Clin Exp Immunol, 2003 Jun, 132(3), 430 - 5 Interleukin-12 alone can not enhance the expression of the cutaneous lymphocyte associated antigen (CLA) by superantigen-stimulated T lymphocytes; Sigmundsdottir H et al.; It has been reported that bacterial superantigens induce interleukin (IL)-12 dependent expression of the cutaneous lymphocyte associated antigen (CLA) and that this may be relevant to the association between certain skin diseases and infections including psoriasis and streptococcal tonsillitis . We have confirmed that the streptococcal pyrogenic superantigen C (SpeC) increases CLA expression by both CD4+ and CD8+ T cells when PBMCs are incubated in medium enriched with fetal calf serum (FCS) . However, such an increase could not be induced in medium enriched with human serum (HS) even when recombinant IL-12 was added to the PBMCs cultures . Strikingly, CD4+ T cells incubated with SpeC in HS showed a marked reduction in CLA expression, which was not due to apoptosis . In contrast, SpeC did induce T cell proliferation and expression of CD25, CD54 and CD103 in the presence of HS indicating that the absence of SpeC induced CLA expression in HS was not due to SpeC inhibitors . Although addition of low amounts of lipopolysaccharide endotoxin (LPS) caused a highly significant increase in CLA expression in the absence of SpeC in cultures enriched with HS, a combination of LPS and SpeC did not increase CLA expression beyond that induced by LPS alone . The superantigen-induced CLA expression in FCS was partially inhibited by anti-IL-12 but not by anti-IL-18 or antibodies to transforming growth factor (TGF)-beta . It is concluded that IL-12 alone can not increase CLA expression but requires the help of other factor(s) present in FCS but not in HS . Although LPS can induce CLA expression it does not seem to be the factor that interacts with IL-12 to induce superantigen-mediated CLA expression in cultures enriched with FCS. Eur J Immunol, 2003 Jun, 33(6), 1497 - 507 Unique T cell proliferation associated with PKCmu activation and impaired ZAP-70 phosphorylation in recognition of overexpressed HLA/partially agonistic peptide complexes; Irie A et al.; Altered peptide ligands (APL) induce T cell responses different from those induced by the original agonistic peptide . As shown for CD4(+) T cells, partial agonists induce partial T cell activation without proliferation because of lower affinities and higher off rates to TCR than those of agonists . To determine whether overexpression of partially agonistic TCR ligands on antigen-presenting cells provides high-avidity TCR ligands, we generated L cell transfectants expressing various numbers of HLA-DR4 covalently linked with APL derived from a streptococcal peptide and observed responses of the cognate T cells . Some overexpressed HLA-DR4/partially agonistic APL complexes induced T cell proliferation in a density-dependent manner . However, tyrosine phosphorylation of zeta-associated protein-70 (ZAP-70) and linker for activation of T cells and kinase activity of ZAP-70 were not detectable . T cell proliferation stimulated with L cell transfectants was sensitive to the PKC inhibitor Go6976, but to a lesser extent to Go6983, suggesting the involvement of mu isotype of PKC (PKCmu) . In vitro kinase assays revealed that PKCmu activity was up-regulated only in T cells stimulated with L cell transfectants that induced T cell proliferation . Our data suggest the presence of a unique signaling pathway coupling TCR ligation with T cell proliferation associated with PKCmu activation and impaired ZAP-70 activation. AANA J, 2003 Feb, 71(1), 37 - 40 Anesthetic implications of necrotizing fasciitis; Howie WO; Necrotizing fasciitis, also known as necrotizing acute soft tissue injury (NASTI), commonly occurs as a consequence of group A streptococcal disease . An estimated 9,400 cases of invasive group A streptococcal disease occur annually in the United States, with 600 cases classified as NASTI . Mortality associated with NASTI is estimated at 20% to 50% . Research indicates that early diagnosis and surgical excision of necrotic tissue is the key to minimalization of morbidity and mortality associated with NASTI . Repeated surgeries typically are required in patients with NASTI, posing unusual anesthetic challenges . This article provides an overview of NASTI and includes preoperative, intraoperative, and postoperative anesthetic considerations. S Afr Med J, 2003 Mar, 93(3), 212 - 8 Intramuscular penicillin is more effective than oral penicillin in secondary prevention of rheumatic fever--a systematic review; Manyemba J et al.; BACKGROUND: People with a history of rheumatic fever (RF) are at high risk of recurrent attacks and of developing rheumatic heart disease following a streptococcal throat infection . Giving penicillin to these people can prevent recurrent attacks of RF and subsequent rheumatic heart disease . However, there is no agreement on the most effective method of giving penicillin . OBJECTIVES: To assess the effects of different penicillin regimens and formulations for preventing streptococcal infection and RF recurrence . SEARCH STRATEGY: We searched the Controlled Trials Register (Cochrane Library Issue 2, 2001), Medline (January 1966-July 2000), Embase (January 1985-July 2000), reference lists of articles, and contacted experts in the field . SELECTION CRITERIA: Randomised and quasi-randomised studies comparing: (i) oral with intramuscular penicillin; and (ii) 2- or 3-weekly with 4-weekly intramuscular penicillin in patients with previous RF . DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data . MAIN RESULTS: Six studies were included (1,707 patients) . Data were not pooled because of clinical and methodological heterogeneity of the trials . Four trials (1,098 patients) compared intramuscular with oral penicillin and all showed that intramuscular penicillin was more effective in reducing RF recurrence and streptococcal throat infections than oral penicillin . One trial (360 patients) compared 2-weekly with 4-weekly intramuscular penicillin . Penicillin given every 2 weeks was better at reducing RF recurrence (relative risk (RR) 0.52, 95% confidence interval (CI): 0.33-0.83) and streptococcal throat infections (RR 0.60, 95% CI: 0.42-0.85) . One trial (249 patients) showed that 3-weekly intramuscular penicillin injections reduced streptococcal throat infections (RR 0.67, 95% CI: 0.48-0.92) compared with 4-weekly intramuscular penicillin . CONCLUSIONS: Intramuscular penicillin seemed to be more effective than oral penicillin in preventing RF recurrence and streptococcal throat infections . Two-weekly or 3-weekly injections appeared to be more effective than 4-weekly injections . However, the evidence is based on poor-quality trials and the use of outdated formulations of oral penicillin. Cancer Immunol Immunother . 2003 May 24; {Epub ahead of print} Streptococcal preparation OK-432: a new maturation factor of monocyte-derived dendritic cells for clinical use; Kuroki H et al.; For vaccinations based on dendritic cells (DCs), maturation of DCs is critical to the induction of T-cell responses . We tested the efficacy of streptococcal preparation OK-432 as a Good Manufacturing Practice (GMP)-grade maturation agent . OK-432 is currently used in Japan as a cancer immunotherapy drug . Immature monocyte-derived dendritic cells (imMo-DCs) isolated from human peripheral blood monocytes stimulated with granulocyte-macrophage colony stimulating factor and interleukin-4 were exposed to maturation factors, i.e., lipopolysaccharide (LPS), tumor necrosis factor alpha (TNF-alpha) plus prostaglandin E(2 )(PGE(2)), and OK-432 for 2 days . OK-432 increased expression of activation- and maturation-related molecules such as HLA-DR, CD80, CD83, and CD86 in imMo-DCs at levels similar to that of TNF-alpha plus PGE(2),()and higher than that of LPS . All agents examined induced allogeneic T-cell proliferation at a similar level . Only OK-432 caused significant production of interleukin-12 (IL-12) p70 and interferon gamma (IFN-gamma) at both the mRNA and protein levels in imMo-DCs . Neutralizing antibody against IL-12 p70 blocked IFN-gamma secretion from OK-432-stimulated Mo-DCs . IL-12 p70 produced by OK-432-stimulated imMo-DCs induced secretion of IFN-gamma by CD4(+) T cells . OK-432 and LPS activated nuclear factor kappa B (NF-kappaB) in imMo-DCs . Both secretion of IL-12 p70 and IFN-gamma and activation of NF-kappaB induced by OK-432 were suppressed when imMo-DCs were pretreated with cytochalasin B . These results indicate that uptake of OK-432 by imMo-DCs is an early critical event for IL-12 p70 production and that NF-kappaB activation induced by OK-432 also contributes partially to IL-12 p70 production . In conclusion, OK-432 is a GMP-grade maturation agent and may be a potential tool for DC-based vaccine therapies. J Biomol NMR, 2003 Jul, 26(3), 193 - 202 A rapid method to attain isotope labeled small soluble peptides for NMR studies; Koenig BW et al.; A widely applicable strategy is presented for efficient and rapid production of small water soluble peptides expressed as fusion proteins with the immunoglobulin-binding domain of streptococcal protein G . A simple extraction and purification scheme that includes a protease cleavage step to release the target peptide is described . The yield of authentic target peptide exceeds 10 mg per liter of culture . Production of U-13C, 15N and highly deuterated U-13C, 15N isotope labeled peptide is demonstrated for the 11 residue S2 peptide, corresponding to the C-terminus of the alpha-subunit of transducin, and the coiled coil trimerization domain from cartilage matrix protein (CMPcc), respectively . Heteronuclear two-dimensional NMR spectra are used for initial peptide characterization. J Mol Microbiol Biotechnol, 2003, 5(3), 161 - 6 Immobilization of Saccharomyces cerevisiae cells to protein G-Sepharose by cell wall engineering; Andres I et al.; In this work, we explored the possibility of using the targeting of a heterologous protein to the cell wall of Saccharomyces cerevisiae, by fusing it to a cell wall protein, to construct yeast strains whose cells display on their surface proteins that bind to a matrix, so as to achieve the immobilization of the whole cells . With this aim, we created a gene fusion that comprises the region responsible for attachment of a cell wall protein to the cell wall, and the IgG binding region of staphylococcal protein A, and expressed it in the mnn1mnn9 strain of S . cerevisiae . The surface display of the protein A-Icwp fusion protein was positively monitored; however, direct immobilization of the cells on an IgG-Sepharose matrix did not produce the expected results, probably due to the fusion protein not being completely exposed on the surface of the cells . To solve this problem we incubated the cells first with rabbit preimmune serum and then with goat anti-rabbit IgGs, so as to create a complex (yeast cell-protein A-rabbit IgG-goat IgG) . Cells treated in this way were successfully immobilized on a protein G-Sepharose matrix, due to the binding properties of goat IgGs to streptococcal protein G . J Dent Res, 2003 Jun, 82(6), 466 - 70 Lipoteichoic acid up-regulates VEGF expression in macrophages and pulp cells; Telles PD et al.; Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis, vascular permeability, and edema . Up-regulation of VEGF expression in the dental pulp may result in increased intra-pulpal pressure, and contribute to pain and irreversible tissue damage . Lipoteichoic acid (LTA) is an amphiphilic molecule from Gram-positive bacteria that has been associated with the pathogenesis of pulpitis . To investigate if LTA regulates expression of VEGF, we exposed mouse odontoblast-like cells (MDPC-23), undifferentiated pulp cells (OD-21), fibroblasts, or macrophages to streptococcal LTA, and evaluated VEGF expression by ELISA and RT-PCR . LTA induced up to a nine-fold increase in VEGF protein expression in macrophages, a 2.4-fold increase in MDPC-23, and a 1.6-fold increase in OD-21 as compared with controls . In contrast, LTA did not induce VEGF expression in fibroblasts . VEGF mRNA expression remained constant upon exposure to LTA, which suggests that VEGF regulation in these cells is primarily post-transcriptional . This work constitutes the first demonstration that lipoteichoic acid is sufficient to induce expression of a pro-angiogenic factor. Med Arh, 2002, 56(3 Suppl 1), 21 - 2 {Morbidity trends in the cardio-rheumatology department of the Pediatric Clinic in Sarajevo during the pre-war, war and post-war periods}; Begic Z et al.; In this work is presented the structure of the morbidity of the patients treated at the Cardiohematology department of the Pediatric Clinic in Sarajevo . It were followed four the most frequent groups of the diseases . The results show the trend of the increasing of the number of the hospitalized children with the congenital anomalies of the heart and juvenile chronic arthritis, with the decrease of the number of the ill become by streptococcal infections of the upper respiratory tract and the rheumatic illness . It is increased the number of the hospitalized children is the result of the beginning of the cardiosurgical way of the taking care of these patients . The decreased of the number of the ill become is the consequence of the improvement of the healthcare protection at the primary level with the continuity of the further trend of the decrease of the number of the patients ill become from acute rheumatic disease. Int Immunopharmacol, 2003 May, 3(5), 643 - 55 Anti-tumor immune response induced by the fractions derived from OK-432, a streptococcal preparation, by using a monoclonal antibody TS-2 that neutralizes the interferon-gamma-inducing activity of OK-432: comparison between the TS-2-binding and TS-2-unbinding