Streptococci

Eur J Pediatr, 1996 Mar, 155(3), 168 - 72
Mitral regurgitation may be related with previous streptococcal infection; Wahid MR et al.; We measured anti M protein antibody (AMPA) titres in children with idiopathic mitral regurgitation (MR), streptococcal infection, rheumatic fever (RF), post-streptococcal acute glomerulonephritis (AGN) and normal healthy children . We investigated the association of MR with streptococcal infection and whether high AMPA titres can be used as persisting evidence of previous streptococcal infection . AMPA titres were measured with an enzyme-linked immunosorbent assay . We found significantly higher antibody titres in patients with MR and in streptococcal infection, RF, and AGN than in healthy controls . In the MR group (n = 15), 54% patients had AMPA titres above the 90th percentile value that was found in normal controls . An elevated AMPA titre persisted for a long period even when the anti-streptolysin O titres had declined to normal in RF patients . Our data suggest that the high AMPA titres in MR should be further investigated to clarify the probable association with previous streptococcal infection . CONCLUSION: High AMPA titre is a risk factor for developing complications after streptococcal infection . Our serological evidence suggests that in some patients, MR may be related to previous streptococcal infection.

Antimicrob Agents Chemother, 1996 Mar, 40(3), 809 - 11
Efficacy of clarithromycin versus that of clindamycin for single-dose prophylaxis of experimental streptococcal endocarditis; Vermot D et al.; Clarithromycin is compared with clindamycin for single-dose prophylaxis of streptococcal endocarditis in rats . Human-like kinetics of the two antibiotics prevented endocarditis in animals challenged with both small and large amounts of bacterial inocula . Clarithromycin was marginally superior to clindamycin against small amounts of inocula . Clarithromycin may be considered for endocarditis chemoprophylaxis in human.

Anal Biochem, 1996 Mar 1, 235(1), 61 - 72
Fiber-optic fluorometric sensing of polymerase chain reaction-amplified DNA using an immobilized DNA capture protein; Mauro JM et al.; A fiber-optic assay for amplified DNA products has been developed . Modifications of the DNA capture strategy described previously by Kemp et al . {Proc . Natl . Acad . Sci . USA 86, 2423-2427 (1989)} were made that allowed selective binding of DNA labeled during the amplification process to the sensing surface of fused silica fibers . The gene for a chimeric protein composed of the IgG-binding beta 2 subdomain of streptococcal protein G fused with the DNA binding domain of yeast GCN4 was constructed, and this PG/GCN4 protein was overexpressed in Escherichia coli . The purified protein was noncovalently bound to IgG-modified fibers utilizing strong and specific interactions between the protein G beta 2 domain and goat IgG that had been covalently immobilized on the fiber surface . Nanomolar concentrations of amplified DNA labeled with the fluorophore tetramethylrhodamine and the AP-1 consensus nucleotide sequence recognized by GCN4 (5'-ATGACTCAT) were rapidly and selectively bound within the evanescent zone of multimode laser-illuminated fibers . Signal from unincorporated fluorescent PCR primer was negligible . Individual fibers could be used for multiple sequential assays, since the fluorescent double-stranded DNA was rapidly and completely stripped from their surfaces with high salt solutions, leaving the IgG-PG/GCN4 DNA binding complex intact to accept another PCR sample.

J Rheumatol Suppl, 1996 Mar, 44, 56 - 60
Combination therapy in rheumatoid arthritis: the animal model perspective; Oliver SJ et al.; Attempts to improve antirheumatic agent efficacy have resulted in exploration of treatment protocols with combinations of 2 or more agents . Hypothetically, an ideal combination therapy would have greater efficacy and less toxicity than any of its component agents used individually . However, even a limited number of available drugs can produce a daunting number of possible combination protocols, each requiring clinical evaluation . Intelligent selection of combination protocols, based on a firm understanding of each agent's specific mechanism(s) of action, may help identify potentially useful regimens . Autoimmune animal models of inflammatory synovitis provide a unique opportunity to study the etiology, pathophysiology, and treatment of rheumatoid arthritis (RA) . Induction of chronic inflammatory synovitis in susceptible inbred strains can allow for in vivo study under reproducible controlled conditions, using experimental protocols not possible in humans . Although animal models can only approximate human rheumatic disease in its complete form, they are nonetheless important for developing new therapeutic strategies . We review the 3 most common animal models of RA, the streptococcal cell wall, adjuvant, and collagen arthritis rat models . Surprisingly, few published studies evaluate combination therapy in RA animal models . We discuss these investigations, which use interventions aimed at angiogenesis, microtubule function, and immune regulation, as examples of animal models to assess and develop effective therapeutic combinations of antirheumatic agents.

Int J Fertil Menopausal Stud, 1996 Mar-Apr, 41(2), 115 - 23
Vaginitis: diagnosis and management; Faro S; The various conditions that give rise to vaginitis include specific and nonspecific entities, such as candidiasis, trichomoniasis, bacterial vaginosis, group B streptococcal vaginitis, purulent vaginitis, volvodynia, and vestibulitis . The patient with chronic vaginitis usually develops this condition because of a misdiagnosis . It is critical that patients who have chronic vaginitis be thoroughly evaluated to determine if there is a specific etiology and whether their condition is recurrent or persistent, or is a reinfection . This also must include obtaining a detailed history, beginning with the patient's best recollection of when she felt perfectly normal . The physician must have an understanding of a healthy vaginal ecosystem and what mechanisms are in place to maintain the equilibrium . The vaginal ecosystem is a complex system of micro-organisms interacting with host factors to maintain its equilibrium . The endogenous microflora consists of a variety of bacteria, which include aerobic, facultative and obligate anaerobic bacteria . These organisms exist in a commensal, synergistic or antagonistic relationship . Therefore, it is important to understand what factors control the delicate equilibrium of the vaginal ecosystem, and which factors, both endogenous and exogenous, can disrupt this system . It is also important for the physician to understand that when a patient has symptoms of vaginitis it is not always due to an infectious etiology . There are situations in which an inflammatory reaction occurs but the specific etiology may not be determined . Thus, it is important that the physician not rush through the history or the examination.

Intern Med, 1996 Mar, 35(3), 203 - 6
Tricuspid valve endocarditis with large vegetations in a non-drug addict without underlying cardiac disease; Iwama T et al.; We report a case of gamma-streptococcal tricuspid valve endocarditis in a patient with no history of intravenous drug abuse . Echocardiography revealed large vegetations on the anterior and septal cusps . The patient had persistent fever and recurrent septic pulmonary embolism despite prolonged antibiotic therapy . However tricuspid valve replacement was successful.

Eur J Clin Microbiol Infect Dis, 1996 Mar, 15(3), 206 - 210
Rapid detection of group B streptococcal colonization of the genital tract by a commercial optical immunoassay; Carroll KC et al.; The performance of a commercial optical immunoassay (OIA) was compared at two institutions with that of routine agar and broth culture methods for the detection of group B streptococcal (GBS) colonization of the genital tract . The Strep B OIA (Bio Star, USA) was used to test 962 vaginal swabs from pregnant women for the presence of GBS antigen . The prevalence of GBS vaginal colonization in this population was 22.4% . The OIA results were compared with those of culture on trypticase soy agar with 5% sheep blood (TSA) and broth enhanced culture (Lim broth) . Sensitivity and specificity values of the OIA method compared to TSA culture alone were 82.5% and 91.8%, respectively . The sensitivity of the OIA method was equivalent to that of TSA culture (62.4% vs . 64.4%; p > 0.5, chi 2 = 0.01) when the data were compared with broth culture . The extent of colonization affected the sensitivity of the OIA method: 100% of 4+, 94% of 3+, 96% of 2+, and 63% of 1+ TSA plates were detected by the OIA test . The commercial OIA method demonstrated sensitivity equivalent to that of TSA culture for the detection of GBS colonization . The OIA test offers two additional advantages over culture: reduced time required to obtain results (30 min vs . days) and the ability to detect GBS antigen in samples with compromised viability . The results of this study suggest that the Strep B OIA test can be a useful diagnostic tool in the management of early-onset GBS disease.

Infection, 1996 Mar-Apr, 24(2), 164 - 7
Streptococcal toxic shock syndrome in a postpartum woman . Case report and review of the literature; Jorup-Ronstrom C et al.; A case of streptococcal toxic shock syndrome in a 29-year-old postpartum woman is described . The patient presented with hypotension, coagulation defects, adult respiratory distress syndrome and scarlet exanthema as a complication of hemolytic group A streptococcal endometritis . One hundred and twenty-two other cases of streptococcal toxic shock syndrome in the literature are reviewed and the criteria of the syndrome discussed . Streptococcal toxic shock syndrome seems to be increasing along with more frequent invasive streptococcal infections in several countries . It is therefore important to recognize and treat the infection as early as possible to minimize the risk of mortality.

Diagn Microbiol Infect Dis, 1996 Mar, 24(3), 125 - 8
Rapid detection of group B streptococcal antigen from vaginal specimens using a new Optical ImmunoAssay technique; Park CH et al.; A total of 531 vaginal specimens were used to evaluate a new Optical ImmunoAssay (OIA) screening technique for the rapid detection of group B streptococcal antigen . The results of the OIA test, the ICON Strep B membrane immunoassay (Hybritech ICON), and conventional culture on sheep blood agar (direct TSA) were compared to broth enhanced culture . Results obtained from the OIA test, ICON, and direct TSA yielded 72, 39, and 68 positives, respectively, as compared to 100 positives using the Lim broth culture method as the standard . The Optical ImmunoAssay technique is as sensitive as the conventional plating method and is capable of providing results in 30 minutes.

Cancer Res, 1996 Mar 1, 56(5), 1104 - 10
Induction of autologous tumor killing by heat treatment of fresh human tumor cells: involvement of gamma delta T cells and heat shock protein 70; Wei Y et al.; Autologous tumor killing (ATK) has been implicated as an important prognostic factor in cancer patients since the ability of blood lymphocytes to kill freshly isolated autologous tumor cells was strongly associated with good prognosis of the patients . The present study was designed to induce or enhance ATK sensitivity of fresh human tumor cells by heat stress . Brief exposure of fresh human tumor cells to elevated temperature increased their susceptibility to lysis by autologous blood lymphocytes in a short-term (51)Cr release assay . In addition, the heat-elevated ATK sensitivity was confirmed by clonogenic assays . An increase in ATK was observed with unstimulated lymphocytes in 42% of the cases and OK432 (streptococcal preparation)-activated lymphocytes in 80% of the cases . Stimulation of blood lymphocytes with autologous, heat-stressed tumor cells and OK432 resulted in an increase in number of gamma delta T cells, which was associated with elevated ATK activity against the stressed tumor cells . At the clonal level, three gamma delta T-cell clones (V gamma 9/V delta 2+) proliferated in response to autologous, heat stressed tumor cells and/or OK432 and exhibited elevated cytotoxicity against the tumor cells . Western blot analysis revealed an increased expression of heat shock protein (HSP) 70 in heat- treated tumor cells . Some of them expressed HSP70 on their surfaces . The elevated cytoxicity against heat-stressed tumor cells was inhibited by treatment of targets with anti-HSP70 monoclonal antibody (mAb) or of effector cells with anti-V delta2 mAb . Reactivity of gamma delta T cells to autologous, heat- stressed tumor cells was also inhibited by anti-HSP70 mAb . These results indicate that exposure to heat of tumor cells induces ATK susceptibility, especially to OK432-activated effector cells, and suggest that gamma delta T cells may be involved in ATK against stressed tumor cells through recognition of HSP70 on the target cells.

Public Health Rep, 1996 Mar-Apr, 111(2), 104 - 13
Racial disparities in preterm births . The role of urogenital infections; Fiscella K; OBJECTIVES: To evaluate the impact of urogenital infections on the racial gap between black and white women in preterm birth rates . METHODS: A computer-assisted search of the medical literature was conducted through MEDLINE aided by a manual bibliographic search of published articles and relevant books . Estimates of the relative risk for preterm birth were extracted from published studies for the following infections: N . gonorrhea, syphilis, trichomoniasis, Chlamydia trachomatis, Group B streptococcal vaginal colonization, asymptomatic bacteriuria, genital mycoplasmas, and bacterial vaginosis . Estimates of the prevalence among black and white women by race for each of these infections were extracted from published studies . The attributable risk for preterm birth for selected infections was then calculated for the black and white populations and the impact on the racial gap in preterm births was estimated . RESULTS: Only bacterial vaginosis and bacteriuria appear to be established risk factors for preterm births . Significantly higher rates of bacterial vaginosis among black women may account for nearly 30% of the racial gap in preterm births . Higher rates of bacteriuria among black women may account for roughly 5% of the gap . CONCLUSION: Although these findings are limited by the reliability of published estimates of prevalence and relative risk for these infections, treatment of infections during pregnancy, particularly bacterial vaginosis, offers hope for reducing the racial gap in preterm births.

Clin Immunol Immunopathol, 1996 Mar, 78(3), 283 - 90
Induction of inflammatory cytokines in effusion cavity by OK-432 injection therapy for patients with malignant effusion: role of interferon-gamma in enhancement of surface expression of ICAM-1 on tumor cells in vivo; Kitsuki H et al.; The intracavitary injection of OK-432, a streptococcal preparation, has been shown to be an effective immunotherapy for patients with malignant effusion . We found that this therapy increases surface expression of intercellular adhesion molecule-1 (ICAM-1) on tumor cells, and that the degree of increased ICAM-1 was correlated with therapeutic effects . In the present study, we investigated the ability of OK-432-induced inflammatory cytokines, such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), to enhance ICAM-1 expression . We treated 17 patients who had a malignant effusion with OK-432 . At 24 hr after OK-432 injection, ICAM-1 levels on tumor cells were increased significantly in responders except in one case (n=9), whereas no change was evident in nonresponders except in two cases (n=8) . Induced maximum levels of IFN-gamma in responders were significantly higher than those in nonresponders . In contrast, there was no significant difference in the induced TNF-alpha or IL-1 beta levels between the two groups . Two types of cultured tumor cells derived from responder patients were successfully established from the 17 different tumor cells in effusion . We performed an in vitro study using these cultured tumor cells . Treatment of the two cultured tumor cells with recombinant IFN-gamma, but not recombinant TNF-alpha or IL-1 beta, significantly increased their ICAM-1 expression to a clinically detectable level . Direct treatment of the tumor cells with cell-free effusion samples obtained from the same patients 24 hr after the therapy successfully increased ICAM-1 expression and this action was blocked completely only by a pretreatment with anti-IFN-gamma mAb . Our results suggests that in this therapy IFN-gamma plays a crucial role in enhancing ICAM-1 expression by tumor cells and that induced IFN-gamma levels may be a useful marker for evaluation of the therapeutic effect.

Acta Paediatr Jpn, 1996 Feb, 38(1), 8 - 11
Evaluation of the therapy for streptococcal pharyngitis using Abbott Test Pack strep A; Kayaba H et al.; A total of 953 children (511 boys and 442 girls) with streptococcal pharyngitis diagnosed with Abbott Test Pack Strep A (ATPSA) or throat cultures were analyzed . ATPSA specimens were repeatedly obtained until ATPSA turned negative during or after the treatment . The percentage of positive ATPSA specimens reached the lowest value (9.2%) on the fourth day of the course of the treatment, which indicates the acquisition from an infected individual is probably uncommon after the initial treatment . Bacteriological treatment failure (positive ATPSA after 14 days of treatment) occurred in 4.1% of the children . Out of 953 subjects studied, 216 (22.7%) had recurrent infections . More than 30% of the recurrent infections occurred within 2 months after initial infection . ATPSA is useful for establishing a rapid diagnosis and confirming the bacteriological success of the treatment.

Mol Microbiol, 1996 Feb, 19(3), 429 - 41
M-related protein (Mrp) contributes to group A streptococcal resistance to phagocytosis by human granulocytes; Podbielski A et al.; The M protein has been postulated to be a major group A streptococcal (GAS) virulence factor because of its contribution to the bacterial resistance to opsonophagocytosis . Direct evidence of this was only provided for GAS strains which expressed a single M protein . The majority of GAS express additional, structurally similar M-related proteins, Mrp and Enn, which have been described as IgG- and IgA-binding proteins . To determine the involvement of Mrp and M protein in phagocytosis resistance, the mrp and emm genes from serotypes M2, M4, and M49 as well as from M-untypeable strain 64/14 were insertionally inactivated . The mrp and emm mutants were subjected to direct bactericidal assays . As judged by numbers of surviving colony-forming units, all mutant strains with the exception of the mrp4 mutant exhibited reduced multiplication factors as compared to the isogenic wild-type strains . Subsequent analysis of phagocytosis by flow cytometry, measuring association of BCECF/AM-labelled bacteria and granulocytes, paralleled the results from direct bactericidal assays regardless of whether isolated granulocytes or whole blood were utilized . Resistant wild-type GAS strains bound to less than 24% of granulocytes, whereas phagocytosis-sensitive controls attached to more than 90% of the white blood cells . 40 to 60% of the granulocytes associated with the mrp and emm mutants within 1 h of co-incubation . Kinetic data suggested that attachment to granulocytes proceeds faster for emm mutants than for corresponding mrp mutants . By adding a dihydro-rhodamine123 stain and measuring fluorescence induced by oxidative burst, the experimental data suggested that bacteria bound to granulocytes were also engulfed and integrated into phagolysosomes . Thus, these data indicated that, if present, both mrp and emm gene products contribute to phagocytosis resistance by decreasing bacterial binding to granulocytes.

Pediatr Res, 1996 Feb, 39(2), 336 - 42
Persistent elevation of immunoglobulin G titer against the C region of recombinant group A streptococcal M protein in patients with rheumatic fever; Mori K et al.; To analyze the immune response to the C region of group A streptococcal M protein in patients with rheumatic fever (RF), we cloned the structural gene for the C region of type 12 M protein and produced recombinant C region of M protein . IgG titers against the C region of M protein were measured by ELISA from sera of patients with RF (n = 10), uncomplicated streptococcal pharyngitis (n = 26), and age-matched controls (n = 49) . IgG titers against the C region were significantly higher in patients with RF than in controls or patients with uncomplicated streptococcal pharyngitis (43 versus 1.5 or 1.8 micrograms/mL, p < 0.01) . Studies using overlapping synthetic peptides of the C region demonstrated that increased IgG reactivity was observed against the amino-terminal halves of the C repeat blocks (C1, C2) in RF, indicating that these domains are the main immunodominant epitopes in the C region.

Pediatr Infect Dis J, 1996 Feb, 15(2), 151 - 6
Risk factors for invasive group A streptococcal infections in children with varicella: a case-control study; Peterson CL et al.; OBJECTIVE: To identify characteristic clinical manifestations and potential risk factors for invasive group A streptococcal (GAS) disease in children with varicella . DESIGN AND PARTICIPANTS: A case-control study was conducted in Los Angeles and Orange Counties, CA . Cases were children with varicella who developed invasive GAS disease between January 1 and May 3, 1994 (n = 25) . Controls were acquaintance, neighborhood or schoolmate children with uncomplicated varicella during the study period (n = 62) . Cases were compared with controls with regard to underlying illness, child care practices, parental home health practices, health care-seeking behaviors, sociodemographic characteristics and clinical characteristics . RESULTS: Controlling for age we found that cases were more likely than controls: (1) to be cared for in the home vs . out-of-home child care (odds ratio (OR), 4.4 (95% confidence interval (95% CI), 1.1 to 17)); (2) to report having asthma (OR, 6.2 (95% CI, 1.2 to 41.0)) and to be taking albuterol (OR, 11.6 ((95% CI, 1.0 to 581)); (3) to be secondary varicella cases within a household (OR, 7.3 (95% CI, 2.2 to 25)); (4) to report fever after Day 2 of varicella; and (5) to have contacted their health care provider later than controls (Day 3.8 rather than Day 1.7, P < 0.001) . CONCLUSIONS: To our knowledge this is the first case-control study exploring potential risk factors for invasive GAS disease in children with varicella . Both previously healthy children with varicella and those with underlying medical problems, including asthma, may be at increased risk for GAS complications . Interventions should be targeted to parents and health care providers to increase awareness of early signs and symptoms of invasive GAS disease in children with varicella . Additional studies are needed to confirm the associations suggested by this study between GAS complications of varicella and asthma, in-home child care, secondary vs . primary varicella household cases and delayed contact with medical care providers.

