 (9%) onset beyond the third month of life . All cases of EOD were detected during the first day of life and 2 of them were premature births . In the infants with LOD, a high incidence of meningitis occurred (78%) . The most common clinical presentation in group B streptococcal infections was fever (81%), followed by irritable crying (42%) and poor feeding (39%) . Seizure was noted in 57% of meningitis cases . Obstetric and neonatal risk factors were compared between EOD and LOD, with prematurity and low birth weight significantly (P=0.01) more common among infants with EOD compared with LOD . Of the strains tested, the sensitivity to penicillin, ampicillin and erythromycin were 83%, 74%, and 75%, respectively . All strains were resistant to tetracycline and gentamicin . There were 2 case fatalities (6%) and 6 (17%) had major neurologic sequelae . These data provide that the vast majority of EOD are recognized on the first day of life and prematurity is an important risk factor . In comparison to the previous report in Taiwan, a changing spectrum of GBS infections in infants occurs during the study period . The observed incidence of EOD is decreased and meningitis is still predominantly in LOD . It is suggested early recognition and aggressive therapy have resulted in a much lower mortality rate than previously reported. J Am Acad Child Adolesc Psychiatry, 1999 Dec, 38(12), 1522 - 5 Case series: increased vulnerability to obsessive-compulsive symptoms with repeated episodes of Sydenham chorea; Asbahr FR et al.; The association between obsessive-compulsive symptoms (OCS) and Sydenham chorea (SC) supports the hypothesis of a common neuroimmunological dysfunction in basal ganglia associated with group A beta-hemolytic streptococcal infection underlying both conditions . Four children with 2 distinct SC episodes were evaluated to assess the course of OCS . All patients developed OCS during their second episodes (3 met criteria for obsessive-compulsive disorder {OCD}), but not in their first episodes (2 developed OCS and met criteria for OCD) . These data suggest that the recurrence of SC episodes may result in a cumulative effect, thus increasing the risk of appearance and intensification of OCS. Child Adolesc Psychiatr Clin N Am, 1999 Oct, 8(4), 767 - 75 Immune mechanisms in pediatric neuropsychiatric disorders . Tourette's syndrome, OCD, and PANDAS; Trifiletti RR et al.; The authors have reviewed recent data supporting the presence of immune abnormalities in several neuropsychiatric disorders (TS, OCD, and PANDAS) . Several groups agree that there is a subset of patients with TS and OCD (perhaps about 10%) for whom there is a clear streptococcal trigger, validating the PANDAS concept . Also, evidence of biochemical markers for TS and OCD have begun to emerge, namely D8/17 and antibrain antibodies, which suggest the presence of similar immune abnormalities, even in idiopathic cases . If this line of research reveals definable, and relatively specific, immune abnormalities in at least some cases of TS and OCD, it will likely have important implications for the diagnosis and treatment of these common neuropsychiatric disorders, particularly in children who respond poorly to conventional therapies . Child psychiatrists are encouraged to stay tuned. Int J Antimicrob Agents, 1999 Oct, 13(2), 79 - 92 New developments in the treatment of infective endocarditis infective cardiovasculitis; Gutschik E; The natural history of infective endocarditis has undergone remarkable changes over the past 100 years as regards both the demographic characteristics of the disease and changes in the incidence of the so-called diagnostic signs . Alongside these changes and the development of new and better diagnostic tools and criteria, we are also facing new problems with the precise definition of cardiovascular infections and calculation of the incidence of the disease . Nosocomial endocarditis presents an emerging problem of diagnosis and treatment after heart valve surgery, with pace-maker catheters, defibrillators and a very large variety of foreign materials used in connection with heart valve surgery . New technological progress including new types of prosthetic valves and use of homografts or the Ross operation will give a greater possibility of choosing the best solution in a particular case . Antimicrobial chemotherapy is mainly based on our understanding of the pathophysiology of the disease and efficacy of the antibiotics achieved in an experimental animal model of endocarditis . Important recommendations of single or combined drug therapy or the dosing regimens of antibiotics are still an expression of expert opinion not always supported by experimental or clinical proof . A typical example is the recommendation of two divided doses of gentamicin for treatment of streptococcal endocarditis . Nevertheless, it is the author's opinion that the development of uncomplicated, easy to handle diagnostic and treatment regimens are justified in order to achieve better compliance with these recommendations. Br J Dermatol, 1999 Oct, 141(4), 717 - 9 Acquired streptococcal necrotizing fasciitis following excision of malignant melanoma; Gibbon KL et al.; Necrotizing fasciitis is an uncommon condition which may complicate any surgical procedure, including 'minor' dermatological procedures . However, it may arise de novo in the absence of any discernible trauma . We report a patient who acquired a fulminant form of this condition following excision of a malignant melanoma . The development of necrotizing fasciitis in association with melanoma has not previously been reported. Int J Immunopharmacol, 1999 Nov, 21(11), 711 - 25 Effects of the phosphodiesterase inhibitor rolipram on streptococcal cell wall-induced arthritis in rats; Laemont KD et al.; The phosphodiesterase-IV (PDE-IV) inhibitor, rolipram, is antiinflammatory in a number of animal models and inhibits the release of a variety of cytokines, including TNFalpha . Arthritis induced in rats by systemic reactivation with streptococcal cell walls (SCW) following intraarticular sensitization is a TNFalpha-dependent, delayed-type hypersensitivity (DTH) reaction . Rolipram administered during the reactivation phase dose-dependently inhibited hind paw edema through day 24, the day of peak swelling . PMN and T-cell recruitment to the arthritic joint were also attenuated in rolipram-treated rats . Histologic examination of ankle sections from rolipram-treated animals showed a marked attenuation of synovial inflammation . Mechanistic studies to determine the role of glucocorticoids in mediating rolipram action showed that the inhibitory effect of rolipram on swelling was not reversed by RU 486, a glucocorticoid antagonist . In contrast, RU 486 reversed the inhibitory effects of rolipram on TNFalpha secretion . To further evaluate the role of cAMP in the model, the beta-adrenergic receptor (betaAR) agonist isoproterenol was tested, and found to inhibit swelling but not the release of TNFalpha . These results are consistent with the view that the inhibitory effects of rolipram may be partially mediated by cAMP-dependent, but TNFalpha-independent, mechanisms . The betaAR antagonists propranolol and nadolol had no appreciable affect on the antiinflammatory effect of rolipram . However, rolipram reversed the lethal effects of the antagonists observed when either was administered alone . Apparently, beta-adrenergic mechanisms moderate the response to challenge, and rolipram treatment, presumably as a result of its effects on cAMP levels, reverses the toxic effect of the antagonists. Obstet Gynecol, 1999 Dec, 94(6), 994 - 9 Randomized comparison of oral misoprostol and oxytocin for labor induction in term prelabor membrane rupture; Butt KD et al.; OBJECTIVES: To compare labor induction intervals between oral misoprostol and intravenous oxytocin in women who present at term with premature rupture of membranes . METHODS: One hundred eight women were randomly assigned to misoprostol 50 microg orally every 4 hours as needed or intravenous oxytocin . The primary outcome measure was time from induction to vaginal delivery . Sample size was calculated using a two-tailed alpha of 0.05 and power of 80% . RESULTS: Baseline demographic data, including maternal age, gestation, parity, Bishop score, birth weight, and group B streptococcal status, were similar . The mean time +/-standard deviation to vaginal birth with oral misoprostol was 720+/-382 minutes compared with 501+/-389 minutes with oxytocin (P = .007) . The durations of the first, second, and third stages of labor were similar . There were no differences in maternal secondary outcomes, including cesarean birth (eight and seven, respectively), infection, maternal satisfaction with labor, epidural use, perineal trauma, manual placental removal, or gastrointestinal side effects . Neonatal outcomes including cord pH, Apgar scores, infection, and admission to neonatal intensive care unit were not different . CONCLUSION: Although labor induction with oral misoprostol was effective, oxytocin resulted in a shorter induction-to-delivery interval . Active labor intervals and other maternal and neonatal outcomes were similar. Br J Ophthalmol, 1999 Dec, 83(12), 1332 - 5 Alterations in the conjunctival bacterial flora following a single dose of azithromycin in a trachoma endemic area; Chern KC et al.; BACKGROUND/AIMS: The World Health Organisation has recommended repeated mass treatment of children in trachoma endemic areas with oral azithromycin . While chlamydia, the causative agent of trachoma, remains universally sensitive to azithromycin, there is concern that large scale programmes may alter the bacterial flora and induce resistance in streptococcal species . In this study the effect of a single dose of azithromcyin on the prevalence, species distribution, and resistance of conjunctival bacterial flora was determined . METHODS: Baseline and 14 day follow up bacterial cultures were taken from the conjunctivae of 121 children who reside in a trachoma endemic area of Nepal . 91 children were treated with azithromycin at baseline and 31 children received deferred treatment at the 14 day follow up . RESULTS: Although the prevalence of bacterial pathogens decreased significantly with azithromycin treatment, a significant change in the distribution of specific bacterial pathogens could not be demonstrated . Streptococcal resistance to azithromycin was found significantly more frequently after treatment . No change in the prevalence, distribution, or resistance pattern was found in the untreated control group . CONCLUSION: Repeated mass treatment of trachoma endemic areas with oral azithromycin will have an effect on bacterial flora . However, further work needs to be done to determine if this will have any clinical relevance. Infect Immun, 1999 Dec, 67(12), 6691 - 4 Attenuated expression of the mga virulence regulon in an M serotype 50 mouse-virulent group A streptococcal strain; Yung DL et al.; The attenuated expression of virulence genes found in a group A streptococcal strain that is naturally pathogenic for mice was postulated to result from a defect in the strain's multigene regulator, Mga . The sequence of the mga gene reveals three amino acid changes in the gene product that might affect protein function . The defect in the mga gene was complemented by providing either the closely similar mga4 allele or a more divergent mga1 allele in trans . Complementation increased the amount of emm50 transcript and the quantity of surface-extractable M protein, restoring virulence function. Infect Immun, 1999 Dec, 67(12), 6375 - 84 Cognate stimulatory B-cell-T-cell interactions are critical for T-cell help recruited by glycoconjugate vaccines; Guttormsen HK et al.; Covalent linkage of a bacterial polysaccharide to an immunogenic protein greatly enhances the carbohydrate's immunogenicity and induces polysaccharide-specific B-cell memory in vivo . These findings have spurred the development of glycoconjugate vaccines for serious bacterial infections . The specific B-cell-T-cell interactions responsible for recruitment of T-cell help by glycoconjugate vaccines are not well defined . We used mice deficient in molecules critical for stimulatory, cognate B-cell-T-cell interactions to study how T cells improve the immunogenicity of a glycoconjugate vaccine against group B streptococcal disease . Isotype switching to immunoglobulin G (IgG) was abrogated in mice deficient in major histocompatibility complex (MHC) class II antigen (Ag)-T-cell receptor (TCR), B7-CD28, or CD40-CD40L interactions . However, expression of either the B7-1 or the B7-2 molecule on antigen-presenting cells was sufficient for optimal T-cell costimulation . T cells activated by the vaccine also played a pivotal role in determining the magnitude of the IgM response to the polysaccharide . Comparable results were obtained with pathway antagonists . These data suggest that MHC class II Ag-TCR, B7-CD28, and CD40-CD40L interactions are critical for immune responses to glycoconjugate vaccines in vivo. Infect Immun, 1999 Dec, 67(12), 6293 - 302 Selective recruitment of T-cell subsets to the udder during staphylococcal and streptococcal mastitis: analysis of lymphocyte subsets and adhesion molecule expression; Soltys J et al.; During bacterial infection of the bovine mammary gland, large numbers of leukocytes migrate into the udder, resulting in the establishment of a host response against the pathogen . Currently, the specific leukocyte populations mediating this immune response are not well defined . In the studies described here, we analyzed blood and milk from healthy cows and cows with naturally occurring mastitis to determine if distinct alphabeta and gammadelta T-lymphocyte subsets were involved in the response of the udder to a mastitis pathogen and if the type of mastitis pathogen influenced the subset composition of these responding leukocytes . Although blood samples from cows with confirmed staphylococcal and streptococcal mastitis were characterized by increased numbers of gammadelta T cells, the most dramatic changes in leukocyte distributions occurred in milk samples from these cows, with a 75% increase in alphabeta T-cell levels and a 100% increase in gammadelta T-cell levels relative to the levels in milk samples from healthy animals . Interestingly, the increase in alphabeta T-cell numbers observed in milk from cows with staphylococcal mastitis was primarily due to increased numbers of CD4(+) T cells, while the increase in alphabeta T-cell numbers observed in cows with streptococcal mastitis was due to a parallel increase in both CD4(+) and CD8(+) T-cell numbers . The increased numbers of gammadelta T cells in milk from cows with staphylococcal and streptococcal mastitis were due to a selective recruitment of a distinct gammadelta T-cell subset (GD3.1(+)), while no change in the numbers of GD197(+) gammadelta T cells was observed . We also analyzed adhesion protein expression on blood and milk leukocytes and found that, in comparison to the situation for healthy cows, L-selectin was down-regulated and CD18 was up-regulated on leukocytes from cows with mastitis . Thus, shedding of L-selectin and up-regulation of CD18 by neutrophils may provide a sensitive indicator of early inflammatory responses during bovine mastitis . Overall, these studies suggest that distinct alphabeta and gammadelta T-cell subsets are involved in the host defense of the udder against mastitis infection and that selective recruitment of these T-cell subsets depends on the infectious agent involved. Gan To Kagaku Ryoho, 1999 Oct, 26(12), 1796 - 800 {Intrapleural administration with OK-432 and cultured autologous pleural effusion lymphocytes for breast cancer patients with malignant pleural effusions: analysis of 84 patients over a 14-year period}; Kan N; Autologous effusion lymphocytes cultured for 9-13 days with condition medium containing T cell growth factor were transferred after intrapleural administration with a streptococcal preparation, OK-432, for 84 breast cancer patients with cytologically-confirmed malignant pleural effusion . Effusion disappeared in 54 and decreased in 19 patients, while in 11 the treatment was ineffective (87% response) . A positive cytology changed to negative in 52 of 55 (95%) of the patients tested, while in 29 patients, effusion sample could not be obtained after treatment . A multivariate analysis of prognostic factors showed a significantly poorer prognosis in patients with the following concomitant metastases: liver metastasis, lung metastasis with lymphangitis carcinomatosa, and simultaneous bilateral effusions . Median survival time (MST) of all patients was 9 months (5-year survival: 18%) . However, MST of the patients with limited disease (patients without liver metastasis, lymphangitis, or bilateral effusion) was 23 months (5-year survival: 28%) . Ten patients survived more than 5 years (3 survived over 10 years) after the treatment among 46 patients with follow-up periods of > 5 years. Clin Diagn Lab Immunol, 1999 Nov, 6(6), 977 - 80 Relative avidities of human immunoglobulin G antibodies for streptococcal pyrogenic exotoxins A and B; Mascini EM et al.; In this pilot study, we investigated the relative avidities for streptococcal pyrogenic exotoxin A (SPE-A) and SPE-B of antibodies in sera from patients with fatal streptococcal toxic shock-like syndrome and from healthy individuals and in intravenous immunoglobulin (IVIG) preparations . We observed a great variation in the relative avidities of patient, control, and IVIG immunoglobulin G (IgG) (values estimated to be between 10(-7) and 10(-11) M), with mean values for patient IgG about 10-fold lower than those of control IgG. J Clin Invest, 1999 Nov, 104(9), 1181 - 9 Epidermal HLA-DR and the enhancement of cutaneous reactivity to superantigenic toxins in psoriasis; Travers JB et al.; Streptococcal and staphylococcal superantigens (SAg's) have been implicated in the pathogenesis of inflammatory skin diseases, but the mechanisms by which these toxins act are unknown . The present study assessed the ability of nanogram quantities of topically applied purified toxic shock syndrome toxin-1 (TSST-1), staphylococcal enterotoxin type B, and streptococcal pyrogenic enterotoxin types A and C to induce inflammatory reactions in clinically uninvolved skin of normal controls and subjects with psoriasis, atopic dermatitis, and lichen planus . These SAg's triggered a significantly greater inflammatory skin response in psoriatics than in normal control subjects or in subjects with atopic dermatitis or lichen planus . Surprisingly, skin biopsies did not exhibit the T-cell receptor Vbeta stimulatory properties predicted for SAg-induced skin reactions . By 6 hours after patch testing with SAg's, TNF-alpha mRNA had increased in the epidermis (but not the dermis) in biopsies from psoriatics, compared with controls . Immunohistochemical studies revealed significantly higher HLA-DR expression in keratinocytes from psoriatics than from controls . However, a mutant TSST-1 protein that fails to bind HLA-DR did not elicit an inflammatory skin reaction . These results indicate that keratinocyte expression of HLA-DR enhances inflammatory skin responses to SAg's . They may also account for previous studies failing to demonstrate selective expansion of T-cell receptor Vbetas in psoriatics colonized with SAg-producing Staphylococcus aureus, and they identify a novel T cell-independent mechanism by which SAg's contribute to the pathogenesis of inflammatory skin diseases. Arch Pediatr, 1999 Oct, 6(10), 1048 - 52 {Sydenham's chorea in children}; Ghram N et al.; BACKGROUND: Sydenham's chorea was the most common form of acquired chorea in childhood . Its incidence has declined since the use of antibiotics . The aim of our study was to determine the hospital incidence of this disease and to illustrate the clinical characteristics and outcome of this disease in Tunisia . POPULATION: Retrospective study of 15 cases of Sydenham's chorea, seen between 1987 and 1997 . RESULTS: Our patients (five boys and ten girls) represented 5.6 per 1000 hospitalized children . Their mean age was 10.5 years . Two patients had a history of rheumatic fever and five had a history of throat infection during the month before chorea . The onset of symptoms was acute in five cases and insidious in ten . Choreic movements were generalized but asymmetrical in 12 cases, and unilateral in three . Psychological disorders were noted in nine cases and hypotonia in six . Rheumatic carditis was found in three patients . No patient had an obvious increase in sedimentation rate, and antistreptolysin were increased in 50% of cases . All patients were given haloperidol and five steroids, 11 were given antibiotics at the attack of chorea and 13 received secondary prevention with benzathine penicillin . Initially, abnormal movements disappeared in all cases after a mean of three months . Three patients relapsed and two among them still show abnormal movements and psychological disorders after a follow-up of 3 and 3.5 years respectively . CONCLUSION: Sydenham's chorea, although less frequent than previously, is not exceptional in Tunisia . Malignant forms are not observed, but two of 15 patients developed a chronic form with sequelae . No correlation is found between outcome and secondary prevention of streptococcal infections. Presse Med, 1999 Oct 9, 28(30), 1635 - 7 {Disclosure of Behcet disease by concomitant dental infection}; Chevalet P et al.; BACKGROUND: Behcet's disease can be aggravated by chronic infection . Our case illustrates how the disease can be disclosed during an acute activation of a chronic infectious focus . CASE REPORT: A 40-year-old man had Behcet's syndrome associating fever, bipolar aphtosis, cutaneous pseudo folliculitis, anterior uveitis, and meningitis following an acute episode of a dental infection, with periapical granuloma . Antibiotic therapy was ineffective in calming this first flare-up of Behcet's disease . Corticosteroid and colchicine therapy were effective . DISCUSSION: Clinical and experimental work would implicat buccal streptococcal flora in the pathogenesis of Behcet's disease . Antibiotics offer interesting perspectives but further studies are needed to define their role in the treatment of Behcet's disease. Fam Pract, 1999 Oct, 16(5), 495 - 500 Influencing antibiotic prescribing in general practice: a trial of prescriber feedback and management guidelines; Zwar N et al.; BACKGROUND: The extent of use of antibiotics to treat upper respiratory infections in general practice is an area for concern due to the increasing problem of bacterial resistance . Effective educational strategies to promote rational prescribing are needed . OBJECTIVES: We aimed to examine the effectiveness of prescriber feedback and management guidelines in reducing antibiotics prescribing by GP trainees for undifferentiated upper respiratory tract infection, and in improving the choice of antibiotic for tonsillitis/streptococcal pharyngitis . The research tested a stepwise approach to targeting educational input to high prescribers . METHOD: General Practice trainees in New South Wales (n = 157) were randomly allocated to a treatment group (n = 78) which received an education intervention on antibiotic use, or to a control group (n = 79) which received an intervention on an unrelated topic . Trainees completed three practice activity surveys, each of 110 consecutive patient encounters, with 6-month intervals between surveys . Prescriber feedback and management guidelines on use of antibiotics for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis were delivered in a written form between surveys 1 and 2 . An educational outreach visit to high prescribers occurred between surveys 2 and 3 . Outcome measures were the rate of antibiotic prescribing for all indications, for URTI and prescribing of select antibiotics for tonsillitis/streptococcal pharyngitis . RESULTS: Antibiotic prescribing by the intervention group declined over three occasions from 25.0 to 23.3 to 19.7 per 100 URTI problems, while the control group increased from 22.0 to 25.0 to 31.7 per 100 URTI problems (P = 0.002) . Prescribing in agreement with accepted guidelines for tonsillitis/streptococcal pharyngitis increased over time in the intervention group from 55.6 to 69.8 to 73.0 per 100 problems, but decreased in the control group from 59.6 to 57.5 to 58.5 (P = 0.05) . CONCLUSION: Prescriber feedback and management guidelines were shown to influence antibiotic prescribing for URTI and choice of antibiotic for tonsillitis/streptococcal pharyngitis . This study provides a model for targeting educational input to those prescribers who most need to change their behaviour. Arch Mal Coeur Vaiss, 1999 Sep, 92(9), 1221 - 4 {Mycotic aneurysm of the splenic artery . A rare complication of surgically treated infectious endocarditis and its causative cardiac lesion}; Corbi P et al.; The authors report the case of a 59 year old woman with mitral valve streptococcal endocarditis complicating rheumatic valvular disease with several metastatic septic complications . In addition to ocular and cerebral localisations, the patient developed a very rare mycotic aneurysm of the splenic artery . Mitral valve replacement was necessary because of severe mitral regurgitation with major dilatation of the left heart chambers . This surgery was performed under high dose heparin therapy . Large aneurysms of the splenic artery carry a high risk of rupture . This splenic artery aneurysm was treated in the same operative session as the valvular disease by a sternolaparotomy: the aneurysm was operated first of all, and then valvular replacement was performed . Three years later, the patient is well and cured of the endocarditis . To the authors' knowledge, this is the third report of mycotic aneurysm of the splenic artery and the first case combined with surgery of the infectious valvular disease and the gastro-intestinal artery aneurysm. Clin Infect Dis, 1999 Sep, 29(3), 586 - 9 Kawasaki syndrome-like illness associated with infection caused by enterotoxin B-secreting Staphylococcus aureus; Hall M et al.; Two children had symptoms and clinical signs that were characteristic of the diagnostic criteria for Kawasaki syndrome, temporally associated with Staphylococcus aureus bacteremia . One child initially had focal osteomyelitis that was evident clinically and radiographically, and radiographic evidence of multifocal osteomyelitis was noted at follow-up . The blood-borne S . aureus isolates from these two patients secreted staphylococcal enterotoxin B and were negative for toxic shock syndrome toxin . Staphylococcal and streptococcal superantigens may play a role in the pathogenesis of some cases of Kawasaki syndrome or Kawasaki syndrome-like illness. J Clin Microbiol, 1999 Nov, 37(11), 3705 - 6 Comparison of selective broth medium plus neomycin-nalidixic acid agar and selective broth medium plus Columbia colistin-nalidixic acid agar for detection of group B streptococcal colonization in women; Dunne WM Jr; The combination of neomycin-nalidixic acid (NNA) agar and a selective broth medium (SBM) has recently been shown to improve the sensitivity of screening cultures for group B streptococcal (GBS) carriage in women . Because of the relatively high cost of NNA agar, a study was initiated to determine whether Columbia colistin-nalidixic acid (CNA) agar would be an equally sensitive, more economical alternative . A total of 580 cervical-vaginal and/or rectal specimens submitted for detection of GBS were included in the study . Each was plated onto NNA and CNA agar and then inoculated into SBM . GBS were recovered from 95 of 580 (16.4%) specimens, including 61 isolates from CNA, 74 from NNA, 73 from the CNA-SMB combination, and 86 from the NNA-SMB tandem . Of those, 22 isolates were recovered on NNA but not CNA, 9 were cultured on CNA but not NNA, 52 were isolated on both media, and 12 were recovered from subcultures of SBM only . The overall sensitivity of CNA alone (64 . 2%) was statistically significantly less than that of NNA agar (77 . 9%), as was the sensitivity of combination of CNA plus SBM (76.8%) compared to that of NNA plus SBM (90.5%) . Based on these findings, CNA should not be considered an acceptable alternative to NNA for the detection of GBS colonization in women despite potential cost savings. J Clin Microbiol, 1999 Nov, 37(11), 3469 - 74 Invasive and noninvasive group A streptococcal isolates with different speA alleles in The Netherlands: genetic relatedness and production of pyrogenic exotoxins A and B; Mascini EM et al.; Streptococcal pyrogenic exotoxin A (SPE-A) and SPE-B have been implicated in the pathogenesis of severe group A streptococcal (GAS) disease . We studied 31 invasive GAS strains including 18 isolates from patients with toxic shock syndrome and 22 noninvasive strains isolated in The Netherlands between 1994 and 1998 . These strains were associated with the different allelic variants of the gene encoding SPE-A . We selected endemic strains with speA-positive M and T serotypes: speA2-associated M1T1 and M22-60T12 strains, speA3-associated M3T3 strains, and speA4-associated M6T6 strains . Since speA1-positive isolates were not frequently encountered, we included speA1 strains of different serotypes . The GAS strains were compared genotypically by pulsed-field gel electrophoresis and phenotypically by the in vitro production of SPE-A and SPE-B . All strains within one M and T type appeared to be of clonal origin . Most strains produced SPE-A and SPE-B, but only a minority of the speA4-positive isolates did so . Among our isolates, speA1- and speA3-positive strains produced significantly more SPE-A than speA2- and speA4-carrying strains, while SPE-B production was most pronounced among speA1- and speA2-containing strains . There was a marked degree of variability in the amounts of exotoxins produced in vitro by strains that shared the same genetic profile . We conclude that the differences in the in vitro production of SPE-A and SPE-B between our selected strains with identical M and T types were not related to either genetic heterogeneity or the clinical course of GAS disease in the patient from whom they were isolated. S D J Med, 1999 Sep, 52(9), 345 - 7 Risperidone in the treatment of choreiform movements and aggressiveness in a child with "PANDAS"; Kleinsasser BJ et al.; The acronym 'PANDAS' (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) is used to describe neuropsychiatric symptoms putatively resulting from autoimmune responses to streptococcal infection in vulnerable children . A case of 'PANDAS' is presented to increase physician awareness of this disorder and to document effectiveness of risperidone in chorea and treatment-resistant disruptive behavior associated with this syndrome . To our knowledge, this is the first case report on risperidone in pediatric chorea, although studies on effectiveness of this agent in Tourette's disorders have been previously published. Pediatrics, 1999 Oct, 104(4 Pt 1), 967 - 9 Varicella complicated by group A streptococcal sepsis and osteonecrosis; Kouwabunpat D et al.; A 5-year-old boy presented with primary varicella zoster virus infection, group A streptococcal sepsis, toxic shock, and multisite osteonecrosis . An association between osteonecrosis and group A streptococcal sepsis has not been previously reported . Clinical recognition with supportive radiologic and pathologic findings are presented . Therapeutic guidelines are suggested. J Am Acad Nurse Pract, 1999 Feb, 11(2), 57 - 62 Managing streptococcal pharyngitis: a review of clinical decision-managing strategies, diagnostic evaluation, and treatment; DiMatteo L; Prompt and accurate diagnosis of GABHS pharyngitis is critical to prevent ARF, tonsillar abscess, toxic-shock-like syndrome, bacteremia, and deep tissue cellulitis which can result in significant morbidity and death . Antibiotic treatment of all patients that have complaints of sore throat incurs unnecessary costs and potential drug resistance . On the other hand, culturing all patients with complaints of sore throat incurs unnecessary costs and false positive cultures in patients . Utilizing a sensitive and specific clinical guideline assists clinicians in deciding who to culture or screen, and who to reassure and educate about their underlying non-GABHS illness . Also, clinicians need to know the sensitivity and specificity of the diagnostic tests used and each tests' limitations . While small numbers of patients fail treatment with penicillin, it remains the drug of choice for the treatment of GABHS and prevention of ARF, and its effectiveness at eradicating GABHS in the pharynx is superior. Ugeskr Laeger, 1999 Aug 23, 161(34), 4747 - 50 {Superantigens and their importance for inflammatory skin diseases}; Olsen JV et al.; Superantigens are a group of bacterial and viral proteins that are characterized by their capacity to stimulate a large number of T-cells simultaneously . Superantigens bind directly to the MHC class II molecule on the antigen-presenting cell and crosslink the cell with T-cells expressing certain V beta-chains on their T-cell receptor which leads to a vigorous polyclonal T-cell activation . Staphylococcal superantigens seem to be involved in the pathogenesis of systemic diseases such as toxic shock syndrome and Kawasaki syndrome . Furthermore, superantigens seem to play an important role in the induction and maintenance of inflammatory skin diseases such as atopic dermatitis and psoriasis . The skin of patients with atopic dermatitis is often colonized with superantigen-releasing Staphylococcus aureus, and application of staphylococcal superantigen on intact human skin induces a local dermatitis reaction . Guttate psoriasis is often preceded by a streptococcal throat infection, and T-cells specific for streptococcal superantigens have been identified in fresh guttate psoriasis lesions. FEMS Immunol Med Microbiol, 1999 Sep, 25(4), 355 - 63 The superantigenic activity of streptococcal pyrogenic exotoxin B is independent of the protease activity; Eriksson A et al.; The nature of the mitogenic activity of pyrogenic streptococcal exotoxin B, also known as streptococcal cysteine protease, has been debated in the literature . Streptococcal exotoxin B has been shown to cleave interleukin-1beta precursor and create biologically active interleukin-1beta, a major cytokine mediating inflammation and shock . This activity could mimic the mitogenicity and cytokine release induced by superantigens in lymphocyte stimulating experiments . In this study, the protease activity of streptococcal exotoxin B was irreversibly inhibited by covalent binding of a tripeptide and the superantigenic properties of streptococcal exotoxin B were found not to be influenced by this inactivation . Native as well as protease-inactivated streptococcal exotoxin B was shown to stimulate T-cell proliferation without a need of metabolically active antigen presenting cells . Furthermore, streptococcal exotoxin B-induced T-cell proliferation was shown to require HLA-DQ since addition of HLA-DQ monoclonal antibodies totally inhibited the mitogenic activity of streptococcal exotoxin B, indicating that streptococcal exotoxin B, as other superantigens, makes direct contact with the T-cell receptor via HLA class II . The aim of this study was to characterize the relationship between the proteolytic and superantigenic properties of streptococcal exotoxin B. Biol Psychiatry, 1999 Sep 15, 46(6), 775 - 80 Antibodies against a neuron-like (HTB-10 neuroblastoma) cell in children with Tourette syndrome; Singer HS et al.; BACKGROUND: Similar to the model for Sydenham's chorea, antineuronal antibodies (ANAb), which develop in response to a preceding streptococcal infection, have been speculated to have a role in the development of Tourette syndrome (TS) . METHODS: Serum antibodies against the neuron-like HTB-10 neuroblastoma cell were assayed by ELISA methods and Western blot analysis on 41 children with TS (mean age 11.3 years) and 39 control subjects (mean age 12.1 years) . RESULTS: Group comparisons of ELISA assay optical density (OD) showed that mean OD values for serum antibodies were not different {control (mean +/- SEM), .506 +/- .076; and TS, .584 +/- .053 (p = .38)} . In contrast, median values {.353 in control subjects and .477 in TS subjects (p = .012)} were significantly different . Western blots identified numerous bands in all TS and control sera with no difference in identified HTB-10 antigens . There was no relationship between the presence of ANAb and age of tic onset, family history, tic severity, attention deficit hyperactivity disorder, or obsessive compulsive disorder . No relationship existed between positive strep titers (ASO > or = 166 and/or antiDNAaseB > or = 170) and ANAb determinations or the severity of tics . CONCLUSIONS: Children with TS have higher median, but not mean, levels of ANAb, as measured by the HTB-10 neuroblastoma cell membrane assay . This assay system identified antibodies in both control and clinical groups and failed to identify a relationship between antibodies and clinical phenotype or one-time markers for streptococcal infection . Further studies are required to define a possible immune-mediated hypothesis for TS. Biochem Biophys Res Commun, 1999 Sep 24, 263(2), 454 - 9 Prevalence of circulating antibodies against a streptokinase C-terminal peptide in normal blood donors; Ojalvo AG et al.; Streptokinase (SK) is a streptococcal protein widely used as a thrombolytic agent . Anti-SK antibodies (Abs) are found in most individuals due to common streptococcal infections . The presence of these Abs increases the possibility of allergic reactions and may reduce the thrombolytic efficacy of SK upon a first therapy . Previous studies report on the immunodominance of the SK C-terminus and the role of this region in plasminogen (Plg) activation . The aim of this study was to assess the prevalence of circulating Abs to the SK C-terminus in normal blood donors . Sera from 1008 subjects aged 30 to 60 years were tested by Ultra-Micro-ELISA using a synthetic peptide resembling the SKC-2 C-terminus . An overall prevalence of 30 . 