fraction; Oshikawa T et al.; We have previously isolated a lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal agent, by affinity chromatography on a CNBr-activated Sepharose 4B bound TS-2 monoclonal antibody (mAb) that neutralizes the interferon (IFN)-gamma-inducing activity of OK-432 . In the current study, we compared the cytokine-inducing and anti-tumor activities of OK-PSA, a TS-2-binding fraction, with those of OK-PTF, a TS-2-unbinding fraction, in order to determine the efficacy of OK-PSA for clinical use in affinity chromatography using TS-2 . In the in vitro experiments using human peripheral blood mononuclear cells (PBMCs), OK-PSA markedly induced Th1-type cytokines, while interleukin (IL)-6 and IL-10, Th2-type cytokines, were induced by OK-PTF . Th1-cytokine induction by OK-PTF was not dose-dependent and was suppressed when PBMCs were treated with a high concentration of OK-PTF . In a mouse model, Th1 cytokines were also induced by OK-PSA and Th2 cytokines were induced by OK-PTF . Th2 cytokine-inducing activity of OK-PTF was accelerated in tumor-bearing mice relative to that in healthy mice . Although the anti-tumor effect of OK-PTF was statistically significant, it was much weaker than that of OK-PSA . A significant difference between the anti-tumor effect of OK-PSA and that of OK-PTF was observed (P<0.05) . Finally, OK-PSA elicited its cytokine-inducing effect via Toll-like receptor (TLR) 4, whereas OK-PTF-induced signaling was mediated by both TLR2 and TLR4 . These findings strongly suggested that the affinity chromatography using TS-2 is a useful strategy to separate the effective component for cancer therapy (OK-PSA) from other components. J Autoimmun, 2003 May, 20(3), 211 - 7 Induction of autoimmune valvulitis in Lewis rats following immunization with peptides from the conserved region of group A streptococcal M protein; Lymbury RS et al.; Rheumatic heart disease (RHD) is considered to be an autoimmune disorder mediated by group A streptococcal (GAS) M protein-specific T cells and antibodies that cross-react with cardiac antigens and epitopes of the GAS M protein . In this study, Lewis rats were immunized with a pool of overlapping peptides spanning the conserved region of the GAS M protein in Complete Freund's Adjuvant, followed by immunization with Bordetella pertussis . Controls received adjuvants alone . Spleen-derived lymphocytes from rats immunized with the conserved region peptides proliferated in response to the immunogen and to cardiac myosin . Moreover, histological examination of cardiac tissue from rats immunized with conserved region peptides revealed the presence of inflammatory lesions in both the myocardium and valve tissue indicating a role for GAS M protein-specific autoreactive T cells in the development of cardiac lesions . This study may support the use of the rat model of autoimmune valvulitis to investigate the immunopathogenesis of RHD and possible preventive strategies. J Med Microbiol, 2003 Jun, 52(Pt 6), 525 - 6 Increasing incidence of group A streptococcal infections amongst injecting drug users in England and Wales; Efstratiou A et al.; During 2000, the UK witnessed a sudden increase in severe infections and related deaths in injecting drug users (IDUs), sparking off a UK-wide investigation . A worrying upward trend in severe group A streptococcal (GAS) infections has recently been observed in IDUs based upon isolate referrals to the PHLS Respiratory and Systemic Infection Laboratory . Most cases were young male adults who presented with skin sepsis and bacteraemia . Serotyping revealed a diverse range of M types, with higher types predominating in some geographical areas . The data suggest that GAS invasive soft-tissue infections may present in an epidemic fashion among IDUs in the absence of a common source. G Ital Nefrol, 2003 Mar-Apr, 20(2), 184 - 99 {Post-infectious glomerulonephritis}; Barbiano Di Belgiojoso G et al.; Post-infectious glomerulonephrites (GNs) include a wide spectrum of nephropathies, with known etiological agent, bacterial, parasitic, viral . Among GNs secondary to bacterial infections, post-streptococcal GN is the most frequent; nevertheless, its incidence in developed countries has decreased during the last 20 years, while some of the characteristics such as types of infection, exposed subjects, clinical and evolutionary patterns have changed . Prognosis has worsened and is correlated with some clinical and histological parameters . The viral infection-related GNs include those associated with HBV, HCV, HIV plus other rarer forms . Membranous GN (MGN), membranoproliferative GN (MPGN) and IgA nephropathy may occur in the course of HBV infection, while different GNs can be detected in relation to HCV, the most frequent being mixed cryoglobulinemic GN, a MPGN with peculiar morphological features . Multiple glomerular involvements are seen from HIV infection, the more characteristic form being the so-called HIV associated nephropathy (HIVAN), a focal segmental glomerulosclerosis with tuft collapse affecting African subjects, which starts with a nephrotic syndrome and rapidly develops into uraemia . Other GNs derive from HIV-related immunecomplexes, some with diffuse proliferative characteristics, or lupus like, with less severe clinical manifestations compared with HIVAN . Among the rare viral infections, we ultimately, mention the association between Parvovirus B19 and "collapsing" focal segmental glomerulosclerosis. Diagn Microbiol Infect Dis, 2003 May, 46(1), 69 - 71 Increasing the detection rate of group B streptococcal carriers by non-selective cervico-vaginal culture accompanied with the selective vagino-anorectal one; Cibali Acikgoz Z et al.; It has been previously well defined that selective vagino-anorectal culture is required for detection of group B streptococcal (GBS) carriage . We interestingly observed that in 5.74% of carriers, GBS were recovered only from cervico-vaginal samples inoculated onto nonselective human blood agar, without recovery from vagino-anorectal samples inoculated to four selective media. Clin Rheumatol, 2003 May, 22(2), 89 - 93 Fever of unknown origin: a review of 20 patients with adult-onset Still's disease; Mert A et al.; In this study we aimed to investigate the findings in patients with adult-onset Still's disease (AOSD) admitted with fever of unknown origin (FUO) during the last 18 years in our unit, in order to discover the ratio of such patients to all patients with FUO during the same period, and to determine the clinical features of AOSD in FUO . The number and the aetiologies of the patients with FUO diagnosed between 1984 and 2001, and the clinical features of those with AOSD, were taken from the patient files . The diagnosis of AOSD was reanalysed according to the diagnostic criteria of Cush et al . {11} . The presumed diagnoses before a diagnosis of AOSD was established were also noted . The chi(2) and Fisher's exact tests were used for statistical analysis . We studied 130 patients with a diagnosis of FUO, 36 (28%) of whom had collagen vascular diseases . Of these 36 patients, 20 (56%, 12 female, 8 male, mean age 34 years, range 16-65) had AOSD . Clinical and laboratory findings were as follows: fever (100%), arthralgia (90%), rash (85%), sore throat (75%), arthritis (65%), myalgia (60%), splenomegaly (40%), hepatomegaly (25%), lymphadenopathy (15%), anaemia (65%), neutrophilic leukocytosis (90%), increased erythrocyte sedimentation rate (100%), elevated transaminase levels (65%), a negative RF (100%), and a negative FANA (80%) . Antibiotics had been prescribed in 18 (90%) of cases . The presumed infectious diagnoses were streptococcal tonsillitis/pharyngitis (50%), infective endocarditis (four patients), sepsis (two patients) and acute bacterial meningitis (two patients) . The presumed non-infectious diagnoses were acute rheumatic fever (three patients), seronegative rheumatoid arthritis (two patients) and polymyositis (two patients) . Sixteen patients were followed for a mean duration of 30 months (range 2-59) . A remission was obtained with indomethacin in three cases (19%), and with prednisolone in the remainder . Relapse was detected in three cases (19%) . AOSD is one of the most frequent aetiologies of FUO . During the diagnostic course of a patient with FUO, a maculopapular rash and/or arthralgia and/or sore throat should raise the suspicion of AOSD . Because the disease has heterogeneous clinical findings, certain bacterial infections (e.g . streptococcal pharyngitis and sepsis) are generally considered and the prescribing of antibiotics is common. Clin Pediatr (Phila), 2003 Apr, 42(3), 219 - 25 Efficacy of penicillin vs . amoxicillin in children with group A beta hemolytic streptococcal tonsillopharyngitis; Curtin-Wirt C et al.; The purpose of this study was to compare the bacteriologic and clinical efficacy of oral penicillin versus amoxicillin as first-line therapy for group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis . The prospective observational study was conducted over 18 months (January 2000-June 2001) . Children enrolled had acute onset of symptoms and signs and a laboratory-documented GABHS tonsillopharyngitis illness . Follow-up examination and laboratory testing occurred 10 +/- 4 days following completion of treatment . In total, 389 patients were enrolled (intent-to-treat group): 195 received penicillin V and 194 received amoxicillin . Fifty-six of the penicillin-treated and 57 amoxicillin-treated patients refused to take the drug, or were noncompliant, or did not return for the follow-up visit, leaving 276 patients in the per-protocol group: 139 penicillin-treated and 137 amoxicillin-treated . Bacteriologic cure for amoxicillin-treated children occurred in 76% versus 64% in the penicillin-treated children (p = 0.04) . The clinical cure rate for amoxicillin-treated children was 84% compared to 73% in the penicillin-treated children (p = 0.03) . Since treatment allocation was not randomized, logistic regression analysis was used to adjust for treatment group differences . The odds ratio (OR) estimate for cure for patients in the amoxicillin versus penicillin V treatment group remained significant (OR = 1.84, 95% confidence interval 1.02-3.29); the same was true for dinical cure (OR = 1.99, 95% CI = 1.02-3.87) . Amoxicillin may be superior to penicillin for bacteriologic and clinical cure of GABHS tonsillopharyngitis. Neth J Med, 2003 Feb, 61(2), 57 - 61 Cardiac failure following group A streptococcal infection with echocardiographically proven pericarditis, still insufficient arguments for acute rheumatic fever: a case report and literature update; Jansen TL et al.; We recently encountered a 49-year-old female who developed fever due to group A streptococcal (GAS) bacteriaemia spreading to an abscess in the iliac muscle and a bacterial monarthritis of the right knee with a sterile arthritis of her left knee . Treatment was started with a six-week course of intravenous penicillin . She developed a mitral valve insufficiency and pericarditis on the tenth day of admission . In the third week heart failure developed with, on echocardiograph, a high output left ventricular failure without signs of valvulitis or myocarditis . Using a diuretic regimen she was recompensated . Because of the pericarditis with mitral valve insufficiency corticosteroids were given, which had a rapid beneficial effect . A discussion follows on the position of acute rheumatic fever versus post-streptococcal reactive arthritis in this clinical picture and the literature is updated. Int J Antimicrob Agents, 2003 May, 21(5), 484 - 7 Shortage of penicillin G: impact on antibiotic prescribing at a US tertiary care centre; Harbarth S et al.; A six-year retrospective study was undertaken to examine the effect of the recent penicillin G (penG) shortage on antibiotic prescribing practices at a tertiary care centre in the US . Prior to the shortage, penG was predominantly used for intrapartum prophylaxis of group B streptococcal disease . As the supply of penG ended temporarily in October 1999, penG use declined dramatically, ampicillin replaced penG in obstetrics and a shift to broad-spectrum agents was noted in non-obstetric patients potentially eligible for penG treatment . Shortage-triggered treatment changes had a negative effect on prescribing patterns, which may contribute to antibiotic resistance. Int J Clin Pract Suppl, 2003 Apr, (135), 50 - 3 The safety of ibuprofen suspension in children; Lesko SM; This paper describes two studies in children with fever in which the safety of ibuprofen was compared with that of paracetamol . The Boston University Fever Study aimed to assess the risk of rare but serious adverse events in febrile children . There were 795 admissions among 84,192 children during the study . There were no significant differences between the drugs in the risk of admission or the risk of secondary endpoints (admissions for asthma or cellulitis, or physician visits for abdominal pain or dyspepsia) and no evidence of clinically significant impairment of renal function . However, ibuprofen was associated with a significantly lower risk of physician visits for asthma: the incidence associated with ibuprofen was 3.0% (CI95% 2.1, 4.1) compared with 5.1% (CI95% 3.5, 7.1) for paracetamol (P = 0.02) . The second study was a case control study to investigate a possible association between antipyretic medication, varicella infection and necrotising fasciitis . We identified 52 children aged under 19 years who were admitted to hospital with varicella and Group A streptococcal infection and 172 matched controls with uncomplicated varicella . The risk of invasive Group A streptococcal infection was associated with demographic and environmental factors and persistent high fever . There was no association with the use of ibuprofen or paracetamol