Pediatr Infect Dis J, 1996 Feb, 15(2), 146 - 50
Invasive group A streptococcal infections in children with varicella in Southern California; Vugia DJ et al.; OBJECTIVE: To describe demographic and clinical features of invasive group A streptococcal (GAS) infections in children with varicella in Southern California in early 1994 . METHODS: From hospitals of Los Angeles and Orange Counties, children with invasive GAS infections after varicella between January 1 and April 8, 1994, were identified by hospital infection control nurses . Medical records of patients were reviewed, and any available GAS isolate was further tested . RESULTS: Twenty-four cases were identified; 54% were male, 50% were Hispanic and the median age was 3 years (range, 0.5 to 8) . Four cases died before hospitalization . The other 20 were hospitalized for a median of 10 days (range, 4 to 50): 14 presented with cellulitis (1 with concomitant epiglottitis), 2 with myositis/necrotizing fasciitis, 2 with pneumonia and 2 with bacteremia without apparent source . Five had evidence of multiorgan involvement including two patients fulfilling criteria of streptococcal toxic shock-like syndrome . Of 19 patients with blood cultures, 10 (53%) had GAS bacteremia . Onset of GAS infection was suggested, as a median, on Day 4 of varicella, with fever, vomiting and localized swelling being commonly reported . The mean maximum temperature on the day of admission was 39.4 degrees C (102.9 degrees F) . Four GAS isolates were M1T1 and one was M3T3 . Five isolates produced streptococcal pyrogenic exotoxins A and B . CONCLUSIONS: Invasive GAS disease, including streptococcal toxic shock-like syndrome, is a serious complication of varicella . Physicians should be alert for the complication of GAS when fever and localized swelling or signs of cellulitis develop 3 days or more after the onset of varicella . Widespread use of varicella vaccine may decrease invasive GAS infections in this setting.

Int J Immunopharmacol, 1996 Feb, 18(2), 141 - 53
Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma; Mukai S et al.; We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma . C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad . Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days . These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v . injection of 2-4 x 10(5) viable BL6 cells . The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer . Transfer of IVS cells from mice immunized by s.c . injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003) . These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003) . Functional IVS cells required in vitro stimulation with tumor cells . However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells . These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells . The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

Aust N Z J Med, 1996 Feb, 26(1), 49 - 53
Anti-streptokinase antibodies and streptokinase resistance in an Aboriginal population in northern Australia; Urdahl KB et al.; BACKGROUND: Thrombolytic treatment with streptokinase in acute myocardial infarction has proven to be safe and effective in Caucasian populations with relatively low levels of anti-streptokinase IgG and streptokinase resistance . Higher levels of antibodies, as seen in previous recipients of streptokinase therapy, cause more adverse reactions and may result in lower efficacy . AIMS: To examine the levels of anti-streptokinase IgG and streptokinase resistance in a population subjected to endemic streptococcal infections . METHODS AND RESULTS: Thirty Aboriginal adults from a remote community in Northern Australia with endemic streptococcal infections and 15 non-Aboriginal adults from an urban community without endemic infections participated in this study . Aboriginal adults exhibited levels of anti-streptokinase IgG and streptokinase resistance that, respectively, were almost 20 and 15 times greater than the values of non-Aboriginal adults . At least 23% of Aboriginal adults had sufficiently high levels of streptokinase resistance to neutralise a standard 1.5 million unit dose of streptokinase . CONCLUSIONS: Aboriginal adults from a remote community had dramatically elevated levels of anti-streptokinase IgG and in vitro streptokinase resistance . Prospective studies are needed to assess the clinical relevance of streptokinase resistance in populations from areas with endemic streptococcal infection.

Rev Rhum Engl Ed, 1996 Feb, 63(2), 119 - 23
Bacterial endocarditis revealed by infectious discitis; Pascaretti C et al.; A study of 30 patients admitted for infectious discitis identified four cases with concomitant bacterial endocarditis . All four patients were male and had concomitant streptococcal septicemia . Two patients had known aortic valve disease . The vertebral infection was located to the thoracic or lumbar spine . Ultrasonography disclosed aortic lesions in all four patients and mitral lesions in two . Management consisted of intravenous antimicrobial therapy for four weeks followed by a three-month course of oral antimicrobial therapy . The outcome of the discitis was favorable within the usual period of time . However, the endocardial lesions continued to progress, and three patients rapidly required valve replacement . Analysis of available data in the 30 patients with discitis showed that half the patients with streptococcal discitis also had bacterial endocarditis and that the latter condition developed in all the patients with streptococcal discitis and a history of valve disease . A number of risk factors were identified . An echocardiogram should be done routinely in patients with infectious discitis and risk factors for bacterial endocarditis.

Eur J Biochem, 1996 Feb 1, 235(3), 543 - 8
Backbone dynamics of a domain of protein L which binds to immunoglobulin light chains; Wikstrom M et al.; Protein L is a multidomain protein expressed at the surface of some strains of the anaerobic bacterial species Peptostreptococcus magnus . The molecule interacts with the variable domain of immunoglobulin (Ig) light chains through five repeated homologous domains denoted B1 to B5 . The fold of the Ig-light-chain-binding B1 domain of protein L (PLB1) has been shown to comprise an alpha-helix packed against a four-stranded beta-sheet and therefore resembles the structure of the IgG-binding domains of streptococcal protein G . In the present study, amide-proton exchange and 15N-relaxation NMR measurements were performed on the B1 domain to investigate its backbone mobility . It was shown that the folded portion of PLB1 is rigid with no regions of significantly higher flexibility than average . The N-terminus, however, is highly flexible consistent with earlier studies on the solution structure of PLB1 . Comparison of the amide-proton-exchange data with similar measurements performed on the IgG-binding domains of protein G indicates that the two proteins have different exchange behaviors in their second beta-strands . Both protein G and L employ this region of their structures for binding to immunoglobulins since the interaction of protein G and protein L with IgG Fab and the Ig light chain, respectively, involves residues from the second beta-strand.

J Am Acad Dermatol, 1996 Feb, 34(2 Pt 1), 229 - 34
Eosinophilic panniculitis: diagnostic considerations and evaluation; Adame J et al.; BACKGROUND: Eosinophilic panniculitis is characterized by a prominent infiltration of subcutaneous fat with eosinophils . It has been identified in patients who have a variety of associated clinical conditions . OBJECTIVE: Our purpose was to describe clinical conditions associated with eosinophilic panniculitis . METHODS: We describe five patients with eosinophilic panniculitis . These patients had a variety of clinical conditions including arthropod bites, gnathostomiasis, and polyarteritis nodosa . We review the literature on patients with eosinophilic panniculitis . RESULTS: Eosinophilic panniculitis most often presents as a nodule . Gnathostomiasis, leukocytoclastic vasculitis, and erythema nodosum appear to be the most common conditions associated with eosinophilic panniculitis . Other disorders include atopic and contact dermatitis, eosinophilic cellulitis, injection granuloma, arthropod bites, streptococcal and other bacterial infections, toxocariasis, B- and T-cell lymphoma, and refractory anemia with excess blasts . CONCLUSION: Once a diagnosis of eosinophilic panniculitis has been established, appropriate evaluation for an associated clinical condition should be performed.

Postgrad Med, 1996 Feb, 99(2), 211 - 4, 219-22
Recurrent streptococcal pharyngitis . Using practical treatment options to interrupt the cycle; Ruoff GE; Most family physicians have seen cases like this: A child is brought in with pharyngitis, which responds to antibiotic therapy . Soon the mother comes in with fever and a sore throat . She also recovers with therapy, but soon she's back with the child, who has pharyngitis again . Dr Ruoff explains why streptococcal infection recurs and how to assess probability so treatment can be started without waiting for test results . He also discusses alternatives to standard penicillin therapy, some of which may avoid the problems of noncompliance.

Cancer Immunol Immunother, 1996 Feb, 42(2), 127 - 31
Combination immunotherapy with OK-432, recombinant granulocyte-colony-stimulating factor and recombinant interleukin-2 for human hepatocellular carcinoma; Himoto T et al.; The antitumor effects of immunotherapy using streptococcal preparations (OK-432), recombinant granulocyte-colony-stimulating factor (rG-CSF) and recombinant interleukin-2 (rIL-2) were examined for human hepatocellular carcinoma (HCC) . Following subcutaneous injection of OK-432 (2 KE) and rG-CSF (50-60 microg), low-dose intratumoral administration of OK-432 (3-12 KE) was performed . Thereafter, 2 x 10(5) JRU of rIL-2 was subcutaneously injected . This therapeutic regimen was repeated twice . Serum alpha-fetoprotein levels were markedly decreased in three of seven patients with HCC by this treatment . Post-therapeutic histological examination revealed that trabecular cords or pseudoglandular arrangements of tumor cells were completely disordered in all cases and that extensive infiltration of lymphocytes into the tumor stroma was present in five cases . The number of CD4- and CD57-positive cells among tumor-infiltrating lymphocytes after immunotherapy was significantly higher than that in patients without immunotherapy (P <0.01) . These findings suggest that even a small intratumoral injection of OK-432 can induce extensive infiltration of helper/inducer and natural killer cells into the tumor stroma when combined with subcutaneous injection of OK-432, rG-CSF and rIL-2 and that these cells might play important roles in tumor cytotoxicity.

J Mol Biol, 1996 Jan 19, 255(2), 275 - 88
An unusually long-lived antisense RNA in plasmid copy number control: in vivo RNAs encoded by the streptococcal plasmid pIP501; Brantl S et al.; The main regulator of pIP501 replication is an antisense RNA (RNAIII) that induces transcriptional attenuation of the essential RNAII . Previous studies identified the termination point in vivo and demonstrated attenuation in vitro . This in vivo analysis confirms the appearance of attenuated RNAII dependent on RNAIII . Half-lives and intracellular levels of RNAII and RNAIII were determined: in a Bacillus subtilis cell harboring a wild-type pIP501 plasmid, approximately 50 molecules RNAII and 1000 to 2000 molecules of RNAIII were measured, respectively . The half-life of RNAII was in the range of that of other target RNAs, whereas that of RNAIII (approximately 30 minutes) was unusually long, representing a so far unprecedented case of a metabolically stable antisense RNA regulating plasmid copy number . Long antisense RNA half-life is predicted to yield sluggish control and instability of maintenance . We propose a model for how plasmid pIP501 may avoid this problem by using both the repressor CopR and the antisense RNAIII for control . Four stem-loop mutants of RNAII/RNAIII with elevated copy numbers were characterized for in vitro antisense/target RNA binding, RNAIII half-life, incompatibility, and attenuation in vivo . Two classes were found: interaction mutants and half-life mutants . The former suggest a key function for loop LIII of RNAIII as recognition loop in the primary steps of RNAII/RNAIII interaction.

FEBS Lett, 1996 Jan 8, 378(2), 190 - 4
The serum albumin-binding domain of streptococcal protein G is a three-helical bundle: a heteronuclear NMR study; Kraulis PJ et al.; Streptococcal protein G (SPG) is a cell surface receptor protein with a multiple domain structure containing tandem repeats of serum albumin-binding domains (ABD) and immunoglobulin-binding domains (IgBD) . In this paper, we have analysed the fold of ABD . Far-UV circular dichroism analysis of ABD indicates high helical content (56%) . Based on an analysis of nuclear magnetic resonance 13C secondary chemical shifts, sequential and short-range NOEs, and a few key nuclear Overhauser effects, we conclude that the ABD is a three-helix bundle . The structure of the ABD is, thus, quite different from the IgBD of protein G {Gronenborn, A.M . et al . (1991) Science 253, 657-661} . This strongly suggests that the ABD and the IgBD of SPG have evolved independently from each other . However, the fold of ABD is similar to that of the IgBD of staphylococcal protein A, possibly indicating a common evolutionary ancestor, despite the lack of sequence homology.

Acta Otolaryngol Suppl, 1996, 523, 75 - 7
Cytokine expression and production by tonsillar lymphocytes; Harabuchi Y et al.; Expression of various cytokines in the tonsillar compartments, and in vitro cytokine production and cytokine mRNA expression by tonsillar lymphocytes (TL), were investigated . In immunohistological analysis, a wide variety of cytokines such as interleukin (IL)-1 beta, IL-2, IL-4, IL-5, IL-10 was expressed intensively in the lymphoepithelial symbiosis (LES) . A certain number of cells producing IL-6, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha was distributed not only in the LES but also in the extrafollicular area . A significant amount of IL-6, IFN-gamma, and TNF-alpha was detected by enzyme-linked immunosorbent assay in the culture supernatants of TL cultured with streptococcal antigen, even without any mitogens . Furthermore, mRNA of IL-6, IFN-gamma, and TNF-alpha was determined by reverse transcription polymerase chain reaction on the TL freshly isolated and with streptococcal stimulated antigen, whereas, production of IL-1 alpha, IL-4, and IL-5, and expression of their mRNA were not found on TL with or without streptococcal stimulation . These data indicate that tonsils are highly active immunological organs containing a wide variety of cytokine-producing cells, and suggest that IFN-gamma, TNF-alpha, and IL-6 may play an important role on the immune response to bacteria in the tonsil.

Biotherapy, 1996, 9(4), 189 - 97
Improvement of glucose tolerance with immunomodulators on type 2 diabetic animals; Zhu XP et al.; Cytokine-inducers prevent insulin-dependent diabetes mellitus (IDDM) in animal models . We extend this therapy to non-insulin-dependent diabetes mellitus (NIDDM), because it was reported that diabetes of KK-Ay mice, a model for NIDDM, was recovered by allogenic bone-marrow transplantation that also prevented IDDM in animal models . An i.p . or i.v . injection of streptococcal preparation (OK-432) lowered fasting blood glucose (FBG) levels and markedly improved glucose tolerance test (GTT) in KK-Ay mice for more than 32 h regardless of the glucose loading routes (oral, i.v . or i.p.), while an i.v . injection of BCG improved FBG and GTT for more than 4 wks without body weight loss . The improvement of FBG and GTT with OK-432 was brought about in other NIDDM animals, GK rats and Wistar fatty rats . Among various cytokines possibly induced by OK-432 and BCG, IL-1 alpha, TNF alpha and lymphotoxin significantly improved FBG and GTT in KK-Ay mice, whereas IL-2 and IFN gamma did not . There were no differences between the OK-432-treated KK-Ay mice and control in histology of the pancreas, degree of insulin-induced decrease in blood glucose levels, and muscle glycogen synthase activities . As to insulin secretion, there is a tendency that the OK-432-treatment less that 1 week did not affect insulin levels during GTT, whereas the treatment more than 2 weeks increased the insulin levels . Thus, cytokine-inducers improved FBG and glucose tolerance of NIDDM animals probably via cytokines . The results imply a role of the cytokines in glucose tolerance of NIDDM, although precise immune and metabolic mechanisms remain to be elucidated.

Reumatizam, 1996, 43(1), 16 - 24
{Polyarteritis nodosa--cutaneous or systemic form? Possible role of bacterial superantigens in the onset of systemic disease}; Malcic I et al.; A boy with diagnostically unclear vasculitis was described, in which development of the disease points out the presence of cutaneous form of poliarteritis nodosa . Nevertheless, there are also signs for systemic form of the disease . His symptoms are marked cutaneous eruptions of the livedo reticularis type, recidives of erythema nodosum on the limbs and trunk, even on the cheeks, sometimes accompanied with fever, arthralgias, myalgias and cutaneous ulcera on the places of mechanical pressure (elbows), but also with monotopic ventricular premature beats and sporadic microhaematuria . Clinical development of the disease and differential diagnosis exclude other autoimmune disorders with great probability . The positive finding of cANCA has pointed out the diagnosis of vasculitis . Microscopical analysis of the skin didn't reveal any pathological changes . In the boy's disease is interposed a streptococcal infection, and maybe, tuberculosis . The paper deals with wide spectrum of diseases in differential diagnosis, and also with a possible role of bacterial superantigens in the genesis of autoimmunity.

Scand J Infect Dis, 1996, 28(5), 497 - 501
6-day amoxicillin versus 10-day penicillin V for group A beta-haemolytic streptococcal acute tonsillitis in adults: a French multicentre, open-label, randomized study . The French Study Group Clamorange; Peyramond D et al.; We compared the efficacy and safety of amoxicillin 1 g b.i.d . for 6 days and penicillin V 1 MU t.i.d . for 10 days in the treatment of group A beta-haemolytic streptococcal (GABHS) tonsillitis in adults . 342 patients with acute tonsillitis and a positive test for streptococcal antigen were included in a multicentre, randomized, open-label study; 338 patients were evaluable in an intention-to-treat analysis, and 234 with a positive throat swab culture in a per-protocol analysis . In the per-protocol analysis, the GABHS eradication rate at the end of treatment was comparable in the two groups: 92% (115/125) on amoxicillin and 92.7% (101/109) on penicillin (p = 0.95), as were the clinical success rates of 96% and 95.4%, respectively (p = 0.92) . At the follow-up visit (day 28-32), 90.8% of patients treated with amoxicillin and 92.6% of those treated with penicillin V were free of GABHS (p = 0.85) . Sore throat disappeared significantly faster on day 2 (p = 0.039) in the amoxicillin group . The intention-to-treat analysis gave similar clinical results . Tolerability was good in both groups . The efficacy and safety of amoxicillin 1 g b.i.d . for 6 days were not statistically different from those of penicillin V 1 MU t.i.d . for 10 days in the treatment of streptococcal tonsillitis in adults.

J Perinat Med, 1996, 24(5), 531 - 8
Neonatal early onset group B streptococcal infection . A nine-year retrospective study in a tertiary care hospital; Adriaanse AH et al.; Retrospectively, morbidity and mortality of neonatal early onset group B streptococcal (GBS) infection were established . Risk factors and prognostic factors were determined . Between 1985 and 1993, 78 patients with early onset GBS disease were identified . The overall mortality rate was 23% . In 60 of 73 cases (82%) at least one of the investigated risk factors was present . Low birth weight was not an independent risk factor . Outcome of 44 of 60 survivors (73%) at the age of at least one year was obtained . Almost 30% of them had sequelae . The most important were spastic disorders and delayed psychomotor development . In 42% of patients with symptoms of GBS-infection within six hours after birth sequelae occurred . There were no sequelae among patients with symptoms after 6 hours . All 9 severely brain damaged infants showed symptoms shortly after birth . Mortality and adverse outcome rate were higher in infants with low gestational age or low 5 minute Apgar scores . Early treatment resulted in less mortality, but not in less sequelae . GBS-sepsis still causes significant mortality and leaves a substantial number of survivors damaged . Alertness to GBS-infection, even in the absence of risk factors, remains crucial for early treatment and good outcome.

Acta Otolaryngol Suppl, 1996, 525, 135 - 41
Final report of a randomized controlled study with streptococcal preparation OK-432 as a supplementary immunopotentiator for laryngeal cancer; Kimura T et al.; We conducted a randomized controlled study of streptococcal preparation OK-432 on 120 newly identified cases of laryngeal squamous cell carcinoma who were registered at 10 participating institutions between November 1984 and October 1989 . The patients were divided into two groups: those in early stages (stage I or II) and those in advanced stages (stage III or IV); these groups were further subdivided into an immunotherapy group (receiving OK-432) and a control group (who did not receive OK-432) . The usefulness of OK-432 was studied using the sealed envelope method . The basic therapy for all cases was radiotherapy and, when required, surgery . As adjuvant therapy, 5Fu or derivatives were administered to all cases from the beginning of the treatment period to one year after the basic therapy, with the exception of cases in whom side effects were serious enough to contraindicate use of the drug . The target administration period was 5 years . Of the initial 120 cases, 11 cases were disqualified (3 cases of double cancer and 8 of incomplete primary therapy) and the remaining 109 were used for evaluation . The 5-year survival rate and the 5-year recurrence-free rate were 76% and 84%, respectively, in the immunized groups (both the early and advanced groups), whereas the same rates for the control groups were 78% and 75% . There was a tendency for the immunized groups to enjoy a slightly longer recurrence-free period . Over a 24-month observation period the immunized group always had higher levels of peripheral leukocytes and peripheral lymphocytes; this difference was significant for the first 21 months . Inhibition of bone marrow function is sometimes observed with radiotherapy . It is hoped that, if this inhibition can be mitigated, it will be possible to assist the compromised immune system and maintain a certain level of immune performance which will prevent recurrence and improve survival rate . In the present study we observed a tendency of the lower recurrence rate in the immunized group, and we hypothesize that OK-432 is effective in extending the recurrence-free period.