4% was found . Prevalence was significantly higher among male than among female donors (RR = 1.70, 1.13 < CI < 2.55) . No age effect was observed . This is the first extensive study about Abs directed against a particular region of SK in normal subjects . J Immunol, 1999 Oct 1, 163(7), 4020 - 6 Inhibition of bacterial cell wall-induced leukocyte recruitment and hepatic granuloma formation by TGF-beta gene transfer; Song X et al.; Intraperitoneal injection of streptococcal cell walls (SCW) into Lewis rats results in dissemination of SCW to the liver, spleen, bone marrow, and peripheral joints . The uptake of SCW by Kupffer cells in the liver initiates a chain of events largely mediated by T lymphocytes and macrophages . Local synthesis and secretion of cytokines and growth factors in response to the persistent SCW lead to the evolution and maintenance of a chronic T cell-dependent granulomatous response and result in granuloma formation and irreversible hepatic fibrosis . In an attempt to impede the development of the chronic granulomatous lesions in the liver, we injected a plasmid DNA encoding TGF-beta 1 i.m . to the SCW animals to determine the effect of TGF-beta 1 gene transfer on the course of liver inflammation and fibrosis . A single injection of plasmid DNA encoding TGF-beta 1 resulted in virtual abolition of the development of the SCW-induced hepatic granuloma formation and matrix expansion . TGF-beta 1 DNA not only reduced key proinflammatory cytokines including TNF-alpha, IL-1 beta, IFN-gamma, and IL-18, but also inhibited both CXC and CC chemokine production, thereby blocking inflammatory cell recruitment and accumulation in the liver . Moreover, TGF-beta 1 gene delivery inhibited its own expression in the liver tissue, which is otherwise up-regulated in SCW-injected animals . Our study suggests that TGF-beta 1 gene transfer suppresses hepatic granuloma formation by blocking the recruitment of inflammatory cells to the liver, and thus may provide a new approach to the control of hepatic granulomatous and fibrotic diseases. Rev Med Interne, 1999 Aug, 20(8), 701 - 4 {Group B streptococcal meningitis revealing an inner ear congenital malformation . A case report in an adult}; Blanco P et al.; INTRODUCTION: Group B streptococcal meningitis is unusual in adults . It occurs in patients with a chronic disease . EXEGESIS: We report a case of group B streptococcal meningitis that occurred in a 32-year-old woman, uncovering inner ear congenital malformation associated with cerebrospinal fluid fistula . There was no recurrent episode of meningitis during a 2-year period following surgical correction of the malformation . CONCLUSION: Clinical signs suggesting cerebrospinal fluid fistula should be considered in any adult patient with severe group B streptococcal infection. J Am Board Fam Pract, 1999 Jul-Aug, 12(4), 278 - 84 Practice patterns of family physicians in practice-based research networks: a report from ASPN . Ambulatory Sentinel Pratice Network; Nutting PA et al.; BACKGROUND: Practice-based research networks are growing and undertaking larger and more complex studies to inform the clinical practice of family physicians . We describe a study that compares clinical behaviors of physicians in the Ambulatory Sentinel Practice Network (ASPN), a large national practice-based research network, with those from the National Ambulatory Medical Care Survey (NAMCS) . METHODS: A survey, replicating NAMCS, was conducted among 129 family physician members of ASPN . Nested logistic regression was used to determine which services could predict ASPN membership after adjustment for common and easily observed patient and physician characteristics . RESULTS: Of 20 specific patient services, only 4 were predictive of membership in ASPN . Of these 4, 2 were screening or diagnostic services; ASPN physicians were 1.18 times more likely to obtain a blood pressure measurement and 0.60 times as likely to order a culture for streptococcal pharyngitis . ASPN physicians were 2.30 times more likely to provide family planning counseling and 1.66 times more likely to provide smoking cessation counseling after adjusting for patient smoking status . CONCLUSIONS: We conclude that there are minimal differences in the practice patterns of family physicians participating in a large national practice-based research network and those included in the probability sample of NAMCS . Additional work is needed to examine further those characteristics of the phenomena observed in practice-based research network research that might affect generalizability of results to the larger community of practicing family physicians. J Eval Clin Pract, 1999 May, 5(2), 153 - 6 Practice standards: the need for a personal element; Herman J; With rare exceptions, guidelines for clinical practice lack a personal element that allows for physicians' varying goals and patients' differing preferences . The importance of this element is illustrated by means of four examples: 1, hormone replacement therapy for the menopause; 2, early detection of breast cancer; 3, the treatment of acute streptococcal pharyngitis and 4, the diagnosis of symptoms that do not implicate any specific organ system . The advantages and disadvantages of guidelines are pointed out . Among the advantages are their usefulness as standards for audit and the fact that, in the process of reaching consensus, personal experience is taken into consideration . Chief among the disadvantages is their possible misuse by people outside of the profession . It is concluded that guidelines can be improved if their recommendations consider individual goals and preferences . They can become more influential if attention is paid to their proper dissemination. Br J Dermatol, 1999 Aug, 141(2), 335 - 8 Erythema elevatum diutinum and HIV infection: a report of five cases; Muratori S et al.; Erythema elevatum diutinum (EED) is emerging as a specific HIV-associated dermatosis, 11 cases having so far been reported in the medical literature and five patients with the disease having been seen by us during the last 4 years . As the disease is poorly known, it is easily confused with Kaposi's sarcoma or bacillary angiomatosis, but the histopathological features are diagnostic . EED is considered to be an immune complex-mediated vasculitis . A streptococcal infection seemed to be the trigger factor in four of our patients . Partial control of the cutaneous lesions was achieved by the use of antibiotics. Nephron, 1999 Sep, 83(1), 47 - 52 Anticardiolipin antibodies in acute poststreptococcal glomerulonephritis and streptococcal impetigo; Ardiles L et al.; Anticardiolipin (aCL) antibodies have been described in diverse clinical situations, linked to the risk of thrombosis in different vascular locations . They have been rarely studied in renal diseases, and occasionally they have been associated with glomerular thrombosis . We analyzed the incidence of aCL (isotypes IgG, IgA, and IgM) in samples, taken during the acute phase of the disease, from 27 well-documented patients having acute poststreptococcal glomerulonephritis . Twelve cases were positive on IgG testing, 1 case on IgA testing only, and no one was positive on IgM testing . A serological follow-up was performed with a second sample taken about 7 months later, for the patients initially positive on IgG testing showing persistence in 9 . Clinical variables during the acute phase and after a follow-up period of 25 (range 6-89) months were analyzed for possible associations with the presence of these antibodies, but non was significantly related . Renal histopathological investigation did not reveal particular findings in the aCL-positive patients, and glomerular thrombosis was not found in any case . In addition, serum samples from 12 streptococcal impetigo patients without renal involvement were analyzed, showing similar incidence (4 positive on IgG testing, 1 of them positive on IgM testing as well, and no one positive on IgA testing) and titers of aCL antibodies . We conclude that the presence of aCL antibodies in acute poststreptococcal glomerulonephritis may be a marginal immunological phenomenon unrelated to the glomerular disease, triggered by the streptococcal infection. FEMS Immunol Med Microbiol, 1999 Aug 15, 25(3), 289 - 98 A surface-displayed cholera toxin B peptide improves antibody responses using food-grade staphylococci for mucosal subunit vaccine delivery; Cano F et al.; The possibility of improving the antibody responses to a model streptococcal antigen, administered by intranasal immunization as surface-displayed on the food-grade bacterium Staphylococcus carnosus, by co-exposure of a peptide (CTBp) comprising amino acids 50-75 of the cholera toxin B subunit, was investigated . It was found that the introduction of the CTBp into the chimeric surface proteins, containing a serum albumin binding protein (ABP) from streptococcal protein G as model antigen, significantly increased serum IgG responses upon intranasal immunization . Similarly, elicited local IgA responses were also found to be improved . Furthermore, it was demonstrated that live delivery of the staphylococci was required to obtain this effect, since UV-irradiated or heat-killed bacteria exposing the same chimeric surface proteins did not show increased anti-ABP IgG responses. Clin Exp Dermatol, 1999 Jul, 24(4), 291 - 5 Which T cells cause psoriasis? Prinz JC. Today, T cells appear to be the main protagonists in the pathogenesis of psoriasis vulgaris . This article summarizes how T cells might contribute to the generation of psoriatic skin lesions . It discusses the preferential T cell receptor usage and the putative mode of T cell activation in psoriatic skin lesions, and how streptococcal throat infections could be involved in disease manifestations . The results are integrated into a pathogenetic concept which considers psoriasis as a T-cell mediated autoimmune disorder. Clin Infect Dis, 1999 Jun, 28(6), 1317 - 9 Severe pulmonary hemorrhage in patients with serious group A streptococcal infections: report of two cases; Ooe K et al.; Severe pulmonary hemorrhage was observed in two patients who died of serious group A streptococcal infections . These two patients initially presented with fever and sore throat . This was followed by sudden onset of septicemia caused by the bacteria and by the subsequent development of severe pulmonary hemorrhage . Hemoptysis, cyanosis, and dyspnea were observed prior to death in both cases . This pulmonary lesion resulted in asphyxia and sudden death in one patient . Pathological examinations of the lung revealed severe intraalveolar hemorrhage, with no evidence of inflammation or necrosis of the pulmonary tissue . There was no evidence of aspiration of blood due to hemorrhage in the upper respiratory or alimentary tract . This visceral lesion appears to be an hitherto undescribed, novel clinicopathologic feature of patients with serious group A streptococcal infections. J Exp Med, 1999 Aug 16, 190(4), 535 - 42 Secretory leukocyte protease inhibitor suppresses the inflammation and joint damage of bacterial cell wall-induced arthritis; Song X et al.; Disruption of the balance between proteases and protease inhibitors is often associated with pathologic tissue destruction . To explore the therapeutic potential of secretory leukocyte protease inhibitor (SLPI) in erosive joint diseases, we cloned, sequenced, and expressed active rat SLPI, which shares the protease-reactive site found in human SLPI . In a rat streptococcal cell wall (SCW)-induced model of inflammatory erosive polyarthritis, endogenous SLPI was unexpectedly upregulated at both mRNA and protein levels in inflamed joint tissues . Systemic delivery of purified recombinant rat SLPI inhibited joint inflammation and cartilage and bone destruction . Inflammatory pathways as reflected by circulating tumor necrosis factor alpha and nuclear factor kappaB activation and cartilage resorption detected by circulating levels of type II collagen collagenase-generated cleavage products were all diminished by SLPI treatment in acute and chronic arthritis, indicating that the action of SLPI may extend beyond inhibition of serine proteases. Surg Neurol, 1999 Aug, 52(2), 189 - 96; discussion 197 Spinal epidural abscess: contemporary trends in etiology, evaluation, and management; Rigamonti D et al.; BACKGROUND: Despite advances in neuroimaging and neurosurgical treatment, spinal epidural abscess remains a challenging problem; early diagnosis is often difficult and treatment is delayed . Optimal management is unclear, and morbidity and mortality are significant . To define contemporary trends in etiology and management, and establish diagnostic and therapeutic guidelines, we reviewed our 10-year experience with spinal epidural abscess . METHODS: We examined medical records, laboratory data, radiological (CT and MRI) studies, and operative reports from 75 cases of spinal epidural abscess between 1983 and 1992 . Demographic characteristics, frequency, clinical features, pathogens, risk factors, surgical and medical treatment, and outcome were analyzed . RESULTS: We found a significant increase in the frequency of spinal epidural abscess over the 10-year period (p-value = 0.0195) . Intravenous drug abuse was present in 28 patients (33%), diabetes mellitus in 22 patients (27%), and prior spinal surgery in 11 patients (17%) . Back pain, progressive neurologic deficit, and low grade fever remained the distinguishing diagnostic features . Erythrocyte sedimentation rate was elevated in 48 of 50 patients (95%); peripheral leukocyte count was elevated in 45 patients (60%) . MRI was the most effective technique for diagnosing spinal epidural abscess, revealing or suggesting the diagnosis in all 59 patients (100%) studied . Sites of spinal epidural abscess were equally distributed along the spinal axis . Staphylococcus aureus was the predominant organism (67% of patients, with 15% having a methicillin-resistant strain); 8% of patients had Streptococcal species . Most patients had open surgical drainage followed by prolonged antibiotic treatment; 22 patients were managed with antibiotics alone; 50 patients (66%) had a good clinical outcome after treatment . Multiple medical problems, prior spinal surgery, and methicillin-resistant Staphylococci were correlated with a significantly worse outcome . CONCLUSIONS: The frequency of diagnosis of spinal epidural abscess is increasing . To prevent serious morbidity and mortality, early diagnosis is essential . Patients with localized back pain who are at risk for developing such abscesses or who have an increased erythrocyte sedimentation rate and/or neurologic deficit should have an immediate MRI scan with contrast enhancement . Surgical drainage and prolonged antibiotic use are the cornerstones of treatment, although selected patients may be treated conservatively. J Infect, 1999 May, 38(3), 193 - 4 Survival following group A streptococcal septicaemia in a centenarian; Galloway A et al.; We report a case of a centenarian who survived group A streptococcal septicaemia without complications . We would be interested to hear if this patient is the oldest survivor of group A streptococcal septicaemia in the U.K. Hepatology, 1999 Aug, 30(2), 430 - 6 Activation of mouse liver natural killer cells and NK1.1(+) T cells by bacterial superantigen-primed Kupffer cells; Dobashi H et al.; Although bacterial superantigens have been well characterized as potent stimulators of T cells, their role in natural killer (NK)-type cells remains largely unknown . In the present study, we examined the effect of bacterial superantigens on mouse liver NK cells and NK1.1 Ag(+) (NK1(+)) T cells . C57BL/6 mice were intravenously injected with staphylococcal enterotoxin B (SEB) or streptococcal pyrogenic exotoxin A (SPE-A), and mononuclear cells (MNC) of various organs were obtained from mice 4 hours after being injected with superantigen . MNC were cultured for 48 hours, and interferon gamma (IFN-gamma) levels of supernatants were measured . The antitumor cytotoxicities of the liver and spleen MNC were also evaluated 24 hours after the mice were injected with superantigen . Liver MNC produced more IFN-gamma than did splenocytes, and peripheral blood and lung MNC did not produce any detectable IFN-gamma . In addition, liver MNC acquired a potent antitumor cytotoxicity by the SEB injection, and both NK cells and NK1(+)T cells but not cluster of differentiation (CD)8(+) T cells were responsible for the cytotoxicity as demonstrated by either in vivo or in vitro cell depletion experiments, and the NK-type cells were partly responsible for the increased serum IFN-gamma . Activation of liver NK-type cells was also supported by the fact that liver NK cells proportionally increased and NK1(+) T cells augmented their CD11a expressions after SEB injection . The pretreatment of mice with anti-IFN-gamma Ab and/or with anti-interleukin-12 (IL-12) Ab diminished the SEB-induced cytotoxicity of liver MNC . Furthermore, the in vivo depletion of Kupffer cells decreased the SEB-induced cytotoxicity of liver MNC . Consistent with these results, liver MNC stimulated with superantigens in the presence of Kupffer cells in vitro produced a greater amount of IFN-gamma than did the liver MNC without Kupffer cells or splenocytes . Our results suggest that bacterial superantigen-primed Kupffer cells produce IL-12 and other monokines, while also nonspecifically activating both NK cells and NK1(+) T cells to produce IFN-gamma. Eur J Clin Microbiol Infect Dis, 1999 May, 18(5), 362 - 4 Invasive group B streptococcal disease in nonpregnant adults; Perovic O et al.; Forty episodes of invasive group B streptococcal infections in nonpregnant adults at Chris Hani Baragwanath Hospital, Soweto, South Africa, were retrospectively reviewed . The mean age of the patients was 45.6 years . Twenty (50%) patients were bacteraemic . Common predisposing conditions included diabetes mellitus (27.5%), trauma (25%), and HIV infection (12.5%) . Soft tissue abscesses and pneumonia accounted for 70% of the presentations . Ten (25%) patients had acquired the infection nosocomially . Death occurred in 14 (35%) patients and was significantly associated with bacteraemia (P = 0.0009) and pneumonia (P = 0.0012) . Trauma is an important predisposing condition, and HIV infection may have played a role in the setting described; both factors probably accounted for the relatively young age of the patients. J Int Med Res, 1999 Jan-Feb, 27(1), 27 - 37 Effects of streptococcal preparation OK-432 on cytokine induction in spleen and tumour tissues of mice bearing MH-134 tumour cells; Nakatani S et al.; Streptococcal preparation OK-432 is a bacterial immunopotentiator extensively used in Japan for adjuvant cancer therapy . Using C3H/He mice bearing MH-134 tumour cells, cytokine inductions of tumour necrosis factor-alpha, interleukin 1 beta, interleukin 6 and interferon-gamma were determined in spleen and tumour tissues by reverse transcriptase-polymerase chain reaction analysis . No significant induction of cytokine mRNA was observed after subcutaneous administration of OK-432 (OK-432, s.c.) or after intratumoural injection of IFN-gamma (IFN-gamma, i.t.), compared with controls, either in spleen or tumour tissues . In contrast, subcutaneous administration of OK-432 followed by intratumoural OK-432 injection (OK-432, s.c . + i.t.) was found to induce some cytokine mRNAs significantly . The mRNA levels of tumour necrosis factor alpha and interferon-gamma in spleen tissue and those of interleukin 1 beta and interferon-gamma in tumour tissues were significantly elevated in mice with OK-432, s.c . + i.t . treatment compared with controls . These results suggest that treatment with OK-432, s.c . + i.t . effectively induced splenic antitumour immunity as well as local immunity against tumour cells. Immunopharmacology, 1999 May, 42(1-3), 53 - 60 The factor H protein family; Zipfel PF et al.; The factor H gene family provides a prime example of a multidomain multifunctional protein family whose individual members are defined by conserved common structural elements and display diverse but often overlapping functions . The six identified members of this protein family represent secreted plasma proteins that are primarily synthesized in the liver . Here, we summarize the current understanding of the function of these proteins and suggest a common role in complement control . Factor H is the best characterized member and acts as a complement regulator . The protein displays cofactor activity for factor I in the degradation of the central complement component C3b, acts as a decay accelerating factor for the C3 convertase, C3bBb and is a competitor for factor B binding to C3b . Factor H is a multifunctional protein and displays functions outside the complement system: it binds to the cellular integrin receptor (CD11b/CD18), interacts with cell surface glycosaminoglycans and also binds to the surface of certain pathogenic microorganisms . In addition, factor H has several binding sites for the C3 protein . The factor H-like protein 1 (FHL-1) or reconectin shares the complement regulatory functions with factor H and interacts with heparin . The protein displays cell spreading activity and binds to the N-terminus of the streptococcal M protein . The function of the factor H-related proteins (FHR-1 to FHR-4) is currently under investigation . These proteins are differently distributed . Three proteins (FHR-1, FHR-2 and FHR-4) are constituents of lipoproteins, while FHR-3 interacts with heparin . Binding to C3b and C3d has been demonstrated for FHR-3 and FHR-4 and the two proteins display a cofactor related activity. Eur J Biochem, 1999 Jul, 263(2), 326 - 37 Analysis of functional regions of YPM, a superantigen derived from gram-negative bacteria; Ito Y et al.; The bacterial superantigens, staphylococcal enterotoxins and streptococcal pyrogenic exotoxins, are grouped in a family by the conservation of amino acid sequence and polypeptide folding patterns . In the case of Yersinia pseudotuberculosis-derived mitogen (YPM), however, there is no noticeable homology with this family, although many of the in vitro functional features conform to the criteria for a superantigen . To study the mode of action of YPM at the molecular level, we first generated a number of YPM point mutants with reduced T-cell proliferative activity using random mutagenesis and localized the amino acid positions involved in either major histocompatibility complex class II or T-cell receptor Vbeta-interaction . Plotting the elucidated positions on the hydrophilicity profile suggested that they reside mostly on the outer portion of the molecule . We also report that the two cysteines positioned almost at opposing ends of the YPM molecule are connected by an S-S bond the destruction of which causes fatal damage . Finally, we obtained evidence that YPM partially competes with staphylococcal enterotoxin E for human leukocyte antigen-DR binding . This raises the question of whether these different types of superantigens have acquired the same function by genetic convergence or originated from a common ancestral gene. Singapore Med J, 1999 Mar, 40(3), 147 - 50 Cutaneous vasculitis seen at a skin referral centre in Singapore; Chua SH et al.; OBJECTIVE: To study the clinical features and course of patients presenting to a skin referral centre with cutaneous vasculitis . METHOD: A retrospective review of patients presenting to the National Skin Centre from 1993 to 1995 with cutaneous vasculitis was done . All patients included in the study had histologically proven vasculitis on skin biopsy . The clinical manifestations and laboratory investigations of the patients were recorded . The response to the various drugs given as first line therapy and course of the disease 1 year after initial presentation was reviewed . RESULTS: Forty-seven patients were included in this study . Females outnumbered males in a ratio of approximately 2:1 (32 females versus 15 males) . The age of the patients ranged from 14 to 78 years, with a mean of 36 years . The aetiology remained elusive in 70% of cases . Of the known secondary causes, drugs and streptococcal infections were the most frequently implicated . The lower limbs were involved in more than 90% of cases . Cutaneous lesions took the form of palpable purpura, ulcers, nodules and urticaria . Extracutaneous manifestations were present in 47% of patients . The main extracutaneous manifestations were arthralgia/arthritis (21%), microscopic haematuria (16%) and abdominal pain (8%) . Direct immunofluorescence on lesional skin was positive in 65% of cases . A raised erythrocyte sedimentation rate was observed in 40% of patients . Positive antinuclear antibodies were detected in 30% of cases . Most patients who were given systemic corticosteroids responded predictably well . The response to other modalities of treatment was more variable . At 1 year follow-up, complete remission was recorded in 47% of the patients, while in 53% of the patients, the disease continued to run a chronic relapsing course. Intensive Care Med, 1999 May, 25(5), 535 - 7 Bronchopleural fistula complicating group A beta-haemolytic streptococcal pneumonia . Use of a Fogarty embolectomy catheter for selective bronchial blockade; McCormick BA et al.; A 36-year-old woman developed severe group A Streptococcal pneumonia, complicated by a bronchopleural fistula, ARDS and multi-organ failure . We describe the use of selective middle lobe bronchus blockade, with a Fogarty embolectomy catheter, to localise and control the air leak . This allowed effective mechanical ventilation and oxygenation on intensive care and during right middle lobectomy . The patient made a prolonged, but full recovery. J Infect Dis, 1999 Aug, 180(2), 410 - 8 Invasive group A streptococcal infections: T1M1 isolates expressing pyrogenic exotoxins A and B in combination with selective lack of toxin-neutralizing antibodies are associated with increased risk of streptococcal toxic shock syndrome; Eriksson BK et al.; Analysis of 132 group A streptococcal (GAS) isolates from 151 invasive episodes, including streptococcal toxic shock syndrome (STSS), from 1983 to 1995 showed great genetic variation by use of T serotyping in combination with restriction fragment length polymorphism . In contrast, genetically homogenous T1M1 isolates appeared in epidemic patterns with significantly increased risk of STSS . The speA gene, with the allelic variants speA2 and speA3 carried by the T1M1 and T3M3 serotypes, respectively, was strongly associated with STSS . Infection with a GAS isolate carrying speA, alcohol abuse, and malignancy recently treated with cytostatic drugs were factors independently related to STSS . Neutralization of SpeA lymphocyte mitogenicity was totally absent in sera from patients with STSS and low in sera from persons with uncomplicated bacteremia compared with levels in sera from uncomplicated erysipelas . Neutralization of SpeB was significantly lower in sera of patients with STSS than in sera from persons with bacteremia or erysipelas. Pediatr Infect Dis J, 1999 Jun, 18(6), 529 - 33 Resource utilization associated with initial hospital stays complicated by early onset group B streptococcal disease; Platt R et al.; BACKGROUND: The epidemiology of early onset neonatal group B streptococcal (GBS) disease has changed appreciably, but there are no recent assessments of the in-hospital resource utilization it incurs . STUDY DESIGN: We performed a retrospective cohort study of infants delivered from 1987 through 1995 at Massachusetts' largest obstetrics hospital . A matched cohort design was used to assess care occurring after transfer to another acute care hospital . RESULTS: There were 135 cases of early onset neonatal GBS infection complicating 85,062 deliveries (1.6/1,000 births) in 9 years, with a substantial decline beginning in 1994, when maternal intrapartum chemoprophylaxis was widely introduced . Most (73%) infants had birth weights of 2500 g or more; 93% survived . Overall both the median and mean lengths of stay were 8 days longer for infants with GBS disease than for those without this infection (P < 0.001) . Total hospital charges for neonates with GBS disease also were higher, with the difference in medians of $5323 and in means of $10,004 (P < 0.001) . Differences were greatest among >2500-g birth weight infants; no excess was evident for infants with birth weights of < 1500 g . CONCLUSION: There was a substantial excess length of stay and charges associated with early onset neonatal GBS disease, although this was less than previously reported. Protein Sci, 1999 Jun, 8(6), 1320 - 31 Autonomous folding of a peptide corresponding to the N-terminal beta-hairpin from ubiquitin; Zerella R et al.; The N-terminal 17 residues of ubiquitin have been shown by 1H NMR to fold autonomously into a beta-hairpin structure in aqueous solution . This structure has a specific, native-like register, though side-chain contacts differ in detail from those observed in the intact protein . An autonomously folding hairpin has previously been identified in the case of streptococcal protein G, which is structurally homologous with ubiquitin, but remarkably, the two are not in topologically equivalent positions in the fold . This suggests that the organization of folding may be quite different for proteins sharing similar tertiary structures . Two smaller peptides have also been studied, corresponding to the isolated arms of the N-terminal hairpin of ubiquitin, and significant differences from simple random coil predictions observed in the spectra of these subfragments, suggestive of significant limitation of the backbone conformational space sampled, presumably as a consequence of the strongly beta-structure favoring composition of the sequences . This illustrates the ability of local sequence elements to express a propensity for beta-structure even in the absence of actual sheet formation . Attempts were made to estimate the population of the folded state of the hairpin, in terms of a simple two-state folding model . Using published "random coil" values to model the unfolded state, and values derived from native ubiquitin for the putative unique, folded state, it was found that the apparent population varied widely for different residues and with different NMR parameters . Use of the spectra of the subfragment peptides to provide a more realistic model of the unfolded state led to better agreement in the estimates that could be obtained from chemical shift and coupling constant measurements, while making it clear that some other approaches to population estimation could not give meaningful results, because of the tendency to populate the beta-region of conformational space even in the absence of the hairpin structure. Biol Psychiatry, 1999 Jun 15, 45(12), 1564 - 71 A pilot study of penicillin prophylaxis for neuropsychiatric exacerbations triggered by streptococcal infections; Garvey MA et al.; BACKGROUND: Some children with obsessive-compulsive disorder (OCD) and tic disorders appear to have symptom exacerbations triggered by group A beta-hemolytic streptococcal infections in a manner that is similar to rheumatic fever and its neurologic variant, Sydenham's chorea . Because penicillin prophylaxis has proven to be effective in preventing recurrences of rheumatic fever, it was postulated that it might also prevent streptococcal-triggered neuropsychiatric symptom exacerbations in children with Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS) . These children are identified by five clinical characteristics: presence of OCD or tic disorder, prepubertal onset, episodic symptom course, neurologic abnormalities (i.e., choreiform movements) and streptococcal-triggered symptom exacerbations . METHODS: Thirty-seven children with PANDAS were enrolled in an 8 month, double-blind, balanced cross-over study . Patients were randomized to receive either 4 months of the active compound (twice daily oral 250 mg penicillin V) followed by 4 months of placebo, or placebo followed by penicillin V . Tic, OCD, and other psychiatric symptoms were monitored monthly . Throat cultures and streptococcal antibody titers were also obtained . RESULTS: There were an equal number of infections in both the active and placebo phases of the study . There was no significant change seen in either the obsessive-compulsive or tic symptom severity between the two phases . CONCLUSIONS: Because of the failure to achieve an acceptable level of streptococcal prophylaxis, no conclusions can be drawn from this study regarding the efficacy of penicillin prophylaxis in preventing tic or OCD symptom exacerbations . Future studies should employ a more effective prophylactic agent, and include a larger sample size. Arthritis Rheum, 1999 Jun, 42(6), 1119 - 27 Hemoglobin protects from streptococcal cell wall-induced arthritis; McCartney-Francis NL et al.; OBJECTIVE: To investigate the ability of hemoglobin (Hgb), a nitric oxide (NO) scavenger, to deplete excess NO and reduce inflammation and injury in synovial tissue from joints with inflammatory arthritis . METHODS: The severity of streptococcal cell wall-induced arthritis was monitored following administration of Hgb . Plasma nitrite and nitrate levels were measured, and inducible NO synthase (iNOS) and cytokine messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) and joint tissue were evaluated . RESULTS: Following systemic administration of Hgb to arthritic rats, plasma levels of nitrite and nitrate as well as iNOS mRNA expression in the joints and PBMC were significantly reduced . Moreover, inflammatory cell accumulation and disease pathology in the joint tissue were dramatically attenuated without obvious side effects . Consistent with this reduction in the inflammatory response, cytokine gene expression was decreased in the synovium of Hgb-treated rats . CONCLUSION: Modulation of NO levels through the use of a NO scavenger, Hgb, influences the development and severity of arthritis . These findings suggest that depletion of excess NO by NO scavengers provides a prototype for further exploration of potential treatments for chronic arthritis. J Virol, 1999 Jul, 73(7), 5637 - 45 Identification of multiple protective epitopes (protectopes) in the central conserved domain of a prototype human respiratory syncytial virus G protein; Plotnicky-Gilquin H et al.; A recombinant fusion protein (BBG2Na) comprising the central conserved domain of the respiratory syncytial virus subgroup A (RSV-A) (Long) G protein (residues 130 to 230) and an albumin binding domain of streptococcal protein G was shown previously to protect mouse upper (URT) and lower (LRT) respiratory tracts against intranasal RSV challenge (U . F . Power, H . Plotnicky-Gilquin, T . Huss, A . Robert, M . Trudel, S . Stahl, M . Uhlen, T . N . Nguyen, and H . Binz, Virology 230:155-166, 1997) . Panels of monoclonal antibodies (MAbs) and synthetic peptides were generated to facilitate dissection of the structural elements of this domain implicated in protective efficacy . All MAbs recognized native RSV-A antigens, and five linear B-cell epitopes were identified; these mapped to residues 152 to 163, 165 to 172, 171 to 187 (two overlapping epitopes), and 196 to 204, thereby covering the highly conserved cysteine noose domain . Antibody passive-transfer and peptide immunization studies revealed that all epitopes were implicated in protection of the LRT, but not likely the URT, against RSV-A challenge . Pepscan analyses of anti-RSV-A and anti-BBG2Na murine polyclonal sera revealed lower-level epitope usage within the central conserved region in the former, suggesting diminished immunogenicity of the implicated epitopes in the context of the whole virus . However, Pepscan analyses of RSV-seropositive human sera revealed that all of the murine B-cell protective epitopes (protectopes) that mapped to the central conserved domain were recognized in man . Should these murine protectopes also be implicated in human LRT protection, their clustering around the highly conserved cysteine noose region will have important implications for the development of RSV vaccines. Br J Cancer, 1999 May, 80(5-6), 775 - 85 Multi-institutional randomized clinical study on the comparative effects of intracavital chemotherapy alone versus immunotherapy alone versus immunochemotherapy for malignant effusion; Nio Y et al.; The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion . Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis . The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers . The patients with malignant effusion were randomly assigned into one of three i.c . therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14) . The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared . There were no differences in the patients' backgrounds . The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups . One patient died after cisplatin (CDDP) administration in Group A . Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases . The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C) . Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C . The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test) . The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C . These results suggest that i.c . immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c . chemotherapy alone or immunotherapy alone. Pediatrics . 1999 Jun;103(6):e77. Risk factors for early-onset group B streptococcal sepsis: estimation of odds ratios by critical literature review; Benitz WE et al.; OBJECTIVE: To identify and to establish the prevalence of ORs factors associated with increased risk for early-onset group B streptococcal (EOGBS) infection in neonates . streptococcal (EOGBS) infection in neonates . STUDY DESIGN: Literature review and reanalysis of published data . RESULTS: Risk factors for EOGBS infection include group B streptococcal (GBS)-positive vaginal culture at delivery (OR: 204), GBS-positive rectovaginal culture at 28 (OR: 9.64) or 36 weeks gestation (OR: 26 . 7), vaginal Strep B OIA test positive at delivery (OR: 15.4), birth weight </= 2500 g (OR: 7.37), gestation <37 weeks (OR: 4.83), gestation <28 weeks (OR: 21.7), prolonged rupture of membranes (PROM) >18 hours (OR: 7.28), intrapartum fever >37.5 degrees C (OR: 4.05), intrapartum fever, PROM, or prematurity (OR: 9.74), intrapartum fever or PROM at term (OR: 11.5), chorioamnionitis (OR: 6.43) . Chorioamnionitis is reported in most (88%) cases in which neonatal infection occurred despite intrapartum maternal antibiotic therapy . ORs could not be estimated for maternal GBS bacteriuria during pregnancy, with preterm premature rupture of membranes, or with a sibling or twin with invasive GBS disease, but these findings seem to be associated with a very high risk . Multiple gestation is not an independent risk factor for GBS infection . CONCLUSIONS: h Mothers with GBS bacteriuria during pregnancy, with another child with GBS disease, or with chorioamnionitis should receive empirical intrapartum antibiotic treatment . Their infants should have complete diagnostic evaluations and receive empirical treatment until infection is excluded by observation and negative cultures because of their particularly high risk for EOGBS infection . Either screening with cultures at 28 weeks gestation or identification of clinical risk factors, ie, PROM, intrapartum fever, or prematurity, may identify parturients whose infants include 65% of those with EOGBS infection . Intrapartum screening using the Strep B OIA rapid test identifies more at-risk infants (75%) than any other method . These risk identifiers may permit judicious selection of patients for prophylactic interventions. Am J Respir Crit Care Med, 1999 Jun, 159(6), 1862 - 7 Combined treatment with surfactant and specific immunoglobulin reduces bacterial proliferation in experimental neonatal group B streptococcal pneumonia; Herting E et al.; Neonates suffering from group B streptococcal (GBS) pneumonia often lack type-specific opsonizing antibodies . We studied the influence of combined intratracheal treatment with surfactant and a specific antibacterial polyclonal antibody (IgG fraction) on bacterial proliferation and lung function in an animal model of GBS pneumonia . Near-term newborn rabbits received an intratracheal injection of either the specific IgG antibody, nonspecific IgG, surfactant, a mixture of surfactant and the antibody, or 0.9% saline . At 30 min the rabbits were infected with a standard dose (10(8)) of the encapsulated GBS strain 090 Ia . After 5 h of mechanical ventilation the mean estimated increase in bacterial number in lung homogenate (log10 colonies/g) was 0.76 in the antibody group, 0.92 in the nonspecific IgG group, 0.55 in the surfactant group, and 1.29 in the saline group . A mean decrease in bacterial number (-0.05) was observed in the group that received combined treatment with surfactant and antibody (p < 0.05 versus all other groups) . Lung-thorax compliance was significantly higher in both groups of surfactant-treated animals compared with saline or IgG treatment . We conclude that in experimental neonatal GBS pneumonia combined treatment with surfactant and a specific immunoglobulin against GBS reduced bacterial proliferation more effectively than either treatment alone. Eur Neurol, 1999, 41(4), 187 - 93 Regional specific changes of cerebral metabolism in systemic lupus erythematosus identified by positron emission tomography; de Jong BM et al.; In order to test the hypothesis whether the pathogenesis of cerebral systemic lupus erythematosus (SLE) may include an immune-mediated deficit in specific vulnerable brain regions, the regional cerebral metabolism in 9 patients with diffuse as well as focal cerebral symptoms was compared with that of 10 age-matched control subjects . The cerebral distribution of 2-{18F}fluoro-2-deoxy-D-glucose (FDG) uptake was measured by means of positron emission tomography . Subsequently performed statistical parametric mapping showed (i) a relative increase in metabolism in the striatum and (ii) regional decreases in the premotor cortex as a common feature in the patient group . Region of interest measurements of absolute FDG uptake confirmed these findings . The increased striatal activity may support the presence of a direct immune response against neuronal tissue in SLE, similar to the cross-reaction against inhibitory components in striatal tissue provoked by streptococcal antigens. Microb Drug Resist, 1999 Spring, 5(1), 9 - 18 Mrp--a new auxiliary gene essential for optimal expression of methicillin resistance in Staphylococcus aureus; Wu SW et al.; Screening of a library of Tn551 insertional mutants selected for reduction in the methicillin resistance level of the parental Staphylococcus aureus strain COL resulted in the isolation of mutant RUSA266 in which the minimal inhibitory concentration (MIC) of the parent was reduced from 1,600 to 1.5 micrograms/mL . Cloning and sequencing of the vicinity of the insertion site omega 726 identified an open reading frame (orf1365) encoding a very large polypeptide of more than 1,365 amino acids . A unique feature of the deduced amino acid sequence was the presence of multiple tandem repeats of 75 amino acids in the polypeptide, reminiscent of the structure of high-molecular-weight cell-surface proteins EF* and Emb identified in some streptococcal strains . Mutant RUSA266 with the inactivated gene, which we shall provisionally refer to as mrp (for multiple repeat polypeptide), produced a peptidoglycan with altered muropeptide composition, and both the reduced antibiotic resistance and the altered cell wall composition were co-transduced in back-crosses into the parental strain COL . Additional sequencing upstream of mrp has revealed that this gene was part of a five-gene cluster occupying a 9.2-kb region of the staphylococcal chromosome and was composed of glmM (directly upstream of mrp), two open reading frames orf310 and orf269 coding for two hypothetical proteins, and the gene encoding the staphylococcal arginase (arg) . Transcriptional analysis demonstrated that the five genes in the cluster were transcribed together. Arch Dis Child Fetal Neonatal Ed, 1999 Mar, 80(2), F139 - 41 Mortality from early onset group B streptococcal infection in the United Kingdom; Embleton N et al.; AIMS: To assess the assumption that group B streptococcal infection is less common in the United Kingdom than it is in the United States . METHODS: All stillbirth and neonatal death records in the former Northern Health Region were scrutinised to determine how many babies had died of infection in 1981-96, and what had been the cause . RESULTS: Fifty one of 630 206 live born babies had died of confirmed group B streptococcal infection after becoming symptomatic within 48 hours of birth (0.8 neonatal deaths per 10,000 live births) . There were a further 27 deaths from infection without a confirmed microbiological diagnosis, and 17 stillbirths from confirmed group B streptococcal infection . CONCLUSIONS: The incidence of death from early onset infection was marginally higher than the officially estimated rate for the United States before widespread prophylaxis was attempted . Strategies for perinatal prevention deserve greater attention in the United Kingdom. Scand J Immunol, 1999 May, 49(5), 506 - 14 Characterization of antibody responses to a Plasmodium falciparum blood-stage antigen induced by a DNA prime/protein boost immunization protocol; Haddad D et al.; The humoral immune responses elicited by priming with a DNA plasmid and boosting with either the plasmid or the corresponding recombinant protein in alum adjuvant were compared . The plasmid DNA encoded a sequence (M3) derived from the Plasmodium falciparum antigen Pf155/RESA, and the recombinant protein consisted of the identical malarial sequence fused to an albumin-binding region (BB) of streptococcal protein G . Mice of different genetic backgrounds (CBA, Balb/c and C57Bl/6) were primed with plasmid DNA and boosted with either plasmid or recombinant protein . In all strains of mice, boosting with protein elicited higher anti-M3 antibody levels than obtained by boosting with plasmid, yet the kinetics and longevity of the secondary responses were comparable . Antiserum obtained after protein boosting displayed an immunoglobulin (Ig)G subclass profile skewed to the IgG1 isotype, regardless of the mouse strain . In contrast, mice receiving a second injection with plasmid responded with a more mixed IgG subclass profile . Inclusion of a P . falciparum circumsporozoite protein-derived T-helper epitope (CS.T3) in the immunization plasmid as well as in the fusion protein, did not significantly change the humoral responses to M3 . The results show the potential of DNA vaccination for the purpose of priming an antibody response against the malarial blood-stage antigen Pf155/RESA . When combined with a protein boost, this DNA priming results in high-titred and long-lasting anamnestic responses. Paediatr Anaesth, 1999, 9(3), 262 - 4 Spinal anaesthesia and meningitis in former preterm infants: cause-effect? Luz G, Buchele H, Innerhofer P, Maurer H. Meningitis associated with spinal anaesthesia is a rare but well-known complication . We report on a case of fatal bacterial meningitis following spinal anaesthesia in a former preterm infant . The aetiology of this meningitis could not be established . Former preterm infants represent a high-risk population because of their susceptibility to group B streptococcal meningitis at this age as documented in a second case . Therefore we discuss whether meningitis was consequential or coincidental with spinal anaesthesia and could have been prevented by more comprehensive preoperative laboratory screening or prophylactic antibiotics. Drugs, 1999 Apr, 57(4), 545 - 55 Current guidelines for the treatment of patients with rheumatic fever; Thatai D et al.; Rheumatic fever is a multisystem inflammatory disease that occurs as a delayed sequelae to group A streptococcal pharyngitis . The important clinical manifestations are migratory polyarthritis, carditis, chorea, subcutaneous nodules and erythema marginatum occurring in varying combinations . The pathogenesis of this disorder remains elusive: an antigenic mimicry hypothesis best explains the affliction of various organ systems after a lag period following pharyngeal infection . In its classic milder form, the disorder is largely self-limited and resolves without sequelae, but carditis may be fatal in severe forms of the disease . Chronic and progressive damage to the heart valves leads to the most important public health manifestations of the disease . Anti-inflammatory agents provide dramatic clinical improvement, but do not prevent the subsequent development of rheumatic heart disease . The role of corticosteroids in treatment of carditis is uncertain and controlled studies have failed to demonstrate improved long term prognosis . Chorea, once considered a benign self-limited disease, is now felt to require more aggressive treatment, in particular with sedatives . Prevention of first and subsequent attacks of rheumatic fever is the mainstay in the limited arsenal available to alter the natural history of this disease. Mund Kiefer Gesichtschir, 1999 Mar, 3(2), 82 - 91 {Odontogenic pyogenic infections . 10-year analysis}; Piesold J et al.; All patients of the Department of Oral and Maxillofacial Surgery at the Erfurt Hospital with odontogenic pyogenic infections have been analyzed in a retrospective study over a period of 10 years, from 1987 to 1997 . This included questions concerning frequency, seriousness and treatment of these infections, social changes in the environ prove effects about the referral behaviour and the course . Odontogenic pyogenic infections are mixed infections . Aerobic agents such as hemolytic streptococcuses and staphylococcuses as well as anaerobic bacteria and fungi can be involved . Cephalosporine, aminobenzylpenicillin in combination with beta-lactamase inhibitor, alcylaminopenicillin and lincosamide are recommended based on analysis of infection resistance as first choice medications with carbapeneme as a reserve antibiotic. Immunology, 1999 Mar, 96(3), 465 - 72 Polyclonal expansion of TCRBV2- and TCRBV6-bearing T cells in patients with Kawasaki disease; Yoshioka T et al.; We examined T-cell receptor (TCR) usage, cytokine production and antibody responses to superantigens in patients with Kawasaki disease (KD) to facilitate a better understanding of the immunopathogenesis of KD . The mean percentage of VB2- or VB6 . 5-bearing T cells in peripheral blood mononuclear cells (PBMC) of patients with acute-phase KD was significantly higher than that of patients in the convalescent phase of KD or in healthy donors . Expansion of VB2- or VB6.5-bearing T cells was polyclonal because DNA sequences in the complementarity determining region 3 of VB2- and VB6.5-positive cDNA clones were all different from each other . The plasma levels of interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and granulocyte colony-stimulating factor (G-CSF) were elevated in the acute phase of KD . We previously reported that streptococcal pyrogenic exotoxin C (SPEC) was a potent stimulator of VB2- and VB6.5-positive T cells and, furthermore, serum levels of anti-SPEC antibodies were significantly higher in patients with acute and convalescent KD than in age-matched controls . The results of the present study, together with those of our previous report, suggest that SPEC induces activation and polyclonal expansion of VB2- and VB6.5-positive T cells, and that SPEC-induced activation of T cells may lead to the pathogenesis of KD. Lancet, 1999 May 1, 353(9163), 1509 - 15 Glomerulonephritis; Couser WG; The differential diagnosis of glomerulonephritis without systemic disease includes poststreptococcal glomerulonephritis, IgA nephropathy, rapidly progressive glomerulonephritis (RPGN), and membranoproliferative glomerulonephritis (MPGN) . Glomerular inflammation is probably induced directly by a nephritogenic streptococcal protein in poststreptococcal glomerulonephritis, and by mesangial deposition of abnormally glycosylated IgA1-containing immune aggregates in IgA nephropathy . In crescentic RPGN the role of cellular rather than humoral immune mechanisms is now becoming clear . Many patients with MPGN have chronic hepatitis C infection . There is no effective disease-specific therapy for poststreptococcal glomerulonephritis or IgA nephropathy . RPGN benefits from high-dose steroids and cytotoxic drug therapy with the addition of plasma exchange in disease induced by antibody to glomerular basement membrane . Antiviral therapies reduce the severity of MPGN due to hepatitis C virus . However, various new therapies directed at specific cytokines, growth factors, fibrin deposition, and other mediators of injury are being developed, as well as more specific and less toxic forms of immunotherapy. Pediatr Infect Dis J, 1999 Apr, 18(4), 327 - 32 Evaluating the use of penicillin to control outbreaks of acute poststreptococcal glomerulonephritis; Johnston F et al.; INTRODUCTION: Outbreaks of acute poststreptococcal glomerulonephritis (APSGN), occur every few years in remote Australian Aboriginal communities . Intervention with benzathine penicillin G (BPG) to all children is effective in reducing streptococcal carriage in a community, but its effectiveness in arresting outbreaks of APSGN has not been established . OBJECTIVE: To study nine recent community outbreaks of APSGN in Australia's Northern Territory and compare them with outbreaks reported in the literature to assess the impact of intervention with BPG . METHODS: Because randomized controlled trials have not been conducted for this purpose, we assessed data from published observational studies and relevant experiences in the Northern Territory (NT) . Eight of the nine outbreaks in the NT were studied prospectively . An outbreak was defined as two or more clinical cases of APSGN occurring within 1 week in a single community . Three intervention methods were used: intramuscular BPG to all children ages 3 to 15 years; BPG only to children with skin lesions; and BPG only to child contacts of clinical cases . The attack rates, number of clinical cases before and after the interventions were documented and the coverage of children with penicillin were estimated . RESULTS: A review of the literature found very little evidence either for or against the effectiveness of intervention with BPG . In our study four communities used the first method of intervention . The community with the lowest uptake of penicillin continued to have cases in untreated children for 9 further weeks, two communities had no new cases from 3 weeks after the intervention and the fourth had a single further case after 4 weeks . The one community that used the second method had a high initial attack rate but no further cases from 1 week after the intervention . Three communities used the third method and in one community no intervention was attempted . CONCLUSION: Our observational study supports the use of BPG in the community to prevent new cases of APSGN . It suggests that targeted treatment of children with skin sores and household contacts of cases, rather than attempted treatment of all children in the community, could be an effective method of intervention. Protein Sci, 1999 Jan, 8(1), 147 - 60 Mechanics and dynamics of B1 domain of protein G: role of packing and surface hydrophobic residues; Ceruso MA et al.; The structural organization of the B1 domain of streptococcal protein G (PGA) has been probed using molecular dynamics simulations, with a particular emphasis on the role of the solvent exposed Ile6 residue . In addition to the native protein (WT-PGA), three single-mutants (I6G-PGA, I6F-PGA, and I6T-PGA), one double-mutant (I6T,T53G-PGA), and three isolated peptide fragments (corresponding to the helix and the two beta-hairpins) were studied in the presence of explicit water molecules . Comparative analysis of the various systems showed that the level of perturbation was directly related to the hydrophobicity and the size of the side chain of residue 6, the internal rigidity of the proteins decreasing in the order I6T-PGA > I6G-PGA > WT-PGA > I6F-PGA . The results emphasized the importance of residue 6 in controlling both the integrity of the sheet's surface and the orientation of the helix in relation to the sheet by modulation of surface/core interactions . The effects of mutations were delocalized across the structure, and glycine residues, in particular, absorbed most of the introduced strain . A qualitative structural decomposition of the native fold into elementary building-blocks was achieved using principal component analysis and mechanical response matrices . Within this framework, internal motions of the protein were described as coordinated articulations of these structural units, mutations affecting mostly the amplitude of the motions rather than the structure/location of the building-blocks . Analysis of the isolated peptidic fragments suggested that packing did not play a determinant role in defining the elementary building-blocks, but that chain topology was mostly responsible. Infect Dis Clin North Am, 1999 Mar, 13(1), 227 - 43, viii Group A streptococcal vaccines; Dale JB; The pathogenesis of group A streptococcal infections, and antigens that contribute to protective immune responses are reviewed . Several approaches to vaccine development are discussed . Data are provided from preclinical studies of multivalent M protein-based vaccines that evoke protective antibodies in laboratory animals . Also discussed are future strategies for the development of broadly protective vaccines, and their potential impact on the incidence of streptococcal infections, and acute rheumatic fever. Postgrad Med J, 1998 Nov, 74(877), 673 - 4 Sudden death associated with group A streptococcal infection in an 8-year-old girl with undiagnosed hypertrophic cardiomyopathy; Bragonier R et al.; An 8-year-old girl died suddenly without prior symptoms . Post-mortem examination identified both systemic group A streptococcal infection and hypertrophic cardiomyopathy . She had no history of cardiac symptoms and was not in a high-risk group for sudden death due to hypertrophic cardiomyopathy . We believe the disseminated but asymptomatic group A streptococcal infection precipitated her early death from hypertrophic cardiomyopathy . Sudden unexpected death during systemic infection should be followed by post-mortem examination to look for evidence of hypertrophic cardiomyopathy, as this diagnosis has genetic implications for other family members. Ear Nose Throat J, 1999 Mar, 78(3), 155 - 8 A role for tonsillectomy in the treatment of psoriasis? McMillin BD, Maddern BR, Graham WR. Our objective was to determine whether tonsillectomy is beneficial in the treatment of recurrent childhood guttate psoriasis that is associated with recurrent streptococcal pharyngitis and tonsillitis . We retrospectively reviewed the cases of two children who were referred to our facility for treatment of repeated exacerbations of psoriasis and recurrent streptococcal pharyngotonsillitis . Both patients experienced a significant improvement in their psoriasis after undergoing adenotonsillectomy, and both were completely free of psoriatic outbreaks after 16 months of follow-up . We conclude that tonsillectomy appears to be of benefit in the treatment of children with recurrent guttate psoriasis and recurrent streptococcal pharyngotonsillitis, and we hope that further investigation will be undertaken. Pediatrics, 1999 Apr, 103(4 Pt 1), 703 - 10 Preventing neonatal group B streptococcal disease: cost-effectiveness in a health maintenance organization and the impact of delayed hospital discharge for newborns who received intrapartum antibiotics; Mohle-Boetani JC et al.; OBJECTIVES: To estimate the cost and health benefits of implementing a risk factor-based prevention strategy for early-onset neonatal group B streptococcal (GBS) disease, using baseline assumptions and costs from a health maintenance organization . With the risk factor-based strategy, intrapartum antibiotics (IPAs) would be provided to women with fever, prolonged rupture of membranes, or preterm labor . A second objective was to determine the impact of an increased length of stay for well term infants with mothers who received IPAs . METHODS: We used decision analysis to compare the costs and benefits of the prevention strategy with usual obstetric practice for a cohort of 100 000 women and their newborn infants . We derived baseline values from a previous study based on chart review and automated cost data from a health maintenance organization in Northern California . In sensitivity analyses, we varied baseline assumptions, including additional costs for observing well term infants who received IPAs . RESULTS: If adherence to guidelines were 100%, 17% of mothers would receive IPAs at a cost of $490,000; $1.6 million would be saved by preventing 66 GBS cases (64% reduction) . The net savings would be $1.1 million and 61 life-years . The net cost is sensitive to the cost of caring for well infants who received IPAs . If each term infant of a mother who received IPAs had 1 more day of observation than other term infants, there would be a net cost of $8.1 million; the cost per GBS case prevented would be $120,000 and the cost per life-year saved would be $130,000 . CONCLUSIONS: Implementation in a health maintenance organization of a risk factor-based strategy to prevent neonatal GBS disease can prevent substantial disease and be cost saving . However, if the length of hospital stay were extended among well term infants whose mothers received IPAs, the strategy would be relatively costly compared with other medical interventions. Pediatr Nephrol, 1999 Jan, 13(1), 39 - 44 Mycoplasma pneumoniae-associated nephritis in children; Said MH et al.; Mycoplasma pneumoniae infection is a rare cause of acute nephritis . Six children (2 girls) aged 5-10 years, admitted for nephritis, had serological tests showing recent Mycoplasma pneumoniae infection . The diagnosis of Mycoplasma pneumoniae infection was based on the presence of serum IgM, detected either by immunofluorescence (IF) (n = 1) or enzyme-linked immunosorbent assay (n = 5) . Four children had a renal biopsy, with analysis of parenchymal Mycoplasma pneumoniae components by indirect IF and polymerase chain reaction . Extrarenal symptoms were: respiratory (n = 3), ear, nose and throat (n = 2), gastrointestinal (n = 3), hepatic (n = 1), neurological (n = 1), articular (n = 1), and hematological (n = 3) . The patients presented with acute nephritis (1 had a nephrotic syndrome) or with acute renal failure and proteinuria . Pathological findings included type 1 membranoproliferative glomerulonephritis (MPGN, n = 1), proliferative endocapillary glomerulonephritis (n = 2) and minimal change disease (n = 1) . The patient with type 1 MPGN progressed rapidly towards end-stage renal failure because of a congenital solitary kidney . Among the patients with endocapillary glomerulonephritis, 1 relapsed 6 months later and remained proteinuric, while the other recovered, as did the child with minimal change disease . The search for Mycoplasma pneumoniae antigens and nucleic acids in renal tissue was negative . However, the absence of the microorganism in the kidney is a common feature of post-streptococcal glomerulonephritis . We conclude that Mycoplasma pneumoniae is a rare yet potential cause of acute glomerulonephritis. Epidemiol Infect, 1999 Feb, 122(1), 67 - 75 Proteinuria is associated with persistence of antibody to streptococcal M protein in Aboriginal Australians; Goodfellow AM et al.; Aboriginal communities in Northern Australia with high rates of group A streptococcal (GAS) skin infection in childhood also have high rates of renal failure in adult life . In a cross-sectional study of one such high risk community, albuminuria was used as a marker of renal disease . The prevalence of albuminuria increased from 0/52 in subjects aged 10-19 years to 10/29 (32.9%) in those aged 50 or more (P < 0.001) . Antibodies to streptococcal M protein, markers of past GAS infection, were present in 48/52 (92%) at ages 10-19 years, 16/32 (50%) at ages 30-39, and 20/29 (69%) in those aged 50 or more . After allowing for the age-dependencies of albuminuria and of M protein antibodies (P < 0.001) albuminuria was significantly associated with M protein antibodies (P < 0.01) . Thus, 72% of adults aged 30 or more with M protein antibodies also had albuminuria, compared with only 21% of those who were seronegative . More detailed modelling suggested that although most Aboriginal people in this community developed M protein antibodies following GAS infection in childhood, the development of proteinuria was associated with the persistence of such seropositivity into adult life . The models predicted that proteinuria developed at a mean age of 30 years in seropositive persons, at 45 years in seronegative persons who were overweight, and at 62 years in seronegative persons of normal weight . We demonstrated a clear association between evidence of childhood GAS infection and individual risk of proteinuria in adult life . This study provided a strong rationale for prevention of renal disease through the more effective control of GAS skin infections in childhood and through the prevention of obesity in adult life. Epidemiol Infect, 1999 Feb, 122(1), 59 - 65 Clinical and epidemiological features of group A streptococcal bacteraemia in a region with hyperendemic superficial streptococcal infection; Carapetis JR et al.; Reports of increasing incidence and severity of invasive group A streptococcal (GAS) infections come mainly from affluent populations where exposure to GAS is relatively infrequent . We conducted a 6-year retrospective review of GAS bacteraemia in the Northern Territory of Australia, comparing the Aboriginal population (24% of the study population), who have high rates of other streptococcal infections and sequelae, to the non-Aboriginal population . Of 72 episodes, 44 (61%) were in Aboriginal patients . All 12 cases in children were Aboriginal . Risk factors were implicated in 82% of episodes (91% in adults) and there was no significant difference in the proportion of Aboriginal compared to non-Aboriginal patients with at least one risk factor . Genetic typing of isolates revealed no dominant strains and no evidence of a clone which has been a common cause of these infections elsewhere. Scand J Rheumatol, 1999, 28(1), 27 - 32 Clinical and biological characteristics of immunopathological disease-related erythema nodosum in children; Picco P et al.; We report a series of 22 children with idiopathic, drug unrelated erythema nodosum (EN) admitted to our Department . In 5 of them an history of streptococcal pharyngitis was referred; the remaining patients came to us with a diagnosis of "EN of unknown origin" . Acute phase reactants, immunoglobulins, stool alpha1 antitrypsin, ANA, anti dsDNA antibodies and ANCA assay, chest roentgenogram, tuberculin test, and ophthalmologic assessment were performed in all patients . Etiologic diagnosis was made in 16 patients: Streptococcal pharyngitis (5 cases), chronic inflammatory bowel disease, IBD (3 cases), Behcet syndrome (2 cases), Yersinia enteritis (2 cases), infectious mononucleosis, atypical mycobacterial infection, immunodeficiency related infection, and SLE-like syndrome due to C4 deficiency (1 case each).We found oral/scrotal aphthae in 3 cases, gastrointestinal symptoms in 5 cases, arthritis in 3 cases . Acute phase reactants were positive in 16 patients without correlation to the underlying disease . Conversely, the increased alpha1 antitrypsin stool excretion and IgA serum concentration seemed to represent helpful indicators of IBD and Behcet syndrome, respectively . Proinflammatory cytokine pattern showed increased IL6 serum concentrations both in infectious and in non infectious disease-related EN, whereas a minor involvement of TNF was found in these patients. Arch Dis Child, 1999 Apr, 80(4), 353 - 8 Rheumatic chorea in northern Australia: a clinical and epidemiological study; Carapetis JR et al.; To describe the epidemiology and clinical features of Sydenham's chorea in the Aboriginal population of northern Australia a review was conducted of 158 episodes in 108 people: 106 were Aborigines, 79 were female, and the mean age was 10.9 years at first episode . Chorea occurred in 28% of cases of acute rheumatic fever, carditis occurred in 25% of episodes of chorea, and arthritis in 8% . Patients with carditis or arthritis tended to have raised acute phase reactants and streptococcal serology . Two episodes lasted at least 30 months . Mean time to first recurrence of chorea was 2.1 years compared with 1.2 years to second recurrence . Established rheumatic heart disease developed in 58% of cases and was more likely in those presenting with acute carditis, although most people who developed rheumatic heart disease did not have evidence of acute carditis with chorea . Differences in the patterns of chorea and other manifestations of acute rheumatic fever in different populations may hold clues to its pathogenesis . Long term adherence to secondary prophylaxis is crucial following all episodes of acute rheumatic fever, including chorea, to prevent recurrence. Postgrad Med, 1999 Mar, 105(3), 229 - 32 A palpable clue to vasculitis; Arvan ME et al.; A 57-year-old woman presented with a rash on her legs that had recurred several times over the last 2 weeks . Initial treatment had consisted of prednisone, 30 mg/day, for 5 days, but the rash had recurred when therapy was discontinued . Laboratory findings at that time revealed an elevated antistreptolysin O titer, but a complete blood cell (CBC) count, electrolyte levels, erythrocyte sedimentation rate (ESR), and complement fixation test all were normal . The patient was subsequently given amoxicillin, which she discontinued after a few days when the rash worsened . Findings on physical examination were normal except for a palpable purpuric rash on the lower legs (figure 1) . A 4-mm punch biopsy was performed, and histopathologic examination confirmed a diagnosis of leukocytoclastic vasculitis . The patient was given prednisone, 60 mg/day orally, tapered over 2 weeks . Erythromycin was also prescribed for the possible persistence of a streptococcal carrier state . The rash cleared within 2 to 3 weeks, with no recurrence during the following year. J Infect Dis, 1999 Mar, 179 Suppl 2, S366 - 74 The flesh-eating bacterium: what's next? Stevens DL. Since the 1980s, there has been a marked increase in the recognition and reporting of highly invasive group A streptococcal (GAS) infections associated with shock and organ failure, with or without necrotizing fasciitis . Such dramatic cases have been defined as streptococcal toxic shock syndrome (StrepTSS) . Strains of GAS isolated from patients with invasive disease have been predominantly M types 1 and 3, which produce either pyrogenic exotoxin A or B or both . The clinical and demographic features of streptococcal bacteremia, myositis, and necrotizing fasciitis are presented and compared with those of StrepTSS . Current concepts in the pathogenesis of invasive streptococcal infection will be presented, with emphasis on the interaction between GAS virulence factors and host defense mechanisms . Finally, new concepts in the treatment of StrepTSS will be discussed. Adv Pediatr Infect Dis, 1999, 14, 129 - 45 Invasive group A streptococcal infections in children; Davies HD et al.; Invasive group A streptococcal infections and STSS have increased as causes of morbidity and mortality among children and adults . In children, respiratory foci appear to be the most common, but skin and soft tissue infection, particularly associated with varicella, also are common . Early diagnosis requires awareness of the presenting features and a high index of suspicion . Antimicrobial therapy that includes clindamycin, therapy with IVIG for those with STSS, and surgical intervention for patients with necrotizing fasciitis may improve outcome . Chemoprophylaxis should be considered among household contacts of patients with severe group A streptococcal disease in high-risk settings . Further studies are ongoing to evaluate the hypothesized link of invasive group A streptococcal infection in children with varicella and NSAID use, to better clarify the pathogenesis of STSS and necrotizing fasciitis, and to better document the risk of secondary spread among close contacts of case patients. Biochemistry, 1999 Mar 16, 38(11), 3228 - 34 Fragment reconstitution of a small protein: disulfide mutant of a short C-terminal fragment derived from streptococcal protein G; Kobayashi N et al.; Hierarchical studies on the folding of protein G B1 domain have shown that the C-terminal fragment (C16) has a considerable amount of beta-hairpin structure that exchanges between the folded and unfolded states at room temperature, and that the C16 fragment binds noncovalently to an N-terminal fragment (N40) under physiological conditions . Those studies have led us to the hypothesis that the amphipathic beta-hairpin structure of C16 initiates folding of the domain . To obtain a more detailed understanding of the folding mechanism of the domain, we designed a mutant of C16 (SS16ox) with a disulfide bond between residues 41 and 56, and then examined the interaction of the mutant with N40 by surface plasmon resonance (SPR) and by thermal denaturation studies using circular dichroism . SS16ox strongly interacted with N40, with an equilibrium constant, KD, that was 7-fold higher than wild-type . The association rate constant, kon, of SS16ox was 8.7-fold higher than that of wild-type . This strong interaction can be explained by the entropic effect of the disulfide bond . The introduction of the disulfide bond into C16 stabilizes the beta-hairpin structure of C16, accelerates the association rate with N40, and then stabilizes the whole complex . These results support a hypothetical folding mechanism of protein G where the amphipathic beta-hairpin structure of C16 acts as a nucleus and accelerates folding of the whole molecule. Vaccine, 1999 Feb 5, 17(5), 406 - 14 The serum albumin-binding region of streptococcal protein G (BB) potentiates the immunogenicity of the G130-230 RSV-A protein; Libon C et al.; BBG2Na is a protein comprising residues 130-230 of the respiratory syncytial virus subgroup A (RSV-A) G protein (G2Na) fused to the albumin-binding domain of streptococcal G protein (BB) . BBG2Na was cloned, expressed in Escherichia coli and renaturated . In rodent models, this subunit RSV vaccine adjuvanted in Alhydrogel induced specific antibodies and conferred protection to RSV infection . Comparison of the antibody production in a BALB/c mouse model revealed that BBG2Na induced a stronger and earlier G2Na antibody response than G2Na alone, without altering the IgG subclass distribution . To address the role of the BB part, we explored its carrier properties and showed that it is a Th dependent antigen, generating a more potent G2Na-specific B cell memory response and able to generate Th cells that provide help for G2Na antibody production. Clin Obstet Gynecol, 1999 Mar, 42(1), 59 - 70; quiz 174-5 Diagnosis of perinatal TORCH infections; Newton ER; Collectively, TORCH infections create more neonatal morbidity than early-onset group B streptococcal sepsis . Fortunately, the incidence of maternal infection by CMV or toxoplasmosis is low (2-10 per 1,000 births) . There have been tremendous advances in direct antigen testing and in the sensitivity and specificity of IgG and IgM testing . Consistently, research laboratories show more accurate results than in the past . Unfortunately, commercial laboratories are using older, single-kit testing . The relatively poor degree of reliability can lead to unnecessary obstetric intervention or elective termination . Any positive pathogen-specific IgM on maternal serum should have additional confirmatory testing in a reputable research laboratory before any intervention . Direct antigen testing or multiple testing would seem to be appropriate for confirmation . This may include amniocentesis of fetal blood sampling . The research on the newer tests is based of the evaluation of blood from seriously immunocompromised subjects . Extrapolations of test accuracy to similar tests on healthy, pregnant women and their fetuses are likely to be in error . The application of these accurate tests to the obstetric population is a critical research need. Ned Tijdschr Geneeskd, 1998 Dec 19, 142(51), 2789 - 92 {Chorea subsequent to acute rheumatic fever in a 9-year-old girl}; Scheurer CD et al.; A nine-year-old girl had acute choreatic symptoms in her face and limbs, after a throat infection 6 weeks previously . On auscultation of the heart a systolic murmur was found and echocardiography showed mitral valve incompetence . There was a positive anti-deoxyribonuclease B titre in the serum, providing evidence of a previously contracted streptococcal infection . Both chorea and acquired carditis are major criteria for the diagnosis of acute rheumatic fever . The course was characterized--as it usually is--by spontaneous, gradual resolution of the symptoms . Protracted penicillin prophylaxis is indicated to prevent recurrence of acute rheumatic fever and cardiac valvular damage. Cytokine, 1998 Dec, 10(12), 940 - 7 The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes; Zinetti M et al.; Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family . Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated . The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells . Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A) . Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation . Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression . The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha . Clin Infect Dis, 1999 Jan, 28(1), 123 - 9 Lymphadenitis due to nontuberculous mycobacteria in children: presentation and response to therapy; Hazra R et al.; The most common manifestation of infection due to nontuberculous mycobacteria (NTM) in children is cervical lymphadenitis in an otherwise healthy patient . We identified and reviewed 19 cases of proven or presumptive lymphadenitis due to NTM seen at our hospital over the course of 13 months . Nine patients underwent initial surgical excision of involved lymph nodes . Ten children did not have involved lymph nodes excised initially and were treated with macrolide-containing antibiotic regimens . Of these patients, five required subsequent surgical excision and five were cured with combination chemotherapy . Six patients underwent radiographic imaging of the head and neck that revealed asymmetrical adenopathy with ring-enhancing masses but minimal inflammatory stranding of the subcutaneous fat, a finding that may distinguish adenitis caused by NTM from staphylococcal and streptococcal adenitis . Our data suggest that if surgical excision is not considered feasible, antimicrobial therapy for adenitis due to NTM may be beneficial for some patients. Infect Immun, 1999 Mar, 67(3), 1086 - 92 The staphylococcal transferrin-binding protein is a cell wall glyceraldehyde-3-phosphate dehydrogenase; Modun B et al.; Staphylococcus aureus and Staphylococcus epidermidis possess a 42-kDa cell wall transferrin-binding protein (Tpn) which is involved in the acquisition of transferrin-bound iron . To characterize this protein further, cell wall fractions were subjected to two-dimensional sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis blotted, and the N-terminus of Tpn was sequenced . Comparison of the first 20 amino acid residues of Tpn with the protein databases revealed a high degree of homology to the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) . Analysis of staphylococcal cell wall fractions for GAPDH activity confirmed the presence of a functional enzyme which, like Tpn, is regulated by the availability of iron in the growth medium . To determine whether Tpn is responsible for this GAPDH activity, it was affinity purified with NAD+ agarose . Both S . epidermidis and S . aureus Tpn catalyzed the conversion of glyceraldehyde-3-phosphate to 1,3-diphosphoglycerate . In contrast, Staphylococcus saprophyticus, which lacks a Tpn, has no cell wall-associated GAPDH activity . Native polyacrylamide gel electrophoresis of the affinity-purified Tpn revealed that it was present in the cell wall as a tetramer, consistent with the structures of all known cytoplasmic GAPDHs . Furthermore, the affinity-purified Tpn retained its ability to bind human transferrin both in its native tetrameric and SDS-denatured monomeric forms . Apart from interacting with human transferrin, Tpn, in common with the group A streptococcal cell wall GAPDH, binds human plasmin . Tpn-bound plasmin is enzymatically active and therefore may contribute to the ability of staphylococci to penetrate tissues during infections . These studies demonstrate that the staphylococcal transferrin receptor protein, Tpn, is a multifunctional cell wall GAPDH. Am J Psychiatry, 1999 Feb, 156(2), 317 - 20 B lymphocyte antigen D8/17 and repetitive behaviors in autism; Hollander E et al.; OBJECTIVE: Monoclonal antibody D8/17 identifies a B lymphocyte antigen with expanded expression in rheumatic fever, Sydenham's chorea, and subgroups of obsessive-compulsive disorder and Tourette's syndrome with repetitive behaviors . The authors examined the rate of D8/17 expression in children with autism and its correlation with severity of repetitive behaviors . METHOD: Blood samples from 18 patients with autism and 14 comparable medically ill children were evaluated for percentage of D8/17-positive B cells by immunofluorescence and for streptococcal antibodies . Severity of repetitive behaviors was also determined . RESULTS: The frequency of individuals with > or =11% D8/17-positive cells was significantly higher in the autistic patients (78%) than the comparison subjects (21%), severity of repetitive behaviors significantly correlated with D8/17 expression, and D8/17-positive patients had significantly higher compulsion scores than D8/17-negative patients . CONCLUSIONS: D8/17 expression is high in patients with autism and may serve as a marker for compulsion severity within autism. Am J Obstet Gynecol, 1999 Feb, 180(2 Pt 1), 416 - 22 Maternal and neonatal infection rates with three different protocols for prevention of group B streptococcal disease; Locksmith GJ et al.; OBJECTIVES: We compared maternal and neonatal infection rates under 3 different group B streptococcal prevention strategies and also evaluated reasons for each protocol's failures in preventing neonatal disease . STUDY DESIGN: Women who were delivered at our center from August 1, 1991, through April 30, 1998, were managed by 1 of 3 protocols for prevention of early-onset neonatal group B streptococcal infection: a selective screening protocol, The American College of Obstetricians and Gynecologists protocol, and the Centers for Disease Control and Prevention-recommended universal screening strategy . We compared maternal infection rates and neonatal group B streptococcal infection rates under each protocol . We also compared reasons for each protocol's failures in preventing neonatal infection . RESULTS: Clinical chorioamnionitis rates were 7.4% with selective screening, 7.7% under The American College of Obstetricians and Gynecologists' protocol, and 5.2% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8) . Endometritis rates were 4.0% with selective screening, 4.6% with The American College of Obstetricians and Gynecologists protocol, and 2 . 8% with universal screening (relative risk 0.7, 95% confidence interval 0.6-0.8) . Overall neonatal group B streptococcal infection rates were lower under the 2 more recent strategies, but not significantly so . Despite the ability of universal screening to find more women at risk for group B streptococcal transmission, half of the neonatal infections under this protocol occurred when the mothers were not considered candidates for prophylaxis . CONCLUSIONS: The Centers for Disease Control and Prevention-endorsed universal screening strategy for group B streptococcal infection prevention was associated with significantly lower rates of clinical chorioamnionitis and endometritis than were the other strategies . We were unable to document statistically significant improvement in neonatal outcome under the universal screening protocol. Biochemistry, 1999 Jan 26, 38(4), 1203 - 13 Fragment reconstitution of a small protein: folding energetics of the reconstituted immunoglobulin binding domain B1 of streptococcal protein G; Honda S et al.; To elucidate early stages in protein folding, we have adopted a fragment reconstitution method for small proteins . This approach is expected to provide nuclei for protein folding and to allow us to investigate folding mechanisms . In previous work {Kobayashi, N., et al . (1995) FEBS Lett . 366, 99-103.} we demonstrated the association of two complementary fragments, derived from the immunoglobulin G-binding domain B1 of streptococcal Protein G, and showed the structural similarity between the reconstituted domain and the uncleaved wild-type domain . In this work we have further characterized the reconstituted domain as well as the uncleaved domain thermodynamically by means of differential scanning calorimetry (DSC) and circular dichroism (CD) measurements . Although composed of short peptide fragments not linked by covalent bonds, the reconstituted domain showed a typical folding/unfolding curve in both DSC and CD melting measurements and behaved like a globular protein . The domain was not very stable, and the small value of the Gibbs free energy corresponded to the class of the weakest protein-protein binding systems . The denaturation temperature of 0 . 78 mM solution was 313 K at pH 5.9 as measured by DSC, which was more than 40 degrees lower than the uncleaved domain . This apparent instability was primarily caused by entropic disadvantage attributed to a bimolecular reaction . The temperature dependence of the enthalpy change from the folded to the unfolded state was almost identical for the reconstituted domain and the uncleaved one . This indicates that most of the noncovalent intramolecular interactions stabilizing the native structure, such as hydrogen bonding and hydrophobic interactions, are regenerated in the reconstituted domain . By comparing the equilibrium constants of the reconstituted and uncleaved domains, we determined the effective concentration to be approximately 6 M at 298 K . Structure-based estimation of the thermodynamic properties from the values of accessible surface areas showed that approximately 35% of the total heat capacity change and approximately 25% of the total enthalpy change can be attributed to the interchain interaction at 298 K . Furthermore, the folding/unfolding equilibrium of beta-hairpin structure of the fragment 41-56 alone was also characterized . These analyses allow us to envision the microdomain folding mechanism of the Protein G B1 domain, in which segment 41-56 first forms a stable beta-hairpin structure and then collides with segment 1-40, followed by spontaneous folding of the whole molecule. Acad Emerg Med, 1999 Jan, 6(1), 8 - 13 Multivariate predictive models for group A beta-hemolytic streptococcal pharyngitis in children; Attia M et al.; OBJECTIVES: To create predictive models for the clinical diagnosis of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children . METHODS: Patients aged 6 months to 18 years presenting to a pediatric ED with suspected GABHS pharyngitis were prospectively enrolled in the study . Clinicians recorded pertinent clinical information using a standardized form and obtained a throat swab to culture GABHS using a reference standard method . Twelve demographic and clinical features of patients with positive throat cultures were compared with the features of patients with negative throat cultures . Significantly different features were entered in a stepwise logistic regression analysis to create predictive models for the diagnosis . RESULTS: Eighty-five patients (29%) were culture-positive and 212 (71%) were culture-negative for GABHS . Respective mean ages were 6.2 years and 6.1 years in the two groups . Univariate chi-square analysis of the 12 features identified six variables that were significantly associated with GABHS . All significant features were initially included in a stepwise logistic regression analysis . In model I, four independent variables were identified: moderate to severe presentation of tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, the presence of scarlatiniform rash, and the absence of moderate to severe coryza, yielding a 95% probability for GABHS . Excluding the rare scarlatiniform rash, the remaining variables were used in the second regression analysis . In model II, three independent variables were identified: moderate to severe tonsillar swelling, moderate to severe tenderness and enlargement of cervical lymph nodes, and absence of moderate to severe coryza, yielding a probability of 65% for the diagnosis . A probability of <15% was observed in the absence of scarlatiniform rash, the absence of moderate to severe tenderness and enlargement of cervical lymph nodes, and the presence of moderate to severe coryza . CONCLUSIONS: In children with moderate to severe presentation of tonsillar swelling, tenderness and enlargement of cervical lymph nodes, and the absence of coryza, the probability of a positive throat culture is >65% . Conversely, in the absence of a moderate to severe presentation of tonsillar swelling, enlargement of cervical nodes, and the presence of coryza, the probability of a positive throat culture is <15% . If prospectively validated, these models could be integrated into a consistent treat, test, and no treatment/no testing approach to the clinical management of childhood pharyngitis. Am J Epidemiol, 1999 Feb 1, 149(3), 282 - 9 Accuracy of ICD-9-CM codes in detecting community-acquired pneumococcal pneumonia for incidence and vaccine efficacy studies; Guevara RE et al.; Studies have used medical record discharge data as coded by the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) to estimate pneumococcal pneumonia incidence and vaccine efficacy . However, the accuracy of coding data to identify laboratory-confirmed pneumococcal pneumonia is not known . With the use of information collected in Ohio for a community-based pneumonia incidence study, the authors calculated the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) of specific codes for pneumococcal pneumonia among hospitalized patients with community-acquired pneumonia . Sensitivities of the most common ICD-9-CM codes listed in the first five positions for patients with laboratory-confirmed pneumococcal pneumonia were 58.3% (code 481.0, pneumococcal pneumonia), 20.4% (38.0, streptococcal septicemia), 19.2% (38.2, pneumococcal septicemia), 15.0% (518.81, respiratory failure), 14.2% (486.0, pneumonia, organism unspecified), and 11.3% (482.3, streptococcal pneumonia) . Using the first five listed ICD-9-CM codes rather than just the first listed code increased sensitivity without causing substantial change in specificity, PPV, and NPV . Sensitivity, PPV, and NPV of individual and groups of codes varied with different case definitions of pneumococcal pneumonia . Incidence and vaccine efficacy studies with the ability to validate diagnoses by medical chart review can use a combination of many ICD-9-CM codes to maximize sensitivity . However, without the ability to review medical charts, researchers must carefully decide which codes would best suit their studies. Mediators Inflamm, 1998, 7(6), 381 - 9 Perpetuation of inflammation associated with experimental arthritis: the role of macrophage activation by neutrophilic myeloperoxidase; Gelderman MP et al.; Rheumatoid arthritis (RA) is characterized by an abnormal cellular and cytokine infiltration of inflamed joints . This study addresses a previously unrecognized interaction between neutrophilic-myeloperoxidase (MPO) and macrophages (Mphi) which could explain the perpetuation of inflammation associated with RA . A monoarticular arthritis was induced in female Lewis rats by injection of streptococcal cell wall extracts (PG-APS) . After swelling and erythema subsided, joints were re-injected with one of the following: porcine MPO or partially inactivated MPO (iMPO) . Injection with either MPO or iMPO induced a 'flare' of experimental RA . Blocking the Mphi-mannose receptor by mannans, ablated exacerbation of disease . These results indicate that MPO or iMPO can play a pivotal role in the perpetuation but not initiation of this RA model. Psychiatry Res, 1998 Dec 14, 81(3), 371 - 80 Serologic survey of adult patients with obsessive-compulsive disorder for neuron-specific and other autoantibodies; Black JL et al.; A subset of patients with pediatric onset obsessive-compulsive disorder (OCD) and tic syndromes (e.g . Tourette's syndrome) have symptom onset or exacerbation associated with infection . Some of these patients have been demonstrated to have antineuronal antibodies reactive with nuclei of the basal ganglion . It has been hypothesized that these patients have an immune process initiated by infection that affects the basal ganglion and causes obsessive-compulsive symptoms . The term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) has been coined to describe those patients with evidence of recent group A beta hemolytic streptococcal infection . We tested the serum from 13 adult patients with obsessive-compulsive disorder for panels of autoantibodies that serve as markers of autoimmunity in the practice of neurology and internal medicine . We investigated the frequency of neuron-specific autoantibodies {N-type and P/Q-type voltage-gated calcium channel antibodies, type 1 Purkinje cell antibodies, types 1 and 2 antineuronal nuclear antibodies, amphiphysin antibodies, and glutamic acid decarboxylase (65 kDa) antibodies}, other organ-specific autoantibodies (muscle acetylcholine receptor-binding antibodies, striated muscle antibodies, thyroid microsomal and thyroglobulin antibodies), and non-organ-specific autoantibodies (antinuclear antibodies, antimitochondrial antibodies, and smooth muscle antibodies) to determine if any of these antibodies might serve as a serological marker for adult OCD or yield evidence of an autoimmune diathesis . Although most of our subjects had onset of OCD before 19 years of age (N=8) or before puberty (N=4), the study revealed no humoral evidence of autoimmunity involving the neuron-, organ-, and non-organ-specific antibodies that we assayed. J Immunother, 1999 Jan, 22(1), 33 - 40 Effects of OK-432 on the proliferation and cytotoxicity of lymphokine-activated killer (LAK) cells; Yamamoto K et al.; We studied the effect of a streptococcal preparation, OK-432, on the cytotoxicity and the proliferation of lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy . Peripheral blood mononuclear cells (PBMC) were derived from healthy donors and patients with malignant brain tumors . We divided PBMC into two groups; these cells then were stimulated with interleukin-2 in the presence or absence of OK-432 . OK-432 was added only in the initial 3 days during the 3-week midterm culture period . Then, we compared OK-432-stimulated LAK (OK-LAK) cells with standard LAK (sLAK) cells in terms of their rate of proliferation and cytotoxicity . OK-LAK cells proliferated more rapidly than sLAK cells . The cytotoxicity of OK-LAK cells increased, whereas that of sLAK cells decreased . We also investigated the phenotypic differences between these two types of LAK cells and found that, on day 21, the OK-LAK cells consisted mostly of CD3-CD56+ NK cells, whereas the sLAK cells consisted mostly of CD3+CD56- T cells . The difference in their level of cytotoxic potential might be explained by the difference of predominant phenotype. Pathol Biol (Paris), 1998 Dec, 46(10), 802 - 12 {Acute articular rheumatism in the child in 1997}; Olivier C; Nine cases of rheumatic fever were seen from 1982 to 1996 . The diagnosis was based on Jones criteria . Four of eight children had carditis characterized by mitral regurgitation with or without aortic regurgitation and/or atrioventricular conduction disturbances . The outcome was favorable in all the patients who had carditis initially; one of the patients without initial carditis developed permanent cardiac lesions during a recurrence with carditis . In industrialized countries, the incidence of rheumatic fever declined starting early in the XXth century, then dropped sharply after World War II, and is now extraordinarily low (mean annual incidence, 0.5/100,000 schoolage children) . In developing countries, by contrast, rheumatic fever was recognized only after World War II and remains endemic (mean annual incidence, 100 to 200/100,000 schoolage children), contributing a substantial proportion of cases of cardiovascular disease . The diagnosis is difficult and rests on clinical grounds since there is no specific laboratory test . Diagnostic delays are potentially serious . Acute attacks should be managed as therapeutic emergencies . Prevention of recurrences rests on long-term antimicrobial therapy . Rheumatic fever is a disease process resulting from an inappropriate immune response to pharyngitis due to a beta-hemolytic group A streptotoccus (BHAS) . A low standard of living may be a factor in developing countries but fails to explain the epidemic flares seen in these areas or the residual background incidence in industrialized countries . A role of host-related susceptibility to the disease has not been demonstrated . The type-specific surface M protein, the main factor associated with high virulence, carries a specific epitope on its distal portion . Rheumatogenic strains have been identified; most produce mucoid colonies . At a given point in time, within a given serotype, the virulence of a specific strain increases . Temporal and spatial variations of observed types contribute additional complexity . Adhesion of the organisms is followed by release of streptococcal degradation products that share antigenic determinants with human tissues including the heart, the synovium, and the neurons . The hyaluronate capsule and M protein of the organisms are capable of initiating immune responses; their presentation to CD4+ T-cells results in lymphokine production, an acute phase humoral response, and a cell-mediated response potentially responsible for permanent valvular damage . In France, the standard of care is to prescribe antimicrobial therapy to all patients with pharyngitis or tonsillitis without performing tests to identify the causative agent . The introduction of tests for the rapid recognition in routine clinical practice of BHAS, which account for only 20 to 30% of all cases of pharyngitis and tonsillitis, should allow a more rational approach to the treatment of these infections . Reserving antimicrobial therapy to those patients with BHAS should not result in an increase in the incidence or rheumatic fever. Heart, 1999 Feb, 81(2), 177 - 81 Comparison of long term outcome in patients with or without aortic ring abscess treated surgically for aortic valve infective endocarditis; Danchin N et al.; OBJECTIVE: To assess the long term prognostic significance of aortic valve ring abscess in patients with aortic endocarditis . PATIENTS: A consecutive series of 75 patients who had surgery for aortic infective endocarditis between 1981 and 1989; 35 had aortic ring abscesses (group 1) and 40 did not (group 2) . Mean age did not differ between the two groups . Prosthetic valve endocarditis was present in 17% of group 1 and 5% of group 2 . Pneumococcal or beta haemolytic streptococcal endocarditis was more common in patients with native valve endocarditis who had aortic ring abscesses (20% v 5%) . DESIGN: Cohort analysis . RESULTS: In-hospital mortality (11.4% v 7.5%) and 10 year survival (56% v 66%) were not significantly different between groups 1 and 2 . In patients with native valve endocarditis, 10 year survival was 62% and 66%, respectively for patients with or without ring abscess, and 10 year reintervention-free survival was 38% v 58% (p = 0.11) . In these patients, the presence of an intercurrent illness, severe congestive heart failure before surgery, and use of valved conduits for surgical treatment were predictors of poorer long term survival . At follow up residual aortic regurgitation was documented in 72% of patients in group 1 and 26% in group 2 (p < 0.01) . CONCLUSIONS: Aortic valve ring abscess is not an independent marker of poor long term outcome in patients with infective endocarditis . However, as residual aortic regurgitation appears frequent at follow up, specific surgical techniques should be considered in patients with paravalvar abscesses. Eur J Dermatol, 1999 Jan-Feb, 9(1), 17 - 21 Peripheral blood mononuclear cell proliferative response against staphylococcal superantigens in patients with psoriasis arthropathy; Yamamoto T et al.; It has been recently hypothesized that superantigens play a precipitating or aggravating role in psoriasis . Aside from streptococcal infection, Staphylococcus aureus can be sometimes detected in the tonsils of patients with psoriasis arthropathy (PA), although its significance in the pathogenesis of PA is still unknown . These focal infections are thought to be a possible triggering factor of the arthralgia, as well as the cutaneous manifestations, in PA . In this study, we have investigated the response of peripheral blood mononuclear cells (PBMC) from patients with PA to staphylococcal superantigens and analyzed its association with clinical and laboratory findings . 3H-TdR uptake by PBMC was examined after 7 days' culture with concanavalin A (Con A), staphylococcal enterotoxin A (SEA), SEB and SEC1 . Results showed that there was no significant difference in either the unstimulated or Con A-stimulated PBMC response between psoriasis vulgaris patients (PASI score < 10) (n = 15), PA patients (n = 11) and normal controls (n = 19) . Among 11 PA patients, 8 patients responded most intensely to SEB, while 2 patients showed the strongest response to SEA, and another responded mainly to SEC1 . The PBMC response against SEB in patients with PA (38,715 719 dpm, stimulation index (SI); 50.2 41.4) (mean SD) was significantly higher than that in normal controls (23,708 466 dpm, SI; 30.9 23.8) (p < 0.05), however, the difference between that of patients with PA and psoriasis vulgaris (33,428 467 dpm, SI; 42.8 30.6) did not reach significance . In addition, PBMC from psoriatic patients with a short episode of severe, disabling lumbago, which occured following sudden onset throat soreness, showed a stronger response against SEB (SI; 73.7 39.7), as compared with that of PA patients without such an episode (SI; 42.6 18.1) . However this difference did not reach significance . Several immune abnormalities, including positive antinuclear antibodies or rheumatoid factor were observed mainly in the group experiencing such an episode of severe lumbago . Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that predominant expression of the T cell receptor (TCR) Vbeta 17 was commonly detected in both synovial tissues and paired peripheral bloods in two cases examined . In one case, Vbeta 12 was preferentially expressed, and in another case, Vbeta 10, 15 and 19 were also strongly expressed in the infiltrating lymphocytes in the synovial tissues . Our data raised the possibility that staphylococcal superantigens may also play an exacerbating role in PA. J Immunol Methods, 1998 Dec 1, 221(1-2), 95 - 106 Indirect immobilization of recombinant proteins to a solid phase using the albumin binding domain of streptococcal protein G and immobilized albumin; Baumann S et al.; Immobilization of proteins to a solid phase leads to denaturation of the adsorbed molecules which may subsequently affect biological interactions . However, for many applications maintenance of the native structure is desired . Therefore, an indirect immobilization system was developed, based on binding of the albumin binding domain (ABP) of streptococcal protein G to rat serum albumin (RSA) precoated on a solid phase (RSA-microtiter plates) . Escherichia coli vectors were adapted for production of recombinant protein fused to ABP and the 6 X His-tag . The expressed ABP tag was found to form homodimers . Plasmon resonance was used to study the interaction between an ABP fusion protein and immobilized RSA . Apparent on- and off-rates were calculated using a model for a bivalent analyte (k(a1) = 3.37 x 10(4) M(-1) s(-1), k(d1) = 1.23 x 10(-4) s(-1)) . Thus, the stability of the ABP-RSA interaction can be explained by a slow off-rate . This was confirmed by chase experiments in an ELISA format . The ABP-RSA interaction remained stable after addition of different albumins . This immobilization system was used for the development of an ELISA to detect antibodies against Borna disease virus protein p40 . The use of RSA-microtiter plates for indirect immobilization of ABP fusion protein was shown to be superior to direct adsorption on plastic . To obtain maximal antibody binding ten times less antigen was needed for indirect immobilization compared to direct adsorption . The binding capacity of the RSA-microtiter plates was determined to be about 0.8 pmol of monomeric ABP protein. Aust N Z J Obstet Gynaecol, 1998 Nov, 38(4), 418 - 23 Group B Streptococcal septicaemia/meningitis in neonates in a Singapore teaching hospital; Tan KW et al.; Our aims were to establish the incidence and clinical characteristics of early and late onset Group B Streptococcal (GBS) septicaemia in neonates in our hospital over a period of 1 year . Routine screening for maternal GBS was not standard practice in the hospital . GBS was isolated from high vaginal swabs (HVS) obtained antenatally or postnatally for risk factors as determined by the obstetrician or neonatologist in charge . Data obtained were analyzed separately and these did not form part of the study . By a system of clinical case review and follow-up, mail, telephone and home visits, the outcome of all 15,062 livebirths in the hospital over a 1-year period were verified and reported . Our results show a low incidence of GBS infection in neonates in the hospital: early onset disease was 0.265 per 1,000 livebirths and late onset a quarter of that . The majority of our cases of early onset GBS disease were in premature infants . Because of our low incidence, prophylaxis schedules would have to ensure an acceptably smaller number of mothers exposed to antibiotics over and above the current level and the cooperation of our obstetricians . We have devised a schedule incorporating a current PROM (prelabour premature rupture of membranes) protocol which would result in only an additional 2.2% of mothers requiring prophylactic antibiotics. Infect Dis Clin North Am, 1998 Dec, 12(4), 879 - 901, vi Outpatient intravenous antibiotic therapy for endocarditis; Rehm SJ; The clinical spectrum of endocarditis continues to evolve, as does its diagnosis and management . Outpatient parenteral antimicrobial therapy has been demonstrated to be safe and effective for medically stable patients with viridans streptococcal endocarditis . Other carefully selected and monitored patients with infective endocarditis may also be considered for completion of therapy outside the hospital setting. Neth J Med, 1998 Dec, 53(6), 266 - 70 Acute nonrheumatic myopericarditis associated with group A hemolytic streptococcal tonsillitis in a male ICU-nurse; Said SA et al.; We present the case of a 38-year-old man who developed acute myopericarditis, mimicking acute myocardial infarction, as manifested by electrocardiographic, echocardiographic alterations and elevated cardiac enzymes complicating Lancefield group A beta-hemolytic streptococcal tonsillitis . After receiving oral penicillin, the clinical recovery was complete . Fever, tachycardia and chest discomfort resolved within a few days . Furthermore, enzyme levels and C-reactive protein returned to normal within eight days. Microb Pathog, 1998 Nov, 25(5), 279 - 90 Identification of domains involved in superantigenicity of streptococcal pyrogenic exotoxin F (SpeF); Eriksson A et al.; A series of 11 synthetic peptides of 30 amino acids, each with 10 amino acids overlap which spanned the entire sequence of streptococcal pyrogenic exotoxin F (SpeF), were employed in proliferation studies on human peripheral blood mononuclear cells (PBMCs) . Regions 41-70, 141-170 and 181-210 were identified as important for SpeF-induced lymphocyte activation . Secondary structure predictions of these peptides showed similarities to regions in other superantigens known to be important for T cell mitogenicity . Furthermore, antisera specific to peptides covering amino acids 1-70 and 181-228 were able to inhibit SpeF-induced mitogenicity by 25% when pre-incubated with SpeF prior to PBMC activation . Clin Diagn Lab Immunol, 1999 Jan, 6(1), 133 - 6 Streptococcal DNase B is immunologically identical to superantigen SpeF but involves separate domains; Eriksson A et al.; The previous suggestion that streptococcal superantigen SpeF might be identical to DNase B was confirmed in this study . Polyclonal SpeF-specific antisera were able to inhibit depolymerization of methyl-green DNA by DNase B . However, T-cell mitogenicity and nuclease activity appear to involve separate immune epitopes on SpeF, since sera with the capacity to neutralize the mitogenic activity of SpeF did not always inhibit the DNase activity. Infection, 1998 Nov-Dec, 26(6), 389 - 95 A survey of the use of teicoplanin in patients with haematological malignancies and solid tumours; Davies JM; A significant number of open and comparative studies have now addressed the use of teicoplanin in the treatment of documented or presumed infection in patients with haematological and non-haematological malignancy . Available evidence suggests that teicoplanin is an effective agent against such infections, with an excellent safety profile . The use of teicoplanin and vancomycin may be justified as part of the initial management of clinically infected right atrial catheters in patients with malignancy . The