alone, but the use of both agents was significantly associated with streptococcal infection . These studies demonstrate that children with fever tolerate treatment with ibuprofen as well as treatment with paracetamol . Neither agent is associated with an increased risk of necrotising soft tissue infections. Vet Rec, 2003 Apr 12, 152(15), 466 - 71 In vitro activity of 10 antimicrobial agents against bacteria isolated from cows with clinical mastitis; Guerin-Faublee V et al.; The susceptibility of 495 strains of bacteria, recently isolated in France from cows with clinical mastitis, to 10 antimicrobial agents--penicillin G, cloxacillin, oxacillin, cephalexin, cefazolin, cephapirin, cefquinome, neomycin, ampicillin and colistin--was determined by measuring their minimum inhibitory concentrations (MICS) . Overall, the levels of resistance were very low except for staphylococci and penicillin G . The 167 streptococcal strains were susceptible to all of the beta-lactams tested, but six (3-6 per cent) were highly resistant to neomycin . Of the 171 staphylococcal isolates, 36.2 per cent were resistant to penicillin G, one strain of Staphylococcus sciuri was classified as methicillin-resistant, but they were all susceptible to neomycin . None of the 122 strains of Escherichia coli was resistant to colistin, but 12 had high MIC values for one or more of the cephalosporins. Crit Care, 2003 Apr, 7(2), 185 - 90 Epub 2003 Mar 03. Protein-losing enteropathy in patients with Fontan circulation: is it triggered by infection? Lenz D, Hambsch J, Schneider P, Hausler HJ, Sauer U, Hess J, Tarnok A. INTRODUCTION: Protein-losing enteropathy (PLE) is a recognised complication of the Fontan circulation . Its pathogenesis is not fully understood, however, and it is unclear why its onset occurs months or even years after Fontan surgery . PATIENTS: We report a 4.5-year-old girl with Fontan circulation who developed PLE almost 1 year after surgery . At the time of onset the patient had rotavirus enteritis and streptococcal tonsillitis . We have reviewed the records of seven other patients with longstanding PLE . In six of these patients we identified infections at the onset of symptoms . None of our patients had evidence of opportunistic infection . DISCUSSION AND CONCLUSION: The immune system of patients with PLE is compromised, but reports on recurrent opportunistic infections are rare . The present observations suggest that infection and inflammation may be associated with the onset of PLE . The mechanism of how infection may trigger PLE warrants further investigation. Int J Infect Dis, 2003 Mar, 7(1), 21 - 6 Preparation of a superantigen-adsorbing device and its superantigen removal efficacies in vitro and in vivo; Miwa K et al.; OBJECTIVE: A new superantigen-adsorbing device (SAAD) was developed, and its characteristics and efficacy in septic animals were evaluated . METHODS: The SAAD was prepared by stepwise chemical modification of a polystyrene-based composite fiber reinforced with polypropylene . Adsorption affinities for several factors and the biological effect of superantigen (SAg) removal were measured in vitro . Also, superantigen-infused rabbits were treated with SAAD, and the efficacy was evaluated in vivo . RESULTS: When the SAAD was evaluated for its ability to adsorb SAg in human plasma (1 ng/mL each), the adsorption rates were 74%, 76% and 85% for staphylococcal enterotoxins A, B and C, respectively, and 80% and 72% for toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A, respectively . In addition, the SAAD showed some affinity towards other molecules, such as streptococcal pyrogenic exotoxin B, beta2-microglobulin, and vancomycin . Residual activities in whole blood samples containing TSST-1 (1 ng/mL) after incubation with the SAAD were 125 pg/mL for tumor necrosis factor alpha (TNF-alpha) production, and 359 pg/mL for interleukin-8 (IL-8) production (the initial activities: 194 pg/mL for TNF-alpha production, and 1029 pg/mL for IL-8 production) . When TSST-1/lipopolysaccharide (LPS)-infused rabbits were subjected to extracorporeal blood purification with a SAAD column, 50% of the animals survived for a 14-day period after the infusion . In contrast, all control animals died within 3 days after the infusion . CONCLUSION: These results indicate that the SAg-adsorbing device may be useful in treating SAg-related diseases. Protein Sci, 2003 May, 12(5), 914 - 22 Comparison of (13)C(alpha)H and (15)NH backbone dynamics in protein GB1; Idiyatullin D et al.; This study presents a site-resolved experimental view of backbone C(alpha)H and NH internal motions in the 56-residue immunoglobulin-binding domain of streptococcal protein G, GB1 . Using (13)C(alpha)H and (15)NH NMR relaxation data {T(1), T(2), and NOE} acquired at three resonance frequencies ((1)H frequencies of 500, 600, and 800 MHz), spectral density functions were calculated as F(omega) = 2omegaJ(omega) to provide a model-independent way to visualize and analyze internal motional correlation time distributions for backbone groups in GB1 . Line broadening in F(omega) curves indicates the presence of nanosecond time scale internal motions (0.8 to 5 nsec) for all C(alpha)H and NH groups . Deconvolution of F(omega) curves effectively separates overall tumbling and internal motional correlation time distributions to yield more accurate order parameters than determined by using standard model free approaches . Compared to NH groups, C(alpha)H internal motions are more broadly distributed on the nanosecond time scale, and larger C(alpha)H order parameters are related to correlated bond rotations for C(alpha)H fluctuations . Motional parameters for NH groups are more structurally correlated, with NH order parameters, for example, being larger for residues in more structured regions of beta-sheet and helix and generally smaller for residues in the loop and turns . This is most likely related to the observation that NH order parameters are correlated to hydrogen bonding . This study contributes to the general understanding of protein dynamics and exemplifies an alternative and easier way to analyze NMR relaxation data. Infez Med, 2000, 8(4), 227 - 233 {Treatment of streptococcal tonsillo-pharyngitis in paediatric patients: short-course therapy with cefaclor}; Esposito S et al.; Short-course treatments of streptococcal pharyngotonsillitis with oral cephalosporins and macrolides have resulted in a similar bacteriologic and clinical cure rate and in better compliance compared to the conventional 10-day course . Cefaclor has never been investigated for this purpose . 138 patients out of 420 recruited patients had a positive culture for S . pyogenes and were randomly assigned to receive cefaclor (25 mg/kg/bid) for a 5- (70 pts) or 10-day (68 pts) course . Patients were assessed clinically and bacteriologically 2-3 days after completing the course and followed up after 20-30 days . All 420 recruited patients belonged to a population of 2,800 children who had been previously screened for a streptococcal carrier state to exclude carriers from final evaluation . Clinical cure and bacteriological eradication was recorded in 92.8% and 92.6% of patients in groups A and B respectively . Therefore, short-course therapy with cefaclor may offer an effective alternative treatment to conventional regimens, with potential for better compliance. Ann Emerg Med, 2003 May, 41(5), 601 - 8 Oral dexamethasone for the treatment of pain in children with acute pharyngitis: a randomized, double-blind, placebo-controlled trial; Bulloch B et al.; STUDY OBJECTIVE: We compare oral dexamethasone with placebo for the relief of pain in children with acute pharyngitis . METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial of children aged 5 to 16 years who presented to the emergency department with acute pharyngitis . Children rated their pain on a standardized color analog scale and had a rapid streptococcal antigen detection test performed to determine group assignment . Children were randomized to dexamethasone (0.6 mg/kg, maximum dose 10 mg) or placebo . Blinded research assistants called all families daily to determine pain scores until the point of complete pain relief . The primary outcome measures were the time to clinically significant pain relief and the time to complete pain relief . RESULTS: A total of 184 children were enrolled in the study . There were 85 children in the antigen-positive group, of whom 45 were randomized to dexamethasone and 40 to placebo . In children with group A beta-hemolytic streptococcal pharyngitis, the median time to clinically significant pain relief was 6 hours in the dexamethasone group versus 11.5 hours in the placebo group (P =.02; effect size of 5.5 hours with 95% confidence interval {CI} of 1.0 and 10.0 hours), and the time to complete pain relief was similar (36 hours for placebo versus 40 hours for dexamethasone, P =.86; effect size of 4.0 hours with 95% CI of -9.3 and 17.3 hours) in the placebo group . There were 99 children enrolled in the antigen-negative group, of whom 47 received dexamethasone and 52 received placebo . In this group, the median time to clinically significant pain relief was 13 hours in the dexamethasone group versus 9 hours in the placebo group (P =.32; effect size of 4 hours with 95% CI of -2 and 10 hours), and the time to complete pain relief was similar (48 hours for placebo versus 50 hours for dexamethasone, P =.61; effect size of 2 hours with 95% CI of -11.8 and 15.8 hours) . CONCLUSION: For all children with acute pharyngitis, oral dexamethasone does not decrease the time to onset of clinically significant pain relief or time to complete pain relief . However, in the subset of children with positive antigen detection test results, there is a statistically significant improvement in time to onset of pain relief, but it is of marginal clinical importance. J Chir (Paris), 2003 Feb, 140(1), 22 - 32 {Life-threatening cellulitis, or Fournier's gangrene of the perineum}; Cadot P et al.; The global mortality for Fournier's gangrene is one in five . In half the cases, the infection is polymicrobial with either anaerobes or gram negative bacilli . Factors which worsen prognosis include renal insufficiency, streptococcal infection, or need for hospital admission . Diagnosis must be prompt and treatment multidisciplinary involving the surgeon, intensivist, and infectious disease specialist; early and adequate surgical debridement must be accompanied by well-chosen antibiotics and hyperbaric oxygen therapy . Post-debridement therapy requires a long period of dressing changes and skin grafting to achieve final wound closure . This is an aggressive disease with a high mortality, but the depth and extent of invasive infection does not determine prognosis; the first priority is prompt and wide surgical excision/debridement of infected tissues to pre-empt the development of systemic sepsis; this should not be deferred while arranging transfer to a facility with a hyperbaric chamber. Trends Microbiol, 2003 Apr, 11(4), 161 - 5 Bacterial "competence" genes: signatures of active transformation, or only remnants? Claverys JP, Martin B. An exhaustive review published ten years ago reported natural genetic transformation, a potential mechanism for intra- and interspecies gene transfer, in approximately 40 species belonging to different taxonomic and trophic groups . Since then, considerable progress has been made in characterizing DNA-uptake machineries and regulatory circuits controlling their expression in cells competent for genetic transformation . In this article, in light of the recent description of a Group A streptococcal isolate capable of DNA transfer in mixed cultures, we discuss whether the detection in completely sequenced microbial genomes of intact homologues of key competence-regulatory and/or DNA-uptake proteins enables the prediction of new transformable species. Infect Immun, 2003 May, 71(5), 2827 - 38 Genome diversification in Staphylococcus aureus: Molecular evolution of a highly variable chromosomal region encoding the Staphylococcal exotoxin-like family of proteins; Fitzgerald JR et al.; Recent genomic studies have revealed extensive variation in natural populations of many pathogenic bacteria . However, the evolutionary processes which contribute to much of this variation remain unclear . A previous whole-genome DNA microarray study identified variation at a large chromosomal region (RD13) of Staphylococcus aureus which encodes a family of proteins with homology to staphylococcal and streptococcal superantigens, designated staphylococcal exotoxin-like (SET) proteins . In the present study, RD13 was found in all 63 S . aureus isolates of divergent clonal, geographic, and disease origins but contained a high level of variation in gene content in different strains . A central variable region which contained from 6 to 10 different set genes, depending on the strain, was identified, and DNA sequence analysis suggests that horizontal gene transfer and recombination have contributed to the diversification of RD13 . Phylogenetic analysis based on the RD13 DNA sequence of 18 strains suggested that loss of various set genes has occurred independently several times, in separate lineages of pathogenic S . aureus, providing a model to explain the molecular variation of RD13 in extant strains . In spite of multiple episodes of set deletion, analysis of the ratio of silent substitutions in set genes to amino acid replacements in their products suggests that purifying selection (selective constraint) is acting to maintain SET function . Further, concurrent transcription in vitro of six of the seven set genes in strain COL was detected, indicating that the expression of set genes has been maintained in contemporary strains, and Western immunoblot analysis indicated that multiple SET proteins are