Acta Otolaryngol Suppl, 1996, 525, 125 - 8
Histological effect of intranodal injection of the streptococcal preparation OK-432 for cervical lymph node metastases of malignant head and neck tumors; Suzuki K et al.; To investigate the histological effect of intranodal injection of the streptococcal preparation OK-432, we performed intranodal injection in 4 patients with cervical lymph node (CLN) metastases of malignant head and neck tumors (squamous cell carcinoma (SCC) of the oropharynx, SCC of the parotid gland, malignant lymphoma, and rhabdomyosarcoma of the nasal cavity) . An initial dose of 5 klinische Einheit (KE) and a maintenance dose of 10 KE of OK-432 were administered into each metastatic or residually involved CLN twice a week . The total dose of OK-432 ranged from 105 KE to 395 KE and the number of administrations ranged from 11 to 40 . Post treatment histological examination of excised tissue specimens revealed no tumor cells; there was only fibrosis and inflammatory cell infiltration . These findings suggest that intranodal injection of OK-432 can be utilized for treatment of relatively small CLN metastases of malignant head and neck tumors.

Scand J Infect Dis Suppl, 1996, 100, 72 - 82
Clinical and immunological considerations in Epstein-Barr virus-associated diseases; Andersson J; Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir, and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to show any effect on the severity or duration of infectious mononucleosis (IM), a condition for which there is currently no established treatment . Clinical symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular, immunoreactivity with limited pathology caused by viral replication itself . However, despite an extensive immune response, 90% of tested IM patients (n = 36) had a spontaneous outgrowth of in vivo EBV-infected B-lymphocytes at onset of disease, indicating lack of specific EBV-restricted cellular cytotoxicity at this time . Establishment of an EBV-specific T-lymphocyte response occurred 90-180 days after onset of disease (human leukocyte antigen-restricted cytotoxicity against EBV-infected B-cells) . Thus, development of a specific cytotoxic response was a gradual and slow process . Assessment of cytokine pattern, at the single cell level, was performed by immunocytochemical technique and by enzyme-linked immunosorbent assay . This revealed an increased production of interleukin (IL)-2, interferon (IFN)-gamma, IL-6 and tumour necrosis factor (TNF) beta in all IM patients . Those with disseminated disease were characterized by lack of IFN-gamma production . This loss was selective since in vitro stimulation with superantigen, such as streptococcal pyrogenic exotoxin A, induced a normal response . These patients lacked signs of EBV-specific T-cell cytotoxicity in vitro . Treatment with intravenous or subcutaneous IFN-gamma, 1.5 MU every second day, in combination with intravenous immunoglobulin G (0.5 g/kg three times per week) and oral aciclovir, 800 mg 5 times daily, has shown promising results in some patients . Cytokine production in tonsil tissue in 4 patients with fulminant IM and respiratory tract obstruction showed a concomitant expression of IL-2, IFN-gamma, IL-6, TNF beta, transforming growth factor (TGF) beta 1-3, granulocyte colony stimulating factor, granulocyte macrophage colony stimulating factor, IL-4 IL-1alpha, IL-beta and TNF alpha . The number of IL-2, IFN-gamma, IL-6 and TNF beta producing cells was significantly higher compared to tonsil tissue obtained from children with tonsillar hypertrophy . Thus, IM is associated with extensive local cytokine production . It is suggested that this extensive cytokine production is closely involved in the pathology of IM and that patients with atypical IM have a dysregulation in the cytokine network . However, the mechanism by which EBV-infected B-lymphocytes triggers this cytokine cascade is still unknown . These findings show the need for evaluation of patients with immunodeficiency and EBV-induced lymphoproliferative disorders and perhaps the introduction of new immunoregulatory treatment strategies.

Infection, 1996 Jan-Feb, 24(1), 43 - 6
Streptococcal toxic shock-like syndrome . Report of two cases from Italy; Girelli CM et al.; Two cases of streptococcal toxic shock-like syndrome that occurred at our hospital are described . They represent the second and third cases reported from Italy . Both patients were women, had a portal of entry from cutaneous infection of a limb and suddenly developed high degree fever, severe hypotension, necrotizing fasciitis, acute renal failure, hepatic damage, thrombocytopenia and bleeding from a stress-related duodenal ulcer . One patient was leukopenic . The first patient needed resuscitation in the intensive care unit and emergency surgical debridement of the affected limb, whereas the second improved with medical therapy, but needed duodenal surgery for uncontrolled bleeding . Both patients slowly recovered and survived . Finally, a short update on the pathogenesis of the syndrome is also presented.

J Rheumatol, 1996 Jan, 23(1), 44 - 51
Potential pathogenicity of deglycosylated IgG cross reactive with streptokinase and fibronectin in the serum of patients with rheumatoid arthritis; Cuchacovich M et al.; OBJECTIVE: Fibronectin (FN) and the streptococcal plasminogen activator streptokinase (SK) share the epitope LTSRPA . This epitope is not reactive in native FN and it reacts with anti-SK antibodies only after plasmin digestion of the protein . To investigate a potential correlation between the high levels of anti-LTSRPA antibodies in sera of patients with rheumatoid arthritis (RA) and the perpetuation of the immune response characteristic of this disease, we analyzed their capacity to activate complement and the process of binding to the serum lectin mannan binding protein (MBP) . METHODS: We used a radioimmunoassay to evaluate immune complexes between anti-LTSRPA IgG and FN, plasmin degraded FN, or the LTSRPA peptide for their capacity to activate complement C5 to C5a . Purified human serum lectin MBP was used to quantify the degree of exposed mannose or N-acetylglucosamine residues in the Fc region of anti-LTSRPA IgG of patients with RA and healthy controls . RESULTS: Anti-LTSRPA IgG from patients with RA have a greater capacity to activate complement C5 to C5a when bound to either the LTSRPA peptide or plasmin degraded FN in vitro . We found a very strong correlation between the complement activating capacity of the RA immune complexes and their binding to MBP . CONCLUSION: The enhanced capacity of RA anti-LTSRPA IgG immune complexes to activate complement C5 to C5a is directly correlated with their binding capacity to MBP . As MBP binding depends on exposed mannose or N-acetylglucosamine residues in the Fc region of the IgG molecule, these studies suggest that defective glycosylation of circulating anti-SK IgG may play a role in the etiology of RA.

Acta Paediatr, 1996 Jan, 85(1), 104 - 5
Systemic group B streptococcal disease in neonates and young infants in Norway 1985-94; Aavitsland P et al.; In the period 1985-94, 237 out of 575,248 (0.41 per 1000) live born infants in Norway were reported to suffer culture-confirmed systemic group B streptococcal disease before their 90th day of life . The annual incidence increased from 0.20 per 1000 live births in 1985 to 0.64 in 1994, due solely to an increase in cases with an onset before the seventh day of life . Future studies should address the possible causes of this increase.

Dermatology, 1996, 192(2), 125 - 8
Effect of prophylactic benzathine penicillin on mucocutaneous symptoms of Behçet's disease; Calguneri M et al.; BACKGROUND . Recent studies point out a probable role of streptococcal antigens in the pathogenesis of Behcet's disease (BD) . This has led to the proposal of benzathine penicillin as a therapeutic modality in BD . OBJECTIVE . A prospective study was conducted to compare the efficacy of colchicine and colchicine + benzathine penicillin treatments on mucocutaneous manifestations of BD . METHODS . 60 patients (group I) were given colchicine alone and 94 (group II) were given colchicine + benzathine penicillin . Frequency, number, duration and severity of oral aphthous ulcers, genital ulcers and erythema nodosum were determined before and after treatment . RESULTS . In group I, all parameters of oral ulcers and the frequency and healing time of genital ulcers and erythema nodosum decreased significantly . In group II, all parameters of oral aphthous ulcers, genital ulcers and erythema nodosum were significantly improved . When treatment results in the two groups were compared, the decrements in the frequency and duration of oral ulcers and erythema nodosum and the frequency of genital ulcers were significantly greater in group II than in group I (p < 0.05) . CONCLUSION . We conclude that prophylactic benzathine penicillin combined with colchicine is more effective in controlling mucocutaneous manifestations of BD than colchicine alone.

Pediatr Res, 1996 Jan, 39(1), 55 - 63
Group B streptococcal sepsis impairs cerebral vascular reactivity to acute hypercarbia in piglets; Rudinsky BF et al.; We investigated whether group B streptococcal (STREP) infusion impairs the cerebral blood flow (CBF) response to acute hypercarbia in piglets, and whether STREP-induced prostanoids or hemodynamic alterations could account for this impairment . Piglets, 2-3 wk old, were anesthetized, paralyzed, and mechanically ventilated (50% O2; partial pressure of arterial CO2 (PaCO2) approximately 40 torr) . CBF was assessed by internal carotid artery blood flow (ICBF) . Group 1 (n = 5) received a continuous infusion of STREP for 4 h (2.0-8.0 x 10(7) org/kg-min) . Group 2 (n = 5) was pretreated with indomethacin (5 mg/kg), then received the identical STREP infusion . Group 3 (n = 6) did not receive STREP, but cardiac output (CO) and systemic blood pressure (BP) were reduced to levels equal to that of group 1 by incremental inflation of a left atrial balloon (LAB) catheter . Cerebral vascular reactivity to acute hypercarbia (PaCO2 approximately 70 torr for 7.5 min) was assessed at baseline and after each hour of STREP infusion or LAB inflation . We found that 4 h of STREP infusion caused CO to fall significantly (634 +/- 121 to 324 +/- 172 mL/min, group 1; 600 +/- 68 to 291 +/- 80 mL/min, group 2) and BP to fall significantly (104 +/- 20 to 57 +/- 4 mm Hg, group 1; 91 +/- 11 to 53 +/- 16 mm Hg, group 2) By design, in group 3 LAB inflation caused CO (573 +/- 181 to 375 +/- 159 mL/min) and BP (104 +/- 14 to 60 +/- 9 mm Hg) to fall to values not significantly different from septic groups 1 and 2 . At 4 h, unilateral ICBF decreased significantly during STREP infusion in group 1 (32.0 +/- 10.8 to 21.0 +/- 7.3 mL/min) and group 2 (22.9 +/- 9.9 to 13.1 +/- 4.3 mL/min), but not in nonseptic group 3 (23.1 +/- 7.4 to 19.6 +/- 6.3 mL/min) . At baseline, hypercarbia induced an increase in ICBF (% delta ICBF = 68.7 +/- 13.0% in group 1, 62.2 +/- 15.6% in group 2, and 87.7 +/- 34.0% in group 3) . After 4 h of STREP, this response was completely ablated as ICBF fell during hypercarbia by -7.8 +/- 23.2% (group 1) . Indomethacin did not protect cerebral vascular reactivity after 4 h of STREP infusion, as % delta ICBF fell during hypercarbia by -10.9 +/- 17.7% (group 2) . In contrast, despite equivalent reductions in CO and BP after 4 h of LAB inflation in nonseptic group 3, ICBF rose during hypercarbia by 61.8 +/- 23.2%, not significantly different from baseline, but significantly different from the decrease in % delta ICBF in groups 1 and 2 . We conclude that STREP infusion reduces ICBF and cerebral vascular reactivity to acute hypercarbia in piglets . This phenomenon is not accounted for by STREP-induced reduction in CO or BP, and is not mediated by prostanoids.

Clin Infect Dis, 1996 Jan, 22(1), 130 - 2
Streptococcal meningitis as a complication of diagnostic myelography: medicolegal aspects; Gelfand MS et al.; Bacterial meningitis is a rare complication of myelography . Most reported cases of bacterial meningitis are caused by a wide variety of streptococcal species, but the source of these organisms is uncertain . We recently participated in the defense of two legal cases arising from this complication . We discuss the medicolegal aspects of streptococcal meningitis that is a complication of myelography.

Scand J Infect Dis, 1996, 28(2), 139 - 42
Incidence and severity of group A streptococcal bacteremia in a medical center in Israel, 1981-1994; Livni G et al.; To determine recent trends in the incidence and severity, group A streptococcal (GAS) bacteremia was studied over the last 14 years (1981-1994) . There were 116 events of GAS bacteremia, representing 1.7% of all bacteremic episodes, without an increase in recent years . A total of 108 patients were available for study . Underlying conditions were found in 95 patients (88%), including mainly malignant diseases, chronic obstructive pulmonary disease, congestive heart failure and diabetes mellitus . A source of the bacteremia was noted in 71 patients (66%), with skin and soft tissue infection being the major portal of entry . All isolates were susceptible to penicillin . Overall mortality was 21% . Mortality had not increased in recent years, but depended significantly on several clinical factors: increased age; admission temperature; source of bacteremia (highest for GAS bacteremia without an identified source); and underlying conditions (highest for diabetes mellitus and chronic pulmonary disease, absent for patients with no underlying disease) . This study shows that neither the incidence nor the severity of GAS bacteremia has increased in recent years . Severity is significantly affected by the source of bacteremia and the presence of underlying conditions.

Protein Sci, 1996 Jan, 5(1), 174 - 7
Rapid screening for structural integrity of expressed proteins by heteronuclear NMR spectroscopy; Gronenborn AM et al.; A simple and rapid method based on 15N labeling and 1H-15N heteronuclear single quantum coherence spectroscopy is presented to directly assess the structural integrity of overexpressed proteins in crude Escherichia coli extracts without the need for any purification . The method is demonstrated using two different expression systems and two different proteins, the B1 immunoglobulin-binding domain of streptococcal protein G (56 residues) and human interleukin-1 beta (153 residues) . It is shown that high quality 1H-15N correlation spectra, recorded in as little as 15 min and displaying only cross-peaks arising from the overexpressed protein of interest, can be obtained from crude E . coli extracts.

Scand J Rheumatol, 1996, 25(3), 127 - 31; discussion 132-3
Towards understanding the pathogenesis of rheumatic fever; Carapetis JR et al.; Acute rheumatic fever results from an immunological response to group A streptococcal infection, but the exact nature of this response, and of the underlying host and organism characteristics, continues to evade researchers . Earlier models of rheumatic fever pathogenesis emphasised the importance of humoral immunity, but more recent work suggests that cellular immunity may play a primary role . Greater understanding of these disease mechanisms is allowing researchers to move towards the development of a vaccine for rheumatic fever.

J Orthop Trauma, 1996, 10(3), 149 - 55
Fatal group A streptococcal infection with toxic shock syndrome: complicating minor orthopedic trauma; Mills WJ et al.; Since 1987, reports have appeared of a streptococcal toxic shock syndrome in various clinical settings . None have appeared in the orthopaedic literature . Between 1989 and 1991 at our institution three patients with relatively minor orthopaedic injuries or procedures died of group A streptococcal infections complicated by toxic shock syndrome . The manifestations of this syndrome included rapid progression of systemic sepsis, necrotizing soft-tissue infections, acute renal failure, adult respiratory distress syndrome, and coagulopathy . All three patients died despite aggressive resuscitative measures and surgical debridement . Optimal treatment of this life-threatening process requires early recognition, aggressive surgical debridement, appropriate antibiotic management, and intensive care unit support.

Int J Immunopharmacol, 1995 Dec, 17(12), 963 - 71
Adoptive immunotherapy of poorly immunogenic tumors with in vitro sensitized cells generated by intratumoral administration of biological response modifiers; Mukai S et al.; We investigated the efficacy of intratumoral administration of biological response modifiers (BRM) in induction of in vitro sensitized (IVS) cells for adoptive immunotherapy of the poorly immunogenic MCA 102 sarcoma and B16-BL6(BL6) melanoma . We used the bacterial immunoadjuvant Nocardia rubra cell wall skeleton (N-CWS), and a streptococcal preparation, OK-432, for MCA 102 and BL6, respectively . After C57BL/6(B6) mice were inoculated subcutaneously (s.c.) with viable MCA 102 or BL6 tumor cells in the foot-pad, mice were injected intratumorally (i.t.) with N-CWS ranging from 10 to 400 micrograms or OK-432 ranging from 1 to 100 micrograms . Draining popliteal lymph nodes (LN) were harvested 7 days after i.t . administration of BRM, and LN cells were cultured with irradiated tumor cells in the presence of IL-2 for 11 days . These IVS cells (7.5 x 10(6) or 2 x 10(6)) were transferred intravenously (i.v.) to B6 mice with 4 day pulmonary metastases established by i.v . injection of viable MCA 102 cells (1 x 10(6)) or viable BL6 cells (3 x 10(5)) . The mice were also received intraperitoneally 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer . The transfer of IVS cells from mice immunized by i.t . injection of 100 micrograms of N-CWS 1 week after inoculation of tumor cells significantly reduced MCA 102 pulmonary metastases, compared with control IVS cells without administration of N-CWS . Moreover, the transfer of IVS cells from mice immunized by i.t . injection of 10 micrograms of OK-432 3 days after inoculation of tumor cells significantly reduced BL6 pulmonary metastases compared with control IVS cells without administration of OK-432 . The administration of N-CWS resulted in no enhancement of in vitro cytotoxicity . Although the administration of 10 micrograms of OK-432 augmented in vitro cytotoxicity of IVS cells against BL6, cytotoxic activity was lower than that of IVS cells immunized with N-CWS . The major phenotype was CD8+ cells in IVS cells immunized with N-CWS or OK-432 . These results suggest that i.t . administration of N-CWS and OK-432 facilitates the production of sensitized T-cells, and this administration route of BRM may be useful in the adoptive immunotherapy of human cancer.

J Paediatr Child Health, 1995 Dec, 31(6), 493 - 4
Prevention of early onset group B streptococcal sepsis in the newborn; Vigneswaran R et al.; There is an urgent need for strategies to prevent early onset group B streptococcal sepsis in the newborn . The most effective mechanism is the identification of maternal carriers of the organism and interruption of transmission during labour . Vaginal culture is currently the most reliable method for the identification of carriers . Antibiotic prophylaxis for known carriers in labour has been demonstrated to be effective as standard management practice in a number of Australian institutions and is the best available strategy at this stage.

Biochem Mol Med, 1995 Dec, 56(2), 176 - 9
Comparison of human VDAC1 with streptococcal streptokinase and bovine bactericidal permeability increasing protein: role of structural information in identifying functionally significant domains; McCabe KM et al.; Comparison of the primary amino acid sequence of the human X-linked voltage-dependent anion channel, with other sequences in data base searches, identified regions of similarity in streptococcal streptokinase and bovine bactericidal permeability increasing protein . These regions of similarity were in different areas of the protein and were relatively short . However, examination of an empirically derived structural model of the channel showed that each region of similarity in streptokinase and bovine bactericidal permeability increasing protein corresponded to contiguous transmembrane domains within the channel protein . We speculate that these transmembrane domains may be functionally significant for streptokinase and bovine bactericidal permeability increasing protein . These investigations demonstrate the need for incorporation of information regarding secondary, tertiary, and quaternary structures, as well as function, in algorithms used for database searches.

Med Hypotheses, 1995 Dec, 45(6), 575 - 87
Immunological influences in attention-deficit disorder and schizophrenia; is there a link between these two conditions?
Holden RJ, Pakula IS.
This paper aims to explore the influence of the immune system on the pathobiochemistry of movement disorders (Tourette syndrome, obsessive compulsive disorders and attention-deficit disorder, with and without hyperactivity) and schizophrenia . In children, a temporal relationship has been observed between contraction of a group A beta-hemolytic streptococcal infection and subsequent presentation with one of the movement disorders . Pathology investigations reveal that elevated antineuronal antibodies are associated with movement disorders . Similarly, elevations in interleukin-1 beta and interleukin-6 have been reported in schizophrenia . It is now known that the immune system can be activated by conditions other than a viral or bacterial infection, such as: neurological insult, neurotoxicity--endogenous and environmental, neurotransmitter and cholesterol dysregulation . These latter avenues of immune system activation will be explored with respect to schizophrenia.