first-line use of glycopeptides may also be appropriate in units where streptococcal and methicillin resistant staphylococcal infections are prevalent . However, such a policy should be reviewed regularly . Except in the above situations, a delay in the introduction of either teicoplanin or vancomycin in cancer patients does not appear to produce any excess mortality, but there may be some additional morbidity in terms of fever and malaise . The introduction of glycopeptides as second-line agents is indicated for sensitive, microbiologically documented infections and for patients who have not responded to empirical, first-line therapy . Non-inpatient treatment with teicoplanin is an area of ongoing interest and may be justified on both humanitarian and pharmacoeconomic grounds . The use of glycopeptides in the prophylactic setting remains controversial and should be avoided while the emergence of resistance, particularly in enterococci, should be monitored closely. Proc Natl Acad Sci U S A, 1998 Dec 22, 95(26), 15671 - 6 Role of the proteasome and NF-kappaB in streptococcal cell wall-induced polyarthritis; Palombella VJ et al.; The transcription factor NF-kappaB activates a number of genes whose protein products are proinflammatory . In quiescent cells, NF-kappaB exists in a latent form and is activated via a signal-dependent proteolytic mechanism in which the inhibitory protein IkappaB is degraded by the ubiquitin-proteasome pathway . Consequently, inhibition of the proteasome suppresses activation of NF-kappaB . This suppression should therefore decrease transcription of many genes encoding proinflammatory proteins and should ultimately have an anti-inflammatory effect . To this end, a series of peptide boronic acid inhibitors of the proteasome, exemplified herein by PS-341, were developed . The proteasome is the large multimeric protease that catalyzes the final proteolytic step of the ubiquitin-proteasome pathway . PS-341, a potent, competitive inhibitor of the proteasome, readily entered cells and inhibited the activation of NF-kappaB and the subsequent transcription of genes that are regulated by NF-kappaB . Significantly, PS-341 displayed similar effects in vivo . Oral administration of PS-341 had anti-inflammatory effects in a model of Streptococcal cell wall-induced polyarthritis and liver inflammation in rats . The attenuation of inflammation in this model was associated with an inhibition of IkappaBalpha degradation and NF-kappaB-dependent gene expression . These experiments clearly demonstrate that the ubiquitin-proteasome pathway and NF-kappaB play important roles in regulating chronic inflammation and that, as predicted, proteasome inhibition has an anti-inflammatory effect. EMBO J, 1998 Dec 15, 17(24), 7404 - 15 The structure of plasmid-encoded transcriptional repressor CopG unliganded and bound to its operator; Gomis-Ruth FX et al.; The structure of the 45 amino acid transcriptional repressor, CopG, has been solved unliganded and bound to its target operator DNA . The protein, encoded by the promiscuous streptococcal plasmid pMV158, is involved in the control of plasmid copy number . The structure of this protein repressor, which is the shortest reported to date and the first isolated from a plasmid, has a homodimeric ribbon-helix-helix arrangement . It is the prototype for a family of homologous plasmid repressors . CopG cooperatively associates, completely protecting several turns on one face of the double helix in both directions from a 13-bp pseudosymmetric primary DNA recognition element . In the complex structure, one protein tetramer binds at one face of a 19-bp oligonucleotide, containing the pseudosymmetric element, with two beta-ribbons inserted into the major groove . The DNA is bent 60 degrees by compression of both major and minor grooves . The protein dimer displays topological similarity to Arc and MetJ repressors . Nevertheless, the functional tetramer has a unique structure with the two vicinal recognition ribbon elements at a short distance, thus inducing strong DNA bend . Further structural resemblance is found with helix-turn-helix regions of unrelated DNA-binding proteins . In contrast to these, however, the bihelical region of CopG has a role in oligomerization instead of DNA recognition . This observation unveils an evolutionary link between ribbon-helix-helix and helix-turn-helix proteins. Anticancer Res, 1998 Sep-Oct, 18(5D), 3917 - 25 The past, the present and future of the OK-432 therapy for patients with malignant effusions; Katano M et al.; For the past 20 years, our group has treated over 400 cases of malignant effusion by the intraperitoneal injection of streptococcal preparation OK432 (OK-432 therapy) and has investigated extensively the antitumor mechanisms of this therapy . Prospective clinical data has demonstrated that the OK-432 therapy induced a definite reduction of the effusions in around 60% (responders) of cases and significantly prolonged the survival time in patients who responded well . In addition, a definite reduction of original tumor mass volume was found in around 20% of cases . We have shown that OK432-induced neutrophils, lymphocytes, and probably macrophages may play an important role in tumor cell destruction in ascites . Tumor necrosis factor alpha (TNF-alpha)-induced CD11b/CD18 expression on leukocytes and interferon-gamma (IFN-gamma)-induced ICAM-1 expression on tumor cells may play an important role in leukocyte-mediated tumor destruction . It has also been shown that OK-432 induces various cytokines, such as TNF-alpha, TNF-beta, IFN-alpha IFN-gamma, interleukin-1 (IL-1), IL-2, IL-6, IL-12, tumor growth inhibitory factor(s) (TGIF), and possibly unknown apoptosis-inducing factor(s) . Some of these cytokines have been adduced as representing the antitumor activity . These data suggest that two pathways of antitumor activity, i.e., cell-mediated and cytokine-mediated, can be induced simultaneously in the peritoneal cavity . OK-432 therapy may be valuable in the management of patients with malignant effusions . Future clinical and basic research should contribute to further progress in OK-432 therapy. Pediatr Res, 1998 Dec, 44(6), 946 - 50 Passive deformability of mature, immature, and active neutrophils in healthy and septicemic neonates; Linderkamp O et al.; Obstruction of narrow vessels by rigid neutrophils may contribute to ischemic organ injury . In septicemia, a substantial portion of the neutrophils may become activated and the number of circulating immature neutrophils may rise sharply . Volume and deformability of mature (PMN) and immature neutrophils in healthy preterm and full-term infants and in septicemic neonates were studied by means of a micropipette system . Membrane cytoplasm tongues were aspirated into 2.5-microm (diameter) pipettes over a period of 60 s . Volume and tongue growth of mature resting PMN were similar in healthy preterm and full-term neonates and adults . Compared with mature PMN (about 360 fl), the volumes of band cells (415 fl), metamyelocytes (470 fl), and less mature cells (myeloblasts, promyelocytes, and myelocytes; 490 fl) were significantly increased (p < 0.005) . Final tongue lengths of band cells, metamyelocytes, and less mature cells were decreased by about 50, 60, and 70%, respectively, when compared with passive mature cells . In septic neonates, the percentage of immature neutrophils was increased, but the deformability and volume of the cell subpopulations were not affected by septicemia . Active PMN were characterized by pseudopod formation . More active PMN were found in group B streptococcal (14% of total PMN), gram-negative (12%), and Staphylococcus epidermidis septicemia (8%) than in healthy neonates and adults (4%) . The main bodies of active PMN were less deformable than passive PMN, and the pseudopods showed very little membrane deformation . The increased number of rigid active and immature neutrophils may contribute to impaired microcirculation and the high risk for organ injury in septic patients. Clin Exp Rheumatol, 1998 Nov-Dec, 16(6), 750 - 2 The clinical spectrum of post-streptococcal syndromes with arthritis in children; Bont L et al.; Acute rheumatic fever (ARF) and post-streptococcal reactive arthritis (PSRA) are well known complications of streptococcal throat infections . We describe four children with arthritis following a streptococcal throat infection . In addition to arthritis, other clinical manifestations included erythema nodosum, livedo reticularis and cutaneous vasculitis . Because of the very diverse clinical manifestations that may appear after a streptococcal throat infection, we suggest a classification and treatment of post-streptococcal syndromes according to the severity of the disease. J Infect Dis, 1999 Jan, 179(1), 142 - 50 Safety and immunogenicity of capsular polysaccharide-tetanus toxoid conjugate vaccines for group B streptococcal types Ia and Ib; Baker CJ et al.; About 40% of invasive group B streptococcal (GBS) isolates are capsular polysaccharide (CPS) types Ia or Ib . Because infant and maternal GBS infections may be preventable by maternal vaccination, individual GBS CPS have been coupled to tetanus toxoid (TT) to prepare vaccines with enhanced immunogenicity . Immunogenicity in rabbits and protective capacity in mice of a series of type Ia- and Ib-TT conjugates increased with the degree of polysaccharide-to-protein cross-linking . In total, 190 healthy, nonpregnant women aged 18-40 years were randomized in four trials to receive Ia- or Ib-TT conjugate (dose range, 3.75-63 microg of CPS component), uncoupled Ia or Ib CPS, or saline . All vaccines were well-tolerated . CPS-specific IgG serum concentrations peaked 4-8 weeks after vaccination and were significantly higher in recipients of conjugated than of uncoupled CPS . Immune responses to the conjugates were dose-dependent and correlated in vitro with opsonophagocytosis . These results support inclusion of Ia- and Ib-TT conjugates when formulating a multivalent GBS vaccine. Arch Dermatol Res, 1998 Oct, 290(10), 533 - 9 Morphometric and ultrastructural analyses of in vivo-activated murine Langerhans cells induced by administration of a streptococcal preparation (OK-432); Teramae H et al.; Langerhans cells (LCs) are activated in the epidermis by external and internal stimuli, such as antigens and cytokines, respectively . To reveal the morphologic and functional properties of in vivo-activated LCs during inflammation, we injected the streptococcal preparation OK-432 intradermally into the earskin of mice and performed time-course analyses by immunofluorescence and electron microscopy . Cellular infiltrate appeared in the dermis at 6 h after OK-432 injection and had progressively extended to the dermoepidermal junction at 12 and 24 h . Immunostaining for class II antigen revealed that LCs were enlarged and extended long dendrites during inflammation . Acidic compartments such as lysosomes and multivesicular bodies also increased in number and Golgi apparatuses developed as demonstrated by electron microscopy and morphometric analysis . Birbeck granules, although not showing numerical changes, were translocated from the Golgi area to the subplasmalemmal area . After epicutaneous application of cationic ferritin, LCs often contained endosomes as the result of engulfment by the cytoplasmic projections . The present results indicate that nonspecifically induced dermal inflammation is capable of inducing activation of LCs in vivo, and that in vivo-activated LCs have the capacity for active endocytosis and intracellular digestion or processing. Ann Dermatol Venereol, 1998 Oct, 125(10), 688 - 93 {Impetigo in French Guyana . A clinical, bacteriological, toxicological and sensitivity to antibiotics study}; Couppie P et al.; OBJECTIVE: We evaluated pertinent features of impetigo in French Guyana due to the increasing number of therapeutic failures with macrolides and fusidic acid . PATIENTS AND METHODS: A prospective study study was conducted over a 14-month period in the dermatology unit of the Cayenne hospital . Two groups of patients were identified: group 1 included patients with impetigo and group 2 patients with infected skin reactions . Epidemiological, bacteriological, toxinological (exofoliatines, leukocidine) and antibiotic data were recorded . RESULTS: Forty-one patients with impetigo and 31 patients with infected skin reactions were included . Staphylococcus infection alone was identified in most patients (68 p . 100) in the impetigo group . Exfoliatine-producing strains were strongly associated with Staphylococcus-induced bullous and non-bullous impetigo (93 p . 100) compared with other origins (impetigo with streptococcal infection or infected skin reactions) . Resistance to macrolides was high (erythromycin 41 p . 100, fusidic acid 42 p . 100) for all isolated strains of Staphylococcus aureus . CONCLUSION: A sub-group of patients with impetigo was identified . These patients had pure staphylococcal infections characterized by strong association with exfoliatine production . The rate of resistance to macrolides was particularly high in this sub-group . Resistance to fusidic acid was high for all Staphylococcus strains isolated. Antimicrob Agents Chemother, 1998 Dec, 42(12), 3169 - 72 In vitro resistance to thrombin-induced platelet microbicidal protein among clinical bacteremic isolates of Staphylococcus aureus correlates with an endovascular infectious source; Bayer AS et al.; Platelet microbicidal proteins (PMPs), small cationic peptides released at sites of endovascular damage, kill common bloodstream pathogens in vitro . Our group previously showed that in vitro resistance of clinical staphylococcal and viridans group streptococcal bacteremic strains to PMPs correlated with the diagnosis of infective endocarditis (IE) (Wu et al., Antimicrob . Agents Chemother . 38:729-732, 1994) . However, that study was limited by (i) the small number of Staphylococcus aureus isolates from IE patients, (ii) the retrospective nature of the case definitions, and (iii) the diverse geographic sources of strains . The present study evaluated the in vitro PMP susceptibility phenotype of a large number of staphylococcemic isolates (n = 60), collected at a single medical center and categorized by defined and validated clinical criteria . A significantly higher proportion of staphylococcemic strains from patients with IE was PMP resistant in vitro than the proportion of strains from patients with soft tissue sepsis (83% and 33%, respectively; P < 0.01) . Moreover, the levels of PMP resistance (mean percent survival of strains after 2-h exposure to PMP in vitro) were significantly higher for isolates from patients with IE and with vascular catheter sepsis than for strains from patients with abscess sepsis (P < 0.005 and P < 0.01, respectively) . These data further support the concept that bloodstream pathogens that exhibit innate or acquired PMP resistance have a survival advantage with respect to either the induction or progression of endovascular infections. J Immunol, 1998 Dec 1, 161(11), 6297 - 304 Oral delivery of group A streptococcal cell walls augments circulating TGF-beta and suppresses streptococcal cell wall arthritis; Chen W et al.; Oral administration of autoantigens can influence the outcome of experimental autoimmune diseases, yet little is known about nonself Ag-induced tolerance . In this study, we administered group A streptococcal cell wall (SCW) peptidoglycan-polysaccharide complexes orally and monitored the impact on SCW-induced erosive polyarthritis . Oral administration of low dose SCW (3 microg/day), initiated 7 days before an arthritogenic dose of systemic SCW, virtually eliminated the joint swelling and destruction typically observed during both the acute and chronic phases of the arthritis . High (300 microg), but not intermediate (30 microg), dose regimens also profoundly inhibited the disease . Most previous studies have demonstrated that prior feeding is required for efficacy, yet oral feeding of low dose SCW suppressed the evolution of arthritis even when administration was begun 10-15 days after induction of the arthritis . While the synovial inflammatory cell infiltration and expression of proinflammatory cytokines were markedly suppressed, no local enhancement of the regulatory cytokines IL-4, IL-10, and TGF-beta was detected . Oral administration of low dose SCW, however, up-regulated circulating levels of TGF-beta, concomitant with decreased circulating TNF-alpha and suppression of chronic arthritis . Moreover, IL-10 was increased in tolerized spleen lymphocytes, and unexpectedly, this SCW-specific IL-10 production was TGF-beta dependent . These data support a pivotal role for TGF-beta, although not necessarily in the joint, in the regulation of specific immune tolerance responsible for suppressed synovial inflammation and matrix destruction . The distant induction and up-regulation of regulatory cytokines and/or cells may contribute to the inhibition of the immune response through blunted infiltration of inflammatory cells to the joint. Arch Dis Child Fetal Neonatal Ed, 1998 Sep, 79(2), F148 - 9 Early onset group B streptococcal neonatal infection in Oxford 1985-96; Moses LM et al.; Of 74,920 babies live born in Oxford between 1985 and 1996, 41 (0.5 per 1000 95% CI 0.4-0.7) developed definite, culture confirmed, early onset (< 48 hours) group B streptococcal infection and 32 (0.4 per 1000 95% CI 0.3-0.6) developed probable infection (sepsis plus colonisation) . There was no significant variation in incidence with time . The mortality from definite infection was 19.5%, and from probable infection 6% . These data suggest that the incidence of group B streptococcal infection in Oxford is considerably lower than that reported in the USA. Cancer, 1998 Nov 15, 83(10), 2054 - 9 OK-432 and 5-fluorouracil, doxorubicin, and mitomycin C (FAM-P) versus FAM chemotherapy in patients with curatively resected gastric carcinoma: a randomized Phase III trial; Kim SY et al.; BACKGROUND: The streptococcal agent OK-432 is used widely as a potent biologic response modifier . Accumulated evidence suggests that OK-432 exerts antineoplastic effects by a direct cytotoxic or inhibitory effect on tumor cells . The clinical efficacy of OK-432 has been reported for various tumors . In this randomized Phase III study, the authors compared 5-fluorouracil (5-FU), doxorubicin, mitomycin C, and the intradermal administration of OK-432 (FAM-P) with the standard FAM regimen in patients with gastric carcinoma who underwent curative resection . METHODS: From May 1988 until November 1991, a total of 99 patients were entered into this randomized trial . The patients were stratified according to the American Joint Committee on Cancer stage of disease (i.e., Stage IB, II, and III) . Fifty patients were treated with the FAM regimen here and throughout text.: 5-FU, 750 mg intravenously (i.v.), on Days 1, 8, 29, and 36; doxorubicin, 30 mg/m2 i.v., on Days 1 and 29; and mitomycin C, 10 mg/m2 i.v., on Day 1 . Forty-nine patients received the FAM-P regimen: 5-FU, 750 mg i.v., on Days 1, 8, 29, and 36; doxorubicin, 30 mg/m2 i.v., on Days 1 and 29; mitomycin C, 10 mg/m2 i.v., on Day 1; and OK-432 5.0 Klinishe Einheit (clinical unit) injected intradermally weekly . RESULTS: The survival difference was statistically significant between the patients receiving the FAM and FAM-P regimens (5-year survival of 52% vs . 62%; P = 0.04) . A comparison between disease free survival in FAM and FAM-P patients showed a borderline advantage for the FAM-P group (P = 0.053) . When Stage IB, Stage II, and Stage III patients were analyzed separately, the difference in survival between two regimens was significant in Stage III patients (P = 0.049) and the disease free survival was of borderline significance (P = 0.06), but not in patients with Stage IB and II disease . The significant toxicity of OK-432 was mild fever, which was controlled with acetaminophen . CONCLUSIONS: The results of this study show that OK-432 may be an active, well tolerated agent for the treatment of curatively resected gastric carcinoma . However, these findings should be confirmed by a multicenter randomized study with a large sample size. J Accid Emerg Med, 1998 Nov, 15(6), 425 - 6 A case of streptococcal myositis (misdiagnosed as hamstring injury); Kang N et al.; Streptococcal myositis is a very rare bacterial infection of muscle with a high mortality . Diagnosis is difficult because of the paucity of clinical signs and symptoms at the onset . However, presentation of the disease appears to have changed over the last 50 years . A case of streptococcal myositis is presented (misdiagnosed as hamstring injury), which more closely reflects the current presentation of the disease . Some of the features that may help emergency clinicians to recognise the onset of the condition are highlighted. South Med J, 1998 Nov, 91(11), 1019 - 23 Serum antibody titers in a systemic lytic therapy with streptokinase; Hohage H et al.; BACKGROUND: Anaphylactic reactions to streptokinase are rare but potentially life-threatening complications . Gamma E immunoglobulin (IgE) mediated mechanisms, probably due to streptococcal infections, have been implicated . We investigated the value of in vitro laboratory or dermatologic tests in predicting anaphylactic reactions due to streptokinase and the value of antistreptolysin titers (ASL) in predicting the amount of specific IgE (sIgE) and specific gamma G immunoglobulin (sIgG) neutralizing antibodies to streptokinase . METHODS: We measured serum levels of total IgE, streptokinase sIgE and sIgG, and ASL in 16 patients before and 9 and 41 days after streptokinase therapy . Immediately before therapy, intracutaneous testing with 100 IU streptokinase was done . RESULTS: Dermatologic testing did not identify patients prone to allergic reactions . Moreover, not all patients with increased sIgE levels had allergic reactions . These reactions were independent of the dose of streptokinase given . In spite of steroid prophylaxis, allergic reactions occurred in 3 of 16 patients, but none showed life-threatening anaphylaxis . Streptokinase sIgE and sIgG concentrations were closely related to ASL titers . CONCLUSIONS: Plasma levels of sIgG, sIgE, and ASL titers showed a good correlation . We believe ASL titers can be used for the estimation of neutralizing antibodies instead of streptokinase sIgG antibodies . Currently, no laboratory or dermatologic test allows reliable predictions of allergic reactions to streptokinase. J Immunol Methods, 1998 Sep 1, 218(1-2), 73 - 83 Use of an albumin-binding domain for the selective immobilisation of recombinant capture antibody fragments on ELISA plates; Konig T et al.; A small albumin-binding domain (ABD) of 46 amino acids derived from streptococcal protein G was employed for the directed attachment of recombinant immunoglobulin (Ig) fragments to microtitre plates that had been coated with human serum albumin (HSA) . Generic vectors were constructed in order to produce the Fv or Fab fragments fused with the ABD in Escherichia coli . Using the anti-lysozyme antibody D1.3 as the capture antibody fragment it was possible to quantify the non-radioactively labelled antigen with high sensitivity in a sandwich ELISA . The new strategy avoids denaturation or an unfavourable orientation of the Ig fragment, which can occur during direct adsorption to the microtitre plate . The HSA that serves to complex the ABD ensures efficient saturation of reactive binding sites on the plastic surface as well so that no additional blocking steps are necessary and the assay can be quickly performed. Proc Natl Acad Sci U S A, 1998 Nov 10, 95(23), 13859 - 64 NF-kappaB activation provides the potential link between inflammation and hyperplasia in the arthritic joint; Miagkov AV et al.; The transcription factor NF-kappaB is a pivotal regulator of inflammatory responses . While the activation of NF-kappaB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood . Here, we examine the role of NF-kappaB in animal models of RA . We demonstrate that in vitro, NF-kappaB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) cytotoxicity . Similar to that observed in human RA, NF-kappaB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis . In vivo suppression of NF-kappaB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IkappaBalpha profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis . This indicated that the activation of NF-kappaB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia . Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints . Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-kappaB . These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-kappaB. Tierarztl Prax Ausg G Grosstiere Nutztiere, 1998 Sep, 26(5), 254 - 60 {Effects of various antibiotic treatments of lactating cows with subclinical mastitis}; Friton GM et al.; 101 cows with 197 udder quarters with subclinical mastitis from 23 dairy farms were selected for different antibiotic treatments under field conditions . Group 1 consisting of 27 animals and 50 infected udder quarters was treated twice intramammaryly with 250 mg Cefacetril . Group 2 (26 animals/50 quarters) was treated twice intramuscular with 10 Mio IU Penethamathydrojodid and with 5 Mio IU respectively . Group 3 was treated twice with the combination of the intramammary and the intramuscular therapies in the above mentioned groups . Group 4 served as control . 23 animals with 36 subclinical infected udder quarters were treated twice intramuscular with 2.0 ml of sterile isotonic sodium-solution . Therapeutic success was controlled with bacteriological and cytological examinations of quarter milk probes one week, two weeks and four weeks after the end of treatments . Concerning bacteriological healing both the intramammary and the combined therapy had an even success with a 72.9% elimination rate of pathogenic bacteria whereas the intramuscular therapy led to bacteriological healing in 36.7% . In comparison cytological healing rates (< 100 x 10(3) cell counts per ml milk) with 29.8% in group 1, 32.3% in group 3 and 8.2% in group 2 were not satisfying . S . aureus was the predominating isolated bacteria . With respect to bacterial species found in the subclinically infected milk probes, elimination rates in Streptococcaceae and in Enterococcaceae was evident higher than in Staphylococcaceae . The results are discussed. Otolaryngol Head Neck Surg, 1998 Nov, 119(5), 523 - 5 Acute coalescent mastoiditis in an infant: an emerging trend? Bach KK, Malis DJ, Magit AE, Pransky SM, Kearns DB, Seid AB. There is some evidence to suggest that the incidence and complications of ACM may be increasing . However, in the current era of widespread access to health care and broad-spectrum antibiotics, an intratemporal or intracranial complication from acute otitis media may not initially be suspected . The reported case is significant in that the patient was very young, had no underlying disease or immunocompromise, and did not have a known antecedent acute otitis media . With the emergence of resistant streptococcal species and prolonged survival in immunocompromised patients, the relative incidence of complications caused by acute otitis media will probably continue to rise, making it imperative that we raise our index of suspicion for previously rare infectious complications of relatively common diseases. Plasmid, 1998 Nov, 40(3), 214 - 24 Identification of a new gene in the streptococcal plasmid pLS1: the rnaI gene; Acebo P et al.; The streptococcal plasmid pMV158 has been reported to harbor five genes: three involved in initiation of rolling circle replication and its control (copG, repB, and maII), one involved in conjugative mobilization (mobM), and the fifth one specifying constitutive resistance to tetracycline (tet) . The mobM gene was removed in the construction of the pMV158-derivative plasmid pLS1, which was used in this study . By in vitro transcription assays, primer extension experiments, and construction of mutations, here we demonstrate the presence of another gene (the sixth of pMV158), termed maI, which is transcribed in opposite orientation with respect to the plasmid mRNAs, to render RNA I . The 5'-end of RNA I has an 8-nt sequence which is complementary to a region of the lagging-strand origin (ssoA) comprising a 6-nt consensus sequence involved in lagging strand synthesis . This suggested that RNA I could influence, positively or negatively, initiation of lagging strand synthesis from the pLS1-ssoA . However, plasmids defective in RNA I synthesis exhibited a phenotype similar to the wild type in terms of efficiency of replication from the ssoA and copy number . When the maI gene was cloned into a compatible plasmid, the resulting recombinants did not exhibit incompatibility toward plasmids with the pLS1 replicon . Thus, RNA I does not seem to be a true copy number control element . We postulate that transcription from the maI promoter may facilitate extrusion of the hairpin of the plasmid double-strand origin, which is the target of the initiator of replication protein . Am Fam Physician, 1998 Oct 15, 58(6), 1335 - 42, 1345 Appropriate use of antibiotics for URIs in children: Part II . Cough, pharyngitis and the common cold . The Pediatric URI Consensus Team; Dowell SF et al.; This article summarizes the principles of judicious antimicrobial therapy for three of the five conditions--cough, pharyngitis, the common cold--that account for most of the outpatient use of these drugs in the United States . The principles governing the other two conditions, otitis media and acute sinusitis, were presented in the previous issue . This article summarizes evidence against the use of antibiotic treatment for illness with cough or bronchitis in children, unless the cough is prolonged . Although empiric treatment may be started in patients with pharyngitis when streptococcal infection is suspected, the authors recommend withholding antibiotic treatment until antigen testing or culture is positive . There is never any indication for antibiotic treatment of the common cold; it is important to understand the natural history of colds, because symptoms such as mucopurulent rhinitis or cough, even when they persist for up to two weeks, do not necessarily indicate bacterial infection. Eur J Clin Microbiol Infect Dis, 1998 Aug, 17(8), 578 - 82 Systemic and deep-seated infections caused by Arcanobacterium haemolyticum; Skov RL et al.; Arcanobacterium haemolyticum has been implicated mainly in non-streptococcal pharyngitis and wound infections . Rarely, it has been reported to cause systemic infection, often in combination with other pathogens . Two cases of systemic and deep-seated infections caused by Arcanobacterium haemolyticum are reported, and the literature is reviewed . Sixteen cases of bacteremia and seven cases of non-bacteremic deep-seated have been published previously . Eight of the bacteremic and two of the non-bacteremic cases occurred in younger, apparently healthy immunocompetent patients . Six patients had infections of the central nervous system . The optimal treatment of infections caused by Arcanobacterium haemolyticum is not known . Although in vitro susceptibility tests have demonstrated tolerance of Arcanobacterium haemolyticum to penicillin, penicillins with or without aminoglycosides have been the most widely used antibiotics, in most cases with success. Int J Clin Pract Suppl, 1998 Jun, 95, 23 - 6 Community-acquired antimicrobial resistance: is it controllable? Linares J. Antimicrobial agents were introduced into medical use about 50 years ago . Since then, the prevalence of antimicrobial resistance in community-acquired pathogens has increased rapidly worldwide . The relationship between antibiotic use and resistance is strongly supported by data from several studies . In Spain, the resistance rates for community-acquired pathogens are among the highest in Europe and coincide with a high consumption of antimicrobial agents . In contrast, in Finland, after a nationwide reduction in the use of macrolides for outpatient therapy, there has been a significant decline in the frequency of erythromycin resistance among group A streptococcal isolates . The control of community-acquired antimicrobial resistance is a challenge for the future and will require the early detection of resistance genes through global and local surveillance, prompt containment of resistant pathogens, and judicious use of antimicrobials. Vaccine, 1998 Nov, 16(19), 1857 - 64 Development of engineered vaccines effective against structurally related bacterial superantigens; Ulrich RG et al.; Staphylococcal and streptococcal superantigens are exotoxins that may be linked to many human pathologies involving impaired immune functions . Despite considerable sequence divergence, bacterial superantigens share extensive secondary and tertiary structure and use similar structural strategies to bind major histocompatibility complex class II receptors . We produced by site-directed mutagenesis of the conserved receptor-binding surfaces of the superantigens staphylococcal enterotoxins A and B . These vaccines protected immunized mice and rhesus monkeys from lethal toxic shock . In addition, antibodies produced against each superantigen recognized and neutralized distantly related superantigens . This antibody cross-reactivity was additive in that mixtures of superantigens used in immunization were more effective than single-component vaccines in protecting mice from challenges with individual or mixed superantigens . We conclude that an optimal combination of these genetically attenuated superantigen vaccines may protect against all structurally related superantigens. Pediatr Infect Dis J, 1998 Sep, 17(9), 809 - 15 Recurrent group A streptococcal tonsillopharyngitis; Pichichero ME et al.; OBJECTIVE: To examine the epidemiology and treatment of group A beta-hemolytic streptococcal (GABHS) recurrent tonsillopharyngitis in private pediatric practice . METHODS: This was a retrospective chart review study covering the time span 1975 to 1996 involving 2140 GABHS episodes . Diagnosis was based on acute clinical symptoms and laboratory confirmation (throat culture or positive rapid antigen detection test) of GABHS . RESULTS: Eighty percent (n=1721) of the episodes evaluated were treated with penicillin or amoxicillin; 352 (20.5%) of these were followed by a recurrence within 30 days and 519 (30.2%) within 60 days . GABHS recurrences within 30 days after penicillin/amoxicillin treatment rose from 9% in 1975 to 1979 to 25.9% in 1980 to 1984, 24.2% in 1985 to 1989, 22.4% in 1990 to 1994 and 25.9% in 1995 to 1996 (P < 0.02); 53.4% of the recurrences were associated with symptoms and signs of GABHS tonsillopharyngitis, 9.9% were asymptomatic and 36.7% could not be classified . Recurrences within 60 days after penicillin/ amoxicillin treatment rose from 10.7% in 1975 to 1979 to 38.7% in 1980 to 1984, 39.0% in 1985 to 1989, 31.7% in 1990 to 1994 and 37.5% in 1995 to 1996 (P < 0.001) . Recurrent GABHS infections occurred more frequently in younger children (1 to 8 years of age, 21.3% recurrence rate) than in adolescents (13 to 19 years, 5% recurrence rate; P=0.002) . Recurrences within 30 days occurred more often after therapy with penicillin (21.8% of 1581 episodes) than with cephalosporins (8.6% of 254 episodes) (P < 0.0001) or with macrolides (14.0% of 143 episodes, P=0.04) . Recurrence rates were unaffected by patient gender or season of the year . CONCLUSIONS: Recurrent GABHS infections occur more frequently in the 1990s than the 1970s, occur more frequently in children younger than 8 years of age than in adolescents and occur more frequently after penicillin treatment than with alternative antibiotic therapy. Clin Perinatol, 1998 Sep, 25(3), 687 - 97, x Prevention of neonatal group B streptococcal infections . Is there a rational prevention strategy? Schimmel MS, Samueloff A, Eidelman AI. Clinicians, both obstetric and pediatric, are currently faced with the need to choose treatment strategies to reduce the persistent high incidence of early-onset GBS neonatal disease without being equipped with adequate data to choose conclusively which of the proposed strategies is ideal . There is an urgent need for well-designed prospective randomized trials comparing the various prevention protocols so as to resolve conclusively the controversy . The ultimate prevention strategy may well be a successful maternal immunization program. J Clin Microbiol, 1998 Nov, 36(11), 3133 - 7 Fluorescent amplified-fragment length polymorphism analysis of an outbreak of group A streptococcal invasive disease; Desai M et al.; Fluorescent amplified-fragment length polymorphism (FAFLP) analysis was carried out for an outbreak of group A streptococcal (GAS) invasive disease . Streptococcal genomic DNAs were digested with endonucleases EcoRI and MseI, site-specific adaptors were ligated, and PCR amplification was carried out with an EcoRI adaptor-specific primer labelled with fluorescent dye . Amplified fragments of up to 600 bp in size were separated on a polyacrylamide sequencing gel which contained internal size markers in