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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 pulm