Scand J Prim Health Care, 1995 Dec, 13(4), 257 - 60
The economic cost of a streptococcal tonsillitis episode; Roos K et al.; OBJECTIVE: To estimate the cost of a streptococcal tonsillitis episode from the data of a questionnaire . SETTING: Five primary health centres in the west of Sweden . PARTICIPANTS: 101 consecutive patients treated for streptococcal tonsillitis . MAIN OUTCOME MEASURE: The cost estimation included costs for physician visit and drug, travel costs to and from the primary health centre, cost of lost production resulting from the patient's or the guardian's absence from work for physician visit or sick-leave, and cost of telephone consultation with a physician or nurse . RESULTS: The period of illness was on average seven days, time to recovery after treatment five days, and the mean period of sick-leave 2.5 days . The total cost of a tonsillitis episode was about SEK 3,300 (385 USD) . Of this sum, the cost for the antibiotic accounted for only 3% and loss of production for 75% . CONCLUSION: Differences in the cost of drugs only have a minor influence on the total cost, while factors causing loss of production, such as efficacy and side effects of the drug, have a greater influence . Economic evaluation of pharmaceuticals will be more relevant in the future, and in the search for the most effective treatment, cost effective studies will be integrated with clinical trials.

Eur Heart J, 1995 Dec, 16(12), 1968 - 74
Procedures associated with infective endocarditis in adults . A case control study; Lacassin F et al.; OBJECT: To assess the relative risk of infective endocarditis associated with various procedures and the protective efficacy of antibiotic prophylaxis by a case-control study . BACKGROUND: Recommendations for the prevention of infective endocarditis are based on the hypothesis of a relationship between procedures and infective endocarditis which is supported by anecdotal reports and data from experimental models . METHODS: Cases met the Von Reyn's diagnostic criteria modified with echocardiographic and macroscopic findings Controls were recruited from cardiology or medicinal wards . Cases (n = 171) and controls were matched as regards sex, age and underlying cardiac condition . They were requested to indicate all the medical, surgical or dental procedures within the previous 3 months . Among potential confounding factors, infectious episodes and skin wounds in the previous 3 months were reported . Antibiotic prophylaxis administration was documented for type, dosage, duration and administration schedule . RESULTS: Cases significantly more frequently than controls had undergone at least one procedure (matched odds ratio, 1.6; 95% confidence interval, 1.01 to 2.53) . Dental procedures considered as a whole were not associated with an increased risk, although scaling and root canal treatment showed a trend towards a higher risk of infective endocarditis (P = 0.065) . Among non-dental procedures, only surgery appeared to be at risk (matched odds ratio, 4.7; 95% confidence interval, 1.02 to 22) . Considering all procedures, the risk of infective endocarditis increased significantly with the number of procedures . While general co-morbid conditions did not differ between the two groups, cases significantly more frequently than controls had experienced an infectious episode or a skin wound . In multivariate analysis, only infectious episodes and skin wounds significantly increased the risk of infective endocarditis . Scaling was the only independent risk factor for viridans streptococcal infective endocarditis . The 46% protective efficacy of antibiotic prophylaxis was not significant . CONCLUSIONS: Procedures do increase the risk of infective endocarditis . The interpretation of the apparent low risk associated with dental procedures may be as a result of the current practice of antibiotic prophylaxis . Our data suggest that surgery should be more clearly mentioned in future guidelines, and reemphasize that a rigorous treatment of any focal infection in cardiac patients is mandatory . From the efficacy rate of antibiotic prophylaxis,it can be estimated that the overall incidence of infective endocarditis might be reduced by 5 to 10% in France by appropriate use of antibiotic prophylaxis in cardiac patients.

Z Lymphol, 1995 Dec, 19(2), 55 - 7
{Anasarca caused by rheumatic carditis}; Ruger K; Report of a 55-year-old-male patient with most serious anasarca caused by insufficiency right heart . The reason of the heart failure was probably rheumatic carditis caused by streptococcal infections which followed recurrent erysipelas both legs with phleblymphedema . The necessity of consistent antibiotic treatment of the erysipelas, that's the only possibility to avoid more difficult secondary complications like this case of rheumatic carditis showed . The treatment of insufficiency heart was followed by physical decongestive therapy of the phleblymphedema of the legs . After a treatment period of 12 weeks a water loss of 112 kg and reduction of abdominal circumference from 250 cm to 150 cm could be achieved.

Pneumologie, 1995 Dec, 49(12), 674 - 7
{Primary germ cell tumors of the mediastinum}; Theegarten D et al.; This is a report on 5 cases of mediastinal germ cell tumours . Of three mature teratomas seen in a 48-year old male and a 21-year old and 19-year old female, one was asymptomatic, another one associated with streptococcal pneumonia and the third associated with progressive cough irritation . In addition, a seminoma was seen in a male of 58 years of age and a yolk sac tumour (mesonephroma type 2) in a male of 23 years . Whereas in mature teratomas surgical resection can be considered sufficient, resection combined with chemotherapy should be performed in patients suffering from malignant germ cell tumours, and in addition also radiotherapy in case of seminoma . This approach may result in a significant improvement of the prognosis in malignant mediastinal germ cell tumours.

Protein Sci, 1995 Dec, 4(12), 2605 - 15
Structural and dynamic characterization of the urea denatured state of the immunoglobulin binding domain of streptococcal protein G by multidimensional heteronuclear NMR spectroscopy; Frank MK et al.; The structure and dynamics of the urea-denatured B1 immunoglobulin binding domain of streptococcal protein G (GB1) has been investigated by multidimensional heteronuclear NMR spectroscopy . Complete 1H, 15N, and 13C assignments are obtained by means of sequential through-bond correlations . The nuclear Overhauser enhancement, chemical shift, and 3JHN alpha coupling constant data provide no evidence for the existence of any significant population of residual native or nonnative ordered structure . 15N relaxation measurements at 500 and 600 MHz, however, provide evidence for conformationally restricted motions in three regions of the polypeptide that correspond to the second beta-hairpin, the N-terminus of the alpha-helix, and the middle of the alpha-helix in the native protein . The time scale of these motions is longer than the apparent overall correlation time (approximately 3 ns) and could range from about 6 ns in the case of one model to between 4 microseconds and 2 ms in another; it is not possible to distinguish between these two cases with certainty because the dynamics are highly complex and hence the analysis of the time scale of this slower motion is highly model dependent . It is suggested that these three regions may correspond to nucleation sites for the folding of the GB1 domain . With the exception of the N- and C-termini, where end effects predominate, the amplitude of the subnanosecond motions, on the other hand, are fairly uniform and model independent, with an overall order parameter S2 ranging from 0.4 to 0.5.

J Exp Med, 1995 Dec 1, 182(6), 1833 - 45
Superantigen binding to a T cell receptor beta chain of known three-dimensional structure; Malchiodi EL et al.; The three-dimensional structure of an unglycosylated T cell antigen receptor (TCR) beta chain has recently been determined to 1.7 A resolution . To investigate whether this soluble beta chain (murine V beta 8.2J beta 2.1C beta 1) retains superantigen (SAG)-binding activity, we measured its affinity for various bacterial SAGs in the absence of MHC class II molecules . Dissociation constants (KDs) were determined using two independent techniques: surface plasmon resonance detection and sedimentation equilibrium . Specific binding was demonstrated to staphylococcal enterotoxins (SEs) B, C1, C2, and C3 and to streptococcal pyrogenic exotoxin A (SPEA), consistent with the known proliferative effects of these SAGs on T cells expressing V beta 8.2 . In contrast, SEA, which does not stimulate V beta 8.2-bearing cells, does not bind the recombinant beta chain . Binding of the beta chain to SAGs was characterized by extremely fast dissociation rates (> 0.1 s-1), similar to those reported for certain leukocyte adhesion molecules . Whereas the beta chain bound SEC1, 2, and 3 with KDs of 0.9-2.5 microM, the corresponding value for SEB was approximately 140 microM . The much weaker binding to SEB than to SEC1, 2, or 3 was surprising, especially since SEB was found to actually be 3- to 10-fold more effective, on a molar basis, than the other toxins in stimulating the parental T cell hybridoma . We interpret these results in terms of the ability of SEC to activate T cells independently of MHC, in contrast to SEB . We have also measured SE binding to the glycosylated form of the beta chain and found that carbohydrate apparently does not contribute to recognition, even though the N-linked glycosylation sites at V beta 8.2 residues Asn24 and Asn74 are at or near the putative SAG-binding site . This result, along with the structural basis for the V beta specificity of SEs, are discussed in relation to the crystal structure of the unglycosylated beta chain.

Science, 1995 Nov 10, 270(5238), 980 - 2
Guidelines for protein design: the energetics of beta sheet side chain interactions; Smith CK et al.; To determine the interaction energy between cross-strand pairs of side chains on an antiparallel beta sheet, pairwise amino acid substitutions were made on the solvent-exposed face of the B1 domain of streptococcal protein G . The measured interaction energies were substantial (1.8 kilocalories per mole) and comparable to the magnitude of the beta sheet propensities . The experimental results paralleled the statistical frequency with which the residue pairs are found in beta sheets of known structure.

Gene, 1995 Nov 7, 165(1), 57 - 60
Cloning, sequence analysis and expression of the group A streptococcal guaB gene encoding inosine monophosphate dehydrogenase; Ashbaugh CD et al.; Inosine monophosphate dehydrogenase (IMPDH) is an essential enzyme in the biosynthesis of purines . We cloned a group A streptococcal (GAS) DNA fragment containing an open reading frame similar to other bacterial guaB genes encoding IMPDH . The GAS guaB consists of 1479 nucleotides encoding a protein of 493 amino acids . Expression of the GAS guaB in an Escherichia coli guaB mutant restored IMPDH activity, confirming the function of the gene product and demonstrating that the GAS enzyme is active in a heterologous bacterial host . Restriction mapping and Southern hybridization analysis of GAS chromosomal DNA localized guaB to a site approximately 5 kb from the hasA and hasB genes which encode enzymes necessary for hyaluronic acid capsule synthesis.

Mol Microbiol, 1995 Nov, 18(3), 569 - 78
Identification of a plasminogen-binding motif in PAM, a bacterial surface protein; Wistedt AC et al.; Surface-associated plasmin(ogen) may contribute to the invasive properties of various cells . Analysis of plasmin(ogen)-binding surface proteins is therefore of interest . The N-terminal variable regions of M-like (ML) proteins from five different group A streptococcal serotypes (33, 41, 52, 53 and 56) exhibiting the plasminogen-binding phenotype were cloned and expressed in Escherichia coli . The recombinant proteins all bound plasminogen with high affinity . The binding involved the kringle domains of plasminogen and was blocked by a lysine analogue, 6-aminohexanoic acid, indicating that lysine residues in the M-like proteins participate in the interaction . Sequence analysis revealed that the proteins contain common 13-16-amino-acid tandem repeats, each with a single central lysine residue . Experiments with fusion proteins and a 30-amino-acid synthetic peptide demonstrated that these repeats harbour the major plasminogen-binding site in the ML53 protein, as well as a binding site for the tissue-type plasminogen activator . Replacement of the lysine in the first repeat with alanine reduced the plasminogen-binding capacity of the ML53 protein by 80% . The results precisely localize the binding domain in a plasminogen surface receptor, thereby providing a unique ligand for the analysis of interactions between kringles and proteins with internal kringle-binding determinants.

J Dairy Sci, 1995 Nov, 78(11), 2366 - 74
Environmental streptococcal intramammary infections of the bovine mammary gland; Todhunter DA et al.; Characteristics of environmental streptococcal IMI were investigated over a 7-yr period for a herd in total confinement . A total of 374 new environmental streptococcal IMI was detected . Approximately 50.5% of IMI were new in the dry period, and 49.5% were new in lactation . The rate of new IMI was .00312 IMI/cow day during the dry period and .00054 IMI/cow day during lactation . The percentages of cows and quarters with an environmental streptococcal IMI present at calving were 10.6 and 3.2%, respectively . The percentage of heifers with an environmental streptococcal IMI at calving was similar to that for cows . The rate of new environmental streptococcal IMI was greater during the 1st mo of lactation than during the remainder of lactation . The rate of IMI during late lactation was higher for older cows than for either heifers or cows in second lactation . The rate of environmental streptococcal IMI during the dry period and during lactation was greatest during summer . The mean days of lactation that cows were infected for all IMI was 12.3 d . Approximately 41% of IMI had a duration of < 8 d . Stage of lactation, season of the year, and parity influenced the rate of new IMI.

Baillieres Clin Rheumatol, 1995 Nov, 9(4), 653 - 71
Innovative treatment approaches for rheumatoid arthritis . T-cell regulation; Choy EH et al.; There is considerable evidence to implicate T cells in the pathogenesis of rheumatoid arthritis (RA) . They initiate and sustain inflammation and therefore are attractive targets for immunotherapy . Several strategies targeting T cells have been tried in RA . The use of monoclonal antibodies to deplete T cells have been used extensively but with little success . Studies have shown that T cell depleting antibodies produce profound peripheral blood lymphopenia but they are less effective in depleting lymphocytes in the joint . Since clinical efficacy is likely to depend on depleting almost all synovial lymphocytes, high doses of monoclonal antibodies would have to be given . However, the invariably severe peripheral blood lymphopenia induced by such a regimen is likely to result in profound immunosuppression . Therefore, this strategy has been abandoned and recent attempts have been made to induce tolerance in RA . In animal models of RA, treatment with high dose non-depleting anti-CD4 monoclonal antibody protects them from arthritis induced by injection of streptococcal cell wall . In addition, it leads to a state of anergy which protects the animals from arthritis induction without further treatment with anti-CD4 monoclonal antibody . This is currently being used in clinical trials of RA . Other tolerance inducing treatment strategies include T cell or T cell receptor vaccination and oral tolerance . The former is particularly difficult since the rheumatoid arthritogenic antigen and the pathogenic T cell remain unknown . The latter has shown promise in placebo controlled trials although the ideal dosage remains unknown . The mechanism of action of oral tolerance involves either immunosuppressive T cell cytokines, T cell anergy or depletion.

Clin Infect Dis, 1995 Nov, 21(5), 1220 - 7
Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone; Carapetis J et al.; We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993 . Forty-two cases were identified . There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period; more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs . 20%, respectively, with an 88% complication rate over the last 12 months) . Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed . An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates . Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable . Invasive GAS disease in Melbourne has become increasingly aggressive . Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains.

Microvasc Res, 1995 Nov, 50(3), 397 - 416
Neutrophil migration through preexisting holes in the basal laminae of alveolar capillaries and epithelium during streptococcal pneumonia; Walker DC et al.; The purpose of this study was to determine whether or not there are preexisting holes in the endothelial and epithelial basal laminae of alveolar walls and to determine the path taken by neutrophils as they migrate from the capillaries to the airspace of the alveoli during inflammation . Using transmission electron microscopy and serial thin sections of normal rabbit and mouse lung, we have demonstrated the presence of slit-like holes in the capillary basal laminae and round holes in the basal laminae of type 2 pneumocytes . The slits in the capillary basal laminae were observed at the intersection of the thick and thin walls where endothelium, pericytes, and fibroblasts make close contact . The round holes in the type 2 cell basal laminae were observed at sites of close contact with fibroblasts . Neutrophils were observed to migrate through these slits and holes during streptococcal pneumonia in rabbit lungs . We conclude that during inflammation in the lung, migrating neutrophils displace pericytes and fibroblasts from the slits in the capillary basal lamina and then crawl through these slits into the alveolar interstitium . We postulate that neutrophils find their way to type 2 pneumocytes by following interstitial fibroblasts . We believe that neutrophils displace fibroblasts from their close contacts with the type 2 cells and then crawl through the holes in the basal lamina into the basal lateral space of the type 2 cells . From there, neutrophils migrate into the alveolar airspace.

Mol Immunol, 1995 Nov, 32(16), 1235 - 43
Characterization of a type II'o group A streptococcal immunoglobulin-binding protein; Pack TD et al.; The opacity factor positive M type 2 group A streptococcal isolate, A207, expresses a unique functional type II'o IgG-binding protein which reacts with all four human IgG subclasses and rabbit IgG . In order to determine the gene product or products responsible for this activity, three genes of the vir regulon from this isolate were cloned, expressed and analysed . The fcr A2 gene coded for a protein binding hyman IgG1, IgG2 and IgG4 but not IgG3 . The enn2 gene coded for a protein reacting exclusively with human IgA, while the emmL2 gene product bound IgG1, IgG2, IgG3 and IgG4 as well as rabbit but not horse or pig IgG . The IgG3-binding activity of the EmmL2 protein was functionally indistinguishable from the Form 1 IgG3-binding activity present in heat extracts of group A isolate A207.

J Okla State Med Assoc, 1995 Nov, 88(11), 472 - 4
Streptococcal necrotizing fasciitis ("flesh-eating strep infection"); Schwartz SN et al.; Streptococcal necrotizing fasciitis, popularized in the lay literature as the "flesh-eating infection" has gained great notoriety . Necrotizing fasciitis may be lethal not only due to its severity, but also because of difficulty in diagnosis during its early stages . Absence of immunity against certain streptococcal proteins increases the severity of infection . Necrotizing fasciitis may be distinguished from other streptococcal skin and soft tissue infections by clinical examination, imaging studies, and biopsy . Treatment requires a combined medical-surgical approach.

J Clin Invest, 1995 Nov, 96(5), 2106 - 12
Evidence for a streptococcal superantigen-driven process in acute guttate psoriasis; Leung DY et al.; Recent studies have suggested that T cells play a critical role in the pathogenesis of psoriasis . Guttate psoriasis is a well-defined form of psoriasis frequently associated with streptococcal throat infection . This study tested the hypothesis that T cells in acute guttate psoriasis skin lesions may be activated by streptococcal superantigens . Peripheral blood as well as lesional and perilesional skin biopsies were analyzed for T cell receptor V beta repertoire using monoclonal antibodies against 10 different V beta families . Skin biopsies from all patients with acute guttate psoriasis, but not skin biopsies from patients with acute atopic dermatitis or inflammatory skin lesions induced in normal subjects with sodium lauryl sulfate, demonstrated selective accumulation of V beta 2+ T cells (P < 0.05) . The expansion of V beta 2+ T cells occurred in both the CD4+ and the CD8+ T cell subsets . Sequence analysis of T cell receptor beta chain genes of V beta 2-expressing T cells from skin biopsies of patients with guttate psoriasis showed extensive junctional region diversity that is more compatible with a superantigen rather than a conventional (nominal) antigen-driven T cell response . All streptococcal isolates from patients with guttate psoriasis secreted streptococcal pyrogenic exotoxin C, a superantigen known to stimulate marked V beta 2+ T cell expansion . These data support the concept that acute guttate psoriasis is associated with superantigenic stimulation of T cells triggered by streptococcal superantigen(s).

Dig Dis Sci, 1995 Nov, 40(11), 2398 - 406
Effect of splenectomy on hepatic metastasis of colon carcinoma and natural killer activity in the liver; Shiratori Y et al.; We have previously demonstrated that administration of killed streptococcal preparation (OK432), a biological modifier, increased the number of asialo GM1-positive cells in the liver, enhanced NK activity of hepatic mononuclear cells, and reduced the number of hepatic metastases of colon 38 adenocarcinoma that were inoculated into the superior mesenteric vein of C57BL/6 strain mice . In the present study, to clarify the role of the spleen in immune surveillance of the liver, the effect of splenectomy on hepatic metastasis of colon carcinoma and on hepatic NK activity has been examined . The number of hepatic metastasis increased in the splenectomized mice, compared with that in sham-operated mice . Administration of OK432 increased the number of asialo GM1-positive cells in the liver and enhanced NK activity of hepatic mononuclear cells in both groups, but NK activity of hepatic mononuclear cells in the splenectomized mice was less than that of the sham-operated mice . An enhanced NK activity of these cells was abolished by treatment with anti-asialo-GM1 antibody plus complement in vitro . Interleukin-2 mRNA expression was increased in the spleen 2 hr after OK432 administration and persisted until 8 hr, but was scarcely noted in the liver . On the other hand, NK activity of hepatic mononuclear cells in the asialo GM1-positive cell-depleted (previous administration of antiserum against asialo GM1) mice was enhanced after OK432 administration in the sham operated and splenectomized mice, but an enhanced NK activity in these mice was only partially or not at all abolished by treatment with anti-asialo GM1 antibody plus complement in vitro, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Immunol Immunopathol, 1995 Nov, 77(2), 119 - 26
Superantigens in Kawasaki syndrome; Leung DY et al.; Kawasaki syndrome (KS) is an acute multisystem vasculitis of infancy and early childhood associated with the development of myocarditis and coronary artery abnormalities . Despite the widely held belief that KS is caused by an infectious agent, there remains considerable controversy over its etiology . Recent immunologic and microbiologic studies suggest a potential role for staphylococcal and streptococcal toxins (superantigens) in the pathogenesis of KS . Confirmation of these findings could result in more effective diagnostic and therapeutic approaches to this common cause of acquired heart disease in children.