each lane . These data were automatically scanned and analyzed, fragments were precisely sized (+/-1 bp), and electropherograms were generated for each genome with GeneScan 2.1 software . All isolates were compared in this way . Among 27 GAS isolates examined, we found 18 FAFLP profiles, compared with 12 macrorestriction profiles by pulsed-field gel electrophoresis . FAFLP readily distinguished genotypes for two clones of GAS serotype M77 which were responsible for outbreaks of invasive disease in a care-of-the-elderly system . It provided an automated analysis of the whole genome of bacterial isolates . It was reproducible, more discriminatory, and capable of higher throughput than other molecular typing methods . Given agreed conditions, FAFLP would be reproducible between laboratories for rapid characterization of outbreak strains. Cytokine, 1998 Sep, 10(9), 690 - 702 Different roles of tumour necrosis factor alpha and interleukin 1 in murine streptococcal cell wall arthritis; Kuiper S et al.; In this study two different aspects of tumour necrosis factor alpha (TNF-alpha) and interleukin 1 (IL-1) in locally induced murine streptococcal cell wall arthritis (SCW) were investigated . First, the kinetics and interdependence of TNF-alpha and IL-1 release; and second; their involvement in inflammation and cartilage destruction . Kinetic studies showed that the TNF-alpha peak level preceded the IL-1 peak level . However, in vivo neutralization of TNF-alpha did not result in decreased IL-1 bioactivity or immunoreactivity, suggesting that there is no dominant TNF-alpha-dependent IL-1 release in this model . Inflammation was studied by measuring knee joint swelling and inflammatory cell influx . Impact on cartilage was studied by measuring chondrocyte proteoglycan synthesis and cartilage proteoglycan depletion . The role of TNF-alpha in these phenomena was investigated using anti-TNF-alpha antibodies and tumour necrosis factor binding protein (TNFbp) . Similarly, the role of IL-1 was studied using anti-IL-1 antibodies or IL-1 receptor antagonist (IL-1Ra) . Anti-TNF-alpha treatment significantly reduced joint swelling, whereas this effect was not found by using anti-IL-1 or IL-1Ra . In contrast, neutralization of IL-1, but not TNF-alpha, resulted in a significant decrease of chondrocyte proteoglycan synthesis inhibition . Moreover, histology revealed that anti-IL-1 treatment reduced cartilage proteoglycan depletion and inflammatory cell influx . Combined anti-TNF-alpha/anti-IL-1 treatment significantly suppressed both inflammation and cartilage damage . However, the impact on these separate parameters did not exceed the effects of either anti-TNF-alpha or anti-TNF-1 . It can be concluded that both TNF-alpha and IL-1 exert specific activities in SCW arthritis . The involvement of TNF-alpha in this model is limited to joint swelling, whereas IL-1 plays a dominant role in cartilage destruction and inflammatory cell influx . Res Microbiol, 1997 Sep-Oct, 148(7), 559 - 72 Group A streptococcal isolate 64/14 expresses surface plasmin-binding structures in addition to Plr; D'Costa SS et al.; A recombinant plasmin receptor (Plr) gene product originally cloned from group A streptococcal isolate 64/14 was analysed for its ability to bind plasmin(ogen) and to account for all the surface plasmin-binding properties of streptococcal isolate 64/14 . Functional analysis of recombinant Plr demonstrated that the protein exhibited equal reactivity with human Lys-plasmin and Lys-plasminogen, but significantly lower reactivity with Glu-plasminogen . Plasmin-binding was both inhibitable and elutable by lysine or lysine analogs, and active plasmin bound to recombinant Plr was not neutralized by alpha 2-antiplasmin . Thus, the plasmin-binding properties of recombinant Plr correlated with the plasmin-binding phenotype of the intact streptococcal isolate 64/14 . In addition, fluid-phase recombinant Plr could completely inhibit binding of plasmin to either immobilized recombinant Plr or group A streptococcal isolate 64/14 with equal efficiency, indicating that surface-expressed Plr could account for all the plasmin-binding properties of the intact organism . An IgM monoclonal antibody to recombinant Plr that specifically recognized a surface structure on streptococcal isolate 64/14 significantly inhibited the binding of plasmin to the recombinant protein; however, the antibody was not successful at inhibiting plasmin-binding to the intact bacteria, indicating the presence of other plasmin-binding structures on the bacterial surface in addition to Plr. Int J Dermatol, 1998 Sep, 37(9), 667 - 72 Erythema nodosum and associated diseases . A study of 129 cases; Cribier B et al.; BACKGROUND: Erythema nodosum (EN) is associated with many infectious diseases . The purpose of this study was to evaluate the relative prevalence of associated diseases in a large series of EN, and to review the previously described causes of EN . MATERIALS AND METHODS: A total of 157 inpatients with a diagnosis of EN made in Strasbourg, France between 1960 and 1995 were studied retrospectively, but only 129 patients with confirmed EN were evaluated . A biopsy was taken in 30 patients with atypical clinical symptoms . Chest radiography, blood cell count, throat swab, and anti-streptolysin dosage were performed systematically . Viral investigations and serodiagnoses for various bacterial infections were carried out in approximately half of the patients . All investigations were analyzed retrospectively and compared with the world literature . RESULTS: The female: male ratio was 5 : 1 and the mean age was 31 years . We found 28% confirmed streptococcal infections, 11% sarcoidosis, 1.5% enteropathies, 1.5% Chlamydia infections, 0.8% Mycoplasma infections, 0.8% Yersinia infections, 0.8% hepatitis B, and 0.8% tuberculosis (one case) . The causative factor could not be determined in 55% of patients . CONCLUSIONS: Our data confirm the predominance of streptococcal infections and sarcoidosis among patients with EN . Tuberculosis has virtually disappeared, since the last case was observed in 1962 . Various viral or bacterial diseases are rarely associated with EN, but all patients were not thoroughly investigated . A large and prospective study should be performed in order to determine the true prevalence of associated diseases in EN . In the absence of specific symptoms, exhaustive investigations are not cost-effective. Int J Dermatol, 1998 Sep, 37(9), 664 - 6 Relapsing cutaneous polyarteritis nodosa associated with streptococcal infections; Albornoz MA et al.; BACKGROUND: Polyarteritis nodosa is an aggressive, often fatal form of vasculitis associated with multi-organ involvement . Cutaneous polyarteritis nodosa is purported to be a more benign form of this disorder with involvement limited to the skin . METHODS: The identification of a female patient from childhood to adulthood documenting repeated episodes of cutaneous polyarteritis nodosa following bouts of recurrent streptococcal pharyngitis . RESULTS: Repeated bouts of streptococcal pharyngitis at ages 11, 28, and 33 years were followed by episodes of cutaneous polyarteritis nodosa, documented by histopathologic skin changes and clinical presentation, and confirmed by therapeutic management . CONCLUSIONS: Various infectious and non-infectious conditions have been linked both to the initiation and relapse of this disease . We describe a patient with recurrent episodes of cutaneous polyarteritis nodosa spanning a period of over 20 years with each episode appearing to be linked to a prior streptococcal infection. Protein Sci, 1998 Sep, 7(9), 1939 - 46 The de novo design of a rubredoxin-like Fe site; Farinas E et al.; A redox center similar to that of rubredoxin was designed into the 56 amino acid immunoglobulin binding B1 domain of Streptococcals protein G . The redox center in rubredoxin contains an iron ion tetrahedrally coordinated by four cysteine residues, {Fe(S-Cys)4}(-1),(-2) . The design criteria for the target site included taking backbone movements into account, tetrahedral metal-binding, and maintaining the structure and stability of the wild-type protein . The optical absorption spectrum of the Co(II) complex of the metal-binding variant is characteristic of tetrahedral chelation by four cysteine residues . Circular dichroism and nuclear magnetic resonance measurements reveal that the metal-free and Cd(II)-bound forms of the variant are folded correctly and are stable . The Fe(III) complex of the metal-binding mutant reproduces the optical and the electron paramagnetic resonance spectra of oxidized rubredoxin . This demonstrates that the engineered protein chelates Fe(III) in a tetrahedral array, and the resulting center is similar to that of oxidized rubredoxin. Arch Pediatr, 1998 Jun, 5(6), 681 - 6 {Diagnosis and treatment of rheumatic fever}; David L; Rheumatic fever has become rare in France as in most developed countries . However, recent outbreaks have underlined the need for practitioners to remain vigilant and to maintain careful prevention . Polyarthritis and polyarthralgia are the main manifestations of rheumatic fever but they are not specific . Carditis is a major feature which affects only half the patients; cardiac ultrasonography is therefore very helpful with respect to positive and false positive diagnoses resulting from innocent murmurs . Fever, acute phase inflammatory markers, and evidence of streptococcal infection are of major importance and rheumatic fever must be disregarded in their absence . The treatment includes: 1) steroids for a 3 month-period; 2) early antibiotic treatment of streptococcal carriage; 3) long-term prophylaxis using intramuscular benzathine penicillin. Arch Pediatr, 1998 Jun, 5(6), 673 - 8 {Plea for an evaluation of beta hemolytic streptococcal tonsillitis: from diagnosis to treatment}; Cohen R et al.; There is no justification to maintain a systematic antibiotic treatment of all tonsillitis as currently practiced in France . Indeed, it is today possible to exclude the streptococcal origin of tonsillitis with a fair probability using a rapid diagnosis test . It is therefore mandatory that these tests are made available to the French practitioner . Additionally, alternatives to the classical 10-day penicillin V treatment of streptococcal tonsillitis must be seriously considered: shorter duration treatment with oral cephalosporins, macrolides or amoxicillin have proved to be as efficient and of lower cost; they are also probably safer due to a better compliance related to the shorter duration. Hum Immunol, 1998 Oct, 59(10), 607 - 14 The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cells; Fujii S et al.; The presentation of antigenic peptides by major histocompatibility complex (MHC) class II to CD4+ T cells is crucial to initiate immune responses . We developed a new system for delivery of an antigenic peptide to the MHC class II pathway, using the invariant chain (Ii) . We designed a mutated human p33-form Ii, CLIP-substituted Ii, in which streptococcal M12p55-68 (RDLEQAYNELSGEA) was substituted for CLIP (class II associated invariant chain peptide) . We examined the peptide presenting function of this construct, in comparison with the previously reported C-terminal fused Ii, in which a cathepsin cleavage site and M12p54-68 was ligated to the C-terminus of Ii . Mouse L cell transfectants expressing either of these two mutated Ii along with HLA-DR4 could process and present M12p55-68 to the peptide specific and DR4-restricted CD4+ T cell clone . CLIP-substituted Ii was much more efficient in antigen presentation than was the C-terminal fused Ii . Similar to the wild-type Ii, the CLIP-substituted Ii was associated intracellularly with DR4 molecules . These results indicate that the peptide substituted for CLIP of Ii p33 bound to the groove of DR molecules in the same manner as CLIP and it was preferentially presented to the CD4+ T cell clone in the absence of HLA-DM molecules . This system may prove useful for immunotherapy with DNA vaccines or for construction of an antigen presenting cell library with diverse peptides. Gastroenterology, 1998 Oct, 115(4), 856 - 65 Subtherapeutic corticosteroids potentiate the ability of interleukin 10 to prevent chronic inflammation in rats; Herfarth HH et al.; BACKGROUND & AIMS: Interleukin (IL)-10, which inhibits macrophages and T-helper lymphocyte type 1 (TH1) lymphocytes, attenuates chronic granulomatous inflammation induced by bacterial cell wall polymers . This study determines whether corticosteroids enhance the protective effects of IL-10 in cultured peripheral blood mononuclear cells (PBMNCs) and in vivo when started before or after the onset of experimental chronic granulomatous inflammation . METHODS: Intestines of Lewis rats were injected intramurally with streptococcal peptidoglycan-polysaccharide (PG-APS) polymers . Daily murine recombinant IL-10 and/or dexamethasone (DEX) therapy was started 12 hours before or at several intervals after PG-APS injection . RESULTS: IL-10 plus corticosteroids additively inhibited IL-1beta secretion in human PBMNCs but preserved the beneficial IL-1RA/IL-1beta ratio induced by IL-10 . IL-10 started before PG-APS injection significantly attenuated intestinal and extraintestinal inflammation, with even more pronounced effects in combination with subtherapeutic doses of DEX . The combination of DEX decreased the effective dose of IL-10 by at least one half . After onset of systemic inflammation using doses effective for prevention, IL-10 monotherapy had nearly no benefit and DEX plus IL-10 was similar to the mild therapeutic effect of DEX alone . CONCLUSIONS: The combination of IL-10 and corticosteroids allows lower doses of both agents in preventing chronic intestinal and systemic inflammation . However, timing of IL-10 administration is a critical variable in regulating inflammation. Infect Immun, 1998 Oct, 66(10), 5020 - 6 Mutational analysis of superantigen activity responsible for the induction of skin erythema by streptococcal pyrogenic exotoxin C; Yamaoka J et al.; Streptococcal pyrogenic exotoxin C (SPEC), when injected intradermally, induces erythema in unsensitized rabbits . In the present study, we examined whether this erythema induction is due to the T-cell stimulatory activity of SPEC as a superantigen . Analysis by using single-residue mutant SPECs indicated that mutant SPECs Y15I, A16E, and Y17I, in which tyrosine 15, alanine 16, and tyrosine 17 were replaced with isoleucine, glutamic acid, and isoleucine, respectively, exhibited significantly reduced mitogenic activity for Vbeta2(+) human T cells in vitro, and Y15I showed as much as a 1, 000-fold reduction . Y15I mutant SPEC, however, retained the ability to bind to major histocompatibility complex class II antigen and to form a homodimer, implying that residue 15 is critically important for the interaction of SPEC with T-cell antigen receptor beta chains . When injected intradermally into normal rabbits, wild-type SPEC induced a characteristic erythema after 3 h in a dose-dependent fashion, which was associated with polymorphonuclear and mononuclear cell infiltration . This erythema formation was found to be severely suppressed by systemic pretreatment with cyclosporin A, suggesting the involvement of host T cells . Y15I mutant SPEC exhibited nearly 1, 000-fold less erythema induction in vivo than wild-type SPEC . Altogether, the present results strongly suggest that erythema induction in rabbits by SPEC is attributable mostly to its T-cell stimulatory activity as a superantigen. Pediatr Nephrol, 1998 Aug, 12(6), 471 - 4 Glomerular deposits and hypoalbuminemia in acute post-streptococcal glomerulonephritis; West CD et al.; In a search for correlations between glomerular morphology and clinical manifestations in acute post-streptococcal glomerulonephritis, data for 40 biopsied patients were reviewed . A major correlation was observed between severe hypoalbuminemia and the absence of deposits on the paramesangial portion of the glomerular basement membrane . Subepithelial deposits were present on both the capillary loop and paramesangial segments of the basement membrane in 29 patients, whereas in 11 the deposits were present only on the capillary loop . Patients with paramesangial segments devoid of deposits had a mean (+/-1 SD) nadir serum albumin level of 1.90 (+/-0.40) g/dl, whereas the mean nadir level in those with deposits in both locations was 2.83 (+/-0.64) g/dl (P<0.001) . Also significant was the difference in paramesangial deposit scores in patients with nadir serum albumin levels < or =2.5 g/dl versus those with levels >2.5 g/dl . The amount of subepithelial deposit on the capillary loop was not significantly different in the two groups, and no correlation was found between loop deposits and serum albumin levels . Except for greater edema and significantly less-frequent gross hematuria in those with absent paramesangial deposits, clinical and laboratory findings for the two groups did not differ. Pediatr Rev, 1998 Sep, 19(9), 291 - 302 Group A beta-hemolytic streptococcal infections; Pichichero ME; GABHS is the most common bacterial cause of tonsillopharyngitis, but this organism also produces acute otitis media; pneumonia; skin and soft-tissue infections; cardiovascular, musculoskeletal, and lymphatic infections; bacteremia; and meningitis . Most children and adolescents who develop a sore throat do not have GABHS as the cause; their infection is viral in etiology . Other bacterial pathogens produce sore throat infrequently (e.g., Chlamydia pneumoniae and Mycoplasma pneumoniae), and when they do, other concomitant clinical illness is present . Classic streptococcal tonsillopharyngitis has an acute onset; produces concurrent headache, stomach ache, and dysphagia; and upon examination is characterized by intense tonsillopharyngeal erythema, yellow exudate, and tender/enlarged anterior cervical glands . Unfortunately only about 20% to 30% of patients present with classic disease . Physicians overdiagnose streptococcal tonsillopharyngitis by a wide margin, which almost always leads to unnecessary treatment with antibiotics . Accordingly, use of throat cultures and/or rapid GABHS detection tests in the office is strongly advocated . Their use has been shown to be cost-effective and to reduce antibiotic overprescribing substantially . Penicillin currently is recommended by the American Academy of Pediatrics and American Heart Association as first-line therapy for GABHS infections; erythromycin is recommended for those allergic to penicillin . Virtually all patients improve clinically with penicillin and other antibiotics . However, penicillin treatment failures do occur, especially in tonsillopharyngitis in which 5% to 35% of patients do not experience bacteriologic eradication . Penicillin treatment failures are more common among patients who have been treated recently with the drug . Cephalosporins or azithromycin are preferred following penicillin treatment failures in selected patients as first-line therapy, based on a history of penicillin failures or lack of compliance and for impetigo . GABHS remain exquisitely sensitive to penicillin in vitro . There are several explanations for penicillin treatment failures, but the possibility of copathogen co-colonization in vivo has received the most attention . Treatment duration with penicillin should be 10 days to optimize cure in GABHS infections . A 5-day regimen is possible and approved by the United States Food and Drug Administration for cefpodoxime (a cephalosporin) and azithromycin (a macrolide) . Prevention of rheumatic fever is the primary objective for antibiotic therapy of GABHS infections, but a reduction in contagion and faster clinical improvement also can be achieved . Development of streptococcal toxic shock syndrome and necrotizing fasciitis ("flesh-eating bacteria") are rising concerns . The portal of entry for these invasive GABHS strains is far more often skin and soft tissue than the tonsillopharynx. Kansenshogaku Zasshi, 1998 Jul, 72(7), 776 - 80 {A fatal case of streptococcal toxic shock-like syndrome probably caused by acupuncture}; Onizuka T et al.; A 41-year-old male received acupuncture in the right shoulder for the sake of arthralgia . Three days after acupuncture he was admitted due to severe epigastralgia . Erythematous change and swelling were observed around the right shoulder . A study by magnetic resonance showed an increased signal intensity in a portion of the right subscapular muscle . Four hours after admission he became hypotensive . The erythematous and necrotic change in the right shoulder skin rapidly spread . Excisional debridement in the right lateral chest wall was immediately done . However, the patient died one day after admission despite administration of a high-dose ampicillin and other supportive therapies . Bacteriological and histological examinations confirmed severe streptococcal myositis . This is a case report of toxic shock-like syndrome probably caused by acupuncture. J Am Acad Dermatol, 1998 Sep, 39(3), 383 - 98; quiz 399-400 Toxin-mediated streptococcal and staphylococcal disease; Manders SM; After several decades of seemingly decreasing virulence, streptococcal and staphylococcal infections have reemerged as a major source of morbidity and mortality . Within the past 2 decades, not only have well-established diseases such as rheumatic fever begun to reappear . but also many new entities, such as toxic shock syndrome, streptococcal toxic shock syndrome, recurrent toxin-mediated perineal erythema, and recalcitrant erythematous desquamating disorder have been described . Central to the renewed importance of these bacteria has been the production of circulating toxins, which often function as superantigens in causing the clinical manifestations, morbidity and mortality associated with these diseases. Proc Natl Acad Sci U S A, 1998 Sep 15, 95(19), 11383 - 8 Macrophage migration inhibitory factor is a critical mediator of the activation of immune cells by exotoxins of Gram-positive bacteria; Calandra T et al.; Discovered in the early 1960s as a T cell cytokine, the protein mediator known as macrophage migration inhibitory factor (MIF) has been found recently to be a pituitary peptide released during the physiological stress response, a proinflammatory macrophage cytokine secreted after LPS stimulation, and a T cell product expressed as part of the antigen-dependent activation response . We report herein that MIF also plays a critical role in the innate host response to staphylococcal and streptococcal exotoxins . In RAW 264.7 or elicited mouse peritoneal macrophages, peak MIF secretion was induced by concentrations of the staphylococcal toxic shock syndrome (TSS) toxin 1 (TSST-1) and the streptococcal pyrogenic exotoxin A as low as 10 pg/ml . Moreover, dose-response studies of splenocyte cytokine production showed that lower concentrations of TSST-1 (10 pg/ml) were needed to release MIF than to induce interleukin 2 or interferon-gamma secretion (1 ng/ml) . We also studied the effect of neutralizing anti-MIF antibodies on TSST-1-induced lymphocyte proliferation and lethal toxic shock . Pretreatment of C57BL/6 mice with anti-MIF antibody 2 hr before TSST-1 injection prevented spleen enlargement and reduced by 50% the proliferation of splenocytes measured ex vivo . In a lethal mouse model of TSST-1-induced shock, anti-MIF antibody increased survival from 8% to 54% (P < 0.0001) . These studies indicate that Gram-positive exotoxins are extremely potent inducers of MIF secretion and establish a critical role for MIF and the macrophage in the pathogenesis of the TSSs and in the innate immune response. J Child Neurol, 1998 Sep, 13(9), 413 - 23 PANDAS: the search for environmental triggers of pediatric neuropsychiatric disorders . Lessons from rheumatic fever; Garvey MA et al.; Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) is a relatively new diagnostic construct applied to children or adolescents who develop, and have repeated exacerbations of, tic disorders and/or obsessive-compulsive disorder following group A beta-hemolytic streptococcal infections . The proposed pathophysiology is that the group A beta-hemolytic streptococcal bacteria trigger antibodies that cross-react with the basal ganglia of genetically susceptible hosts leading to obsessive-compulsive disorder and/or tics . This is similar to the etiologic mechanisms proposed for Sydenham's chorea, in which group A beta-hemolytic streptococcal antibodies cross-react with the basal ganglia and result in abnormal behavior and involuntary movements . When first proposed, there was much controversy about the idea that streptococcal infections were etiologically related to rheumatic fever . In a like manner, discussion has arisen about the concept of infection-triggered obsessive-compulsive disorder and tic disorders . We review the historical background to these controversies, give an update on the findings provided by research on PANDAS, and address areas of future study. Nervenarzt, 1997 Nov, 68(11), 914 - 6 {Immunoglobulin therapy in Gilles de la Tourette syndrome}; Muller N et al.; It has known for a long time that Sydenham's chorea and tics, as seen in Gilles de la Tourette's syndrome (GTS), are phenomenologically very similar . Tics may occur as symptoms of acute Sydenham's chorea or persist over years as residual symptoms . Investigating of children suffering from GTS, including obsessive-compulsive symptoms, have provided signs of a poststreptococcal autoimmune process but also shown that treatment based on immunological interventions has been effective . We treated a 14-year-old boy showing all diagnostic criteria of GTS, familial susceptibility, and an increase in the antibody titer of streptococcal antigens with 75 immunoglobulins i.v . over 5 days . Response to this therapy was good regarding motor tics, vocal tics, and behavioral symptoms such as disturbed impulse control which still persisted after 9 months . These findings and the successful therapy underline reports of the literature and point to a pathogenetic mechanism of an immunologically triggered disturbance of the striatal dopaminergic system, at least in a subgroup of GTS. Am J Ophthalmol, 1998 Aug, 126(2), 317 - 8 Poststreptococcal uveitis; Leiba H et al.; PURPOSE: To report that uveitis may be a manifestation of poststreptococcal syndrome . METHODS: Case report . Documented attacks of bilateral uveitis were clearly associated with streptococcal infection . RESULTS: Group A streptococcal infection was evident in all bilateral uveitis attacks, which were treated with local or systemic corticosteroids and penicillin . The frequency and severity of the attacks were reduced by penicillin prophylaxis and tonsillectomy . CONCLUSIONS: Uveitis should be included as a possible manifestation of poststreptococcal syndrome . If coexisting streptococcal infection is demonstrated, penicillin prophylaxis should be considered. Proc Natl Acad Sci U S A, 1998 Sep 1, 95(18), 10505 - 10 Lagging strand replication of rolling-circle plasmids: specific recognition of the ssoA-type origins in different gram-positive bacteria; Kramer MG et al.; Many bacterial plasmids replicate by a rolling-circle mechanism that involves the generation of single-stranded DNA (ssDNA) intermediates . Replication of the lagging strand of such plasmids initiates from their single strand origin (sso) . Many different types of ssos have been identified . One group of ssos, termed ssoA, which have conserved sequence and structural features, function efficiently only in their natural hosts in vivo . To study the host specificity of sso sequences, we have analyzed the functions of two closely related ssoAs belonging to the staphylococcal plasmid pE194 and the streptococcal plasmid pLS1 in Staphylococcus aureus . The pLS1 ssoA functioned poorly in vivo in S . aureus as evidenced by accumulation of high levels of ssDNA but supported efficient replication in vitro in staphylococcal extracts . These results suggest that one or more host factors that are present in sufficient quantities in S . aureus cell-free extracts may be limiting in vivo . Mapping of the initiation points of lagging strand synthesis in vivo and in vitro showed that DNA synthesis initiates from specific sites within the pLS1 ssoA . These results demonstrate that specific initiation of replication can occur from the pLS1 ssoA in S . aureus although it plays a minimal role in lagging strand synthesis in vivo . Therefore, the poor functionality of the pLS1 in vivo in a nonnative host is caused by the low efficiency rather than a lack of specificity of the initiation process . We also have identified ssDNA promoters and mapped the primer RNAs synthesized by the S . aureus and Bacillus subtilis RNA polymerases from the pE194 and pLS1 ssoAs . The S . aureus RNA polymerase bound more efficiently to the native pE194 ssoA as compared with the pLS1 ssoA, suggesting that the strength of RNA polymerase-ssoA interaction may play a major role in the functionality of the ssoA sequences in Gram-positive bacteria. Proteins, 1998 Aug 1, 32(2), 248 - 61 Structural features of the plasmid pMV158-encoded transcriptional repressor CopG, a protein sharing similarities with both helix-turn-helix and beta-sheet DNA binding proteins; Acebo P et al.; The small transcriptional repressor CopG protein (45 amino acids) encoded by the streptococcal plasmid pMV158 was purified to near homogeneity . Gel filtration chromatography and analytical ultracentrifugation showed that the native protein is a spherical dimer of identical subunits . Circular dichroism measurements of CopG indicated a consensus average content of more than 50% alpha-helix and 10-35% beta-strand and turns, which is compatible with the predicted secondary structure of the protein . CopG exhibited a prolonged intracellular half-life, but deletions in regions other than the C-terminal affected the global structure of the protein, severely reducing the half-lives of the CopG variants . This indicates that CopG has a compact structure, perhaps constituted by a single domain . Molecular modeling of CopG showed a good fitting between the helix-turn-helix motifs of well-known repressor proteins and a bihelical unit of CopG . However, modeling of CopG with ribbon-helix-helix class of DNA binding proteins also exhibited an excellent fit . Eleven out of the 12 replicons belonging to the pMV158 plasmid family could also encode Cop proteins, which share features with both helix-turn-helix and beta-sheet DNA binding proteins. J Immunol, 1998 Aug 15, 161(4), 2020 - 31 Molecular analysis of polyreactive monoclonal antibodies from rheumatic carditis: human anti-N-acetylglucosamine/anti-myosin antibody V region genes; Adderson EE et al.; Anti-myosin Abs are associated with inflammatory heart diseases such as rheumatic carditis and myocarditis . In this study, human cross-reactive anti-streptococcal/anti-myosin mAbs 1.C8, 1.H9, 5.G3, and 3.B6, produced from peripheral blood lymphocytes of patients with rheumatic carditis, and mAb 10.2.5, produced from a tonsil, were characterized, and the nucleotide sequences of their V(H) and V(H)L genes were analyzed . Human mAbs 1.C8, 1.H9, 10.2.5, and 3.B6 reacted with human cardiac myosin while mAb 5.G3 did not . The mAbs were strongly reactive with N-acetyl-beta-D-glucosamine, the dominant epitope of the group A streptococcal carbohydrate . mAb 1.H9 was moderately cytotoxic to rat heart cells in vitro in the presence of complement . The anti-myosin mAbs from rheumatic carditis were found to react with specific peptides from the light meromyosin region of the human cardiac myosin molecule . Anti-streptococcal/anti-myosin mAbs from normal individuals reacted with distinctly different light meromyosin peptides . The mAbs were encoded by V(H)3 gene segments V3-8, V3-23, and V3-30 and by the V(H)4 gene segment V4-59 . The variable region genes encoding the anti-streptococcal/anti-myosin repertoire were heterogeneous and exhibited little evidence of Ag-driven somatic mutation. Pediatr Rev, 1998 Aug, 19(8), 276 - 9 Infectious mononucleosis; Peter J et al.; EBV-induced IM is a generally self-limited infection characterized by fever, pharyngitis, and adenopathy . Management consists of basic supportive measures and treatment of streptococcal pharyngitis when present . Corticosteroids may be considered for individuals who exhibit evidence of significant upper airway obstruction . To date there is little evidence to support the use of antiviral agents in immunocompetent patients . Complications of IM may arise, which can be life-threatening, but these are relatively rare. Eur J Clin Microbiol Infect Dis, 1998 Apr, 17(4), 235 - 9 Azithromycin versus cefaclor in the treatment of pediatric patients with acute group A beta-hemolytic streptococcal tonsillopharyngitis; Cremer J et al.; An open, comparative multicenter study was performed to evaluate the efficacy and safety of azithromycin (10 mg/kg) given once daily for three days in comparison with cefaclor (30 mg/kg) divided into three daily doses and given for a period of ten days . One hundred and twenty-two children aged 1-12 years with clinical symptoms of group A beta-hemolytic streptococcal tonsillopharyngitis and a positive throat culture were randomly allocated to the treatment groups . Overall, the clinical success (cure or improvement) of both regimens was identical in the evaluable patients (86.3%, 44 of 51 patients in either treatment group) . In contrast, bacterial eradication after completion of treatment was lower with azithromycin than with cefaclor . Possible reasons for this discrepancy between clinical success and eradication rates could be antibiotic resistance, pre-disease carriage or insufficient dosage . Both agents were well tolerated; only mild or moderate side effects most frequently involving the gastrointestinal tract, were recorded in either therapy group. Acta Paediatr Jpn, 1998 Jun, 40(3), 256 - 8 Seasonal benzathine penicillin G prophylaxis for recurrent streptococcal pharyngitis in children; Aksit S et al.; BACKGROUND: To assess the efficacy of benzathine penicillin G (BPG) prophylaxis in recurrent streptococcal pharyngitis in children . METHODS: One hundred and sixty children, aged 4-11 years, who experienced at least two episodes of group A beta-hemolytic streptococcal (GABHS) pharyngitis during a 4-month observation period between September and December 1995 were randomly divided into two groups . During the following 4-month period between January and April 1996, 80 children received BPG prophylaxis every 3 weeks as a single intramuscular injection of 1.2 million units for a body weight greater than 27 kg and a half dose for 27 kg or less . Eighty children were accepted as a control group and were not given BPG prophylaxis . RESULTS: The children in the BPG group experienced significantly less GABHS pharyngitis than those in the control group during the second 4-month period (16 vs 244 episodes, respectively, P < 0.001) . BPG prophylaxis decreased streptococcal pharyngitis by 92% in the children in the study group, while the frequency of GABHS pharyngitis was unchanged in those in the control group during the second 4-month period compared with the first 4-month period . CONCLUSIONS: The data in the present study demonstrated that intramuscular BPG prophylaxis is very effective in preventing GABHS pharyngitis in children . It is recommended that it is used every 3 weeks in at least the fall-winter seasons in children susceptible to frequent GABHS pharyngitis. Ter Arkh, 1998, 70(6), 38 - 41 {Unsolved questions of infectious endocarditis prophylaxis in outpatients practice}; Alekseeva LA et al.; AIM: To check practical feasibility of recommendations of prevention of infectious endocarditis (IE) and to provide more accurate figures on the occurrence of valvular lesions in working population . MATERIALS AND METHODS: Subacute IE manifestations have been analysed in 10 patients of a general outpatient clinic . Echocardiograms of 6209 patients under 60 years of age were studied retrospectively . RESULTS: In one-third of the patients IE developed in the presence of streptococcal and staphylococcal infection . In all the cases cardiac valve involvement was stated . In 4 cases changes in the valve were not accompanied my impairment of the valvular function . By echocardiography, valvular structure changes without valvular disease were detected 2.3 times more frequently that valvular disease . Difficulties presenting in outpatient IE prophylaxis are outlined . CONCLUSION: Advances in IE prevention will be achieved if echo-CG becomes a mandatory examination in the program of working population check-up, if early diagnosis of streptococcal ENT infection is made, if physicians of different specialties work as a team. Dtsch Tierarztl Wochenschr, 1998 Jun, 105(6), 213 - 6 {Nature and amount of aerial pollutants from livestock buildings}; Hartung J; The air in animal housing contains gases, odours, dust particles and microorganisms which are discharged by way of the ventilation system into the environment . There is increasing concern within parts of the population that these compounds may affect the respiratory health of people living close to livestock enterprises . A brief survey is presented on airborne emissions from livestock buildings . About 136 gaseous compounds are analysed in animal house air of which only 22 are quantified . The most environment-related compounds are ammonia and methane . It is assumed that German animal husbandry emits up to 750,000 Mg ammonia per year . The concentrations of airborne microorganisms in livestock buildings are between some 100 and several 1000 per liter . Staphylococcae, streptococcae, colilike bacteria, fungi, moulds and yeasts are regularly found . The 24 h average concentrations of dust in animal barns vary considerably . In poultry houses the highest inhalable resp . respirable dust concentrations (up to 10 mg/m3 resp . 