expressed during the course of human infections . Overall, we have shown that the chromosomal region RD13 has diversified extensively through episodes of gene deletion and recombination . The coexpression of many set genes and the production of multiple SET proteins during human infection suggests an important role in host-pathogen interactions. Emerg Infect Dis, 2003 Apr, 9(4), 443 - 7 Risk for severe group A streptococcal disease among patients' household contacts; Robinson KA et al.; From January 1997 to April 1999, we determined attack rates for cases of invasive group A streptococcal (GAS) disease in household contacts of index patients using data from Active Bacterial Core Surveillance sites . Of 680 eligible index-patient households, 525 (77.2%) were enrolled in surveillance . Of 1,514 household contacts surveyed, 127 (8.4%) sought medical care, 24 (1.6%) required hospital care, and none died during the 30-day reference period . One confirmed GAS case in a household contact was reported (attack rate, 66.1/100,000 household contacts) . One household contact had severe GAS-compatible illness without confirmed etiology . Our study suggests that subsequent cases of invasive GAS disease can occur, albeit rarely . The risk estimate from this study is important for developing recommendations on the use of chemoprophylaxis for household contacts of persons with invasive GAS disease. J Neurol Neurosurg Psychiatry, 2003 May, 74(5), 602 - 7 Tourette's syndrome: a cross sectional study to examine the PANDAS hypothesis; Church AJ et al.; BACKGROUND: The classical neurological disorder after group A beta haemolytic streptococcal infection is Sydenham's chorea . Recently a tic disorder occurring after group A streptococcal infection has been described and termed PANDAS (paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) . It is proposed that antibodies induced after group A streptococcal infection react with basal ganglia neurones in Sydenham's chorea and PANDAS . Anti-basal ganglia antibodies (ABGA) are present in most cases of acute Sydenham's chorea, but rarely in controls . OBJECTIVE: To investigate the hypothesis that Tourette's syndrome may be associated with group A streptococcal infection and ABGA . METHODS: 100 patients with Tourette's syndrome (DSM-IV-TR) were enrolled in a cross sectional study . Children with neurological disease (n = 50) and recent uncomplicated streptococcal infection (n = 40), adults with neurological disease (n = 50), and healthy adults (n = 50) were studied as controls . Recent group A streptococcal infection was defined using antistreptolysin O titre (ASOT) . ABGA were detected using western immunoblotting and indirect immunofluorescence . RESULTS: ASOT was raised in 64% of children with Tourette's syndrome compared with 15% of paediatric neurological disease controls (p < 0.0001), and in 68% of adults with Tourette's syndrome compared with 12% of adult neurological controls and 8% of adult healthy controls (p < 0.05) . Western immunoblotting showed positive binding in 20% of children and 27% of adults with Tourette's syndrome, compared with 2-4% of control groups (p < 0.05) . The most common basal ganglia binding was to a 60 kDa antigen, similar to the proposed antigen in Sydenham's chorea . Indirect immunofluorescence revealed autoantibody binding to basal ganglia neurones . Serological evidence of recent group A streptococcal infection, assessed by a raised ASOT, was detected in 91% (21/23) of Tourette's syndrome patients with positive ABGA compared with 57% (44/77) with negative ABGA (p < 0.01) . CONCLUSIONS: The results support a role of group A streptococcal infection and basal ganglia autoimmunity in a subgroup of patients with Tourette's syndrome and suggest a pathogenic similarity between Sydenham's chorea and some patients with Tourette's syndrome. Pediatr Neurol, 2003 Feb, 28(2), 119 - 25 Antistreptococcal, neuronal, and nuclear antibodies in Tourette syndrome; Loiselle CR et al.; Previous studies have suggested associations between Tourette syndrome and attention-deficit-hyperactivity disorder and antistreptococcal antibodies and between Tourette syndrome and antinuclear antibodies . In this study, antistreptolysin O, antideoxyribonuclease B, antinuclear, and antineuronal antibodies were measured in 41 children with Tourette syndrome and 38 controls, selected without regard to history of streptococcal infection . Results revealed that mean antistreptococcal titers did not differ between diagnostic groups . In addition, multiple regression analysis was unable to predict antistreptococcal antibody titers according to age and diagnosis . The frequency of elevated antistreptolysin O titers, based on a cutoff of 1:240, was significantly higher (P = 0.04) in patients with attention-deficit-hyperactivity disorder (64%) than in the group without attention-deficit-hyperactivity disorder (34%) but not when dichotomized according to age-matched normal values . No analysis of antideoxyribonuclease B titers identified any differences between groups . Antinuclear antibody titers were at least 1:160 in three of 33 Tourette syndrome patients; only one subject manifested a homogeneous staining pattern . Multiple regression analyses were unable to predict antinuclear, antineuronal, or anti-HTB-10 antibody titers according to the combination of age, diagnosis, and antistreptococcal titer . We suggest that longitudinal rather than single-point-in-time laboratory measurements be evaluated before definitive conclusions are drawn on associations between the diagnosis of Tourette syndrome, attention-deficit-hyperactivity disorder, or obsessive-compulsive disorders and antistreptococcal or antinuclear antibody titers. Pediatr Dev Pathol, 2003 May-Jun, 6(3), 251 - 6 Epub 2003 Apr 14. Late-onset and recurrent neonatal Group B streptococcal disease associated with breast-milk transmission; Kotiw M et al.; The purpose of the study was to determine the epidemiological relationships in three unrelated cases of neonatal late-onset Group B streptococcal (GBS) disease and maternal breast-milk infection with GBS . All deliveries were by cesarean section; case 1 was at term, and cases 2 and 3 were at 32- and 33-wk gestation, respectively . Case 1 relates to a mother with clinical mastitis and recurrent GBS infection in a 20-day-old male infant . Following antibiotic therapy and cessation of breast-feeding, the infant recovered without sequelae . Case 2 refers to a mother with clinical mastitis and the occurrence of late-onset GBS disease in 5-wk-old male twins . Despite intervention, one infant died and the second became ill . Following antibiotic therapy and cessation of breast-feeding, the surviving infant recovered without sequelae . Case 3 refers to a mother with sub-clinical mastitis and late-onset GBS infection occurring in a 6-day-old female twin . Following intervention, the infant recovered but suffered a bilateral thalamic infarction resulting in developmental delay and a severe seizure disorder . Following recovery of GBS from an inapparent mastitis and cessation of breast-feeding, the second infant remained well . Blood cultures from all affected infants and maternal breast milk were positive for GBS . Epidemiological relationships between neonatal- and maternal-derived GBS isolates were confirmed by a random amplified polymorphic DNA polymerase chain reaction assay (RAPD-PCR) . This study is significant in that it has demonstrated that maternal milk (in cases of either clinical or sub-clinical mastitis) can be a potential source of infection resulting in either late-onset or recurrent neonatal GBS disease. Klin Med (Mosk), 2003, 81(2), 8 - 15 {Management of patients with infectious endocarditis}; Demin AA et al.; The paper presents clinical manifestations of infectious endocarditis (IE), its new clinical classification, diagnostic criteria, potentialities and limitations of echocardiography . General principles of management of patients with IE are considered . The management algorithm is given, which involves the initial assessment of these patients, empirical therapy, etiotropic chemotherapy (CT) regimens in streptococcal, staphylococcal, gram-negative, fungal endocarditis, and IE of unknown etiology . Possible complications due to IE (refractory heart failure, infection dissemination, thrombohemorrhagic syndrome, immune diseases, persistent fever) are described, which need supplementary treatment, particularly schemes for correction of hemostatic and immune disorders . Clinical and microbiological criteria are proposed for evaluating the efficiency of treatment for IE . The conditions showing a higher risk for the types of IE that require antibiotic prophylaxis and the criteria for choosing its regimen are given . New trends in the treatment of IE, such as shorter courses of antibacterial CT, stepwise antibacterial therapy (ABT), and parenteral ABT at home, are outlined. Cancer Immunol Immunother, 2003 Apr, 52(4), 207 - 14 Epub 2003 Feb 25. Streptococcal preparation OK432 promotes functional maturation of human monocyte-derived dendritic cells; Itoh T et al.; Streptococcal preparation OK432 is an immunomodulatory agent extensively used as adjuvant therapy for gastric cancer in Japan . OK432 augments the cytotoxic activity of various effector cells such as lymphocytes, macrophages and (natural killer) NK cells and induces the production of multiple cytokines . Dendritic cells (DC) are professional antigen-presenting cells (APC) that can be used for cancer vaccine therapy . In the present study, we investigated the effect of OK432 on the activation of DC . Here we report that OK432 induced phenotypic and functional maturation of human monocyte-derived DC . In vitro culture of immature DC generated from adherent peripheral blood mononuclear cells (PBMC) using granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) with OK432 at various doses (0.01 to 0.1 KE/ml) for 2 days resulted in increased cell surface expression of CD80, CD83, CD86 and ICAM-1 in a dose-dependent manner . The expression of CD83, a selective marker of mature DC, on DC activated by OK432 (OK-DC) was maximally enhanced after 3 days of incubation . Assay of cytokine production in OK-DC after 2 days in culture revealed that OK432 was a strong inducer of IL-12 and interferon-gamma (IFN-gamma) . OK432 efficiently augmented the primary allogeneic T-cell responses by DC . This distinct phenotypic profile and allostimulatory capacity of OK-DC was stable for at least 48 h of additional culture in the absence of any cytokines . Moreover, the antiviral cytotoxic T lymphocytes (CTL) response in vitro was also enhanced by the addition of OK432 to the cultures . These findings suggest that OK432 is a potent stimulator of DC, and that stimulated DC are strong inducers of the T helper 1 (Th1)-type response . We conclude that OK-DC are likely candidates for use as an adjuvant for DC-based cancer immunotherapy. J Immunol Methods, 2003 Apr 1, 275(1-2), 69 - 79 A model of human whole blood lymphokine release for in vitro and ex vivo use; Hermann C et al.; Endotoxin (lipopolysaccharide, LPS) inducible cytokine release by human whole blood is increasingly used to model inflammatory responses in vitro, to detect the presence of pyrogenic contaminations as well as to monitor disease states or immunomodulatory treatments ex vivo . However, the LPS-stimulated blood model primarily allows the assessment of monocyte responses . Here, a whole blood model was established which allows assessment of lymphocyte responses . Four different superantigens, namely staphylococcal enterotoxin A and B (SEA, SEB), toxic shock syndrome toxin-1 (TSST-1) or streptococcal exotoxin A (SPEA) were tested with respect to the induction of lymphokine release . All superantigens were capable of inducing significant amounts of the lymphokines interferon-gamma (IFNgamma), interleukin 2 (IL-2), IL-4, IL-5, IL-13 and tumor necrosis factor beta (TNFbeta) after 72 h of incubation . Concentration-dependencies and kinetics were determined . Blood from 160 healthy donors was used to assess the variability of SEB-inducible lymphokine release . Interindividual differences were more pronounced compared to LPS-inducible monokine release . However, the individual response was maintained when blood from six donors was tested once a week for 8 weeks, suggesting that the individual response represents a donor characteristic . The model appears to be suitable for the evaluation of immunomodulatory agents in vitro as well as ex vivo. Biochemistry, 2003 Apr 8, 42(13), 3742 - 50 Characterization of an Escherichia coli mutant MutY with a cysteine to alanine mutation at the iron-sulfur cluster domain; Lu AL et al.; Escherichia coli MutY is an adenine and a weak guanine DNA glycosylase involved in reducing mutagenic effects of 7,8-dihydro-8-oxoguanine (8-oxoG) . The {4Fe-4S} cluster of MutY is ligated by four conserved cysteine residues and has been shown to be important in substrate recognition . Here, we show that the C199A mutant MutY is very insoluble and can be denatured and renatured to regain activity only if iron and sulfur are present in the renaturation steps . The solubility of C199A-MutY can be improved substantially as a fusion protein containing streptococcal protein G (GB1 domain) at its N-terminus . Here, we describe the first biochemical characterization of the purified GB1-C199A-MutY protein which contains a {3Fe-4S} cluster . The apparent dissociation constant (K(d)) values of GB1-C199A-MutY with both A/G and A/8-oxoG mismatches are slightly higher than that of the wild-type protein . The DNA glycosylase activity of GB1-C199A-MutY is comparable to that of the wild-type enzyme . Interestingly, the major difference between the C199A-MutY and wild-type proteins is their trapping activities (formation of Schiff base intermediates) . The