Zhonghua Nei Ke Za Zhi, 1995 Oct, 34(10), 687 - 9
{An approach to the diagnosis of recurrent attack of rheumatic fever in patients with rheumatic heart disease}; Huang C; In order to evaluate recurrent attack of rheumatic fever (RARF) in patients with rheumatic heart disease (RHD), 97 patients with diagnosis of RHD for two years and more were included in this study . Progression of the lesions of cardiac valves was found in every case by comparing the echocardiographic and Doppler findings at present and two years ago . The history of the initial attack of acute rheumatic fever or the appearance of RHD were reviewed . The present complaints at admission and necessary laboratory procedures were studied . The data showed that 75 of the 97 patients had history of initial attack of ARF and the remaining 22 were symptomless with indolent carditis or carditis of insidious onset two years ago . In this admission, only 25 of the 97 patients had ARF in the Jones criteria were followed strictly, while the remaining 72 did not fulfill the criteria . It is suggested that if there is evidence of recent group a streptococcal infection, the conditions for diagnosis of RARF are as follows: 1) When one major or more than two minor criteria are present in a patient with RHD, a definite diagnosis of RARF may be made . 2) A presumptive diagnosis of RARF may be made, when a patient presents one minor criteria and several other manifestations such as anemia, abdominal pain, rapid sleeping pulse rate, tachycardia out of proportion to fever, malaise, epistaxis, precordial pain and an elevated level of IgG, IgA, C3 and circulating immune complexes.

Int J Immunopharmacol, 1995 Oct, 17(10), 841 - 8
Tumor necrosis factor production by human T-cells stimulated with bacterial superantigens; Imanishi K et al.; Tumor necrosis factor (TNF) production from T-cells stimulated with superantigenic exotoxins, staphylococcal enterotoxin B and streptococcal pyrogenic exotoxin A was investigated in the presence of cells bearing distinct isotypes of HLA class II molecules . The main T-cell subset for TNF production was investigated in parallel . Similarly high levels of TNF production were induced upon stimulation with the toxins in the presence of DR+ or DQ+ cells, but only marginal levels of TNF production were induced in the presence of DP+ cells . Although both CD4+ T-cells and CD8+ T-cells produced TNF-alpha and TNF-beta in response to toxin stimulation in the presence of HLA class II+ cells, the former T-cell subset was the major source of producers of TNF-alpha and TNF-beta.

Clin Infect Dis, 1995 Oct, 21(4), 977 - 80
Could nonsteroidal antiinflammatory drugs (NSAIDs) enhance the progression of bacterial infections to toxic shock syndrome?
Stevens DL.
Anecdotal reports suggest an association between the use of nonsteroidal antiinflammatory drugs (NSAIDs) and the progression of invasive group A streptococcal infections to shock and multiorgan failure . There is a biochemical rationale that could support this theory . Though NSAIDs are frequently used to relieve pain or reduce fever, they also attenuate granulocyte functions such as chemotaxis, phagocytosis, and bacterial killing . In addition, findings in recent studies involving human volunteers injected with endotoxin suggest that pretreatment with NSAIDs enhances production of tumor necrosis factor, which leads to higher blood levels of this cytokine, probably by preventing feedback inhibition by prostaglandin E2 . Thus, NSAIDs may contribute to the sudden onset of shock, organ failure, and aggressive infection by inhibiting neutrophil function, augmenting cytokine production, and attenuating the cardinal manifestations of inflammation.

Proteins, 1995 Oct, 23(2), 256 - 63
Metal search: a computer program that helps design tetrahedral metal-binding sites; Clarke ND et al.; We describe a computer program (Metal Search) that helps design tetrahedrally coordinated metal binding sites in proteins of known structure . The program takes as input the backbone coordinates of a protein and outputs lists of four residues that might form tetrahedral sites if wild-type amino acids were replaced by cysteine or histidine . The program also outputs the side chain dihedral angles of the amino acids and the coordinates of the predicted metal ion . The only function evaluated by Metal Search is the ability of side chains to meet simple geometric criteria for formation of a tetrahedral site, but these criteria are sufficient to produce a manageably small list that can then be evaluated by other means . The program has been used in the introduction of zinc binding sites in the designed four-helix bundle protein alpha 4 and in the B1 domain of streptococcal protein G, and in both cases the tetrahedral coordination of a bound metal ion has been confirmed (Klemba, M., Gardner, K . H., Marino, S., Clarke, N.D., and Regan, L., Nature: Structural Biology 2:368-373, 1995).

Endocr J, 1995 Oct, 42(5), 675 - 81
17 alpha-Hydroxyprogesterone suppresses neovascularization induced by HPLC-purified ovarian hyaluronic acid-like glycosaminoglycan in mice; Okada M et al.; HPLC-purified glycosaminoglycans (hpGAG) prepared from extracts of non-luteal mouse (JcL:ICR strain) ovaries were assayed for neovascularization by implanting Elvax films, containing test samples, on the lateral wall of the sheath of m . rectus abdominis in adult female mice of the same strain . Neovascularization occurred in a dose-dependent manner, and was characterized by capillary outgrowth extending into the tissue surrounding the implant . The single major peak of purified GAG on a column of TSK gel DEAE got out of order after treatment with streptococcal hyaluronidase or nitrous acid . The activity of this fraction was also greatly reduced when treated with streptococcal hyaluronidase or nitrous acid . When hpGAG was embedded in the implant with 17 alpha-hydroxyprogesterone at a dose of 20 micrograms/film, neovascularization induced by means of hpGAGs was suppressed . Progesterone at a dose of 50 micrograms/film did not suppress the neovascularization induced by ovarian hpGAG . These findings suggest that 17 alpha-hydroxyprogesterone suppresses the angiogenic activity of hyaluronic acid-like hpGAG in the ovary.

J R Coll Surg Edinb, 1995 Oct, 40(5), 328 - 9
Streptococcal myositis and the acute abdomen: a case report; Segar A et al.; Spontaneous streptococcal myositis, previously rare, is now reported more frequently . The condition is caused by overwhelming group A beta-haemolytic streptococcal infection and is not necessarily fatal.

J Anat, 1995 Oct, 187 ( Pt 2), 271 - 7
Antibodies against proteins of streptococcal hyaluronate synthase bind to human fibroblasts and are present in patients with rheumatic fever; Prehm S et al.; Antibodies directed against the streptococcal 42 kDa hyaluronate synthase and a 56 kDa auxiliary protein bound to the surface of intact human fibroblasts in vitro . Staining was most prominent during the detachment phase of mitosis . In eukaryotic plasma membranes a 52 kDa protein was recognized by the antiserum against the 56 kDa streptococcal protein . Since the cross-reacting proteins could be involved in immunological mimicry between streptococcal and human antigens leading to heart cell necrosis, the reactivity of sera from patients with rheumatic fever was compared with that of sera from healthy or streptococcal infected persons . The sera from patients with rheumatic fever showed a higher reactivity against the 56 kDa protein than those from healthy persons or from patients with an antibiotic treated streptococcal infection . This difference was not observed for the 42 kDa protein . These sera were able to lead to cell lysis in the presence of complement.

Br J Rheumatol, 1995 Oct, 34(10), 942 - 5
Cutaneous leucocytoclastic vasculitis: a clinical and aetiological study; Jessop SJ; Cutaneous vasculitis may be the presenting sign in many different clinical disorders . The aetiology and clinical and laboratory findings were recorded in 69 consecutive patients with cutaneous leucocytoclastic vasculitis . Underlying connective tissue disease or malignancy was found in 19 patients . Evidence of recent streptococcal infection was detected in 24 patients . Application of the classification criteria proposed by the American College of Rheumatology (ACR) identified 35 patients with Henoch-Schonlein purpura (HSP) and 42 with hypersensitivity vasculitis (HSV) . Thirty-three subjects fulfilled criteria for both HSP and HSV.

Scand J Immunol, 1995 Oct, 42(4), 433 - 41
Allosteric and temperature effects on the plasma protein binding by streptococcal M protein family members; Cedervall T et al.; Most group A streptococcal strains bind immunoglobulins (Ig) and fibrinogen to their cell walls . It is shown in this paper that the Ig-binding of three different strains was much weaker at 37 degrees C than at room temperature (20 degrees C), whereas the fibrinogen binding was unaffected by temperature . The binding properties and molecular sizes of two purified group A streptococcal cell surface proteins from the M protein family were studied at various temperatures, M1 protein with affinity for IgG, fibrinogen and albumin, and protein Sir22 with affinity for IgA and IgG . Both proteins appeared as monomers which bound all their ligands, including fibrinogen, very weakly at 37 degrees C, and as strongly binding dimers at 10 and 20 degrees C . Furthermore, the results demonstrated that the plasma protein binding of the bacterial proteins was allosterically regulated, i.e . the binding of a ligand to one site modulated the binding of a ligand to a second site . For example, the binding of albumin or IgG to purified M1 protein at 10 and 20 degrees C strongly enhanced the binding of fibrinogen at 37 degrees C . This indicates that the high affinity dimer form of the bacterial proteins can be stabilized at 37 degrees C, a possible explanation for the strong fibrinogen binding of whole bacteria . Finally, the sizes and binding properties of three M1 protein fragments were studied and the results indicated that the centrally located C-repeats, which are conserved among the members of the M protein family, are important for the formation of the high-affinity dimers of the bacterial proteins.

Pediatrics, 1995 Oct, 96(4 Pt 1), 758 - 64
Treatment of acute streptococcal pharyngitis and prevention of rheumatic fever: a statement for health professionals . Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, the American Heart Association; Dajani A et al.; Primary prevention of acute rheumatic fever is accomplished by proper identification and adequate antibiotic treatment of group A beta-hemolytic streptococcal (GAS) tonsillopharyngitis . Diagnosis of GAS pharyngitis is best accomplished by a throat culture . Penicillin (either oral penicillin V or injectable benzathine penicillin) remains the treatment of choice, because it is cost effective, has a narrow spectrum of activity, has long-standing proven efficacy, and GAS resistant to penicillin have not been documented . Various macrolides, oral cephalosporins, and other beta-lactam agents are acceptable alternatives, particularly in penicillin-allergic individuals . The individual who has had an attack of rheumatic fever is at very high risk of developing recurrences after subsequent GAS pharyngitis and needs continuous antimicrobial prophylaxis to prevent such recurrences (secondary prevention) . The duration of prophylaxis depends on the number of previous attacks, the time lapsed since the last attack, the risk of exposure to streptococcal infections, the age of the patient, and the presence or absence of cardiac involvement . Penicillin is again the agent of choice for secondary prophylaxis, but sulfadiazine or erythromycin are acceptable alternatives in penicillin-allergic individuals . This report is an update of a 1988 statement by this committee . It expands on the previous statement, includes more recent therapeutic modalities, and makes more specific recommendations for the duration of secondary prophylaxis.

Br J Ophthalmol, 1995 Oct, 79(10), 888 - 91
Paediatric post-traumatic endophthalmitis; Alfaro DV et al.; AIMS--A retrospective analysis of children with post-traumatic endophthalmitis was performed to determine if microbiological differences exist between this disease in the paediatric population compared with this disease in adults . METHOD--Twelve cases of post-traumatic endophthalmitis in children were analysed to determine characteristics of this disease in youth . Patient ages varied from 18 months to 13 years; the mean age was 8 years . Gram positive organisms were isolated in eight eyes, Gram negative organisms from four eyes, fungus from one eye, and negative cultures in three eyes . The most common isolates were streptococcal species (56.6%) and staphylococcal species (22.2%) . Vitrectomy was performed on eight (66.7%) eyes . RESULTS--Visual acuity of 20/200 or better was obtained in eight eyes (66.7%) . Three eyes had vision less than 5/200 . One eye developed phthisis bulbi . Nine (75%) patients were younger than 10 years of age, and six (66.7%) of these nine obtained a final visual acuity of 20/200 or better . CONCLUSION--Useful vision can be obtained in children with post-traumatic endophthalmitis with early, aggressive treatment . The microbiology of paediatric post-traumatic endophthalmitis differs from adult disease with streptococcal species as the most common infecting organisms.

Med J Aust, 1995 Sep 18, 163(6), 302 - 6
Early-onset group B streptococcal infections in Aboriginal and non-Aboriginal infants . Australasian Study Group for Neonatal Infections; Relapsing invasive group B streptococcal infection in adults; Department of International Health, Johns Hopkins University, Baltimore, MD 21205, USAOBJECTIVE: To study recurrent group B streptococcal infection in adults . DESIGN: Patients with more than one reported group B streptococcal infection were identified through active surveillance for this infection . Sterile-site group B streptococcal isolates were evaluated for serotype and molecular subtyping using restriction endonuclease analysis of chromosomal DNA (REAC) . SETTING: All acute-care hospitals in Maryland . PATIENTS: Nonpregnant residents of Maryland 18 years of age or older . RESULTS: 22 adults had at least two group B streptococcal episodes that were separated by 2 to 95 weeks (mean, 24 weeks) . Of 395 patients with invasive group B streptococcal infection who survived the first episode and were followed for at least 1 year, 17 (4.3% {95% CI, 2.6% to 6.9%}) had more than one episode . Several patients were found to have endocarditis or osteomyelitis during the second episode . Group B streptococcal isolates from both episodes were obtained from 18 of 22 patients . Of the 18 isolate pairs, 13 (72% {CI, 46% to 90%}) had identical REAC patterns; the probability that at least 13 matches would be found by chance alone was less than 0.000001 . Among patients with recurrent infection caused by the same strain, the interval between episodes was shorter (mean, 14 weeks) than that among patients with recurrent infection caused by another strain (mean, 43 weeks; P = 0.05) . CONCLUSIONS: Recurrent group B streptococcal infection is common among adults and in most cases appears to be caused by relapse . The optimal management of adults with a first episode of group B streptococcal infection needs to be further defined to minimize the likelihood of recurrent disease.

Ann Intern Med, 1995 Sep 15, 123(6), 415 - 20
Risk factors for group B streptococcal disease in adults; Jackson LA et al.; OBJECTIVE: To determine risk factors for community-acquired and nosocomial group B streptococcal disease in adults . DESIGN: Case-control study . SETTING: 3 metropolitan areas in the United States with an aggregate population of 6.6 million persons . PATIENTS: 219 nonpregnant adults with invasive group B streptococcal infection identified by a population-based surveillance in 1991 and 1992 and 645 hospital-matched controls . RESULTS: The following conditions were associated with a significantly increased risk for community-acquired group B streptococcal infection after controlling for age in multivariate analysis: cirrhosis (odds ratio, 9.7 {95% CI, 3.5 to 26.9}; P < 0.001), diabetes (odds ratio, 3.0 {CI, 1.9 to 4.7}; P < 0.001), stroke (odds ratio, 3.5 {CI, 1.9 to 6.4}; P < 0.001), breast cancer (odds ratio, 4.0 {CI, 1.6 to 9.8}; P = 0.002), decubitus ulcer (odd ratio, 4.0 {CI, 1.6 to 9.8}; P = 0.002), and neurogenic bladder (odds ratio, 4.6 {CI, 1.4 to 15.1}; P = 0.01) . Sixty-three percent of community case-patients had at least one of these conditions . Nosocomial infection (48 cases {22%}) was independently associated with the placement of a central venous line (odds ratio, 30.9 {CI, 5.2 to 184.1}; P < 0.001), diabetes, congestive heart failure, and seizure disorder . CONCLUSIONS: Several chronic conditions were independently associated with group B streptococcal disease, and most case-patients had at least one of these conditions . If group B streptococcal vaccines being developed for prevention of neonatal disease are protective in adults, a vaccination strategy targeting those at highest risk has the potential to substantially reduce the burden of invasive group B streptococcal infection in adults.

J Foot Ankle Surg, 1995 Sep-Oct, 34(5), 442 - 6
Aeromonas hydrophila--its implications in freshwater injuries; Weber CA et al.; Lacerations or puncture wounds sustained in freshwater environments are susceptible to contamination by Aeromonas hydrophila . Numerous cases have been reported of cellulitis secondary to water-related injuries requiring hospitalization where A . hydrophila was the isolated organism . The typical presentation of an infection of A . hydrophila mimics a streptococcal soft tissue infection, which may result in delay in administration of appropriate antibiotics . A case is presented of a nonimmunocompromised patient who developed an A . hydrophila infection following freshwater-related injuries.

FEMS Immunol Med Microbiol, 1995 Sep, 12(1), 73 - 82
Purification and characterization of M3 protein expressed on the surface of group A streptococcal type 3 strain C203; Hong K et al.; Monoclonal antibodies (mAbs) have been produced by immunizing BALB/C mice with whole M+ bacteria in incomplete Freund adjuvant and the resulting mAbs for M3 protein have been selected by an indirect immuno-fluorescent technique using formaldehyde-fixed M+ and M- bacteria . Four mAbs reacted with a 65 kDa protein in an extract obtained from the cell wall of M+ bacteria after treatment with N-acetyl muramidase and lysozyme . The purified 65 kDa protein neutralized the phagocytic activity of rabbit anti-M3 antibody . The N-terminal amino acid sequence of the 65 kDa protein was identical with that of protein generated by the M3 gene which has been previously cloned and sequenced . The evidence indicates that the 65 kDa protein is M3 protein . The M3 protein bound not only human fibrinogen but also human serum albumin (HSA) . When the M3 protein was purified by gel-filtration and ion-exchange chromatography in the absence of phenylmethyl sulfonyl fluoride (PMSF), four fragments (35 kDa, 32 kDa, 30 kDa, and 25 kDa) in addition to the intact molecule appeared . N-terminal amino acid sequence analysis showed that 35 kDa and 25 kDa fragments were ANAAD and DARSV, respectively, being identical at positions 1-5 and 198-202 to the M3 gene derived protein . Therefore, the 35 kDa and 25 kDa fragments, which were presumed to be cleavage products, may be derived from the C-terminal part and N-terminal part of the intact molecule, respectively . When the effect of purified M3 protein in the bactericidal activity of normal human blood in the presence of M- bacteria was investigated, the M3 protein was responsible for the organism's resistance to attack by phagocytic cells.

J Rheumatol, 1995 Sep, 22(9), 1710 - 3
Poststreptococcal reactive arthritis, clinical course, and outcome in 6 adult patients; Gutierrez-Urena S et al.; OBJECTIVE . To analyze the clinical course and laboratory features, as well as the outcome of 6 adult patients with articular manifestations, and evidence of streptococcal infection . METHODS . A retrospective review was performed of all patients seen in a rheumatology clinic at Louisiana State University Medical Center, with a diagnosis of poststreptococcal reactive arthritis (PSReA) to summarize the clinical features, laboratory findings, and clinical outcome between July 1991 and August 1994 . RESULTS . Six patients were identified with PSReA . All had acute, severe inflammatory articular involvement that began shortly after a sore throat, with serological evidence of streptococcal infection, and accompanied by extraarticular clinical manifestations including glomerulonephritis and vasculitis, and poor response to aspirin and other nonsteroidal antiinflammatory drugs . In all cases the echocardiogram was negative, and on followup there was no evidence of cardiac involvement . In these patients antibiotic prophylaxis was not required . CONCLUSION . The clinical picture and serologic abnormalities exhibited by this group of patients suggest a diagnosis of PSReA rather than acute rheumatic fever . These cases also emphasize the resurgence of poststreptococcal infection related articular manifestations in our clinic population.