1.2 mg/m3) were found, followed by pig houses (5.5 mg/m3) and cattle barns (1.22 mg/m3 resp . 0.17 mg/m3) . The concentrations of endotoxins in the airborne dust can range from 0.6 ng/m3 (cattle, respirable dust) to 860 ng/m3 (laying hens, inhalable dust) . The presently discussed occupational health threshold at the workplace is around 5 ng/m3 (50 EU/m3) . The emission rate for respirable dust from piggeries is at about 60 mg/h, from poultry houses nearly 300 mg/h and from cattle barns at 20 mg/h, related to 500 kg liveweight of the animals . Little is known about the distances these particles are transported through the air outside the animal buildings. Kidney Int, 1998 Aug, 54(2), 509 - 17 Antibody to streptococcal zymogen in the serum of patients with acute glomerulonephritis: a multicentric study; Parra G et al.; BACKGROUND: Cationic streptococcal proteinase (erythrotoxin B) and its precursor, zymogen, are putative nephritogenic antigens . The present study was designed to test whether serum titers to these antigens were good markers of streptococcal infection associated with glomerulonephritis . METHODS: We studied 153 patients (male/female = 104/49, age range, 2 to 23 years old) with acute poststreptococcal glomerulonephritis (APSGN) from three countries (Venezuela, Chile and Argentina) . The site of the initial infection was the skin in 84 patients, the throat in 55 patients and was unknown in 14 patients . In addition, we studied 23 patients (1 to 24 years old) with streptococcal infection not associated with glomerulonephritis (14 patients with impetigo and 9 patients with pharyngitis) . As control group, 93 healthy individuals (54 males, 2 to 19 years old) were studied . Anti-zymogen and anti-proteinase titers were determined in a single laboratory by ELISA, and the intra- and interassay coefficients of variation were 5.3% and 8.5%, respectively . ASO titers and anti-DNAse B titers were also done . RESULTS: Anti-zymogen titers of 1:800 to 1:3200 had likelihood ratios (sensitivity/1-specificity) for detection of streptococcal infection in APSGN patients ranging from 2.00 to 44.2 in Argentina, Chile and Venezuela . Anti-zymogen titers decreased one to two months after APSGN and they were 1 to 3 log2 dilutions higher that anti-proteinase titers . Receiver operating characteristic (ROC) curves showed that anti-zymogen titers were consistently superior to anti-streptolysin O and anti-DNAse B titers as markers for streptococcal infection in APSGN . CONCLUSIONS: These results suggest that increased anti-zymogen antibody titers are the best available marker for streptococcal infection associated with acute glomerulonephritis. J Trop Pediatr, 1998 Jun, 44(3), 142 - 7 Nutritional factors associated with rheumatic fever; Zaman MM et al.; The determinants for a child with group A beta-haemolytic streptococcal throat infection (BHS infection) to develop rheumatic fever (RF) remain unclear . In this case-control study, we deal with BHS infected children to examine whether nutritional factors are related to RF . In a RF hospital in Dhaka (Bangladesh) we examined 218 consecutive out-patients who had antecedent BHS infection . Sixty of them met the updated Jones criteria for RF (cases) while 104 did not (controls) . Fifty-four possible RF patients were excluded . We used anthropometric measurements and a food frequency questionnaire to assess nutritional factors . Higher risk of RF was observed for low height for age (odds ratio 3.82, 95% confidence interval 1.73-8.42); low weight for age (2.41, 1.12-5.57); low upper arm circumference for age (3.76, 1.87-7.89); and low consumption of eggs (3.81, 1.95-7.63), milk (2.60, 1.36-5.08), chicken (2.62, 1.35-5.21), pulses (1.98, 1.03-3.84), fruits 2.29, 1.20-4.45), and ruti (home-made bread) (3.15, 1.61-6.34) . Reduced risk was observed for soybean oil consumption (0.28, 0.12-0.62) . The significant association of upper arm circumference and eggs persisted after adjustment for multiple sociodemographic confounders . The association of ruti and soybean oil appeared to be suggestive (0.05 < p < 0.1) . Protein-energy malnutrition is likely to be associated with RF . The protective effect of moderate consumption of eggs and soybean oil may support other published work which suggests that the anti-inflammatory substance present in these food items may prevent maturation of the rheumatic process. Mol Microbiol, 1998 Jun, 28(6), 1323 - 34 The group A streptococcal dipeptide permease (Dpp) is involved in the uptake of essential amino acids and affects the expression of cysteine protease; Podbielski A et al.; The majority of characterized bacterial dipeptide permeases (Dpp) are membrane-associated complexes of five proteins belonging to the ABC-transporter family . They have been found to be involved in the uptake of essential amino acids, haem production, chemotaxis and sporulation . A 5.8 kb genomic DNA fragment of the serotype M49 group A streptococcal (GAS) strain CS101 was sequenced and found to contain five putative GAS Dpp genes (dppA to dppE) . Deduced amino acid sequences exhibited 17-54% similarity to corresponding ABC-transporter sequences . The operon organization of the five genes was confirmed by transcriptional analysis, and a shorter, more abundant, dppA-only transcript was detected similar to that found in the GAS oligopeptide permease (Opp) system . Insertional inactivation was used to create serotype M2 and M49 strains that did not express the dppD and dppEATPase genes or nearly the entire operon . In feeding experiments with di- to hexapeptides, the wild-type strain grew with each peptide tested . The dpp mutants were unable to grow on dipeptides, whereas hexapeptides did not sustain the growth of opp mutants . Expression of the dpp operon was induced approximately fourfold in late exponential growth phase . In addition, a striking increase in the dppA to dppA-E ratio from 5:1 to more than 20:1 occurred during late exponential growth phase in complex medium . Growth in chemically defined medium (CDM) supplemented with various dipeptides specifically induced the expression of dpp and reduced both the dppA to dppA-E and oppA to oppA-F mRNA ratios . Expression of the virulence factor SpeB (major cysteine protease) was reduced eightfold in dpp mutants, whereas dpp expression was decreased about fourfold in a Mga virulence regulator mutant . Taken together, these data indicate a correlation between levels of intracellular essential amino acids and the regulation of virulence factor expression. Int J Dermatol, 1998 Jul, 37(7), 515 - 9 Etiologic aspects of chronic urticaria; Liutu M et al.; BACKGROUND: Urticaria is a common disease that is always a challenge to the dermatologist due to its evasive etiology . PATIENTS AND METHODS: One hundred and seven chronic urticaria patients were studied . Routine laboratory investigations were performed and Helicobacter pylori (H . pylori) immunoglobulin G (IgG) antibody determinations, autoimmune reactivity, infections, allergies, and hyperreactivities were investigated . RESULTS: Pathologic findings were seen in 92 patients . Concomitant diseases suggesting autoimmune reactivity were detected in nine patients and, in 16 patients, infections including maxillary sinusitis, streptococcal tonsillitis, and tooth infection were found . Elevated total IgE level was detected in 37 out of 75 patients and positive skin prick test results in 47 out of 91 patients . Fifty-five patients had a history of recent dyspeptic symptoms . A diagnosis of adult celiac disease was made in two patients and, additionally, IgA antigliadin antibodies were seen in four patients . H . pylori IgG antibodies were found in 40 out of 107 patients . Active gastritis was verified by esophagogastroduodenoscopy in 30 out of 32 patients with positive Helicobacter staining in 24 samples . An elevated IgE level was detected in 64% of H . pylori-positive and in 39% of H . pylori-negative patients . CONCLUSIONS: In this study, several findings suggesting aberrant immunologic activation were detected in chronic urticaria patients . Inflammation in the gastrointestinal tract, e.g . caused by H . pylori infection, may have an important role in the etiology of chronic urticaria. Clin Infect Dis, 1998 Jul, 27(1), 150 - 7 Invasive group A streptococcal disease in metropolitan Atlanta: a population-based assessment; Zurawski CA et al.; Active, population-based surveillance for invasive group A streptococcal (GAS) disease was conducted in laboratories in metropolitan Atlanta from 1 January 1994 through 30 June 1995 . Clinical and laboratory records were reviewed and isolates characterized . One hundred and eighty-three cases of invasive GAS disease were identified (annual incidence, 5.2 cases/100,000) . The incidence was highest among blacks (9.7/100,000 per year; relative risk (RR), 1.92; confidence interval (CI), 1.69-2.19; P < .0001) and the elderly, particularly nursing home residents (RR, 13.66; CI, 7.07-26.40; P < .0001) . The mean age of patients was 41.3 years (range, 0-95 years) . Skin and soft-tissue infections were most common . Mortality was 14.4%; risk of death was significantly higher for patients with streptococcal toxic shock syndrome (STSS) (RR, 9.73; CI, 3.34-29; P = .0008) and individuals infected with M-type 1 (RR, 7.40; CI, 1.5-16; P = .0084) . Fourteen percent of invasive GAS infections were STSS and 3% were necrotizing fasciitis . Invasive GAS disease was associated with varicella infection in children (RR, 12.19; CI, 5.58-26.62; P < .0001) . M (or emm) types included M1 (16%), M12 (12%), and M3 (11%) . Continued study of GAS disease is essential to further define risk factors and risk of secondary cases and to develop effective prevention strategies. Int J Cardiol, 1998 May 15, 64(3), 259 - 63 Group B streptococcal tricuspid valve endocarditis: a case report and review of literature; Azzam ZS et al.; Group B streptococcal endocarditis involving the tricuspid valve is an uncommon disease . We describe herein a young healthy woman who developed this disease following an elective abortion . She was treated with penicillin and gentamycin with no response . The patient was operated urgently and recovered . Few reports have described the disease in the last 25 years (our case is the thirteenth) . Five of them were IV drug abusers, four patients suffered from debilitating diseases and in five women endocarditis developed following an obstetric procedure . In general the mortality from tricuspid valve endocarditis is low, indeed 2/13 (15%) died . The drug of choice is penicillin with gentamycin. Vet Rec, 1998 Jun 13, 142(24), 665 - 9 Suspected bacterial meningoencephalitis in two adult horses; Newton SA; Bacterial infections (such as meningitis or meningoencephalitis) of the central nervous system are rare in horses . They are most prevalent in neonates as a result of septicaemia . A few cases have been reported in the adult and most have been fatal . Streptococcal species appear to be the organism most commonly identified in these cases . Thus, this disease may be a secondary complication of upper respiratory tract infections . Clinical signs are extremely variable making diagnosis difficult . In most cases, postmortem has been the definite diagnostic procedure . This paper describes the clinical course of disease, diagnosis and successful treatment of two presumptive cases of meningoencephalitis in adult horses. Pediatr Res, 1998 Jul, 44(1), 27 - 31 Transient low T cell response to streptococcal pyrogenic exotoxin-C in patients with Kawasaki disease; Masuda K et al.; Superantigens (SAs) are known to induce transient anergy followed by T cell activation . Recent reports have suggested that SAs are involved in the pathogenesis of Kawasaki disease (KD) . In the present study, we investigated the peripheral T cell response to SAs by measuring proliferation and IL-2 production to determine whether the T cell anergy is induced by SAs in patients with KD . T cells were obtained from 45 Japanese patients with KD in different stages of the disease and were stimulated by streptococcal pyrogenic exotoxin (SPE)-A, SPE-C, and toxic shock syndrome toxin-1 (TSST-1) . T cells from patients with KD in the acute or convalescent stage up to 2 mo showed significantly lower proliferation and IL-2 production than did T cells from healthy control subjects stimulated by SPE-C, but not SPE-A or TSST-1 . The T cell response to SPE-C normalized within 1 y . The low T cell response to SPE-C in the acute stage correlated with a peak platelet count and the C-reactive protein-positive period . These findings suggest that the transient low T cell response to SPE-C in patients with KD may have been related to SA-induced anergy or disappearance of SPE-C-responding cells from the circulation . The present results suggested that SPE-C may be involved in the pathogenesis of KD. J Cardiol, 1998, 31 Suppl 1, 85 - 9; discussion 90 {Surgical treatment for prosthetic valve endocarditis}; Hirose S et al.; From April 1993 to May 1997, 21 patients underwent surgical treatment for prosthetic valve endocarditis (PVE) . There were 13 males and eight females aged from 46 to 79 years old (mean 62 years) . There were four cases of early PVE (onset of PVE within 60 days from previous valve replacement), and 17 cases of late PVE (after 60 days) . The predominant organisms were Staphylococcus epidermidis (eight cases), Staphylococcus aureus (two cases), MRSA (one case), streptococcal species (three cases), Candida (two cases), Pseudomonas cepacia (one case) and Enterococcus (one case) . The predominant organisms were identified in 16 of 20 cases by preoperative blood culture, and in 11 of 20 cases by intraoperative tissue culture, and in 19 cases in all . There were four cases of preoperative cerebral complications, and three cases resurged . The hospital mortality rate was 24% (five patients) . Reoperation was required in four patients for recurrence of PVE . Autopsy was performed in four of five patients . Intramyocardial abscess was detected in three patients . Earlier diagnosis and earlier surgical treatment could prevent emboli due to vegetations, which might cause catastrophic results, and could achieve better outcomes . Identification of the predominant organisms, especially from operative tissue cultures, is required. Curr Opin Hematol, 1998 May, 5(3), 215 - 20 Potential use of granulocyte colon-stimulating factor and granulocyte-macrophage colony-stimulating factor in neonates; Bracho F et al.; The immaturity of neonatal phagocytic immunity contributes to increased mortality during neonatal sepsis . Neonates have both quantitative and qualitative neutrophil defects with decreased bone marrow neutrophil storage pool (NSP) reserves, an inability to increase neutrophil production, and defective neutrophil functional activity . Neonates respond to overwhelming sepsis with depletion of the NSP and the development of peripheral neutropenia . The myelopoietic cytokines granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been documented to induce neutrophilia in neonatal animals and human infants, increase the NSP, and upregulate neutrophils for improved functional activity . Preclinical studies in neonatal rats demonstrate increased survival with prophylactic G-CSF during experimental group B streptococcal sepsis . In pilot phase I/II human trials, G-CSF and GM-CSF were demonstrated to be both safe and well tolerated and to induce significant increases in absolute neutrophil count and NSP . Prophylactic GM-CSF in the very low birth weight neonate may reduce the incidence of nosocomial infections . Phase III trials are needed to further delineate the clinical usefulness of these myelopoietic cytokines in neonates with a high predisposition to sepsis. Southeast Asian J Trop Med Public Health, 1997 Dec, 28(4), 826 - 30 Estimation of ASO titer as an indicator of streptococcal infection precipitating acute adenolymphangitis in brugian lymphatic filariasis; Suma TK et al.; Recurrent episodes of acute adenolymphangitis (ADL) are important clinical manifestations of lymphatic filariasis which contribute significantly to the progression of lymphedema . It is increasingly being recognized that secondary bacterial infections play an important role in the etiology of ADL . We examined the role of streptococcal infection as a precipitating factor of ADL in brugian filariasis, by determining the anti-streptolysin O (ASO) titers and by isolating the causative organism wherever possible . The study population consisted of 30 patients with filariasis related ADL (Group A), 30 patients with chronic filarial edema (Group B) and 60 age and sex matched healthy adults (Group C) . ASO titer was estimated by the latex agglutination method at the time of entry into the study, at the 15th day and at 3, 6 and 12 months . ASO titers were persistently elevated in 90% of patients in Group A and a portal of entry for bacterial infection was detected in all of these patients . In Group B only six patients had persistently elevated ASO titers . These patients had grade III lymphedema and three of them had monilial infections in the affected limb . In the control group none had persistently elevated ASO titers . The elevated ASO titers and the detection of a site of entry for bacteria in patients with ADL supports a streptococcal etiology for this condition. Lijec Vjesn, 1998 Jan-Feb, 120(1-2), 8 - 13 {Acute respiratory infection in general clinical practice}; Budak A et al.; Due to high frequency, certain risk of related complications, absenteeism, direct and indirect costs related to them, acute respiratory infections represent a significant health problem . The aim of the paper is to examine the frequency and characteristics of acute respiratory infections, as well as the characteristics of patients with these infections among the population in care of general practitioners/family physicians . In 11 teaching general practices in Zagreb, data were collected from medical records on patients and acute respiratory infections which the patients developed over the period from October 1, 1994 to September 30, 1995 . For statistical data processing description, distribution analysis and chi-square test were used . Out of 17,888 patients in care of general practitioners involved in the study, acute respiratory infections were noticed in 4,114 (22.9%) patients ranging in age from newborn to 97 years out of which 1,473 (35.8%) were males and 2,641 (64.2%) were females . A total of 5,892 acute respiratory infections were observed, in average 1.43 infections per patient, for which the patients visited their general practitioners 11,610 times (1.97 visits per infection) . Most of the patients 2,958 (71.9%) attended their general practitioners because of one acute respiratory infection . The initial diagnosis of acute upper respiratory tract infection was registered in 4,601 (78.1%) infections, and final diagnosis in 4,475 (75.9%) infections . The most frequent diagnoses included: pharyngitis and tonsillitis (including streptococcal pharyngitis and tonsillitis), nasopharyngitis, sinusitis and bronchitis . In 4,874 (82.7%) cases, general practitioners based their diagnosis on patient history and clinical examination . Antibiotics were prescribed in 3,892 (66.1%) cases . Out of 42 (1.2%) patients treated in hospital, seven patients were admitted for tuberculosis and two for bronchi cancer detected during the acute respiratory infection . Follow-up was reported in 3,644 (60.3%) cases, and sick leave in 1,236 (31%) cases . The results of this study have shown significantly higher frequency of acute respiratory infections in the morbidity in outpatient health care, and also that management of patients with these diseases is mainly the responsibility of general practitioners . In order to improve professional competence of general practitioner/family physician and quality of work in the management of patients with acute respiratory infections in general practice/family medicine, it is necessary to continuously improve the knowledge on all characteristics of the management of patient with these diseases in general practice, as well as to make a critical assessment of the existing practice. Obstet Gynecol, 1998 Jul, 92(1), 38 - 42 Preterm contractions in community settings: I . Treatment of preterm contractions; Hueston WJ; OBJECTIVE: To explore how physicians in community hospitals (non-level III nursery facilities) diagnose preterm labor and treat women with preterm contractions . METHODS: Chart audits were performed for women presenting with preterm contractions at a network of 11 Wisconsin non-level III hospitals . RESULTS: Ninety percent (239 of 266) of the women presenting with premature contractions agreed to participate . The average gestational age was 31.6 weeks' gestation . Only 44 (17%) of these women had any cervical change with their contractions . However, tocolytic agents were used frequently, regardless of whether cervical changed occurred (61%) or not (76%, P=.10), and tocolytics were prescribed frequently upon discharge for those patients who left the hospital (54% of those with cervical change versus 62% in those without changes, P=.57) . Examining the use of appropriate treatments for women who did deliver prematurely, we found that only 26% of women who delivered prematurely received antenatal antibiotics to prevent group B streptococcal disease in the newborn, and only 33% of those who delivered at 34 weeks' gestation or earlier received corticosteroids to accelerate fetal lung maturity . CONCLUSION: Women presenting at community hospitals with preterm contractions but no evidence of labor are overtreated frequently with agents of equivocal benefit, whereas those who have active labors and deliver are not receiving agents such as steroids or antibiotics that have been shown to benefit outcomes. Obstet Gynecol, 1998 Jul, 92(1), 21 - 7 Neonatal group B streptococcal infection in a managed care population . Perinatal Group B Streptococcal Infection Study Group; Lieu TA et al.; OBJECTIVE: In a health maintenance organization population, we determined the incidence of early-onset (at less than or equal to 7 days) neonatal group B streptococcal (GBS) disease, the sensitivity and prevalence of labor risk factors, the adherence to a protocol for intrapartum antibiotics, and the costs for care of and outcomes of affected infants . METHODS: Mothers and infants at four health maintenance organization hospitals in northern California in 1989 to 1995 were studied retrospectively using computerized databases and chart review . In 1994, two of the four hospitals had adopted protocols similar to the ACOG recommendations for intrapartum antibiotics for women with labor risk factors (preterm, temperature 100.4F or higher, or rupture of membranes (ROM) 18 hours or more) . RESULTS: Among the 79,940 live births, the incidence of early-onset neonatal GBS infection was higher among preterm than among term infants (3.1 compared with 0.9 per 1000) . Before protocol adoption, 68% of 65 infants with GBS had mothers with labor risk factors . Approximately 18% of all mothers had labor risk factors: 7.7% had preterm delivery, and 10.6% had term delivery with fever and/or ROM 18 hours or more . At the two hospitals that adopted GBS protocols, GBS incidence was reduced from 1.3 per 1000 in the preprotocol period to 0.8 per 1000 in the postprotocol period (P=.08) . Six cases of neonatal GBS occurred after protocol adoption . Of these, four were not preventable under the protocol and two might have been preventable if protocol had been followed . Three of the 19 preterm infants with group B streptococcal disease died . CONCLUSION: Risk factor-based protocols hold some promise to reduce GBS disease, but clinical strategies to promote protocol adherence are needed. J Parasitol, 1998 Jun, 84(3), 557 - 61 Filariasis and erisipela in Santo Domingo; Vincent AL et al.; This study examined acute-convalescent changes in diagnostic anti-streptococcal antibodies by the anti-streptolysin O (ASO) and anti-DNAase B (ADAB) tests among patients (n 28) with lymphedema and recurrent erisipela of the lower limb, comparing them with endemic normal control residents (n=25) . The study was based in Villa Francisca, an urban focus of Bancroftian filariasis in eastern Santo Domingo, capital of the Dominican Republic . The acute signs and symptoms of erisipela were consistent with a diagnosis of bacterial cellulitis . The ASO test was especially successful at demonstrating a rise in mean titer during convalescence, whereas the ADAB produced about the same frequency of significant increases (0.2 log titer) as did the ASO . When subjects were scored as responders if mounting a minimal titer increase by either test, patients were found more frequently positive than were controls (chi2=5.3, P=0.02) . About half (54%) of all patients mounted at least a minimal antibody increase . Filaria-specific IgG4 antibodies were absent from all sera of 20 residents of a nonendemic Dominican mountain town but appeared in about two-thirds of the sampled residents of the endemic barrio . Notably however, levels did not change between the acute phase and convalescence . These findings are consistent with the hypothesis that recurrent streptococcal invasion of the lymphatics may be a significant factor triggering or amplifying lymphedema and elephantiasis in patients with chronic filariasis. J Am Podiatr Med Assoc, 1998 Jun, 88(6), 305 - 7 Emergence of non-group A streptococcal necrotizing diabetic foot infections; Reyzelman AM et al.; Recently the authors have noted a disturbing trend toward an increased incidence of necrotizing infections caused by non-group A streptococcal species . This article describes the typical clinical course of such an infection . Prompt surgical intervention, coupled with an antibiotic regimen aimed at mitigating exotoxin release, may be both limb- and life-preserving. Lakartidningen, 1998 May 27, 95(22), 2580 - 4 {Specimen culture from all children in a day care center because of an outbreak of streptococcal infection}; Tindberg Y et al.; In an outbreak of recurrent group A streptococcal (GAS) pharyngotonsillitis between January and February 1997 at a Swedish preschool, involving 58% (11/19) of the children and several family members, clinical examination showed few of the children to manifest signs and symptoms of tonsillitis . However, throat specimens yielded GAS growth of the same T-type in 42% (8/19) of the children and in 30% (6/20) of family members, but in none of the staff . Strict hygiene, appropriate antibiotic treatment of all culture-positive individuals irrespective of symptoms, and non-attendance at the preschool during the first two days of treatment promptly terminated the outbreak and there were no cases of recurrence. J Clin Invest, 1998 Jun 15, 101(12), 2615 - 21 Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model; Song XY et al.; Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities . Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases . To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis . A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0 . 17 vs . 1.25+/-0.76, n = 6, day 26, P < 0.01) . Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis . Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model . Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent . These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis. Neurology, 1998 Jun, 50(6), 1618 - 24 Antibodies against human putamen in children with Tourette syndrome; Singer HS et al.; BACKGROUND: Similar to the model for Sydenham's chorea, antineuronal antibodies, which develop in response to a preceding streptococcal infection, have been speculated to have a role in the development of Tourette syndrome (TS) . METHODS: Serum antibodies against human caudate, putamen, and globus pallidus (interna and externa) were assayed by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques and results were correlated with clinical characteristics and markers of streptococcal infection . SUBJECTS: A total of 41 children with TS (mean age, 11.3 years) and 39 controls (mean age, 12.1 years) were included . RESULTS: Compared with controls, TS subjects had a significant increase in the mean (p=0.006) and median (p=0.002) ELISA optical density (OD) levels of serum antibodies against putamen, but not caudate or globus pallidus . Western blots on 20 control and 20 TS serum samples showed that specific antibodies to caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa; antigens were present in a synaptosomal fraction . TS subjects with a positive family history of tics had higher OD values (p < or = 0.04), but no association was shown with age of tic onset, tic severity, sudden onset of tics, or presence of attention-deficit hyperactivity disorder or obsessive-compulsive disorder . Risk ratio calculations in TS and control groups and in study subjects dichotomized for high and low putamen OD values were similar for titers of antistreptolysin O > or = 166 or antideoxyribonuclease B > or = 170 . A subgroup analysis limited to subjects with elevated streptococcal titers, however, showed a significantly (p < or = 0.004) larger number of TS subjects with elevated OD levels . CONCLUSION: Children and adolescents with TS had significantly higher serum levels of antineuronal antibodies against putamen than did controls, but their relation to clinical characteristics and markers for streptococcal infection remains equivocal. Neurology, 1998 Jun, 50(6), 1530 - 4 Tourette's syndrome and 'PANDAS': will the relation bear out? Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection; Kurlan R; Despite strong evidence of the importance of hereditary factors in the etiology of Tourette's syndrome (TS), research findings have consistently pointed to a role of environmental influences . A recent line of research has suggested that tic disorders and associated behavioral disturbances, such as obsessive-compulsive disorder, might develop following streptococcal infection by the process of molecular mimicry, whereby antibodies directed against bacterial antigens cross-react with brain targets . Such investigations have given rise to the notion that there is a spectrum of childhood neurobehavioral disorders (termed pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection {PANDAS}) that arise by postinfectious autoimmune mechanisms . This article reviews research results supporting the concept of PANDAS and discusses their limitations . Well-designed and adequately controlled studies are needed to determine whether there is a true etiologic relation between streptococcal infection and the onset or exacerbation of childhood neuropsychiatric disorders and whether the use of immune-modifying therapies for these conditions is rational. Clin Cardiol, 1998 Jun, 21(6), 435 - 8 Streptococcal mural endocarditis and myocardial abscess occurring in a left ventricular aneurysm--case report and review; Lo SS et al.; Infection of the mural endocardium within a left ventricular aneurysm without valvular involvement is exceedingly rare . The presenting clinical features can be non-specific, and a high index of suspicion is required for its diagnosis . Delay in diagnosis invariably leads to a fatal outcome . Although no controlled studies are available to guide therapy and management of these patients, appropriate antibiotic therapy and early surgical resection of the infected ventricular aneurysm remain the cornerstone of therapy. Eur J Clin Microbiol Infect Dis, 1998 Feb, 17(2), 101 - 3 Necrotizing fasciitis caused by Staphylococcus aureus; Regev A et al.; Two patients with rapidly progressive necrotizing fasciitis of a lower extremity due to Staphylococcus aureus as a single pathogen are described . In both patients the portal of entry was attributed to needle puncture (intra-articular injection and intravenous catheter, respectively), followed by bacteremia . Necrotizing fasciitis occurred in a site remote from the needle puncture, suggesting metastatic infection . One patient developed toxic shock syndrome and the other a sunburn-like rash and erythematous mucosae with strawberry tongue . One patient died, and the other required above-knee amputation due to secondary infectious complications . Staphylococcus aureus may mimic the presentation of invasive group A streptococcal infections . A history of needle puncture should alert the physician to the possibility of Staphylococcus aureus infection. Ann N Y Acad Sci, 1998 May 1, 840, 456 - 69 A novel endogenous corticotropin release inhibiting factor; Redei E et al.; ACTH is the major regulator of the body's adaptive response to stress and the physiological stimulus for glucocorticoid secretion . A hypothalamic corticotropin release inhibiting factor (CRIF) that inhibits ACTH synthesis and secretion has long been postulated but was not characterized until recently . We have recently identified a 22 amino acid peptide, prepro-thyrotropin releasing hormone (TRH) 178-199 that inhibits basal and stimulated ACTH synthesis and secretion in vitro and stress-induced ACTH secretion in vivo . Prepro-TRH 178-199 is abundant in several brain regions, including the external zone of the median eminence, where its concentration changes in response to stress . We propose that this peptide is a physiological regulator of ACTH production: an endogenous CRIF . Because prepro-TRH 178-199 is encoded within the same precursor as TRH, its expression is likely to be negatively regulated by thyroid hormones leading to changes in endogenous glucocorticoid levels . Streptococcal cell wall (SCW)-induced inflammation, a model of rheumatoid arthritis (RA), was alleviated after long-term thyroxine treatment . Inversely, a hypothyroid milieu led to decreased basal hypothalamic-pituitary-adrenal activity, but increased expression of IL-1 beta and MIP-1 alpha, specific markers for RA in humans . These results suggest that this putative CRIF may be an important component in the development of RA and that regulation of prepro TRH may be highly relevant to the development of other autoimmune diseases that are also exacerbated by low endogenous glucocorticoid levels. Ann N Y Acad Sci, 1998 May 1, 840, 21 - 32 Corticotropin-releasing hormone and inflammation; Webster EL et al.; Corticotropin-releasing hormone (CRH) is a major regulator of the hypothalamic-pituitary-adrenal axis (HPA) and principal coordinator of the stress response . As in stress, intracerebroventricular administration of CRH suppresses the immune system indirectly, via glucocorticoid and/or sympathetic system-mediated mechanisms . Also, during inflammatory stress, the cytokines TNF alpha, IL-1, and IL-6 stimulate hypothalamic CRH and/or vasopressin secretion as a way of preventing the inflammatory reaction from overreacting . Recently, CRH receptors were described in peripheral sites of the immune system, and CRH was found to promote several immune functions in vitro . We demonstrated a direct role of CRH in the inflammatory immune process in vivo, by first studying the effect of systemic CRH immunoneutralization in an experimental model of carrageenin-induced aseptic inflammation in Spague-Dawley rats . We extended these observations to other forms of experimental inflammation, including streptococcal cell wall polysaccharide- and adjuvant-induced arthritides and peptide R16 (epitope of the interphotoreceptor retinoid-binding protein)-induced uveitis in Lewis rats . We also studied human disease states, including rheumatoid arthritis, Hashimoto thyroiditis, and ulcerative colitis . Inflamed tissues contained large amounts of IR CRH, reaching levels similar to those observed in the hypophyseal portal system . We also demonstrated the presence of CRH mRNA and CRH receptors in inflammatory cells and identified the mast cells as a major immune target for CRH . In addition to production by immune cells, the peripheral nervous system, including the postganglionic sympathetic neurons and the sensory fibers type C, appears to contribute to IR CRH production in inflammatory sites . The production of CRH from the postganglionic sympathetic neurons may be responsible for the stress-induced activation of allergic/autoimmune phenomena, such as asthma and eczema, via mast cell degranulation . Antalarmin, a novel nonpeptide CRH receptor antagonist, displaced 125I-labeled ovine CRH binding in rat pituitary, frontal