GB1-C199A-MutY mutant has a weaker trapping activity than the wild-type enzyme . Importantly, highly expressed GB1-C199A-MutY and untagged C199A-MutY can complement mutY mutants; however, GB1-C199A-MutY and untagged C199A-MutY cannot complement mutY mutants in vivo when both proteins are poorly expressed . Therefore, an intact {4Fe-4S} cluster domain is critical for MutY stability and activity. Immunol Lett, 2003 Feb 3, 85(3), 231 - 5 Differential binding characteristics of protein G and protein A for Fc fragments of papain-digested mouse IgG; Aybay C; It has been previously reported that staphylococcal protein A (SPA) bound only to the Fc region of mouse immunoglobulin G (IgG) and streptococcal protein G (SPG) bound to both Fab and Fc regions of mouse IgG and the binding sites for SPG and SPA on Fc were overlapped . In this study the binding characteristics of SPG and SPA for papain-digested mouse IgG were analysed . Papain digestion of mouse IgG purified from CAy-IFNg99C hybridoma (secreting IgG1 monoclonal antibody specific for human interferon gamma)-induced ascites resulted in Fab and two major Fc fragments referred to as the high molecular weight (HMW) and the low molecular weight (LMW) Fc fragments . SPG bound to Fab and the LMW Fc fragments of the papain-digested IgG . However SPG did not bind to the HMW Fc fragment . SPA showed practically no reactivity with the Fab and the LMW Fc fragments of the papain-digested mouse IgG but only to the HMW Fc fragment . SPG and SPA binding assays showed that papain digestion discriminated the SPG and SPA binding sites in the Fc fragment of mouse IgG . These results demonstrated a clear evidence for the presence of two independent SPG and SPA binding sites in the Fc fragment of mouse IgG. Ann Otol Rhinol Laryngol, 2003 Mar, 112(3), 214 - 20 Treatment of ranula wth intracystic injection of the streptococcal preparation OK-432; Fukase S et al.; Intracystic injection of OK-432 was developed as a therapy for operatively difficult lymphangioma (cystic hygroma) and is currently becoming a treatment of first choice for this disease . We tried this therapy in 32 patients with ranula (oral floor type in 21 cases and plunging type in 11 cases) . Disappearance or marked reduction of the lesion was observed in 31 patients (97%) who had this therapy, and local scarring did not occur in any patient . As side effects, local pain at the injection site and fever (37 degrees C to 39 degrees C) were observed in almost half of the patients who had this therapy, but such problems resolved within a few days . We treated the initial 4 cases in the hospital for 4 to 5 days, but after the safety of this method had been confirmed, we treated the other 28 cases on an outpatient basis . Thus, we confirmed that intracystic injection therapy with OK-432 is relatively safe and can be used as a substitute for surgery in the treatment of ranulas. J Biol Chem, 2003 May 30, 278(22), 19808 - 14 Epub 2003 Mar 22. Alteration of polysaccharide size distribution of a vertebrate hyaluronan synthase by mutation; Pummill PE et al.; Hyaluronan (HA) is a nonsulfated glycosaminoglycan that has long been known to play structural roles in vertebrates . Recently, it has become increasingly obvious that this linear polysaccharide has many more uses than simply scaffolding or space filler . HA has been found to be involved in development, cell signaling, cell motility, and metastasis . These roles are often dictated by the length of the HA polymer, which can vary from a few to about 10,000 sugar residues in length . Three distinct isoforms of HA synthase exist in mammals . It has been shown previously by others that each isoform produces HA that differs in size distribution, but the regulatory mechanism is not yet known . Mutations have been described that alter the size distribution of the HA produced by the streptococcal HA synthases . We show that by mutating one particular amino acid residue of a vertebrate HA synthase, depending on the introduced side chain, the size of HA produced can be either reduced or increased . We postulate that several cysteine residues and a serine residue may be involved in binding directly or indirectly to the nascent HA chain . These data support the theory that the relative strength of the interaction between the catalyst and the polymer may be a major factor in HA size control. Acta Paediatr, 2003, 92(1), 125 - 7 Group A streptococcal osteomyelitis: severe presentation and course; Turner D et al.; AIM: To evaluate the course of group A streptococcal osteomyelitis associated with severe disease nowadays . METHODS: Three consecutive cases of severe group A streptococcal disease with osteomyelitis in children that were documented in Beer Sheva, Israel are described in detail . RESULTS: Two of the three cases were postvaricella . Early in the course of the disease, the presentation resembled that of severe cellulitis . All three patients had severe osteomyelitis and required surgery, and one patient developed chronic osteomyelitis . Sepsis was diagnosed in two cases . CONCLUSION: Our cases are distinguishable from typical haematogenous staphylococcal osteomyelitis by the severe course and the extensive involvement of bone and soft tissues . The increase in severity of invasive group A streptococcal infections documented throughout the world could account for the difference between our complex cases and the previous reports. Infect Dis Obstet Gynecol, 2002, 10(4), 223 - 9 Compliance with a protocol for intrapartum antibiotic prophylaxis against neonatal group B streptococcal sepsis in women with clinical risk factors; Sanders TR et al.; OBJECTIVE: The aim of this study was to determine the prevalence of clinical risk factors (CRF) for neonatal sepsis in laboring women and to evaluate clinician compliance with a CRF-based protocol for intrapartum antibiotic prophylaxis (IAP) . METHODS: A retrospective chart audit was undertaken at a district hospital (A) and a tertiary obstetric hospital (B) in Sydney, Australia between 1996 and 1998, to determine compliance with IAP in women with defined CRF . RESULTS: Eighty-five (12%) women at Hospital A and 117 (19%) at Hospital B had one or more CRF . Overall compliance rates with the IAP protocols were 65 and 50% at Hospitals A and B respectively, but varied according to maternal, obstetric and sepsis-related risk factors . We postulate that differences between the hospitals were related to protocol implementation . CONCLUSIONS: Compliance with a CRF-based protocol was lower than previously reported . Improvements in protocol development, implementation and maintenance are required to enhance compliance with IAP based on CRF. Infect Dis Obstet Gynecol, 2002, 10(4), 217 - 22 Two cases of delayed diagnosis of postpartal streptococcal toxic shock syndrome; Schummer W et al.; BACKGROUND: Puerperal sepsis due to group A beta-hemolytic streptococcal (GAS) toxic shock syndrome is associated with very high morbidity and mortality . Luckily it is now rare, but diagnosis is not always easy . This report demonstrates the problem of recognizing this disease, and summarizes the current knowledge on the pathomechanism and management of streptococcal toxic shock syndrome . CASE: Two cases of postpartum streptococcal toxic shock syndrome due to GAS are described . In both cases the correct diagnosis was delayed for several days . The first patient was sent home with the diagnosis of German measles; the second patient was transferred to our neurological intensive care unit with the diagnosis of meningitis . Both patients were admitted to the intensive care unit in profound shock, both developed multiple organ failure, and one patient died . CONCLUSIONS: GAS may produce virulence factors that cause host tissue pathology . Besides aggressive modern intensive care treatment, early diagnosis and correct choice of anti-streptococcal antibiotics are crucial . A possible adverse effect of non-steroidal anti-inflammatory agents requires confirmation in a multicenter study. Infect Dis Obstet Gynecol, 2002, 10(4), 209 - 16 Group A streptococcal toxic shock syndrome developing in the third trimester of pregnancy; Crum NF et al.; BACKGROUND: Group A streptococcal (GAS) toxic shock syndrome (TSS) is an uncommon, but life-threatening infection during pregnancy and should be considered in rapid onset of shock . Most cases described in the literature have occurred in the puerperium . We report a case of GAS TSS occurring during the third trimester of pregnancy in a previously healthy woman . CASE: A 31-year-old female, who was 34 weeks pregnant, presented with fevers and a prodromal 'flu-like' illness . She rapidly developed shock and multiorgan failure . Blood cultures revealed GAS bacteremia and the patient met criteria for streptococcal TSS . Despite her eventual recovery, her infant died on postpartum day 15 as a consequence of the mother's TSS . CONCLUSIONS: This case is unusual in that there were no identifiable initiating events or source of the streptococcal infection, and the TSS developed during pregnancy rather than after delivery . Early recognition of GAS infections is important given the rapid onset and high morbidity and mortality associated with these infections . This is the first reported case utilizing intravenous immunoglobulin for GAS TSS in the puerperium. Eur J Pediatr, 2003 Apr, 162(4), 245 - 7 Epub 2003 Feb 06. Fulminant liver failure in a child with invasive group A streptococcal infection; Biesel-Desthieux MN et al.; Liver involvement is mentioned in streptococcal toxic shock syndrome, but never as fulminant liver failure (FLF) . We report the case of a 2-year-old child who developed isolated FLF secondary to invasive group A streptococcal infection without shock due to a M1T1-type strain expressing speA, speB and speC toxin genes . On antibiotics, he recovered rapidly without liver transplantation . CONCLUSION: A streptococcal pyrogenic exotoxin likely constituted the initial insult leading to FLF . This etiology can be included in the differential diagnosis of FLF and would support early introduction of antibiotics. Rev Med Chir Soc Med Nat Iasi, 2002 Apr-Jun, 107(2), 356 - 9 Tolerance to penicillin in Staphylococcus pyogenes isolated from skin infections; Panzaru C et al.; The tolerance to penicillin of S . pyogenes has been mentioned in pharyngeal strains and associated by some authors with penicillin treatment failure in streptococcal angina . In this study we followed the presence of tolerance in S . pyogenes strains isolated from children hospitalized in the Clinic of Infantile Surgery and Clinic of Dermatology Iasi for skin infections . From 138 samples of pus examined we isolated 14 strains of S . pyogenes . In 7 strains we pointed out the tolerance to penicillin by both, beta-lactamase disc test and time-killing curve methods . We did not correlate to our cases the tolerance presence with penicillin treatment failure. Intern Med, 2003 Feb, 42(2), 211 - 8 A new therapeutic strategy for streptococcal toxic shock syndrome: a key target for cytokines; Kawaguchi T et al.; We searched for innovative treatments specifically targeted to the cytokines of three critically ill patients with streptococcal toxic shock syndrome (STSS) . Direct hemoperfusion with polymyxin B-immobilized fiber improved the hemodynamics in all three patients who had developed shock at presentation . Continuous hemodiafiltration coupled with plasma exchange for simultaneous removal of several mediators of the inflammatory cascade improved outcome in case 2 and lessened the aggressive clinical course and prolonged survival in case 3 . The application of these technologies appears to open new and interesting therapeutic options and may lead to improved survival in STSS. Int J Med Microbiol, 2003 Feb, 292(7-8), 429 - 40 Staphylococcal and streptococcal superantigens: molecular, biological and clinical aspects; Alouf JE et al.; Superantigens (SAgs) include a class of certain bacterial and viral proteins exhibiting highly potent lymphocyte-transforming (mitogenic) activity towards human and or other mammalian T lymphocytes . Unlike conventional antigens, SAgs bind to certain regions of major histocompatibility complex (MHC) class II molecules of antigen-presenting cells (APCs) outside the classical antigen-binding groove and concomitantly bind in their native form to T cells at specific motifs of the variable region of the beta chain (Vbeta) of the T cell receptor (TcR) . This interaction triggers the activation (proliferation) of the targeted T lymphocytes and leads to the in vivo or in vitro release of high amounts of various cytokines and other effectors by immune cells . Each SAg interacts specifically with a characteristic set of Vbeta motifs . The review summarizes our current knowledge on S . aureus and S . pyogenes superantigen proteins . The repertoire of the staphylococcal and streptococcal SAgs comprises 24 and 8 proteins, respectively . The staphylococcal SAgs include (i) the classical enterotoxins A, B, C (and antigenic variants), D, E, and the recently discovered enterotoxins G to Q, (ii) toxic shock syndrome toxin-1, (iii) exfoliatins A and B . The streptococcal SAgs include the classical pyrogenic exotoxins A and C and the newly identified pyrogenic toxins, G, H, I, J, SMEZ, and SSA . The structural and genomic aspects of these toxins and their molecular relatedness are described as well as the available 3-D crystal structure of some of them and that of certain of their complexes with MHC class II molecules and the TcR, respectively . The pathophysiological properties and clinical disorders related to these SAgs are reviewed. J Med Invest, 2003 Feb, 50(1-2), 9 - 24 Toll-like receptor signaling in anti-cancer immunity; Okamoto M et al.; It is important to augment the anti-cancer host response in cancer treatment . Recent studies suggested that the signaling via Toll-like receptors (TLRs) which are newly identified receptor molecules recognizing many pathogens, are involved in the induction of anti-cancer immunity . Seya et al . demonstrated that maturation of dendritic cells (DCs) and cytokine induction by the cell wall skeleton of Mycobacterium bovis bacillus Calmette-Guerin (BCG-CWS) are induced via both TLR2 and TLR4 . Akira et al . discovered a new molecule of TLR family, TLR9, recognizing unmethylated bacterial CpG-DNA, whose clinical use is expected for cancer therapy as a potent inducer of a helper T cell 1 (Th1)-type T-cell response . TLR9-deficient mice did not show any responses to CpG-DNA, including Th 1 cytokine production and maturation of DCs . We have obtained two molecules, a lipoteichoic acid-related molecule isolated from streptococcal agent OK-432, and a plant-derived 55-kDa protein that can induce Th1 response and elicit a strong anti-cancer effect in vivo and in vitro . Our basic experiments demonstrate that TLR4 signaling is intimately involved in anti-cancer immunity induced by these immunopotentiators . Our clinical examination in oral cancer patients also suggests the requirement of both TLR4 and MD-2 in the OK-432-induced anti-cancer host response . Establishment and clinical use of the methodology for human cancer therapy by utilizing TLR signaling is greatly expected. Can J Urol, 2003 Feb, 10(1), 1768 - 9 Group A streptococcal hydrocele infection and sepsis in a renal transplant recipient; Beiko DT et al.; A case of hydrocele infection secondary to a cutaneous b-hemolytic group A streptococcal infection is described in a renal transplant recipient . Sepsis and renal failure occurred in the setting of this severe, life-threatening infection . This case represents the first description of a group A streptococcal hydrocele infection in an adult . This type of infection can progress rapidly to sepsis and its attendant complications, especially in an immunocompromised patient . Early diagnosis and treatment is crucial in order to optimize the outcome. J Clin Microbiol, 2003 Mar, 41(3), 937 - 42 Epidemiologic analysis of invasive and noninvasive group a streptococcal isolates in Hong Kong; Ho PL et al.; Since the mid-1980s, there has been a resurgence of severe forms of invasive group A streptococcal (GAS) disease in many Western countries . In Hong Kong, a similar increase has also been observed in recent years . One hundred seven GAS isolates collected from 1995 to 1998 from individuals with necrotizing fasciitis, toxic shock syndrome, meningitis, or other type of bacteremic sepsis (invasive group, n = 24) as well as from individuals with minor skin and throat infections (noninvasive group, n = 83) were characterized through serologic and/or emm sequence typing . Thirty-two M protein gene sequence types were identified . Types M1, M4, and M12 were the most prevalent in both the invasive group and the noninvasive group; together they accounted for 70.8 and 37.3% of the isolates, respectively . No clear pattern of skin and throat infection M types was observed . Type M1 was overrepresented in the invasive and pharyngeal isolates . The same pulsed-field gel electrophoresis pattern was shared by most invasive and all pharyngeal M1 isolates . Overall, resistance to erythromycin (32%) and tetracycline (53%) was high, but M1 isolates were significantly less likely to have resistance to either antimicrobial agent than non-M1 isolates . One novel emm sequence type, stHK, was identified in an isolate from a patient with necrotizing fasciitis . Minor emm gene sequence alterations were noted for 31 isolates, and for 13 of these isolates, deletion, insertion, or point mutations were seen in the hypervariable 50 N-terminal residues. Arch Pediatr Adolesc Med, 2003 Mar, 157(3), 257 - 60 Influence of the news media on diagnostic testing in the emergency department; Sharma V et al.; OBJECTIVE: To examine the association between mass media attention regarding invasive group A streptococcal (GAS) disease and testing for GAS in a pediatric emergency department (ED) . DESIGN, SETTING, AND PARTICIPANTS: An observational analysis was performed of patients who had GAS tests done in a pediatric ED between December 1, 1999, and November 30, 2001 . Data were analyzed by dividing each of the 2 years into 4 consecutive 90-day intervals . Data including age, date of the visit, presenting complaint, primary discharge diagnosis, whether a GAS test was obtained, and the results were collected from an electronic data repository . The date of the news stories, the station, and the duration of the broadcast were collected from electronic archives of the local newspaper and a broadcast monitoring service . MAIN OUTCOME MEASURE: The rate of GAS tests done per 1000 ED visits and the rate of positive tests per 1000 ED visits . RESULTS: An average of 103 GAS tests were performed per 1000 ED visits in the December through February period in year 2 compared with 55 GAS tests per 1000 ED visits in a similar period in year 1 . This difference was statistically significant (difference, 48 tests; 95% confidence interval, 24-72 tests; P<.001) . There were no significant differences in the proportion of positive tests (32% in year 1 vs 20% in year 2; mean difference, -11%; 95% confidence interval, -23% to 1%; P =.07) . There were a total of 16 newspaper articles and 34 television stories on GAS during the 2-year study period . The peak in GAS tests and the peak in media events were concomitant . CONCLUSION: A surge in news stories regarding GAS disease was associated with an increase in testing for GAS in a pediatric ED. Anal Chem, 2003 Feb 15, 75(4), 835 - 42 Comparative study of IgG binding to proteins G and A: nonequilibrium kinetic and binding constant determination with the acoustic waveguide device; Saha K et al.; The aim of this work was to measure and compare the binding constants of antibody immunoglobulin G (IgG) to bacterial cell wall proteins, streptococcal protein G and Staphylococcus aureus protein A, using an acoustic wave sensor . Devices, which used shear-horizontal acoustic waves propagating in a waveguide configuration at 108 and 155 MHz, were employed in the detection of apparent IgG binding constants at the solid-liquid interface in the range of 6.7-667 nM IgG . Real-time data during IgG-protein G and IgG-protein A binding yielded apparent association constants of 3.29 x 10(4) and 8.02 x 10(3) M(-1) s(-1) leading to equilibrium constants of 1.13 x 10(8) and 2.90 x 10(7) M(-1), respectively . The measured apparent rate constants are consistent with literature reports of higher affinity of protein G for IgG . Furthermore, protein binding through the Fc region of IgG is suggested to occur below 333 nM, while different mechanisms are suggested to occur above 333 nM . For the first time, nonequilibrium studies of IgG-protein G and A binding at a solid-liquid interface has yielded valuable quantitative kinetic information about binding mechanisms . The promise of this detection method is shown by providing quick determination of binding constants with low sample volumes. Int Immunol, 2003 Mar, 15(3), 417 - 26 Evidence of allosteric conformational changes in the antibody constant region upon antigen binding; Oda M et al.; We have addressed the question of whether antigen binding induces a conformational change in the heavy chain constant (C(H)) domain of antibodies using staphylococcal protein A or streptococcal protein G as probes, since these proteins are known to bind to IgG domains such as C(H)1 and C(H)2-C(H)3 domains . Biosensor assays on interactions between these proteins and mouse IgG specific to (4-hydroxy-3-nitrophenyl)acetyl (NP) or their enzymatic fragments conducted in the presence or absence of the hapten, NP-epsilon-aminocaproic acid (NP-Cap), showed that the binding of IgG to these proteins was inhibited by the binding of NP-Cap . The results of isothermal titration calorimetry also revealed that the association constant for the interaction of protein A with IgG2b decreased by the addition of NP-Cap . These results suggested that antigen binding induced conformational changes in binding sites for protein G or protein A located at C(H)1 and C(H)2-C(H)3 domains, respectively. QJM, 2003 Mar, 96(3), 183 - 91 Autoimmunity and the basal ganglia: new insights into old diseases; Dale RC; Sydenham's chorea (SC) occurs weeks or months after Group A streptococcal infection, and is characterized by involuntary, purposeless movements of the limbs, in addition to behavioural alteration . There is a body of evidence which suggests that SC is an immune-mediated brain disorder with regional localization to the basal ganglia . Recent reports have suggested that the spectrum of post-streptococcal CNS disease is broader than chorea alone, and includes other hyperkinetic movement disorders (tics, dystonia and myoclonus) . In addition, there are high rates of behavioural sequelae, particularly emotional disorders such as obsessive-compulsive disorder, anxiety and depression . These findings have lead to the hypothesis that similar immune-mediated basal ganglia processes may be operating in common neuropsychiatric disease such as tic disorders, Tourette syndrome and obsessive-compulsive disorder . This review analyses the historical aspects of post-streptococcal CNS disease, and the recent immunological studies which have addressed the hypothesis that common neuropsychiatric disorders may be secondary to basal ganglia autoimmunity. Pediatrics, 2003 Mar, 111(3), 541 - 7 Early-onset group B streptococcal infection after a combined maternal and neonatal group B streptococcal chemoprophylaxis strategy; Velaphi S et al.; OBJECTIVE: In January 1995, a combined maternal and neonatal protocol for prevention of early-onset group B streptococcal (GBS) infection was implemented that consisted of a risk factor-based approach for maternal intrapartum chemoprophylaxis using ampicillin combined with a single intramuscular dose of penicillin given to all newborns within 1 hour of delivery . The objective of this study was to review the cases of early-onset GBS infections that occurred from 1995 to 1999 to identify factors associated with their continued occurrence despite implementation of a GBS chemoprophylaxis protocol . METHODS: Infants <or=72 hours of age with early-onset GBS infection born at Parkland Memorial Hospital in Dallas from January 1995 to December 1999 were identified through a prospective laboratory-based surveillance system . Maternal and infant medical records were reviewed for clinical and demographic data . RESULTS: There were 32 cases (0.47/1000 live births) of early-onset GBS infection for the 5-year period . This represented a 76% reduction compared with the rate from 1986 to 1994 (1.95/1000), when there was no protocol for GBS chemoprophylaxis . Thirteen cases (41%) did not have any identifiable maternal risk factor . Of the 19 cases (59%) with risk factors, maternal intrapartum fever was the most frequent (15 {79%}), followed by prematurity (6 {32%}) and prolonged rupture of membranes (6 {32%}) . Among the 19 mothers with risk factors, 15 (79%) mothers received intrapartum chemoprophylaxis, and 12 (80%) of the 15 mothers had intrapartum fever . Only 33% of mothers with risk factors received >or=2 doses of intrapartum chemoprophylaxis, and among those with intrapartum fever, 25% received >or=2 doses . None of the 32 infants with early-onset GBS infection received the combination of intrapartum ampicillin and postnatal penicillin . CONCLUSIONS: A combined obstetric and neonatal chemoprophylaxis protocol significantly reduced early-onset GBS infection . Maternal intrapartum fever was the most frequent risk factor associated with failure of chemoprophylaxis. Vestn Ross Akad Med Nauk, 2002, (12), 36 - 8 {Study of IS-elements aimed at establishing a degree of the relationship of multiple-serotype Streptococcal strains of group B}; Dmitriev AV et al.; The presence and restriction fragment length polymorphism of IS 861 and IS 1548 were analyzed among 113 streptococcal strains of group B . 13 strains were found to possess both IS 861 and IS 1548, 54 strains were found to possess only IS 861, and 46 strains had neither IS 861 nor IS 1548 . 