Chemotherapy, 1995 Sep-Oct, 41(5), 399 - 411
Teicoplanin in endocarditis: a multicentre, open European study; Lewis PJ et al.; The efficacy of teicoplanin, a glycopeptide antibiotic, in endocarditis is controversial, with differences observed in the efficacies of the regimens used in clinical trials in the USA and Europe . This retrospective study examined the outcomes, efficacy and safety of mono- and combination antibiotic therapy using teicoplanin, particularly in cases of Staphylococcus aureus endocarditis . A total of 115 patients, typically mixed endocarditis patients intolerant of previous antibiotic treatment, was enrolled at 29 centres throughout Europe . Combination therapy was more successful than monotherapy for treating native valve endocarditis (NVE) (93 vs . 85%, p > 0.05, NS) and for treating S . aureus NVE (84 vs . 50%, p > 0.05) . Efficacies for prosthetic valve endocarditis (PVE) were similar (75 vs . 79%), while combination therapy was more successful in S . aureus PVE (100 vs . 67%) though the number of such patients was small (NS) . Adverse events were reported by 24% of patients, with 19% probably or possibly related to teicoplanin . In 9% of cases the adverse event led to the termination of therapy . Teicoplanin was judged to be efficacious in mono- or combination therapy in streptococcal endocarditis, though augmentation with an aminoglycoside is recommended . The efficacy of teicoplanin demonstrated in enterococcal endocarditis represents a major therapeutic advance.

Support Care Cancer, 1995 Sep, 3(5), 319 - 21
Prophylaxis of streptococcal bacteraemia with oral penicillin V in children undergoing bone marrow transplantation; Castagnola E et al.; The work described aimed to evaluate the incidence of streptococcal bacteraemia in children undergoing bone marrow transplantation and receiving prophylaxis with penicillin V . From January 1991 to December 1993 oral penicillin V was administered as prophylaxis for streptococcal bacteraemia to patients undergoing bone marrow transplantation at G . Gaslini Children's Hospital, Genoa, Italy . The data were compared with those from a similar population receiving bone marrow transplantation from September 1984 to July 1990 and not receiving this kind of prophylaxis . Streptococcal bacteraemia was diagnosed in 7/17 (41%) episodes of bacteraemia observed in the period January 1991 to December 1993, while it accounted for 71% of all bacteraemias in the period from September 1984 to July 1990 and was especially frequent from January 1988 to July 1990, comprising 13/15 (87%) of observed bacteremias . The decrease of this complication observed after the beginning of the prophylaxis programme was statistically significant . Oral penicillin V is effective as prophylaxis of streptococcal bacteraemias in children receiving bone marrow transplantation in a centre with a high incidence of this complication.

Pediatrics, 1995 Sep, 96(3 Pt 1), 428 - 33
Group A beta-hemolytic streptococcal bacteremia: historical overview, changing incidence, and recent association with varicella; Doctor A et al.; OBJECTIVE . To quantitate the increase in invasive group A beta-hemolytic streptococcal (GABHS) infections and to define a possible association between GABHS bacteremia and primary varicella zoster virus (VZV) infections . METHODS . This was a retrospective chart review conducted at Children's Hospital . Participants were patients with documented GABHS bacteremia occurring from January 1977 through December 1993 . MEASUREMENTS/MAIN RESULTS . We identified 63 episodes of GABHS bacteremia in 62 patients . From 1977 to 1992, a mean of 3.2 +/- 2 cases occurred per year (range, 0 to 6), increasing by a factor of 3 (10 cases) in 1993 . The median age was 4 years (range, 1 day to 20 years; mean, 8 years +/- 3 months); 36 were male; five children were immunocompromised . One child was dead on arrival and one had a cardiac arrest during evaluation in the emergency department . Primary sites of infection (oropharynx, skin, or middle ear) were identified in 40 (75%) of the cases; in addition, 10 cases occurred in patients with primary VZV . From 1977 to 1992, we identified five VZV-associated cases; an average of 7 +/- 11.5% of the patients with GABHS had concurrent VZV infection annually, with no more than one case per year . In 1993, 50% of the 10 new GABHS cases were in children with VZV infection (P = .003, Fisher's exact test) . The diagnosis of invasive GABHS infection in patients with VZV was not readily recognized, requiring a median of two (range, one to four) physician visits before admission and the administration of antibiotics . All 10 children were diagnosed on the fourth or fifth day of the exanthem and were febrile (39.6 +/- 1.1 degrees C, range, 38.3 to 40.8 degrees C), with a mean white blood cell count (WBC) of 11,500 +/- 8,400/mm3 (8 of 10 cases had a WBC less than 15,000/mm3) . None of the five VZV-associated cases in 1993 had signs of cutaneous bacterial superinfection; among these were two cases of streptococcal toxic shock syndrome (one death), one case of osteomyelitis, and two cases of occult bacteremia . Of the five VZV-associated cases before 1993, one patient was diagnosed with supraglottitis, one with septic arthritis, one with orbital cellulitis, and two solely with impetiginized or cellulitic lesions . CONCLUSIONS . We found that the incidence of invasive GABHS infections has risen dramatically, increasing by a factor of 3 over the past year . In 1993, 50% of new cases of invasive GABHS disease were associated with VZV infection . Invasive GABHS should be considered in children with VZV who manifest fever on or beyond the fourth day of the exanthem . The absence of an elevated WBC and impetiginized or cellulitic lesions should not eliminate this diagnosis from consideration.

J Can Dent Assoc, 1995 Sep, 61(9), 782 - 4
Human bites to the hand; Carr MM; Human bites to the hand or penetrating injuries contaminated with saliva can be a source of aggressive infection and debilitating injury . These types of injuries may also be a mode for the transmission of disease, notably hepatitis B . Dental personnel have an increased risk of experiencing bite injuries and should understand the general principles of appropriate management . Staphylococcal or streptococcal species are often associated with infected bite injuries, and amoxicillin and clavulanate are currently advised for prophylaxis . Wound cleansing and careful monitoring, combined with appropriate prophylaxis, are the mainstays of treatment.

Gan To Kagaku Ryoho, 1995 Sep, 22(11), 1644 - 6
{Immunopotentiation by OK-432 ointment to apply to the mouse abdominal skin}; Matsuoka H et al.; The immunopotentiating effect of a streptococcal preparation, OK-432 (Picibanil), mixed with an ointment based Lanolin, was examined . The mixture was applied to mouse abdomen . The effect of OK-432 ointment was compared with those of OK-432 ip and sc . The leucocyte count in the abdominal cavity increased in 3.6 x 10(6) and 12.5 x 10(6) on the 3rd day after ointment application and ip injection of 5 KE OK-432, respectively . The result indicated that OK-432-Lanolin applied to the abdominal skin wall affected the abdominal cavity . IL-6 and IFN-gamma in the abdominal cavity increased in 1.4 ng and 9 ng, respectively, after applying 5 KE OK-432 ointment . From these results the treatment with OK-432 ointment on the abdominal skin exhibited an immunomodulatory effect on the abdominal cavity.

Ann Rheum Dis, 1995 Sep, 54(9), 740 - 3
Rheumatic fever: autoantibodies against a variety of cardiac, nuclear, and streptococcal antigens; Eichbaum QG et al.; OBJECTIVE--To measure antibody titres to cardiac, nuclear, and streptococcal antigens in different groups of rheumatic fever (n = 60) and control subjects (n = 80) with the aim of identifying cross reactive antigens of potential laboratory diagnostic value . METHODS--Enzyme linked immunosorbent assays (ELISA), immunocytochemical, and electrophoretic techniques were used to measure titres of antibodies to a variety of cardiac, nuclear, and streptococcal antigens in seven groups comprising patients with rheumatic fever and control subjects . RESULTS--Increased concentrations of antibodies to several streptococcal and cardiac antigens, in addition to increased IgA and IgG levels, were noted in sera from patients with acute rheumatic fever and chronic rheumatic heart disease . Autoantibodies to nuclear antigens were evident in three rheumatic fever sera . CONCLUSION--Although we were unable to identify any unique cross reactivity between cardiac and streptococcal antigens, these results demonstrate that there is an exaggerated humoral response to several cardiac, nuclear and streptococcal antigens in patients with rheumatic fever.

Public Health, 1995 Sep, 109(5), 347 - 51
Should nurses in Israeli primary care clinics be expected to manage streptococcal throat infections?
Kahan E, Appelbaum T, Bograd H, Shahaf P, Weingarten MA.
INTRODUCTION: Legal regulations in Israel allow nurses to perform only limited clinical procedures . OBJECTIVE: To determine the probability of streptococcal infection in adults with sore throat, as assessed clinically by standard nursing procedures . DESIGN: Using throat culture as the standard, the contribution of various clinical findings (fever, exudate, erythrocyte sedimentation rate (ESR), white blood count) to the determination of the diagnosis of streptococcal infection was assessed, using logistic regression analysis . SETTING: Israeli general practice . PATIENTS: 100 consecutive adult patients presenting with a red, sore throat . RESULTS: Six patients showed the full clinical picture of exudate, increased ESR and leukocytosis, with an 82% probability of streptococcal infection . Forty-nine patients showed none of these three findings, and only one of them (among the three patients with rhinitis) had a positive throat swab . Forty-five patients showed an intermediate clinical picture which did not provide a reliable basis for the diagnosis or exclusion of streptococcal infection . Fever alone did not significantly (P < 0.05) predict streptococcal infection . CONCLUSIONS: Nurses may safely discharge adult patients with a red, sore throat without antibiotic treatment only if they have no additional signs or symptoms . The few patients with all the clinical findings may be treated with antibiotics without a throat swab . All other patients should be referred for examination by a doctor.

Postgrad Med J, 1995 Sep, 71(839), 553 - 4
Rapidly progressive glomerulonephritis complicating acute rheumatic fever; Akasheh MS et al.; A case of acute rheumatic fever and glomerulonephritis following streptococcal throat infection is presented . The coincidence of rheumatic fever and post-streptococcal glomerulonephritis is uncommon, but well recognised . This case is of additional interest since the nephritis was crescentic.

J Immunol, 1995 Aug 15, 155(4), 2203 - 10
Complement membrane attack complex, perforin, and bacterial exotoxins induce in K562 cells calcium-dependent cross-protection from lysis; Reiter Y et al.; The complement membrane attack complex (MAC), the cytolytic granule protein of cytotoxic lymphocytes perforin, the streptococcal exotoxin streptolysin O (SLO), and the bee venom polypeptide melittin utilize a similar mechanism to incorporate into cell membranes, induce a Ca2+ influx and a rise in intracellular Ca2+ concentration, and produce cell lysis . At sublytic concentrations, these proteins trigger several cellular activities, including protein phosphorylation and synthesis . We have recently demonstrated that human leukemic cells treated with sublytic doses of human complement become more resistant to lytic complement doses . The study has now been extended to include three other pore-formers: murine perforin, SLO and melittin . As shown here, sublytic MAC induces in the K562 human erythroleukemic cells protection from lytic perforin, and vice versa, sublytic perforin induces protection from complement . Also, sublytic SLO and melittin increase resistance of K562 cells to lytic complement and perforin doses . The capacity of Ca2+ ionophores to induce resistance to the lytic proteins has been examined . Exposure of K562 cells to sublytic concentrations of ionomycin or A23187 for 1 h at 37 degrees C confers on them resistance to complement- and perforin-mediated lysis . The protective effects of the ionophores can be abrogated by chelation of extracellular Ca2+ and by inhibition of RNA or protein synthesis in the cells . These results indicate the following: 1) nucleated cells exposed to sublytic complement MAC, perforin, SLO, or melittin may become resistant to the four pore-formers . Physiologically, this may be regarded as an immunologic tachyphylaxis . 2) Ca2+ influx induced by these pore-formers is an essential and sufficient factor to produce this tachyphylaxis.

J Obstet Gynaecol, 1995 Aug, 21(4), 367 - 72
Prelabour rupture of membranes to delivery interval related to the incidence of maternal and neonatal infection; Chua S et al.; OBJECTIVE: To assess the infectious morbidity associated with prelabour rupture of membranes (PROM) to delivery interval, and the incidence of maternal and neonatal infection in a population managed by either immediate stimulation or by overnight conservatism . METHOD: A retrospective study of 117 women admitted with PROM to the labour ward in the National University Hospital, Singapore, in the period between June 1990 and May 1991, and who were managed by immediate stimulation or by stimulation after overnight conservatism . Statistical analysis was performed using Chi-square and Student's t-test . RESULTS: More than one third of infants whose mothers had ruptured membranes for > 48 hrs had signs of neonatal infection, compared with an incidence of 8.8% and 8.9%, respectively for those with an interval of < 12 hrs and 12-24 hrs between PROM to delivery . Group B streptococcal infection was a major cause of neonatal infectious morbidity . Clinical evidence of maternal infection occurred in 3 of the 117 women; these patients had an interval between rupture of membranes and delivery of between 24-76 hrs . CONCLUSIONS: Prolongation of PROM to delivery interval for > 48 hrs increases the incidence of infection . Conservative policy of management of PROM at term should aim to deliver the babies < 48 hrs after PROM . The difference in maternal and neonatal infection rates were not significant in the group treated with a policy of overnight conservatism compared with the group in whom labour was stimulated immediately on admission.

Res Commun Mol Pathol Pharmacol, 1995 Aug, 89(2), 241 - 55
Tracking the in vivo localization of streptococcal cell membrane (SCM) monoclonal antibodies: potential model for post-streptococcal sequelae; Lange CF; Placement of ten different anti-streptococcal monoclonal antibody (mAb) secreting hybridoma cells, as well as positive and negative controls into animals and sacrificing on a daily basis showed a difference in the tissue sites of accumulating mAb as noted by fluorescent antibody testing . Initial binding of the mAb was noted by day two on the kidney GBM in all the animals . Striated muscle tissues tested positive starting at day nine with only four of the mAbs, by which time the GBM was strongly positive . Fluorescent antibody testing of heart and skeletal muscle from animals in which one of the polyreactive IgM mAb secreting hybridoma cell lines was placed showed a distinctive staining of the Z-lines . Indirect fluorescent and immunoperoxidase testing as well as competitive blocking experiments confirmed the reactivity of this mAb for the Z-line of heart and skeletal muscle . Immunodots and Western blots along with direct and blocking assays confirmed that the critical cross-reactive Z-line antigen was alpha-actinin, supporting the concept that this anti-SCM mAb was reactive both in vivo and in vitro . These results confirm the cross-reactive nature of anti-SCM antibodies for mammalian tissue and bear important implications on the etiology of post-streptococcal glomerulonephritis and rheumatic heart disease.

Pediatr Infect Dis J, 1995 Aug, 14(8), 662 - 7
Barriers to prevention of perinatal group B streptococcal disease; Jafari HS et al.; During 1992 the American College of Obstetricians and Gynecologists (ACOG) and the American Academy of Pediatrics (AAP) issued statements on prevention of group B streptococcal (GBS) disease . To assess prevention practices and identify barriers to preventing GBS disease, we surveyed obstetricians, family practitioners and general practitioners in Georgia during 1993 . A standard questionnaire was mailed to 1190 clinicians in August and to nonresponders again in September . Of 436 (38%) physicians who responded, 192 (44%) provided obstetric care . Among these 192 obstetric care providers, 121 (63%) screened patients for GBS carriage antenatally . The most frequently cited reasons for not screening were "no clear guidelines" and "not cost-effective" (52 and 39%, respectively) . Clinicians who screened patients were significantly more likely to believe that screening was cost-effective (P = 0.05) . Of obstetric care providers who screened, only 9% obtained specimens using culture sites recommended by ACOG or AAP . Although most clinicians were aware that antenatal antibiotic treatment of carriers does not prevent perinatal GBS disease, 64% of those who screened reported that they gave oral antibiotics when carriage was detected during pregnancy . Of clinicians who reported using obstetric risk factors to guide prophylaxis choices, < 15% reported using intrapartum antibiotics for the conditions identified in the ACOG and AAP statements as those that suggest the need for prophylaxis when screening is not performed . Many Georgia obstetric care providers do not use effective practices to prevent perinatal GBS disease . Education on appropriate culture methods, obstetric risk factors and the cost effectiveness of prevention strategies might lead to more effective preventive practices.

Cancer Immunol Immunother, 1995 Aug, 41(2), 82 - 6
Cytokine-gene-modified tumor vaccination intensified by a streptococcal preparation OK-432; Abe J et al.; Vaccinations with tumor cells engineered to express certain cytokines have been demonstrated to induce potent and specific antitumor immunity . In our previous report, we carried out a comparative study on the ability of cytokine-gene-modified tumor vaccines to induce host immune responses, and found that irradiated tumor cells, genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine), were the most potent stimulators of systemic antitumor immunity . In this report, using the experimental tumor models in which the GM-CSF tumor vaccine was less effective in immunopotentiation, we found that the combined use of a biological response modifier (BRM) OK-432 remarkably enhanced the antitumor activity induced by the GM-CSF tumor vaccine . These data indicate the possible role of a BRM such as OK-432 to intensify further the specific tumor vaccination therapy.

Circulation, 1995 Aug 1, 92(3), 415 - 20
Human heart-infiltrating T-cell clones from rheumatic heart disease patients recognize both streptococcal and cardiac proteins; Guilherme L et al.; BACKGROUND: beta-Hemolytic streptococcal infection in developing countries still causes thousands of causes of rheumatic heart disease, demanding surgical valve correction . Antigenic mimicry between self and streptococcal components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility . Although heart streptococcal-M protein cross-reactive antibodies have been demonstrated, heart tissue damage seems to be T lymphocyte-dependent . We studied the infiltrating T lymphocytes in rheumatic heart lesions with the aim of understanding the role of cellular immune response at the site of the lesions . METHODS AND RESULTS: We obtained 107 T-cell clones from surgical fragments of cardiac tissue from four rheumatic heart disease patients . We tested their capacity to recognize streptococcal M protein-derived synthetic peptides and heart proteins . We found eight infiltrating T-cell clones from all four patients that simultaneously recognize streptococcal M and heart proteins . Among the M-protein sequences tested, only synthetic peptides corresponding to regions 1 through 25, 81 through 103, and 163 through 177 were simultaneously recognized with heart protein fractions . Interestingly, regions 81 through 103 and 163 through 177 have been known to bear heart cross-reactive epitopes at the antibody level . Five of these clones are CD4+, and one is CD8+ . CONCLUSIONS: The presence of heart-M protein cross-reactive T-cell clones in rheumatic heart lesions suggests their direct involvement in the pathogenesis of this disease . The dissection of protective and pathogenic epitopes of streptococcal M protein is an important step in allowing the development of a safe anti-streptococcal synthetic vaccine.

J Am Coll Cardiol, 1995 Aug, 26(2), 452 - 7
Immune response factors in rheumatic heart disease: meta-analysis of HLA-DR associations and evaluation of additional class II alleles; Carlquist JF et al.; OBJECTIVES . This study used a meta-analysis to examine HLA-DR frequencies in rheumatic heart disease and prospectively examined other class II allelic disease associations . BACKGROUND . Studies of rheumatic heart disease have reported HLA class II allelic associations, but these are inconsistent . METHODS . A meta-analysis combined all known (n = 10) studies to determine disease risk associated with HLA-DR antigen expression . Meta-analysis of studies grouped by ethnic derivation of subjects was also performed . The present study also examined DQA, DQB and DPB allele frequencies by DNA-based strategies . RESULTS . Meta-analysis showed a significant negative disease association with DR5 (odds ratio {OR} 0.67, p < 0.00003) for all combined studies . Among black patients, DR1 was increased (OR 2.80, p < 0.004); DR6 was increased (OR, 2.03, p < 0.003); and DR 8 was decreased (OR 0.32, p < 0.02) . Among Eastern Indian patients, DR3 was increased (OR 2.44, p < 0.00003), with decreased expression for DR2 (OR 0.31, p < 0.00001) and DR5 (OR 0.52, p < 0.05) . DR4 was increased among American whites (OR 1.74, p < 0.03), although there was significant heterogeneity among studies of whites . DQA, DQB and DPB allele frequencies were similar for control subjects and patients . CONCLUSIONS . Our findings support an association between major histocompatibility complex class II alleles and risk for rheumatic heart disease . However, heterogeneity in associations was observed among different ethnic and racial groups; regional and temporal differences in streptococcal outbreaks may compound this heterogeneity . Further studies are necessary to elucidate the respective contributions of these variables.