cortex, and cerebellum, but not heart, consistent with antagonism at the CRHR1 receptor . In vivo antalarmin significantly inhibited CRH-stimulated ACTH release and carrageenin-induced subcutaneous inflammation in rats . Thus, antalarmin and other related compounds that antagonize CRH at the level of its own receptor have therapeutic potential in some forms of inflammation directly mediated by type 1 CRH receptors and promise to enhance our understanding of the many roles of CRH in immune/inflammatory reactions. Proteins, 1998 Jun 1, 31(4), 391 - 405 Structural investigation of C4b-binding protein by molecular modeling: localization of putative binding sites; Villoutreix BO et al.; C4b-binding protein (C4BP) contributes to the regulation of the classical pathway of the complement system and plays an important role in blood coagulation . The main human C4BP isoform is composed of one beta-chain and seven alpha-chains essentially built from three and eight complement control protein (CCP) modules, respectively, followed by a nonrepeat carboxy-terminal region involved in polymerization of the chains . C4BP is known to interact with heparin, C4b, complement factor I, serum amyloid P component, streptococcal Arp and Sir proteins, and factor VIII/VIIIa via its alpha-chains and with protein S through its beta-chain . The principal aim of the present study was to localize regions of C4BP involved in the interaction with C4b, Arp, and heparin . For this purpose, a computer model of the 8 CCP modules of C4BP alpha-chain was constructed, taking into account data from previous electron microscopy (EM) studies . This structure was investigated in the context of known and/or new experimental data . Analysis of the alpha-chain model, together with monoclonal antibody studies and heparin binding experiments, suggests that a patch of positively charged residues, at the interface between the first and second CCP modules, plays an important role in the interaction between C4BP and C4b/Arp/Sir/heparin . Putative binding sites, secondary-structure prediction for the central core, and an overall reevaluation of the size of the C4BP molecule are also presented . An understanding of these intermolecular interactions should contribute to the rational design of potential therapeutic agents aiming at interfering specifically some of these protein-protein interactions. Nat Struct Biol, 1998 Jun, 5(6), 470 - 5 Design, structure and stability of a hyperthermophilic protein variant; Malakauskas SM et al.; Here we report the use of an objective computer algorithm in the design of a hyperstable variant of the Streptococcal protein Gbeta1 domain (Gbeta1) . The designed seven-fold mutant, Gbeta1-c3b4, has a melting temperature in excess of 100 degrees C and an enhancement in thermodynamic stability of 4.3 kcal mol(-1) at 50 degrees C over the wild-type protein . Gbeta1-c3b4 maintains the Gbeta1 fold, as determined by nuclear magnetic resonance spectroscopy, and also retains a significant level of binding to human IgG in qualitative comparisons with wild type . The basis of the stability enhancement appears to have multiple components including optimized core packing, increased burial of hydrophobic surface area, more favorable helix dipole interactions, and improvement of secondary structure propensity . The design algorithm is able to model such complex contributions simultaneously using empirical physical/chemical potential functions and a combinatorial optimization algorithm based on the dead-end elimination theorem . Because the design methodology is based on general principles, there is the potential of applying the methodology to the stabilization of other unrelated protein folds. Cancer Immunol Immunother, 1998 May, 46(3), 128 - 36 Antitumor vaccination effect of dendritic cells can be augmented by locally utilizing Th1-type cytokines from OK432-reactive CD4+ T cells; Tamada K et al.; In order to enhance the antitumor vaccination effect of dendritic cells (DC) pulsed with class I tumor peptide, we tried to utilize the local cytokine help of CD4+ T cells reactive to a streptococcal preparation OK432 . DC were prepared from murine bone marrow cells by culture with both granulocyte/macrophage-colony-stimulating factor and interleukin(IL)-4 . The peritumoral injections of OK432 induced OK432-reactive CD4+ T cells in the draining lymph nodes, and their in vitro production of interferon gamma was thus significantly enhanced by restimulation with OK432-pulsed DC . In addition, anti-P815 mastocytoma cytotoxic T lymphocytes were generated from the in vivo OK432-treated P815-draining lymph node cells only when the lymph node cells were restimulated in vitro with the DC pulsed with both P1A peptide and OK432 . Moreover, the peritumoral injections of OK432 and the subsequent vaccination of the DC, pulsed with both OK432 and P1A peptide, significantly suppressed the growth of s.c . inoculated P815 . Interestingly, a significant level of IL-12 was detected in the coculture supernatant of both OK432-pulsed DC and OK432-reactive CD4+ T cells . Collectively, our results suggest that the antitumor vaccination effect of DC pulsed with class I tumor peptide could thus be effectively augmented by locally utilizing the Th1-type cytokines from OK432-reactive CD4+ T cells. Ned Tijdschr Geneeskd, 1998 May 16, 142(20), 1113 - 6 {Invasive streptococcal infection as a complication of chickenpox}; Geelen SP et al.; Two girls aged 11 months and 6 years, presented with an invasive group A streptococcal (GAS) infection during the course of primary varicella . The infant had severe cellulitis of the left arm and leg, fever and bacteraemia . She developed osteomyelitis of ulna and tibia . The 6-year-old girl had a fever > 38.5 degrees C, hypotension, an acute respiratory distress syndrome, liver function abnormalities, and positive cultures of blood and joints . Her clinical picture was compatible with a GAS-associated toxic shock syndrome . If during the course of primary varicella persistent fever, secondary fever or pain in one or more extremities occurs, invasive bacterial infection by GAS or Staphylococcus aureus should be considered, even in the absence of skin infection or cellulitis. J Mol Biol, 1998 May 1, 278(2), 439 - 56 Calculations on folding of segment B1 of streptococcal protein G; Sheinerman FB et al.; We present an investigation of the folding thermodynamics and mechanism of segment B1 of streptococcal protein G . Molecular dynamics simulations of the fully solvated protein are used to probe thermodynamically significant states at different stages of folding . We performed several unfolding simulations to generate a database of initial conditions . The database is analyzed and clustered . The cluster centers extracted from this database were then used as starting points for umbrella sampling of the folding free energy landscape under folding conditions . The resulting sampling was combined with the weighted histogram analysis method . One and two-dimensional free energy surfaces were constructed along several order parameters and used to analyze the folding process . Our findings indicate that an initial collapse precedes the formation of significant native structure . Elements of local structure originate in the regions of the protein shown to have higher H/2H exchange protection factors in early stages of folding . A non-native contact, observed experimentally at the N terminus of the alpha-helix in a peptide excised from the protein, is seen to pre-organize the chain in early stages of folding . Collapse and early structure formation yields a compact globule with a significant number of water molecules present . Desolvation of the protein core is coincident with the final stages of folding from the compact state . Int J Dermatol, 1998 May, 37(5), 350 - 7 Immunoregulatory mechanisms and stress hormones in psoriasis (part 1) Weigl BA. BACKGROUND: In an earlier paper, the author noted that psoriatic eruptions may be produced in phases of humoral and cellular immunodeficiency and in the presence of streptococcal antigen-releasing inflammatory foci . In this study it was investigated as to whether stress hormones glucocorticoids, catecholamines) are substantially involved in the activity phases (eruptions) of psoriasis . METHODS: During a series of investigations over two years, the following were determined for 70 chronic psoriasis patients and 50 controls: cortisol-adrenaline serum levels, polyclonal serum immunoglobulins IgM, IgG, IgA, total serum IgE, complements C3, C4, T-cells and subpopulations, streptococcal antibody titres ASO/ADNase B . RESULTS: Phases of clinical inactivity are associated with a mechanism called immunologic regulation: elevated antibacterial titres and unremarkable findings for all other parameters . Phases of clinical activity (in 25/70 patient) showed absolutely elevated serum cortisol levels, absolutely decreased serum epinephrine levels, deficient serum IgM or IgG and IgE levels, increased C3, decreased C4 and T4:T8 ratio, and significantly elevated streptococcal titres . CONCLUSIONS: The greatly elevated serum cortisol levels indicate that glucocorticoids are produced in excess via the pituitary adrenal axis and are significantly involved in the triggering of immunosuppressive phases (eruptions) in psoriasis. Invest Ophthalmol Vis Sci, 1998 Jun, 39(7), 1251 - 6 Lipoteichoic acid as an inducer of acute uveitis in the rat; Merino G et al.; PURPOSE: To examine the capacity of lipoteichoic acid (LTA) to induce intraocular inflammation in the rat . METHODS: LTA obtained from Staphylococcus aureus and three different streptococcal species were suspended in saline solution in various concentrations and were injected into one footpad of female Lewis rats . The uveitic changes were assessed by conventional clinical and histopathologic procedures, whereas the intensity of inflammation in the anterior chamber (AC) was evaluated by the measurement of protein concentration and cell density in the aqueous humor (AH) . RESULTS: LTA from S . aureus induced a strong intraocular inflammation between 24 and 30 hours after injection . The inflammatory reaction was observed in a dose-dependent manner . At a dose of 15 mg/kg LTA, the protein concentration and cell counts in the AH were 5.6 +/- 0.5 mg/ml and 4075 +/- 1193 cells/microl, respectively . When LTAs of streptococcal origin were used, cells were undetected in the AH and protein concentration increased only two- or threefold compared with the control group . In pathologic examination, inflammatory cells were found in the AC and posterior chamber only after the injection of S . aureus LTA . In systemic evaluations of the liver, kidney, spleen, heart, lung, gut, brain, joint, and eye performed 6, 24, and 48 hours after the challenge, inflammatory lesions were found only in the eye . CONCLUSIONS: LTA, especially of S . aureus origin, induces anterior uveitis in the rat . This model may be useful for investigation of Gram-positive bacterial infection and uveitis. Cytokine, 1998 May, 10(5), 361 - 9 Regulatory role of interleukin 10 in joint inflammation and cartilage destruction in murine streptococcal cell wall (SCW) arthritis . More therapeutic benefit with IL-4/IL-10 combination therapy than with IL-10 treatment alone; Lubberts E et al.; Interleukin 10 (IL-10) and IL-4 are important downregulators of a number of macrophage functions . The authors investigated the role of endogenous IL-4 and IL-10 and the therapeutic effect of addition of these cytokines on joint inflammation and cartilage destruction in the early stages of the macrophage dependent murine streptococcal cell wall (SCW) arthritis model . It was demonstrated that endogenous IL-10, but not IL-4, plays a pivotal role in the regulation of SCW arthritis . Blocking endogenous IL-10 with anti-IL-10 antibodies resulted in a sustained arthritis with more dense synovial infiltrate as well as enhanced cartilage damage . Adding exogenous IL-10 further enlarged the suppressive effect of endogenous IL-10 . Even more pronounced amelioration was found with the combination IL-4/IL-10 . This resulted in a reduced swelling and a restorative overshoot in chondrocyte proteoglycan synthesis at day 4 (140%) . Treatment with the combination IL-4/IL-10 not only a marked reduction of tumour necrosis factor alpha (TNF-alpha) levels, like IL-10 treatment alone, but also the IL-1 beta levels were strongly reduced in the synovium . In conclusion, the data is consistent with a dominant role of IL-10 in natural suppression of arthritis expression, whereas combined treatment with IL-4 and IL-10 appears to be of potential therapeutic value. Aust Vet J, 1998 Apr, 76(4), 253 - 4 Streptococcal peritonitis in a young dromedary camel; Heller M et al.; A male dromedary camel was presented for a primary Streptococcal zooepidemicus septic peritonitis . An underlying gross lesion was not identified during abdominal exploratory surgery . The camel responded to peritoneal lavage, peritoneal drainage and systemic antibiotic therapy . Thrombophlebitis of the left jugular vein was diagnosed 14 days after surgery . The camel died of an unknown cause 24 days after surgery. J Emerg Med, 1998 May-Jun, 16(3), 403 - 7 Magnetic resonance imaging in the early diagnosis of group A beta streptococcal necrotizing fasciitis: a case report; Drake DB et al.; Early diagnosis of invasive group A beta streptococcal (GABS) infection has been achieved in a patient using magnetic resonance imaging (MRI) complemented by needle aspiration . Life-saving treatments of GABS infection that include immediate surgical debridement along with the administration of i.v . antibiotics, gamma globulin, and hyperbaric oxygen were then implemented successfully to prevent the development of streptococcal toxic shock syndrome . While MRI is valuable in making early diagnosis of GABS, it should not delay surgical intervention. Cardiovasc Surg, 1998 Apr, 6(2), 126 - 32 Long-term survival after aortic valve replacement for native active infective endocarditis; Pompilio G et al.; BACKGROUND: The objective of this study was to analyse the impact of acute surgery for native aortic valve endocarditis and its influence on the long-term prognosis after surgery . METHODS: A total of 161 patients underwent aortic valve replacement for native active aortic valve endocarditis (NAAVE) during a 29-year period, from 1967 to 1995 (age range: 10 to 72 years; mean 48 +/- 12) . The main indication for surgery was progressive congestive heart failure (76%) . Other indications were untreatable sepsis (27%), peripheral or central emboli (12%) and, from 1978, echocardiographic evidence of friable, pedunculated vegetations (3%) . Streptococcal and staphylococcal infections predominated . Concomitant procedures were performed in 27% of the patients, including mitral and tricuspid valve surgery and coronary bypass procedures . RESULTS: Operative mortality was 8% in the majority of cases caused by heart failure or multi-organ failure . Multivariate logistic regression analysis identified NYHA class IV to be an independent predictor for postoperative death . Long-term survival for discharged patients was 75% at 10 years and 58% at 15 years, with a mortality rate of 3.6%/patient/year . Cox regression analysis identified the year of operation, trivalvular endocarditis and staphylococcal infection as independent predictors of survival . At 10 and 15 years after aortic valve replacement, 91% and 84% of the patients, respectively, were free of recurrent endocarditis . The presence of an abscess cavity at first operation was found to be predictive of recurrent endocarditis . CONCLUSIONS: Valve replacement for NAAVE offers a good chance for a cure and satisfactory long-term survival . Improvements in pre- and per-operative management of the very ill patient, and the use of allograft valves are likely to further improve long-term results . Finally, the presence of staphylococcal endocarditis requires long-term postoperative antibiotic therapy. J Neuroimmunol, 1998 Mar 1, 82(2), 140 - 8 Adrenergic regulation of macrophage-derived tumor necrosis factor-alpha generation during a chronic polyarthritis pain model; Chou RC et al.; Increases in the levels of proinflammatory cytokines, such as TNF alpha, have been intricately linked with arthritis and the pathogenesis of several models of neuropathic pain . In addition, arthritis (as well as other types of persistent pain) is associated with increased sympathetic activity and alterations of other responses in autonomic nervous activity . Adrenergic regulation of LPS-stimulated TNF production by M phi isolated from rats with streptococcal-cell-wall (SCW)-induced arthritis has been examined . Serum TNF levels and the cellular composition of peritoneal exudates have also been assessed . M phi were obtained from: (1) normal control rats, (2) animals injected with complete Freund's adjuvant (CFA), 3 rats injected with SCW and arthritic, and (4) those injected with SCW, which failed to develop arthritis . Serum levels of TNF alpha in rats that develop arthritis are significantly greater (2.4 fold) than levels from the other groups . The proportion of OX19-positive T cell subpopulations are the same in peritoneal exudates from all groups . Immunocytochemical staining also reveals differences between M phi subgroups in the degree of activation . Peritoneal exudates from rats that develop arthritis contain a greater proportion of the high TNF producing subclass of M phi, as identified by positive ED3 staining (p < 0.001) . In contrast, Ia antigen presenting M phi (OX6-positive) in the peritoneal exudate cells are only elevated in rats administered CFA . The selective blockade of adrenergic receptors by idazoxan or propranolol demonstrates that the constitutive involvement of either alpha 2 or beta-adrenergic regulation of M phi-derived TNF production is pronounced in rats with arthritis (p < 0.001) . These investigations demonstrate a distinctive pattern of peripheral M phi populations in rats that develop chronic polyarthritic pain . We believe that identification of interactions between the adrenergic responses and proinflammatory cytokines will lead to the development of improved strategies to treat patients with chronic pain. Ann Trop Paediatr, 1997 Dec, 17(4), 381 - 6 Group A beta-haemolytic streptococcal infection and Henoch-Schonlein purpura with cardiac, renal and neurological complications; Mattoo TK et al.; A 6-year-old girl had a group A beta-haemolytic streptococcal (GABS) throat infection and Henoch-Schonlein purpura (HSP) . The clinical course was complicated by nephrotic syndrome due to crescentic glomerulonephritis, transient neurological symptoms due to focal ischaemia of the brain, and congestive cardiac failure due to myocarditis . The clinical presentation highlights the diversity of systemic involvement in HSP, the transient nature of apparently serious central nervous system involvement, and a possible role of GABS in its aetiology. Caries Res, 1998, 32(3), 233 - 8 Inhibition of salivary amylase by black and green teas and their effects on the intraoral hydrolysis of starch; Zhang J et al.; Tea decoctions prepared from a number of black and green teas inhibited amylase in human saliva . Black teas gave higher levels of inhibition than green teas, and removal of tea tannins with gelatin led to the loss of inhibitory activity from all decoctions . Streptococcal amylase was similarly inhibited by tea decoctions . Fluoride was without effect on amylase . Since salivary amylase hydrolyzes food starch to low molecular weight fermentable carbohydrates, experiments were carried out to determine whether tea decoctions would interfere with the release of maltose in food particles that became entrapped on the dentition . Subjects consumed salted crackers and rinsed subsequently for 30 s with black or green tea decoctions, or water . Maltose release was reduced by up to about 70% after rinsing with the teas . Black tea decoction was significantly more effective than green tea, in agreement with the in vitro data . The observations supported the hypothesis that tea consumption can be effective in reducing the cariogenic potential of starch-containing foods such as crackers and cakes . Tea may reduce the tendency for these foods to serve as slow-release sources of fermentable carbohydrate. Langenbecks Arch Chir Suppl Kongressbd, 1997, 114, 550 - 2 {Streptococcal toxic shock-like syndrome"--a rare complication of pyogenic skin infections}; Willis S et al.; In recent years there is an increasing incidence of streptococcal toxic shock-like syndrome in otherwise healthy adults . It is characterized by feaver, rash, hypotension and early shock with consecutive organ failure and a mortality rate of about 30% . Only early, aggressive and repeated surgical debridement can reduce the bacterial load and decrease circulating exotoxins and thereby in combination with antibiotic therapy decrease the high mortality of this entity. Pediatr Dermatol, 1998 Mar-Apr, 15(2), 103 - 7 Cutaneous polyarteritis nodosa in a child; Ginarte M et al.; Cutaneous polyarteritis nodosa (CPAN) is a benign form of vasculitis of small and medium-size arteries with a recurrent but benign course without systemic involvement . This entity is very rare in children, with about 45 cases described in the literature we reviewed . Herein we report a 10-year-old girl with typical CPAN . Trigger factors such as streptococcal infection were not detected . Of four episodes over the last 2 years, only one required treatment with a moderate-sized oral dose of prednisone . In diagnosing CPAN, it is necessary to rule out systemic polyarteritis nodosa, which is also rare in children, as well as other panniculitides and vasculitides. J Immunol, 1998 Feb 1, 160(3), 1466 - 71 Streptococcal cell wall-induced arthritis: requirements for IL-4, IL-10, IFN-gamma, and monocyte chemoattractant protein-1; Schimmer RC et al.; Intra-articular injection of streptococcal cell wall Ag followed by i.v . challenge ("reactivation") results in a destructive lymphocyte-dependent monoarticular arthritis . To further define the role of immune mechanisms in the model, Abs to Th1 and Th2-related cytokines were evaluated . Treatment of rats with antibodies to IL-4 reduced swelling, while treatment with anti-IL-10 or anti-IFN-gamma either had no effect or slightly enhanced the inflammatory response . These results suggest that Th-2 immune mechanisms may be, at least in part, operative in the model . To more precisely define the role of IL-4, the effects of anti-IL-4 on monocyte chemoattractant protein-1 (MCP-1) expression were evaluated . Initial studies demonstrated that mRNA (as determined by in situ hybridization) and protein (as determined by immunofluorescence) for MCP-1 were detectable in inflamed synovial tissue in a time-dependent manner . Anti-IL-4 treatment significantly reduced the expression of mRNA for MCP-1 24 and 72 h after reactivation . In addition, anti-MCP-1 inhibited swelling and reduced influx of (111)In-labeled T cells . These data suggest that the reactivation model of streptococcal cell wall Ag-induced arthritis is Th-2 dependent, and that an inter-relationship exists between IL-4 and the expression of MCP-1. J Marmara Univ Dent Fac, 1996 Sep, 2(2-3), 520 - 2 Antistreptolysin O, rheumatoid factor and C-reactive protein determination in patients with recurrent oral ulcer; Ogan A et al.; Recurrent oral ulcer (ROU) is a common disease whose the etiologic factors have not yet been identified . Although the autoimmune mechanism due to streptococcal antigens may be involved in this disease, serum immunoglobulins are reported to be higher than normal controls in various phases of ROU . Oral ulcers are one of the criteria in the diagnosis of some systemic diseases such as Wegener's granulomatosis, Behcet's syndrome, suppurative arthritis, Reiter's syndrome and neutropenias . Any patient with recurring oral ulcers should be evaluated medically for the possible presence or future development of serious systemic diseases . In this study of the 58% of the ROU patients who had positive ASO values, only one female patient had a moderate increase: ++ASO(= 400 IU), the rest had a slight increase: +ASO(= 200 IU) . In the control group only 3 female subjects had +ASO (= 200 IU) . The aim of this study was to determine whether there is any relationship between ROU and rheumatoid arthritis . Patients with ROU were examined for antistreptolysin O, rheumatoid factor and C-reactive protein and compared to healthy controls. Fold Des, 1998, 3(2), 79 - 85 Reading protein sequences backwards; Lacroix E et al.; BACKGROUND: Reading a protein sequence backwards provides a new polypeptide that does not align with its parent sequence . The foldability of this new sequence is questionable . On one hand, structure prediction at low resolution using lattice simulations for such a protein provided a model close to the native parent fold or to a topological mirror image of it . On the other hand, there is no experimental evidence yet to tell whether such a retro protein folds (and to which structure) or not . RESULTS: In this work, we have analysed the possibility of a retro protein folding in two different ways . First, we modelled the retro sequence of the alpha-spectrin SH3 domain through distance geometry and molecular dynamics . This contradicted the plausibility of a mirror image of the native domain, whereas basic considerations opposed the likelihood of the native fold . Second, we obtained experimental evidence that the retro sequences of the SH3 domain, as well as the B domain of Staphylococcal protein A and the B1 domain of Streptococcal protein G, are unfolded proteins, even though some propensities for the formation of secondary structures might remain . CONCLUSIONS: Retro proteins are no more similar to their parent sequences than any random sequence despite their common hydrophobic/hydrophilic pattern, global amino acid composition and possible tertiary contacts . Although simple folding models contribute to our global understanding of protein folding, they cannot yet be used to predict the structure of new proteins. Clin Otolaryngol, 1998 Feb, 23(1), 67 - 8 Tonsillitis and chronic psoriasis; Wardrop P et al.; Although the relationship between streptococcal tonsillitis and acute guttate psoriasis is well recognized, its relationship to chronic forms of psoriasis is less established . In order to explore this further, the authors questioned 35 patients with severe psoriasis and 35 age-matched eczema controls about their history of significant sore throats (i.e . requiring a GP visit) and any resultant worsening of the skin condition . A third of the psoriasis patients reported recurrent sore throats which worsened their skin condition . This was true of only one (3%) of the 35 eczema controls . The authors discuss these findings in the context of recent laboratory work on the association between streptococcal infection and psoriasis. Ned Tijdschr Geneeskd, 1998 Feb 7, 142(6), 273 - 6 {A classic example of infectious endocarditis?}; van der Schaaf MR et al.; A 15-year-old girl in whom the diagnosis of infective endocarditis was established was sent to our cardiothoracic centre for mitral valve replacement because of a streptococcal endocarditis resistant to adequate antibiotic therapy . Despite the combination of fever, a 'new' heart murmur, 'positive blood cultures' and 'vegetations' on the mitral valve, the clinical picture gave rise to some doubt about the diagnosis . Finally the diagnosis of systemic lupus erythematosus was made and after treatment with corticosteroids all symptoms disappeared . In our modern era 'simple symptoms' still play a very important part in clinical decision making. JAMA, 1998 Apr 15, 279(15), 1206 - 10 Prevention of invasive group A streptococcal disease among household contacts of case-patients: is prophylaxis warranted? The Working Group on Prevention of Invasive Group A Streptococcal Infections; A case report of immunotherapy on a patient with advanced gastric cancer by adoptive transfer of OK-432-reactive HLA-matched allogeneic lymphocytes; Second Department of Surgery, Kyoto Prefectural University of Medicine Kawaramachi Hirokoji, JapanAdoptive immunotherapy (AIT) for non-hematological malignancies, using HLA-matched donor lymphocytes, has been rarely reported . For a 35-year-old male patient with peritoneal disseminated advanced gastric cancer, we performed AIT using lymphocytes from his HLA-matched 37-year-old brother and a streptococcal preparation, OK-432, as an antigen . After the donor had been immunized by intradermal administration of OK-432, OK-432-reactive lymphocytes were induced in vitro and transferred to the patient intravenously with OK-432 . Low-dose systemic immunochemotherapy, using interleukin-2, 5-fluorouracil and cyclophosphamide, was concurrently administered with AIT . As a result, the Schnitzler metastasis in the patient reduced in size without any significant graft-versus-host-related complications . One of the effector mechanisms of therapeutic benefit was suggested to be cytokine release from the transferred OK-432-reactive lymphocytes . Our findings suggest the safety and efficacy of AIT using lymphocytes from an HLA-matched sibling and OK-432 as an antigen . Further studies to investigate the use of tumor-associated antigen and an HLA-matched sibling's lymphocytes for AIT of advanced cancer are warranted. Acta Otorrinolaringol Esp, 1998 Jan-Feb, 49(1), 41 - 4 {Bacteriology in infectious and obstructive adenoid-tonsillar pathology}; Lopez Gonzalez MA et al.; Infectious and obstructive adenotonsillar processes are common in the pediatric population . Bacteriological and serological studies were made of acute tonsillitis, recurrent acute tonsillitis with tonsillar hypertrophy, and tonsillar hypertrophy . Positive cultures were more frequent in tonsils than in adenoids . Pathogenic microorganisms were isolated more often in infectious than in obstructive processes . Anti-streptococcal antibody titers were raised in infectious processes, but remained within normal limits in obstructive processes . Serum total IgE levels were similar in both processes . These findings show that tonsillar hypertrophy is not related directly with microorganisms or atopic pathology. J Immunol, 1997 Dec 1, 159(11), 5422 - 30 Molecular analysis of V gene sequences encoding cytotoxic anti-streptococcal/anti-myosin monoclonal antibody 36.2.2 that recognizes the heart cell surface protein laminin; Antone SM et al.; Anti-streptococcal/anti-myosin mAb 36.2.2 is unique among the cross-reactive anti-streptococcal mAbs due to its cytotoxicity for rat heart cells and its ability to strongly label the surface of heart cells in indirect immunofluorescence assays . In this study, cytotoxic mAb 36.2.2 was found to react strongly with the extracellular matrix protein laminin in immunoblots and inhibition assays, while 11 other cross-reactive anti-streptococcal mAbs did not react with laminin and were not cytotoxic . Cytotoxicity appeared to correlate with the presence of laminin on the surface of cells . Heavy and light chain variable region genes encoding mAb 36.2.2 were highly homologous to other V genes encoding anti-carbohydrate and/or autoantibodies . VH, JH, and Jkappa segments of mAb 36.2.2 may be encoded by germline gene segments . The VH segment may be identical with an as yet unidentified VH7183 family germline sequence, and the 36.2.2 Vkappa region gene is encoded by a Vkappa8 family member. Am J Forensic Med Pathol, 1998 Mar, 19(1), 93 - 7 Streptococcal toxic shock syndrome presenting as suspected child abuse; Nields H et al.; Natural disease processes can predispose individuals to develop external body lesions that mimic traumatic injury . This can be particularly problematic in pediatric cases in which clinicians are alerted to the problems of child abuse . Streptococcal toxic shock syndrome is a systemic infectious illness that can manifest itself with erythematous and necrotizing skin lesions . We report a fatal case of streptococcal toxic shock syndrome in a 4-year-old girl who presented with skin lesions that were initially thought to be traumatic in origin . A report of possible child abuse was filed with the state . Based on the morphologic findings and bacteriologic culture results at autopsy, these lesions and the cause of death in this case were instead determined to result from streptococcal toxic shock syndrome. Am J Ophthalmol, 1997 Jun, 123(6), 841 - 3 Streptococcal toxic shock syndrome complicating preseptal cellulitis; Meyer MA; PURPOSE: Although substantial morbidity is uncommon in preseptal cellulitis, the incidence of severe infection resulting from group A streptococcal infection is increasing . METHODS: A 62-year-old man was initially examined for preseptal cellulitis sustained after minor trauma to his brow . The patient rapidly experienced shock and multisystem organ failure . Intensive medical therapy prevented circulatory collapse and death . RESULTS: A diagnosis of streptococcal toxic shock syndrome secondary to group A beta hemolytic streptococcal infection was made based on culture results and clinical course . CONCLUSIONS: The ophthalmologist plays an essential role in diagnosing this condition . Aggressive and timely treatment are essential to preventing death. J Infect Dis, 1998 Apr, 177(4), 998 - 1002 Serotype distribution of invasive group B streptococcal isolates in Maryland: implications for vaccine formulation . Maryland Emerging Infections Program; Harrison LH et al.; Invasive group B streptococcal (GBS) infection is a major health problem among infants and adults . The formulation of GBS vaccines depends on knowledge of the GBS serotype distribution . Serotype V GBS infection appears to have recently emerged, suggesting that the serotype distribution changes over time . GBS isolates from 210 pediatric patients, 23 pregnant women, and 314 nonpregnant adults with invasive infection in Maryland were studied . The predominant serotypes from infants with early-onset disease were as follows: serotype III, 38% of isolates; serotype Ia, 36%; serotype V, 13%; and serotype II, 11% . Although the majority (60%) of isolates among infants with late-onset infection were serotype III, serotype Ia (23%) was also common . The predominant serotype among isolates from nonpregnant adult patients was serotype V, accounting for 29% of the isolates . The serotype distribution differs between pediatric patients and adults and is changing over time . The inclusion of a relatively small number of serotypes in a GBS vaccine could provide protection against the vast majority of isolates. J Infect Dis, 1998 Apr, 177(4), 991 - 7 Role of emm and mrp genes in the virulence of group A streptococcal isolate 64/14 in a mouse model of skin infection; Boyle MD et al.; The virulence of group A streptococcal isolate 64/14 and paired isogenic mutants in which either the emm or mrp gene had been insertionally inactivated was compared in mice . Loss of expression of the emm gene product resulted in a significant loss of virulence when the isolate was injected into the skin but had no significant difference when injected intraperitoneally . By contrast, inactivation of the mrp gene caused the organism to be more virulent in the skin, while having no significant effect intraperitoneally . An isogenic mutant, in which the mga gene was inactivated and neither the emm gene nor the mrp gene was expressed, demonstrated no significant difference in virulence from the wild type organism . Organisms recovered from the spleen of mice lethally infected with the mga mutant expressed all Mga-regulated IgG-binding gene products despite the presence of the spectinomycin-resistance cassette, which was used to inactivate the mga gene, in its original position. Arch Dis Child, 1998 Jan, 78(1), 33 - 9 Kawasaki disease in Australia, 1993-95; Royle JA et al.; AIM: To describe the epidemiology, management, and rate of cardiac sequelae of Kawasaki disease in Australia . DESIGN: Cases were notified to the Australian Paediatric Surveillance Unit, an active national surveillance scheme, from May 1993 to June 1995 . RESULTS: 139 cases of Kawasaki disease were confirmed . In 1994, the annual incidence was 3.7/100,000 children < 5 years old . Sixteen children were not admitted to hospital . Coronary artery abnormalities were reported in 35 (25%) children . Two patients were diagnosed at postmortem examination . Sixty six per cent of patients were diagnosed within 10 days of onset and 81% of these received intravenous gammaglobulin within 10 days . Forty five of the notified children did not fulfil the study criteria because of streptococcal infection or insufficient clinical criteria . One child with streptococcal infection had coronary artery dilatation . CONCLUSION: Diagnosis of Kawasaki disease was delayed beyond 10 days in one third of patients, and almost 20% of children who could have received gammaglobulin within 10 days did not . The distinction between Kawasaki disease, streptococcal infection, and other possible diagnoses is problematic in some children.
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