9 HindIII and 6 EcoRI restriction patterns, hybridizing correspondingly with IS 861 and IS 1548, were discovered . A certain correlation between IS 1548 and IS 861 hybridizing patterns, on the one hand, and restriction patterns, found by pulse-electrophoresis, on the other hand, was established . It was demonstrated that restriction fragment length polymorphism of IS 1548 and 861 can be used to evaluate the degree of relationship between the strains. Pediatr Allergy Immunol, 2003 Feb, 14(1), 50 - 4 Relationship between group A beta-hemolytic streptococcal tonsillopharyngitis and asthma; Del Carmen Trojavchich M et al.; Increasing morbidity due to asthma in children and antimicrobial resistance among human pathogens are both major public-health concerns . Frequent use of antibiotics during childhood might be a factor underlying the rising severity and prevalence of asthma and other allergic disorders . The objective of the study was to determine if pediatric patients with asthma or allergic rhinitis have an altered rate of group A beta hemolytic streptococcal (GABHS) tonsillopharyngeal infection which might support any change in guidelines for antibiotic prescription . A prospective analysis of all patients presenting a clinical feature of GABHS pharyngitis with a sore throat in two pediatric clinics located in Detroit, MI, USA and San Antonio de Areco, Buenos Aires, Argentina . Eligible patients aged between 2 and 18 years were screened for the presence of asthma and/or allergic rhinitis and administered a test (rapid strep test) and throat culture to determine GABHS infection . At the Redford Medical Center, Detroit, 500 patients met the eligibility criteria, with 168 (33.6%) having a positive strep test . At the San Antonio de Areco's Hospital, in a rural area 100 km away from Buenos Aires, 188 patients met the eligibility criteria, with 41 (21.8%) having a positive strep test or GABHS throat cultures . In both the Detroit {odds ratio (OR) = 1.36; 95% confidence interval (CI) 0.72-2.57} and Buenos Aires clinics (OR = 0.50; 95% CI 0.23-1.07), patients with asthma or allergic rhinitis were not at an increased risk for true GABHS tonsillopharyngeal infections when compared with the general pediatric population . These results suggest that children with asthma do not differ from the normal population in their risk of developing GABHS tonsillopharyngeal infection and should not be liberally prescribed antibiotics. Proteins, 2003 Apr 1, 51(1), 109 - 25 Molecular dynamics simulations of peptides and proteins with a continuum electrostatic model based on screened Coulomb potentials; Hassan SA et al.; A continuum electrostatics approach for molecular dynamics (MD) simulations of macromolecules is presented and analyzed for its performance on a peptide and a globular protein . The approach incorporates the screened Coulomb potential (SCP) continuum model of electrostatics, which was reported earlier . The model was validated in a broad set of tests some of which were based on Monte Carlo simulations that included single amino acids, peptides, and proteins . The implementation for large-scale MD simulations presented in this article is based on a pairwise potential that makes the electrostatic model suitable for fast analytical calculation of forces . To assess the suitability of the approach, a preliminary validation is conducted, which consists of (i) a 3-ns MD simulation of the immunoglobulin-binding domain of streptococcal protein G, a 56-residue globular protein and (ii) a 3-ns simulation of Dynorphin, a biological peptide of 17 amino acids . In both cases, the results are compared with those obtained from MD simulations using explicit water (EW) molecules in an all-atom representation . The initial structure of Dynorphin was assumed to be an alpha-helix between residues 1 and 9 as suggested from NMR measurements in micelles . The results obtained in the MD simulations show that the helical structure collapses early in the simulation, a behavior observed in the EW simulation and consistent with spectroscopic data that suggest that the peptide may adopt mainly an extended conformation in water . The dynamics of protein G calculated with the SCP implicit solvent model (SCP-ISM) reveals a stable structure that conserves all the elements of secondary structure throughout the entire simulation time . The average structures calculated from the trajectories with the implicit and explicit solvent models had a cRMSD of 1.1 A, whereas each average structure had a cRMSD of about 0.8A with respect to the X-ray structure . The main conformational differences of the average structures with respect to the crystal structure occur in the loop involving residues 8-14 . Despite the overall similarity of the simulated dynamics with EW and SCP models, fluctuations of side-chains are larger when the implicit solvent is used, especially in solvent exposed side-chains . The MD simulation of Dynorphin was extended to 40 ns to study its behavior in an aqueous environment . This long simulation showed that the peptide has a tendency to form an alpha-helical structure in water, but the stabilization free energy is too weak, resulting in frequent interconversions between random and helical conformations during the simulation time . The results reported here suggest that the SCP implicit solvent model is adequate to describe electrostatic effects in MD simulation of both peptides and proteins using the same set of parameters . It is suggested that the present approach could form the basis for the development of a reliable and general continuum approach for use in molecular biology, and directions are outlined for attaining this long-term goal . Pediatr Res, 2003 Mar, 53(3), 403 - 10 Relation of streptococcal pyrogenic exotoxin C as a causative superantigen for Kawasaki disease; Yoshioka T et al.; We previously reported that the frequency of TCRBV2 and TCRBV6S5-bearing T-cells was high in patients in the acute phase of Kawasaki disease (KD) and that streptococcal pyrogenic exotoxin C (SPE-C) was a potent stimulator of these TCRBV-bearing T-cells . To further elucidate the pathogenesis of KD, we examined the T-cell receptor (TCR) repertoire, human leukocyte antigen (HLA)-DRB1 genotype, and antibody responses to recombinant(r) SPE-C in patients with KD . We also performed in vitro stimulation with rSPE-A and rSPE-C of peripheral blood mononuclear cells from healthy donors and characterized the reacting T-cells . The percentage of T-cells bearing TCRBV2 and TCRBV6S5 was high in patients in the acute stage of KD . rSPE-C stimulation of PBMC from healthy donors induced expansion of TCRBV2 and TCRBV6S5-bearing T-cells . Furthermore, serum levels of anti-SPEC antibodies, which did not display antimitogenic activity, were higher in patients with acute KD than in age-matched controls . The frequencies of the DRB1*04051, 0406, and 0901 were high, whereas that of the DRB1*1101 was low among patients with KD as compared with the healthy adults. Infect Immun, 2003 Mar, 71(3), 1548 - 50 The zinc-dependent major histocompatibility complex class II binding site of streptococcal pyrogenic exotoxin C is critical for maximal superantigen function and toxic activity; Tripp TJ et al.; The cocrystal structure of streptococcal pyrogenic exotoxin C (SPE C) with HLA-DR2a (DRA*0101,DRB5*0101) revealed a zinc-dependent interaction site through residues 167, 201, and 203 on SPE C and residue 81 on the beta-chain of HLA-DR2a (DRA*0101,DRB5*0101) . Mutation of these SPE C residues resulted in dramatically reduced biological activities . Thus, the zinc-dependent major histocompatibility complex II binding site is critical for maximal biological function of SPE C. J Natl Cancer Inst, 2003 Feb 19, 95(4), 316 - 26 Involvement of Toll-like receptor 4 signaling in interferon-gamma production and antitumor effect by streptococcal agent OK-432; Okamoto M et al.; BACKGROUND: The streptococcal agent OK-432 has been used for immunotherapy of head and neck cancer, among other malignancies, but its mechanism of action is unknown . Because the Toll-like receptor 4 (TLR4)/MD-2 complex is important in enabling the mammalian immune system to recognize bacterial components, we investigated whether expression of the TLR4 and MD-2 genes is associated with OK-432-induced anticancer immunity . METHODS: Peripheral blood mononuclear cells (PBMCs) from 28 patients with head and neck cancer were analyzed for TLR4 and MD-2 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR) analysis . PBMCs were treated in vitro with OK-432 or with OK-PSA (a lipoteichoic-acid-related molecule that is an active component of OK-432), and interferon-gamma (IFN-gamma) mRNA expression, an immune response measure, was analyzed by RT-PCR . Patient sera collected 24 hours after OK-432 administration were examined for IFN-gamma protein using an enzyme-linked immunosorbent assay . Lewis lung carcinoma-bearing wild-type C57BL/6 and TLR4-deficient mice (four mice per group) received intraperitoneal injections of OK-432, and tumor volumes and sera IFN-gamma levels were measured over time . All statistical tests were two-sided . RESULTS: Twenty patients expressed both TLR4 and MD-2 . Expression of TLR4 and MD-2 genes was associated with the in vivo IFN-gamma induction in 19 patients administered OK-432 (Fisher's exact test P<.001) . Although both OK-432 and OK-PSA induced IFN-gamma expression from PBMCs in vitro, expression of TLR4 and MD-2 was associated only with IFN-gamma expression induced by OK-PSA (P<.001) . In vivo intraperitoneal administration of OK-432 resulted in an increase of IFN-gamma in sera from wild-type mice but not in sera from TLR4-deficient mice . Tumors in wild-type mice treated with OK-432 were statistically significantly smaller than those in mice treated with saline (P =.007) . By contrast, in TLR4-deficient mice, there was no difference in tumor volume between the two treatment groups . CONCLUSIONS: TLR4 and MD-2 may mediate OK-432-induced anticancer immunity. Bangladesh Med Res Counc Bull, 2002 Apr, 28(1), 1 - 6 Streptococcal antibodies among rural school children in Bangladesh; Zaman MM et al.; The upper limit of normal values of group A streptococcal antibodies should be known for a population concerned because it is influenced by many local conditions . As yet the reference value of the these antibodies has not been determined by using a quantitative method among Bangladeshi children . We determined the reference value of anti-streptolysin O and anti-deoxyribonuclease B among 361 apparently healthy rural Bangladeshi primary school children (aged 5 to 14 years, mean 9.2 years) . Anti-streptolysin O was measured by an auto-analyzer and antideoxyribonuclease B was measured by microtitre method . The geometric mean titres for the entire group was 241 IU/ml and 222 IU/ml for anti-streptolysin O and anti-deoxyribonuclease B respectively . The upper limit of normal values (80th percentile) was 390 and 340 for anti-streptolysin O and anti-deoxyribonuclease B, respectively . These limits should be of value to physicians, epidemiologists and clinical laboratory personnel as well. Scand J Infect Dis, 2002, 34(12), 880 - 6 Upper respiratory tract infections in general practice: diagnosis, antibiotic prescribing, duration of symptoms and use of diagnostic tests; Andre M et al.; A diagnosis/antibiotic prescribing study was performed in 5 counties in Sweden for 1 week in November 2000 . As part of this study, the characteristics and clinical management of patients with upper respiratory tract infections (n = 2899) in primary care were analyzed . Almost half of the patients were aged < 15 y and one-fifth of the patients consulted out of hours . Of all patients seeking primary care for upper respiratory tract infections, 56.0% were prescribed an antibiotic . Almost all patients who were given the diagnoses streptococcal tonsillitis, acute otitis media or acute sinusitis were prescribed antibiotics, compared to 10% of patients with common cold or acute pharyngitis . The most frequently prescribed antibiotic was penicillin V (79.2%) and this was even more pronounced out of hours, when the diagnoses otitis media and streptococcal tonsillitis were more frequently used . In patients with common cold and acute pharyngitis, the percentage who received antibiotics increased with increasing length of symptoms and increasing CRP levels . In patients with acute pharyngitis or streptococcal tonsillitis, antibiotics were prescribed less frequently provided streptococcal tests were performed . The management of patients with upper respiratory tract infections in general practice seems to be in good agreement with current Swedish guidelines . However, the study indicates some areas for improvement . The diagnosis of acute sinusitis seems to have been overestimated and used only to justify antibiotic treatment. Biopolymers, 2003, 72(2), 116 - 22 Study of protein-protein interactions by fluorescence of tryptophan analogs: application to immunoglobulin G binding domain of streptococcal protein G; Li Q et al.; The protein-protein interaction system often contains many fluorophores that may significantly interfere with the quantitative determination of the binding abilities . To solve this perplexing problem, we biosynthetically incorporated the two tryptophan analogs, 5-hydroxytryptophan and 7-azatryptophan, into the immunoglobulin G (IgG) binding domain of streptococcal protein G (PGBD) . The exclusive excitation and novel fluorescence changes in both the intensity and anisotropy are beneficial to reporting the details of the interactions between PGBD and the IgG fragments and enable assessment of the binding abilities . The dissociation constants are estimated to be 0.28 microM for the binding of human Fc and 8.0 microM for mouse Fc . The results clearly demonstrate that labeling of tryptophan analogs has very little effect on the binding abilities and is broadly applicable to quantitatively studying protein-protein interactions in a whole biomolecular complex . Acta Paediatr, 2002, 91(12), 1397 - 9 Early-onset group B streptococcal sepsis in a preterm infant with Kostmann syndrome; Fujiu T et al.; A preterm infant died of group B streptococcal sepsis 7 h after birth . The infant's complete blood count showed total agranulocytosis . Histopathology of the major organs showed significant bacterial invasion without infiltration of polymorphonuclear leucocytes . Examination of the bone marrow revealed normal cellularity of the granulocyte precursors with arrested maturation . These findings are consistent with Kostmann syndrome . CONCLUSION: It is suggested that in patients with deteriorating early-onset infection, underlying congenital abnormalities in host defence, such as Kostmann syndrome, should be considered. Acta Paediatr, 2002, 91(12), 1279 - 81 Kostmann disease--infantile genetic agranulocytosis: historical views and new aspects; Zetterstrom R; The results in the main reports on infantile genetic agranulocytosis or Kostmann Syndrome are summarized . New views on the pathogensis of the syndrome are given in a recent paper by Putsep et al . Kostmann syndrome may cause early onset Group B streptococcal neonatal sepsis as reported in this issue of Acta Paediatrica (9) . CONCLUSION: Patients with Kostmann Syndrome who are successfully treated for agranulocytosis with serum colony stimulating factor remain deficient in cathelin-LL-37, a