J Paediatr Child Health, 1995 Aug, 31(4), 355 - 7
Kawasaki disease associated with streptococcal infection within a family; Anderson DG et al.; OBJECTIVE: To describe the illness occurring in four members of a family, which had clinical and laboratory features of Kawasaki disease and streptococcal infection . METHODOLOGY: A retrospective report of three siblings and an adult male living in one household . The children had serology, blood counts, cultures and echocardiography performed and were treated with antibiotics and gammaglobulin infusions . RESULTS: The patients developed clinical, and exhibited laboratory, features suggesting streptococcal infection and 4/5 criteria suggesting the diagnosis of Kawasaki disease . All made a good clinical recovery but the youngest developed a coronary artery aneurysm . CONCLUSIONS: It may be difficult to distinguish streptococcal infection and Kawasaki disease . It is possible that some cases of Kawasaki disease are precipitated by streptococcal infection.

J Clin Pathol, 1995 Aug, 48(8), 777 - 9
Microbiological investigation of polyarthralgia; Jones JW et al.; Results of serological investigations on patients with joint pain, arthralgia or polyarthritis were analysed and this information was used to develop a diagnostic algorithm to ensure optimal utilisation of laboratory resources . Accordingly, all cases are now examined for parvovirus IgM, mycoplasma IgM and streptococcal antibodies . Further tests are undertaken by following the algorithm after obtaining supplementary information from a questionnaire . This approach is put forward as a preliminary standard which other laboratories may like to evaluate and develop according to local requirements.

Med Microbiol Immunol (Berl), 1995 Aug, 184(2), 87 - 96
Sister chromatid exchange-inducing DNA lesions and depression of activation markers on the surface of cultured peripheral blood mononuclear cells after the addition of streptococcal pyrogenic exotoxins A and C; Bussing A et al.; Cultivation of peripheral blood mononuclear cells (PBMC) in the presence of streptococcal pyrogenic exotoxins (SPE) A and C resulted in a significant induction of sister chromatid exchange (SCE)-inducing DNA lesions . Concomitantly, the expression of interleukin-2 receptor alpha chain (IL-2R alpha chain), transferrin receptor (TfR), and major histocompatibility complex class II molecule HLA-DR on the surface of phytohemagglutinin-activated T cells from whole blood culture cells (WBCC) significantly decreased within 72 h, that is at least two cell cycles, whereas unstimulated T cells from WBCC did not express these markers but had lost their CD3 molecules, an effect reported to precede apoptosis as part of a T cell inactivation pathway . However, no apoptotic cells were observed within a cultivation period of 120 h . We observed clearcut differences in the responses towards SPE A in WBCC and isolated lymphocytes, since SPE A-treated lymphocytes showed an increase in the {3H}thymidine incorporation and did express IL-2R alpha chain and TfR on their cell surface . Regardless of the precise underlying mechanism, T cells from WBCC seem to be in a state of functional incompetence . The data presented here are the first to provide strong evidence that streptococcal toxins produce SCE-inducing DNA lesions in PBMC, an effect that might contribute to the process of immune cell lethality in streptococcal toxic shock-like syndrome and could be of pivotal importance in the pathogenesis of severe streptococcal disease.

FEMS Microbiol Lett, 1995 Jul 15, 130(1), 81 - 5
Cloning, nucleotide sequence determination and expression of the Staphylococcus aureus hyaluronate lyase gene; Farrell AM et al.; The Staphylococcus aureus 8325-4 hyaluronate lyase gene (hysA) was identified after detecting hyaluronate lyase activity expressed by phages from a genomic library . The hysA open reading frame, capable of encoding a protein of 91 980 Da, was identified by Tn5 mutagenesis and nucleotide sequencing . HysA shares 35 and 36% amino acid sequence identity with group B streptococcal hyaluronate lyase and pneumococcal hyaluronidase, respectively . A 94-kDa protein was expressed in Escherichia coli minicells, a result consistent with the coding capacity of hysA . Identification of the S . aureus 8325-4 hyaluronate lyase gene will allow the regulation of this putative virulence determinant to be studied.

J Mol Biol, 1995 Jul 7, 250(2), 128 - 33
Mapping of the immunoglobulin light chain-binding site of protein L; Wikstrom M et al.; Protein L is a cell surface protein expressed by some strains of the anaerobic bacterial species Peptostreptococcus magnus . The molecule binds specifically and with high affinity to immunoglobulins (Ig) of a wide range of animal species . The Ig-binding activity is mediated through five highly homologous domains, each 72 to 76 amino acid residues long, which interact with framework regions in the variable domain of Ig light chains . The interaction does not interfere with the antigen binding capacity of the antibody . The fold of the Ig light chain-binding domains of Protein L is comprised of an alpha-helix packed against a four stranded beta-sheet and is similar to the fold of the IgG heavy chain-binding domains of streptococcal protein G, despite the fact that the two proteins show no significant sequence homology . In the present work, heteronuclear NMR spectroscopy has been utilized to define the interaction between the N-terminal Ig-binding domain of Protein L and the variable domain of a human Ig kappa light chain . The Ig-binding region of the Protein L domain involves most of the residues in the second beta-strand, the C-terminal residues of the alpha-helix and the loop connecting the alpha-helix with the third beta-strand . The Ig light chain-binding surface of Protein L thus resembles the surface of Protein G which binds to the C gamma 1 domain of IgG, but is different from the portion of Protein G involved in the contact with the C gamma 2-C gamma 3 interface region . The data suggest that the global fold shared by the Ig-binding domains of Proteins L and G provide bacteria with a flexible template for the evolution of surface structures capable of interacting with different conserved parts of Ig molecules of the infected host.

Indian Heart J, 1995 Jul-Aug, 47(4), 395 - 8
Present status of rheumatic fever and rheumatic heart disease in India; Padmavati S; This paper examines the present status of Rheumatic fever (RF) and Rheumatic heart disease (RHD) in India with reference to both prevalence and incidence, and evaluates the currently available methods of control . Data available over the last 10 years shows that the prevalence of RF/RHD in the most vulnerable group i.e . school children between 5 to 15 years of age is still unacceptably high . RHD is encountered in 1 to 5.4 per 1,000 in large samples of school children and RF in 0.3 to 0.5 per 1,000 children . There appears to be no obvious decline in its prevalence in school children over a 20 year period . Because of preoccupation with adult cardiac diseases specially ischemic heart disease (IHD), the problem of RF/RHD has been sidelined and studies on prevalence, treatment and prevention receive scant attention . Only exotic palliative methods such as balloon mitral valvotomy (BMV) have become the centre stage . Studies are needed on the lines of WHO recommendations for the regional prevalence of RF/RHD in school children throughout the country to detect regional variations . The most effective method for control is primary prevention by treating streptococcal sore throat and secondary prevention by early detection and continuous penicillin prophylaxis . This could be done most effectively by general physicians (GP's) who need motivation and education and through school health services . The latter needs to be organised on a state-wise basis throughout the country as it is available in only a few cities . Public health education by all available media specially, through video films is also recommended . The lacunae in our knowledge of RF/RHD calls for further research.

J Hepatol, 1995 Jul, 23(1), 87 - 94
The immuno-stimulant OK-432 enhances liver regeneration after 70% hepatectomy; Kato K et al.; The effect of reticuloendothelial system activation on hepatic regeneration after 70% hepatectomy was investigated . OK-432, a killed streptococcal preparation which increases reticuloendothelial system function, was administered to rats prior to 70% hepatectomy . Hepatic incorporation of 3H-thymidine 24 h after 70% hepatectomy was enhanced by OK-432 pretreatment . DNA synthesis was greater in pretreated than in control rats and correlated highly with reticuloendothelial system phagocytic activity prior to surgery . Methyl palmitate, which decreases reticuloendothelial system function, was administered to rats prior to 70% hepatectemy . Hepatic incorporation of 3H-thymidine 24 h after 70% hepatoctomy was significantly depressed by methylpalmitate-pretreatment . These data suggest that reticuloendothelial system plays a role in liver regeneration and that hepatocyte proliferation might be enhanced by protection from surgical stress and endotoxins with reticuloendothelial system stimulation by OK-432.

J Infect, 1995 Jul, 31(1), 33 - 7
Group A streptococcal bacteraemias in Denmark 1987-89; Andersen MM et al.; A retrospective study of laboratory-verified cases of Group A Streptococcal bacteraemias in Denmark was conducted for the period 1987-1989 after a sudden increase occurred during the winter 1988-1989 . The aim of the study was to describe the epidemiology in the period and to compare cases during the outbreak period with cases in a period with a baseline risk . Based on isolates, a total of 242 cases in 240 patients were included in the study and information on previous health of the patients, source of infection (community-acquired or nosocomial) and outcome were obtained from hospital records . During the epidemic period the total incidence increased three-fold . The frequency of type 1 increased from 1 in 5 to 1 in 2 . The number of previously healthy individuals falling ill with type 1 increased 25-fold . The relative increase was higher among patients with community-acquired infection than among patients with nosocomial infection . The lethality rate was 48% during the epidemic in which 38% of the cases occurred . As early diagnosis and treatment are the two most important measures to prevent serious outcome, effectiveness and timeliness of surveillance systems are of extreme importance.

Arch Pediatr Adolesc Med, 1995 Jul, 149(7), 727 - 32
Guideline maintenance and revision . 50 years of the Jones criteria for diagnosis of rheumatic fever; Shiffman RN; OBJECTIVE: To understand better the factors that led to revisions of the Jones criteria, a widely used diagnostic guideline for diagnosis of rheumatic fever . DESIGN: The original publication of the Jones criteria and the four revisions were examined to identify changes . A computer software maintenance paradigm was applied, and modifications were categorized as corrective (error correction), perfective (enhancements in response to user needs), or adaptive (responses to new knowledge) . RESULTS: Modifications of the Jones criteria were primarily corrective and perfective . Disease characteristics, originally characterized as major manifestations, were subsequently categorized as minor manifestations and vice versa . Twenty years after the initial publication, a requirement was added to enhance specificity (evidence for antecedent streptococcal infection) . Descriptions of rheumatic manifestations became more detailed over time to eliminate ambiguous definitions and provide information to help clinicians decide about borderline cases . This emphasis on corrective and perfective maintenance contrasts with an expectation that adaptive changes would predominate, as with most knowledge-based systems . In fact, despite 50 years of technologic and methodologic advances in medicine, only echocardiography and new antibody testing contributed new knowledge that bears on the diagnosis of rheumatic fever . CONCLUSIONS: Corrective and perfective maintenance can be avoided by making effective use of knowledge that exists at the time a guideline is published . Despite the apparent durability of the Jones criteria, carefully structured, evidence-based guidelines should require less corrective and perfective maintenance . Adaptive maintenance can be anticipated if the quality of evidence or the level of consensus that supports each recommendation is explicitly recorded.

Endocrinology, 1995 Jul, 136(7), 3107 - 12
Glucocorticoid and/or glucocorticoid antagonist effects in inflammatory disease-susceptible Lewis rats and inflammatory disease-resistant Fischer rats; Karalis K et al.; Lewis (LEW/N) and Fischer (F344) rats are inbred strains that respond antithetically to administration of several inflammatory stimuli . Thus, in response to streptococcal cell wall-derived peptidoglycan/polysaccharide, 6-week-old female Lewis rats develop acute and chronic polyarthritis, whereas age- and sex-matched Fischer rats are arthritis-resistant . The susceptibility of Lewis rats to development of chronic severe inflammatory disease has been attributed to their inability to appropriately activate their hypothalamic-pituitary-adrenal axis in response to inflammatory stimuli, leading to a functional glucocorticoid deficiency . To investigate whether the acute neurogenic inflammatory response was also different in the two strains, we studied the air-pouch model of carrageenin-induced neurogenic inflammation in adult male Lewis and Fischer rats . Both the volume and the leukocyte concentration of the inflammatory exudate were significantly higher in Lewis than in Fischer rats, suggesting that the known differences in the handling of chronic inflammation between the two strains pertain to the acute neurogenic type of inflammation as well . To confirm that glucocorticoids play a major role in the differential response of the two strains to this inflammatory stimulus, we administered graded doses of the glucocorticoid agonist dexamethasone or antagonist RU 486 to both strains and examined their responses to concomitantly administered carrageenin . RU 486 increased, whereas dexamethasone decreased, the inflammatory response of Fischer and Lewis rats, respectively, to approach the magnitude of each other's natural response, suggesting that glucocorticoids are involved in this phenomenon as well . To rule out any differences in end-organ sensitivity to glucocorticoids between the two strains, we evaluated dose-response relations of whole body, thymus, spleen, and adrenal weights after 1 week daily administration of graded doses of dexamethasone . We found similar ED50 for both Lewis and Fischer rats . We conclude that the differences in the susceptibility to acute, carrageenin-induced, neurogenic inflammation between the LEW/N and F344 rat strains are similar to those of chronic inflammatory responses in these strains and likewise glucocorticoid-dependent . No apparent major differences exist in the sensitivity of target tissues to exogenous glucocorticoids between Lewis and Fischer rats.

Cornea, 1995 Jul, 14(4), 418 - 22
Ocular surface flora in drowning victims; Lindquist TD et al.; Contaminated allograft donor tissue represents a potential source of infection unique to keratoplasty . We prospectively studied perilimbal cultures of drowning victims over 30 months to determine if the ocular surface flora of drowning victims was unique . Twenty-eight donor eyes were cultured from 14 drowning victims . Ninety-three percent of limbal cultures were positive for one or more organisms, compared to results of a previous study of surface contamination of donor globes in which 65% were found to be culture positive . Fifty-seven percent (16 of 28) of donor eyes grew at least one streptococcal species, while 46% (13 of 28) grew two or more streptococcal species . A previous study identified streptococcal species in 7.9% of perilimbal cultures from nondrowning donor eyes, which demonstrates the unique effect of drowning on the ocular flora . The incidence of gram-negative isolates was also markedly higher in drowning victims, compared to previous studies of donor globes . This prospective study has shown that the ocular surface flora of drowning victims harbors markedly increased numbers of streptococcal species as well as gram-negative organisms . These findings demand careful globe decontamination, and emphasize the need for appropriate antibiotic coverage in corneal storage media.

Br J Dermatol, 1995 Jul, 133(1), 135 - 9
Pustulosis acuta generalisata is a post-streptococcal disease and is distinct from acute generalized exanthematous pustulosis; Auer-Grumbach P et al.; Generalized pustular eruptions with fever present a diagnostic and therapeutic problem . Based on a case of pustulosis acuta generalisata and a review of the literature, this entity can be regarded as an exclusively post-streptococcal disorder with an elevated antistreptolysin titre . It has a distinct clinical presentation of isolated pustules on normal skin, predominantly in an acral location . We propose criteria for the clear separation of this disease from acute generalized exanthematous pustulosis and from pustular psoriasis.

Eur J Biochem, 1995 Jul 1, 231(1), 166 - 80
Synthesis, three-dimensional structure, and specific 15N-labelling of the streptococcal protein G B1-domain; Boutillon C et al.; The 55-amino-acid B1-domain of the streptococcal protein G shows a high binding affinity to IgG isolated from a wide range of mammalian species . Since the B1-domain forms an extremely stable globular folding unit containing the major secondary structure elements and is devoid of proline residues and disulfide bridges, it is also a useful tool for protein folding and stability studies . Its small size makes this protein an ideal candidate for production by chemical synthesis, allowing incorporation of non-natural amino acids with the possibility of assessing the influence of such residues on both the functional and structural characteristics of proteins . In this study, we employed three successive chemical syntheses of the B1-domain in order to define the optimal conditions of coupling and protection . The stepwise solid-phase methodology using the tertbutyloxycarbonyl/benzyl strategy was used for this purpose . First, the sequence assembly difficulties were evaluated . After analyzing of the problems found during assembly, a second optimized synthesis was performed leading to formation of a synthetic B1-domain with a higher yield; the synthetic B1-domain was completely functional in its binding properties to IgG . Three orthogonal purification steps (gel-permeation, reverse-phase and ion-exchange HPLC) were required to obtain a sample suitable for structural analysis by high-resolution NMR . This study led to the conclusion that the synthetic B1-domain adopts a three-dimensional structure identical to that of the molecule obtained by recombinant techniques {Gronenborn, A.M., Filpula, D . R., Essig, N . Z., Achari, A., Whitlow, M., Wingfield, P . T . & Clore, G . M . (1991) Science 253, 657-661} . To demonstrate the usefulness of the chemical approach for the specific introduction of labelled amino acids in the primary structure, fourteen alpha-15N-labelled amino acids were incorporated at selected critical positions during the third synthesis . This analog is the first in a series of molecules planned to study in detail the folding dynamics of the B1-domain.

Histol Histopathol, 1995 Jul, 10(3), 583 - 8
The role of proteoglycans in maintaining collagen fibril morphology; Dell'Orbo C et al.; The aortic wall contains various heterogenous proteoglycan populations which interact in different ways with other components of extracellular matrix . Proteoglycans (PGs) are known to provide structural support to the vessel wall as well as to influence specific physiological functions of the tissues . The aim of the present study was to investigate the effects of Chondroitinase AC (Chase), Streptococcal Hyaluronidase (Hyase) and Heparanase on human aortic wall collagen which had been treated previously with 4M GuHCl, in order to verify the effects of selective glycanolytic treatment on type I collagen fibril ultrastructure . Following 4M GuHCl treatment, collagen fibrils are seen to have a clearly visible period . Subsequent to GuHCl and Streptococcal Hyase treatment all collagen fibrils appear to be completely swollen in thin aperiodic filaments; the typical 64 nm collagen period is completely undetectable . After GuHCl and Chase treatment a small number of collagen fibrils are seen to be swollen in thin fibrils which are mainly localized at some distance from elastic fibres . Following GuHCl and Heparanase/Heparitinase III treatment a considerable number of collagen fibrils appear to be swollen in thin fibrils; the majority of which are situated in the vicinity of elastic fibrils . The swelling of collagen fibrils underlines the fundamental role of proteoglycans in maintaining collagen fibril integrity and periodicity . It is as yet impossible to precisely map interactions between these proteoglycans and collagen fibres . The role of Hyaluronic acid requires further investigation, although the nature of this interaction is undoubtedly a matter of considerable interest.

FEBS Lett, 1995 Jun 12, 366(2-3), 99 - 103
Complement assembly of two fragments of the streptococcal protein G B1 domain in aqueous solution; Kobayashi N et al.; We examined the complementation of various pairs of fragments derived from the streptococcal protein G B1 domain by NMR and CD . Most were not associated; however, one pair of fragments (1-40) and (41-56) interacted sufficiently enough to regenerated a stable 1:1 complex, Kd = 9 x 10(-6) M . A 2D-NMR analysis showed that the structure of the complex resembled that of native domain . Here we discuss the complementation from the viewpoint of the folding pathway of the protein.

Arch Intern Med, 1995 Jun 12, 155(11), 1170 - 6
Streptococcal group C bacteremia . Survey in Israel and analytic review; Carmeli Y et al.; BACKGROUND: Data concerning group C streptococcal bacteremia come mainly from case reports; thus, population-based studies from different geographic areas are needed to validate these findings . METHODS: Eight years of data on group C streptococcal infection in Israel and cases of bacteremia in five hospitals were reviewed . We compared data from our survey as well as from other population-based studies with multiple cases published as case reports . RESULTS: The organisms were isolated in 78 cases (excluding pharyngitis); 16 had bacteremia . Ten cases of bacteremia were reviewed in five hospitals; none of the patients reported exposure to animals, and nine had severe underlying diseases . The clinical syndromes included four cases of primary bacteremia, four cutaneous infections, and one case each of meningitis and pneumonia . There were two deaths, one patient underwent amputation of a toe, one had a stroke, and one had a relapse . We compared 80 cases published as case reports with 59 cases reported in five population-based studies from different countries . We found higher rates of underlying diseases, alcohol abuse, liver diseases, and cutaneous infections, and lower rates of exposure to animals or raw products, endovascular infections, and central nervous system infections in population-based studies . Morbidity and mortality were 20% to 30% each in both types of studies . CONCLUSIONS: Group C streptococcal bacteremia affects patients with underlying diseases; exposure to animals is variable and less frequent than previously reported . Morbidity and mortality are high and probably reflect the patients' underlying state as well as the severity of the infection.