peptide antibiotic, which is normally present in neutrophils and saliva . This deficiency may explain that patients who are successfully treated for agranulocytosis continue to suffer from oral infections such as chronic periodontitis. J Rheumatol, 2003 Feb, 30(2), 355 - 63 Inhibition of disease progression by a novel retinoid antagonist in animal models of arthritis; Beehler BC et al.; OBJECTIVE: To investigate the usefulness of a novel retinoic acid receptor (RAR) antagonist (BMS-189453) in animal models of arthritis . METHODS: BMS-189453 was tested in HIG-82 rabbit synovial fibroblasts to determine its ability to repress collagenase (matrix metalloproteinase-1, MMP-1) mRNA expression in vitro . Cells were stimulated with phorbol myristate acetate or interleukin 1 beta and mRNA quantified by slot-blot analysis . In vivo, BMS-189453 was evaluated in 2 animal models of arthritis: collagen induced arthritis (CIA) in mice and streptococcal cell wall induced arthritis (SCWA) in rats . Clinical scores for arthritis were recorded weekly . At the end of each study, limbs were evaluated histologically . In CIA, these results were correlated with mRNA levels for collagenase-3 (MMP-13) and stromelysin-1 (MMP-3) as determined by Northern blot . RESULTS: BMS-189453 reduced MMP-1 expression in HIG-82 synovial fibroblasts in culture . BMS-189453 treatment blocked the clinical progression of arthritis beyond soft tissue inflammation in the CIA model . In the SCWA model, BMS-189453 treatment resulted in significantly reduced swelling with no notable progression to joint distortion/destruction . Histological evaluation of the joints from animals in both models confirmed this result . Analysis of mRNA from the CIA paws showed that BMS-189453 prevented the overexpression of MMP-13 and MMP-3 in arthritic joints . CONCLUSION: Improvement in clinical and histologic variables in 2 separate animal models, along with simultaneous reduction in MMP expression in the affected joint, suggests that RAR antagonists such as BMS-189453 may be useful as agents to treat rheumatoid arthritis and for determining the role of MMP in disease progression . This is the first study to show the clinical potential of RAR antagonists in arthritis. Pediatr Dermatol, 2003 Jan-Feb, 20(1), 11 - 5 Treatment of psoriasis in children: is there a role for antibiotic therapy and tonsillectomy? Wilson JK, Al-Suwaidan SN, Krowchuk D, Feldman SR. Numerous studies implicate subclinical or recurrent streptococcal infection as a trigger or maintenance factor in the pathogenesis of psoriasis in children . The purpose of this article is to review the efficacy of antibiotic therapy and tonsillectomy as treatments for childhood psoriasis . Clinical trials assessing the efficacy of antibiotics or tonsillectomy as treatments for childhood psoriasis were identified with a search of the medical literature and the results were compared . Only one controlled clinical trial was identified and it did not find a significant effect of antibiotic treatment on psoriasis . In other studies, the percentage of psoriasis patients who experienced disease clearance with antibiotic therapy ranged from 0% to 55%, with no patients experiencing disease worsening during treatment . No controlled trials of tonsillectomy for psoriasis were identified . The percentage of patients who experienced disease clearance after tonsillectomy in uncontrolled trials ranged from 32% to 53% and a similar percentage reported significant improvement in their psoriasis, with a maximum of 7% noting worsening of the disease after the operation . The available evidence does not demonstrate the efficacy of either antibiotic therapy or tonsillectomy in the treatment of childhood psoriasis . Because these treatments are relatively benign compared to other treatments for severe psoriasis, the use of antibiotic therapy or tonsillectomy may still be worth considering, especially for those patients with recurrent streptococcal infections that seem to trigger or maintain their skin disease. Epidemiol Infect, 2002 Dec, 129(3), 471 - 8 Invasive group A streptococcal infections in the San Francisco Bay area, 1989-99; Passaro DJ et al.; To describe the epidemiology of invasive group A streptococcal (iGAS) infections in the San Francisco Bay Area, population-based active surveillance for laboratory-confirmed iGAS was conducted by the California Emerging Infections Program in three California counties . From January 1989 to December 1999, 1415 cases of iGAS were identified . Mean iGAS incidence was 4.06/100,000 person-years and case fatality ratio was 13%, with no linear trends over time . Incidence was lowest in adolescents, was higher in men than women (4.4 vs . 3.2/100,000 person-years), and was higher in African-Americans (6.7) than in non-Hispanic (4.1) or Hispanic (3.4) Whites, Asians (2.2) or Native Americans (17/100,000 person-years) . Injecting drug use was the riskiest underlying condition and was associated with the highest attributable risk . Cases were associated with several underlying conditions, but 23% occurred in previously healthy persons . From 1989-1999, iGAS infections in the San Francisco Bay Area became neither more common nor more deadly. Indian J Pediatr, 2002 Dec, 69(12), 1071 - 5 Acute and crescentic glomerulonephritis; Vijayakumar M; Acute nephritic syndrome is clinically characterized by hematuria, proteinuria, oliguria, and volume overload with or without azotemia and histologically be acute proliferative glomerulonephritis . Acute post streptococcal glomerulonephritis is the commonest cause in children . There is a preceding infection prior to this condition in majority . This is one of the comonest causes of renal edema in children . Early recognition, prompt and aggressive therapy and adequate follow-up are mandatory . Prognosis is usually good unless associated with severe renal failure and crescentic glomerulonephritis where the outcome is relatively poor unless treatment is early and adequate . Pathologically acute proliferative nephritis is with diffuse proliferative glomerulonephritis with or without crescents . Immunosuppressive therapy is not needed in simple acute proliferative glomerulonephritis but is essential in modifying the outcome of crescentic glomerulonephritis . Delayed resolution, severe renal failure at onset, progressive renal failure and associated systemic features like skin rashes, joint pains, hepatosplenomegaly and persistent fever are the indications for biopsy . Overall the prognosis in classical post streptococcal acute proliferative glomerulonephritis is good. Am J Kidney Dis, 2003 Feb, 41(2), 366 - 70 Group A streptococcal antigen in the glomeruli of children with Henoch-Schönlein nephritis; Masuda M et al.; BACKGROUND: Although the pathogenesis of Henoch-Schonlein nephritis (HSN) remains unclear, there is substantial evidence that it is an immune complex-mediated disease . HSN is preceded by upper-respiratory tract infection in 30% to 50% of patients, but there is no evidence that group A streptococcal (GAS) infection has a pathogenetic role in this disease . Recently, nephritis-associated plasmin receptor (NAPlr), a GAS antigen, was found primarily in the glomerular mesangium of patients with early-stage acute poststreptococcal glomerulonephritis . METHODS: To determine the possible role of NAPlr in HSN, expression of the receptor was determined in glomeruli using fluorescein isothiocyanate-labeled rabbit polyclonal anti-NAPIr antibody, and serum antistreptolysin O (ASO) titers were measured in children with HSN . RESULTS: Ten of 33 patients (30%) with HSN showed segmental or global mesangial staining with NAPlr antibody, whereas only 4 of 120 patients (3%) with other renal diseases were positive (P < 0.001, Fisher's exact test) . Patients with HSN also showed significantly greater ASO titers than patients with other renal diseases (P = 0.03, Mann-Whitney U test) . Serum ASO titers were significantly greater in patients with HSN with than without glomerular NAPlr antigen (P = 0.03, Mann-Whitney U test) . CONCLUSION: These findings suggest that the deposition of NAPlr in the mesangium, induced by GAS infection, may have a role in the pathogenesis of HSN in some patients . Am J Kidney Dis 41:366-370 . J Infect Dis, 2003 Feb 1, 187(3), 398 - 407 Epub 2003 Jan 24. Selective modulation of superantigen-induced responses by streptococcal cysteine protease; Kansal RG et al.; Streptococcal pyrogenic exotoxin (Spe) B, a streptococcal cysteine protease, is believed to be important in group A streptococcal (GAS) pathogenesis . The present study examined the effect of SpeB on the activity of superantigenic exotoxins secreted by M1T1 GAS isolates . The proliferative response of human lymphocytes to culture supernatant (SUP) from an SpeB(+) isolate increased significantly (P<.05) when the isolate was grown with N-{N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl}-agmatine, a cysteine protease inhibitor . The lymphocyte-stimulating activity of SUP from a spontaneous SpeB(-) variant or SpeB(-) knockout (DeltaSpeB) mutant was also significantly higher than that of SUP from the SpeB(+) parent isolate (P<.001) . The addition of recombinant SpeB to the DeltaSpeB mutant reduced the lymphocyte response to a level comparable to that with the SpeB(+) isolate . SpeB affected superantigens that stimulate cells expressing T cell receptor Vbeta (TCRBV)-4, TCRBV7, and TCRBV8 but not those that stimulate TCRBV2 . SpeB has a selective proteolytic effect on GAS superantigens. Crit Care Med, 2003 Jan, 31(1), 171 - 8 Application of a rat model of streptococcal shock to evaluate on-line hemoperfusion and removal of circulating superantigens; Fenwick P et al.; OBJECTIVE: To evaluate the efficacy of on-line hemoperfusion for the removal of circulating superantigens in a rat model of streptococcal shock . DESIGN: In vitro and experimental animal studies . SETTING: University research laboratories . INTERVENTIONS: Chemically modified polystyrene-based composite fiber reinforced with polypropylene was formulated in discs and used to evaluate the removal of superantigenic toxins from culture supernatants in vitro, and from blood in vivo . MEASUREMENTS AND MAIN RESULTS: Incubation of streptococcal supernatant with a single disc reduced the concentration of the superantigen streptococcal pyrogenic exotoxin A from 90.9 +/- 12.7 ng/mL with the control fiber to 32.5 +/- 3.6 ng/mL with active fiber (p <.001) . The active discs also brought about a dose-dependent reduction in mitogenic activity that was highly significant (counts reduced from 82,133 +/- 2747 using three control discs to 26,307 +/- 3547 with three active discs {p <.001}) . Beginning 6 hrs after infection, animals were hemoperfused for 3 hrs over columns containing control or active fiber . At the end of the treatment period, there was a significant decrease in the number of circulating bacteria in the active group (3.5 x 10(4) vs . 3.1 x 10(3) colony-forming units/mL, p<.05) . However, bacterial counts subsequently increased and by 15 hrs and at all subsequent time points, the number of circulating bacteria was no different between the two groups . There was a highly significant and sustained difference in circulating streptococcal pyrogenic exotoxin A levels between the groups . Streptococcal pyrogenic exotoxin A levels at 9 hrs were 19.9 ng/mL in the controls vs . 2.1 ng/mL in the active group (p =.05) . Animals perfused over active fibers had a highly significant survival advantage compared with control or nonperfused groups (p <.01) . CONCLUSIONS: Hemoperfusion and on-line removal of superantigens merits further study as a possible treatment strategy for streptococcal shock syndromes . The mechanism by which the fibers are operating requires further investigation. Anticancer Res, 2002 Nov-Dec, 22(6A), 3229 - 39 Enhancement of anti-tumor immunity by lipoteichoic acid-related molecule isolated from OK-432, a streptococcal agent, in athymic nude mice bearing human salivary adenocarcinoma: role of natural killer cells; Okamoto M et al.; BACKGROUND: OK-PSA, a lipoteichoic acid (LTA)-related molecule isolated from a streptococcal agent OK-432, enhances anti-tumor immunity as a potent inducer of Th1-type cytokines . Recently, we obtained the data suggesting that natural killer (NK) cells may play a significant role for OK-PSA-induced cytokine production in vitro . MATERIALS AND METHODS: We conducted the animal experiments using athymic nude mice bearing human salivary adenocarcinoma to examine the role of NK cells in OK-PSA-induced anti-tumor immunity . OK-PSA was peritumorally injected into the mice . Cytokines in the sera were analyzed by ELISA . mRNAs for cytokines were detected by RT-PCR . 51Cr release test was performed to measure killer cell activities . RESULTS: OK-PSA markedly increased the amounts of IFN-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-12 and IL-18 that are generally called "Th1-type cytokines" in the sera derived from tumor-bearing nude mice, and also accelerated the killing activities of tumor-infiltrating lymphocytes as well as of draining lymph node cells . Furthermore, OK-PSA administration resulted in significant inhibition of tumor growth, but the effect of OK-PSA was almost completely inhibited by the deletion of NK cells using anti-asialo GM1 antibody . CONCLUSION: These findings strongly suggested that NK cells are closely involved in OK-PSA-mediated anti-tumor immunity. Clin Infect Dis, 2003 Jan 15, 36(2), 149 - 58 Epub 2003 Jan 03. Epidemiology and risk factors for gram-positive coccal infections in neutropenia: toward a more targeted antibiotic strategy; Cordonnier C et al.; The objective of this study was to evaluate the risk of acquiring gram-positive coccal infections in febrile neutropenic patients and to develop risk indexes for gram-positive and