Protein Eng, 1995 Jun, 8(6), 601 - 8
A combinatorial library of an alpha-helical bacterial receptor domain; Nord K et al.; The construction and characterization of a combinatorial library of a solvent-exposed surface of an alpha-helical domain derived from a bacterial receptor is described . Using a novel solid-phase approach, the library was assembled in a directed and successive manner utilizing single-stranded oligonucleotides containing multiple random substitutions for the variegated segments of the gene fragment . The simultaneous substitution of 13 residues to all 20 possible amino acids was carried out in a region spanning 81 nucleotides . The randomization was made in codons for amino acids that were modelled to be solvent accessible at a surface made up from two of the three alpha-helices of a monovalent Fc-binding domain of staphylococcal protein A . After cloning of the PCR-amplified library into a phagemid vector adapted for phage display of the mutants, DNA sequencing analysis suggested a random distribution of codons in the mutagenized positions . Four members of the library with multiple substitutions were produced in Escherichia coli as fusions to an albumin-binding affinity tag derived from streptococcal protein G . The fusion proteins were purified by human serum albumin affinity chromatography and subsequently characterized by SDS-electrophoresis, CD spectroscopy and biosensor analysis . The analyses showed that the mutant protein A derivatives could all be secreted as soluble full-length proteins . Furthermore, the CD analysis showed that all mutants, except one with a proline introduced into helix 2, have secondary structures in close agreement with the wild-type domain . These results proved that members of this alpha-helical receptor library with multiple substitutions in the solvent-exposed surface remain stable and soluble in E . coli.(ABSTRACT TRUNCATED AT 250 WORDS)

J Pediatr, 1995 Jun, 126(6), 933 - 6
Diagnosis of group A streptococcal pharyngitis in a private clinic: comparative evaluation of an optical immunoassay method and culture; Fries SM; We compared the sensitivity and specificity of the Strep A Optical ImmunoAssay (OIA) method with our routine trypticase soy agar with 5% sheep blood (TSA) culture technique and with a broth-enhanced culture in the diagnosis of group A beta-hemolytic streptococcal infection . Compared with broth-enhanced culture, the Strep A OIA had a sensitivity and specificity of 94.8% and 98.8%, respectively; TSA culture had a sensitivity and specificity of 92.5% and 99.4%, respectively . The Strep A OIA, which takes 10 minutes to perform, offered sensitivity and specificity equivalent to that of TSA culture in the diagnosis of group A beta-hemolytic streptococcal pharyngitis.

Invest Ophthalmol Vis Sci, 1995 Jun, 36(7), 1231 - 9
Effect of group B streptococcal meningitis on retinal and choroidal blood flow in newborn pigs; Bottoli I et al.; PURPOSE . To assess the effect of group B streptococcal (GBS) meningitis on retinal blood flow (RetBF) and choroidal blood flow (ChBF) autoregulation in sedated newborn piglets (1 to 5 days of age) . METHODS . Fourteen study animals injected with 0.5 ml heat-killed GBS (10(9)) were compared to 10 control animals injected with 0.5 ml saline . The site of injection for both groups was the cerebral lateral ventricles . RetBF and ChBF were measured by radioactive microspheres (141Ce, 51Cr, 113Sn, 85Sr, 95Nb, 46Sc) over a mean arterial blood pressure (MABP) range of 20 to 150 mm Hg . Hypertension and hypotension were induced 2 hours apart in random sequence on each animal by inflating balloon-tipped catheters placed at the descending aorta and the aortic root, respectively . RetBF and ChBF were measured 15 minutes before and after injection of GBS or saline (baseline) and during hypotension or hypertension . RESULTS . Fifth-order polynomial regression analyses of RetBF and ChBF (ml/100 g per minute) versus MABP showed that in control animals, blood flows were constant at MABP of 60 to 110 mm Hg for RetBF and was pressure passive above and below these ranges . However, no autoregulation was observed for ChBF throughout the MABP range . In contrast, RetBF of GBS-treated animals increased with increasing blood pressure throughout range of MABP studied, and absence of autoregulation was maintained in the choroid . Vascular resistance (mm Hg/ml per minute/100 g) increased as MABP was raised to maintain constant flow and was correlated linearly with MABP at 60 to 110 mm Hg (r = 0.6682, P = 0.0003) in RetBF of control animals but not in GBS-treated animals (r = -0.291, P = NS) . Vascular resistance did not change with MABP for ChBF of control animals (r = -0.264, P = NS) but decreased as MABP was raised in GBS-treated animals (r = -0.548, P < 0.0001) . GBS did not alter oxygen delivery, which varied directly with MABP in control animals (RetBF: r = 0.74, P < 0.001; ChBF: r = 0.68, P < 0.001) and in GBS-treated animals (RetBF: r = 0.55, P < 0.001; ChBF: r = 0.68, P < 0.001) . CONCLUSION . Group B streptococcal meningitis significantly impairs eye blood flow autoregulation and may contribute to increased risk of retinal damage in infants with meningitis.

Eur J Pediatr, 1995 Jun, 154(6), 475 - 6
Acute post-streptococcal polymyalgia: two new cases with a review of the literature; Venuta A et al.; Two patients with acute post-streptococcal polymyalgia are described with a review of the seven cases previously reported cases . The common features are sudden onset of muscular pain with fever usually after an acute upper respiratory tract infection . Antistreptolysin O titre and inflammatory indexes are increased and muscle enzymes are normal . CONCLUSION: Acute post-streptococcal polymyalgia should be considered as a possible diagnosis in every child complaining acute polymyalgia.

J Clin Gastroenterol, 1995 Jun, 20(4), 310 - 6
On the use of antibiotics in Crohn's disease; Van Kruiningen HJ; It is difficult to understand how a disease process characterized by ulcerations, fissures, abscesses, fistulas, lymphangitis, and granulomas has not attracted greater use of antibiotics, particularly as the sites are constantly contaminated by intestinal bacteria . I have had a favorable experience with broad-spectrum antibiotics in the treatment of a variety of forms of ileocolitis in animals and now advocate that Crohn's disease be treated at length with these drugs . Microbiologic culture of serosa, mesenteric lymph nodes, and fistulas has demonstrated that bacterial species are present in a significant proportion of cases, and serology has shown that patients have elevated antibody levels to many of these same microorganisms . Now immunocytochemistry provides documentation of Escherichia coli and streptococcal antigen within the lesions of a majority of patients . That these bacteria may be secondary invaders should not decrease our need to address them . Several chronic granulomatous diseases that were once thought to be intractable now yield to long-term antibiotic treatment, including Whipple's disease, malakoplakia, and granulomatous colitis of Boxer dogs . Many of the perianal lesions of Crohn's disease respond to short-term metronidazole, and the medium-term (3-6 months) use of broad-spectrum antibiotics, most recently ciprofloxacin, has shown promising results . In view of the increasing evidence of bacterial participation in this disease, it is now important that physicians test some of our newer broad-spectrum antibiotics, in a controlled format, and over an extended time.

J Clin Microbiol, 1995 Jun, 33(6), 1551 - 3
Comparison of BioStar Strep A OIA optical immune assay, Abbott TestPack Plus Strep A, and culture with selective media for diagnosis of group A streptococcal pharyngitis; Roe M et al.; We directly compared three techniques for the diagnosis of group A streptococcal pharyngitis in 500 symptomatic children seen in the Emergency Department or Child Care Clinic of The Children's Hospital of Denver . Throats were vigorously swabbed with two rayon swabs, which were transported immediately to the Microbiology Laboratory . Each swab was cultured aerobically on Strep A Isolation Agar (Remel) and then tested for antigen-one swab by the Strep A OIA optical immune assay (BioStar) and the other by the TestPack Plus Strep A (Abbott) technique . Each test was performed blind to the others . The refrigerated pledget was cultured in Todd-Hewitt broth if an antigen test was positive and both direct plate cultures were negative (the "gold standard" was any culture positive) . All isolates were serologically grouped . Of 500 complete patient cultures, 151 (30%) were positive for group A streptococcal growth . The two antigen tests gave comparable results with an average sensitivity of 83% . Each was significantly (P < 0.02) less sensitive than its corresponding culture . The BioStar Strep A OIA optical immune assay produced significantly (P < 0.003) more false-positive results than did the Abbott test . Rapid antigen testing is not sensitive enough to eliminate the need for backup cultures.

Pediatr Nephrol, 1995 Jun, 9(3), 317 - 9
Acute post-streptococcal glomerulonephritis in a renal allograft; Sorof JM et al.; We report a 12-year-old male with acute post-streptococcal glomerulonephritis (APSGN) occurring 1 year after a cadaveric renal transplant . Although recurrent and de novo renal transplant glomerulonephritides have been well described in large series of adult and pediatric renal transplant recipients, post-infectious glomerulonephritis has been rarely reported, and APSGN has never been reported in either adult or pediatric transplant series . We speculate on the reasons for the lack of occurrence of APSGN in renal transplant recipients.

Nippon Jinzo Gakkai Shi, 1995 Jun, 37(6), 323 - 9
Streptococcal pneumoniae polysaccharide increases IgA-class antibody activity under the immunological memory of a protein antigen: two signals on experimental IgA nephropathy; Imai H et al.; We designed the following experiment in order to clarify the factors that induce a hyper-immune state of IgA . Six-week-old Balb/c mice were immunized with bovine gammaglobulin (BGG) at 0 and 2 weeks, followed by the administration of phosphorylcholine-BGG (PC-BGG) at 3 and 5 weeks to obtain an immunological memory . At 6 weeks, we divided the mice into three groups: one was a saline group used as a control, another was a PC-BGG group used to investigate T-cell dependent antigen, and the last was a streptococcal pneumoniae polysaccharide (R36A) group used to investigate T-cell independent antigen . We compared the antibody activity in response to BGG, and glomerular immune deposition among the groups . In the control group, antibody activities did not change, and all stainings on glomerular immune deposits were negative . In the PC-BGG group, IgG-class antibody activity was significantly suppressed (p < 0.05), but IgA- and IgM-class antibodies were not affected . The intensity of glomerular deposition of IgM was level one positivity (TFS: 116.7 +/- 20.2 (mean +/- SD)) . In the R36A group, polysaccharide produced significant increases (almost four times) in IgA-class and IgM-class antibody activity under the condition of immunological memory (IgA: p < 0.05, IgM: p < 0.005) . The intensity of IgA was between weak and level one positivity (TFS: 60.8 +/- 6.3), but the intensity of IgM was weak positive (TFS: 36.7 +/- 10.4) . This became a predominant glomerular deposition of IgA in the R36A group.(ABSTRACT TRUNCATED AT 250 WORDS)

Science, 1995 May 5, 268(5211), 716 - 9
Generation and assembly of secretory antibodies in plants; Ma JK et al.; Four transgenic Nicotiana tabacum plants were generated that expressed a murine monoclonal antibody kappa chain, a hybrid immunoglobulin A-G heavy chain, a murine joining chain, and a rabbit secretory component, respectively . Successive sexual crosses between these plants and filial recombinants resulted in plants that expressed all four protein chains simultaneously . These chains were assembled into a functional, high molecular weight secretory immunoglobulin that recognized the native streptococcal antigen I/II cell surface adhesion molecule . In plants, single cells are able to assemble secretory antibodies, whereas two different cell types are required in mammals . Transgenic plants may be suitable for large-scale production of recombinant secretory immunoglobulin A for passive mucosal immunotherapy . Plant cells also possess the requisite mechanisms for assembly and expression of other complex recombinant protein molecules.

J Pediatr Hematol Oncol, 1995 May, 17(2), 151 - 5
Oral care with vancomycin paste for reduction in incidence of alpha-hemolytic streptococcal sepsis; Barker GJ et al.; PURPOSE: alpha-Hemolytic streptococcal (AHS) sepsis is increasing in oncology patients receiving myelosuppressive chemotherapy . In response to a high rate of AHS sepsis in this population at our institution, an oral care protocol was instituted, including vancomycin 0.5% in flavored methylcellulose (vanc paste) applied orally t.i.d . at the oncologists' discretion . PATIENTS AND METHODS: A retrospective cohort study of 239 neutropenic episodes among 42 children receiving myelosuppressive chemotherapy between 1988 and 1991 compared the incidence of septicemia based on the prophylactic use of vanc paste . RESULTS: A total of 236 consecutive neutropenic episodes were evaluable, 121 with vanc paste and 115 without . AHS sepsis occurred in one child using vanc paste and in six children not using vanc paste (p = 0.06) . Excluding staph-only positive blood cultures, which would not be reduced with a topical oral antibiotic drug, there were 6 and 13 positive blood cultures in the vanc-paste and nonvanc-paste patients, respectively (p = 0.09) . There was no increase in incidence of gram-negative bacteremia among vanc-paste recipients . Vancomycin resistance was not encountered . CONCLUSION: This analysis suggests that vanc paste effectively reduces AHS sepsis, does not increase gram-negative bacteremia, and is not associated with vancomycin resistance . A multicentered, placebo-controlled, double-blind study is currently planned.

J Immunol, 1995 May 1, 154(9), 4322 - 32
Mucosal immunization with a bacterial protein antigen genetically coupled to cholera toxin A2/B subunits; Hajishengallis G et al.; The generation of secretory IgA Abs for specific immune protection of mucosal surfaces depends on stimulation of the mucosal immune system, but this is not effectively achieved by parenteral or even oral administration of most soluble Ags . To harness the exceptional mucosal immunogenicity of cholera toxin (CT), which is largely attributed to the cell-binding property of its B subunit, for the generation of other oral vaccines, we have genetically replaced the toxic A1 subunit of CT with a 42-kDa segment of a streptococcal protein adhesin . This construct was expressed in Escherichia coli as a chimeric protein that retained the GM1 ganglioside-binding activity of CT subunit B and the antigenicity of the streptococcal adhesin, as shown by GM1-ELISA developed with Abs to the steptococcal segment . The protein composition of chromatographically purified chimeric protein was verified by SDS-PAGE and Western blotting with Abs to both antigenic components of the construct . Peroral administration of this chimeric immunogen in mice elicited high levels of mucosal IgA and serum IgG Abs to the streptococcal adhesin, which persisted for at least 6 mo . This strategy allows the development of similar constructs from other candidate Ags for oral immunization against a variety of mucosally acquired infections.

Aust N Z J Obstet Gynaecol, 1995 May, 35(2), 120 - 6
Prevention of neonatal group B streptococcal sepsis: is routine antenatal screening appropriate; Gilbert GL et al.; Four strategies for prevention of early onset neonatal group B streptococcal (GBS) sepsis were considered: A: routine antenatal screening for GBS vaginal carriage at 26-28 weeks' gestation and intrapartum antibiotic prophylaxis for all carriers; B: screening as above and prophylaxis only for carriers with risk factors for sepsis; C: prophylaxis for all women with risk factors; D: as for C plus screening at 37 weeks' gestation and prophylaxis for carriers . The outcomes considered for each option were: the proportion of women given prophylaxis; the risk of anaphylaxis; cases of neonatal GBS sepsis and deaths prevented; costs of screening, prophylaxis and of acute care of remaining cases . Published local and overseas studies of neonatal GBS sepsis, effectiveness of antenatal screening and prophylaxis and estimated costs were evaluated . Any of the proposed strategies can prevent a significant proportion of cases of neonatal GBS sepsis and a strategy for prevention of neonatal group B streptococcal sepsis should be part of routine obstetric practice . Strategy C is simple, effective, inexpensive and avoids unnecessary antibiotic use; it is recommended particularly when antenatal care is provided mainly in community or private practice . Strategy A (using vaginal and rectal swabs for screening) could prevent more cases, but at greater cost which could be justified only if protocols can be properly implemented and monitored.

Nat Struct Biol, 1995 May, 2(5), 368 - 73
Novel metal-binding proteins by design; Klemba M et al.; We describe the successful design of a tetrahedral His3Cys Zn(II)-binding site in a small protein of known structure: the B1 domain of Streptococcal protein G . The B1 variants containing the novel metal-binding site were characterized using a combination of optical absorption, circular dichroism and NMR spectroscopies . The results indicate that the designed proteins bind Zn(II) with high affinity and tetrahedral coordination geometry, and that the overall secondary and tertiary structure of the B1 domain is maintained.

No To Hattatsu, 1995 May, 27(3), 239 - 44
{A case of focal encephalitis with psychological symptoms similar to chorea minor}; Yasuda K et al.; We reported a patient with choreic movements, emotional lability, and compulsive-obsessive behavior that developed 4 weeks after onset of fever and lasted for several years . There was no evidence of streptococcal infection or rheumatic fever . T2-weighted MRI showed hyperintense lesions in the bilateral caudate nuclei and putamina . A diagnosis of focal encephalitis was made according to initial fever, convulsion, and CSF pleocytosis . Treatments with haloperidol and prednisolone were effective in some degree . The neurobehavioral syndrome as well as the involuntary movements in this patient can be attributed to the striatal damage, which may disrupt the basal ganglia-limbic-frontal lobe tracts . A symptomatic similarity between the syndrome in this patient and chorea minor suggests a striatal damage in chorea minor, where the causative lesions remain unknown.

No To Hattatsu, 1995 May, 27(3), 191 - 6
{Effectiveness of haloperidol in the treatment of chorea minor}; Miyakawa M et al.; Chorea minor is the most curious manifestation of rheumatic fever, first described by Sydenham in 1686 . Subsequent evidence showed that chorea could be a late manifestation of rheumatic fever, often occurring several months after a streptococcal infection in contrast to other major manifestations . During the ten-year period between 1984 and 1993, 11 children with rheumatic fever were seen at our hospital, two cases of these being accompanied with chorea minor . Case 1, a male aged 12, presented with involuntary movements . He was diagnosed as having rheumatic fever because of chorea and systolic ejection murmur at the apex of the heart . Plain cranial CT was normal . However, positron emission computed tomography revealed an increased 11C-glucose uptake in the caudate nucleus as compared with the cerebral cortex . Case 2, a female aged 14, presented with involuntary movements . Plain cranial CT was normal, but single photon emission CT showed a difference between the right and left brain . These two patients were given penicillin G (PCG), predonisolone (PSL) and haloperidol . Haloperidol was administered, because PCG and PSL had no effect to improve the clinical manifestations . After administer decreased to a half with a clinical improvement, but the level of GABA did not change . Haloperidol seemed to be an effective and useful agent for motor manifestations of the disease.

Rev Rhum Engl Ed, 1995 May, 62(5), 343 - 8
The role of ambiental agents in Behçet's disease; Heymann RE et al.; OBJECTIVE . To evaluate the potential role of environmental agents in the etiopathogenesis of Behcet's disease . METHODS . Twenty-eight Behcet's disease patients and 56 controls were recruited prospectively from the outpatient rheumatic disease clinic at the Escola Paulista de Medicina between July 1991 and July 1992 . Behcet's disease was diagnosed using one of the accepted sets of criteria (Japanese Committee, International Committee, O'Duffy, Mason & Barnes, and James) . The control patients, who had other rheumatic diseases, were matched on age and sex with the Behcet's disease patients . To investigate environmental factors, a standardized questionnaire was administered to each subject during an interview . Clinical and laboratory investigations were performed in each subject according to a predefined protocol . RESULTS . Analysis using the Chi-square test or Fisher's exact test (Cochran's restriction) disclosed significant associations between Behcet's disease and a history of herpes simplex virus type 1 infection or streptococcal infection . CONCLUSIONS . Despite the small sample size, our data strongly support a role of infectious agents in the etiopathogenesis of Behcet's disease . Further studies in larger patient populations are needed to confirm our results.

Jpn Heart J, 1995 May, 36(3), 341 - 8
Role of calcium and protein kinase C in the activation of T cells in Takayasu's arteritis; Dhar J et al.; The roles of protein kinase C and calcium in the T cells of patients suffering from Takayasu's arteritis (TA) in response to the mitogens phorbol-myristate acetate (PMA) and streptococcal antigens have been studied . In TA there was an increased basal activity of protein kinase C (1.074 +/- 0.223 nmoles/mg protein/min) as compared with that of controls (0.570 +/- .12) (p < 0.001) . There was 75% translocation from the cytosol to membrane fraction in response to PMA . Intracellular calcium levels showed increased basal levels in TA (177.07 +/- 12.56 nmoles) compared with the controls (112.83 +/- 10.6 nmoles) (p < 0.001) and there was a further rise on stimulation, indicating the T cells were in an activated state . There was a positive correlation between the calcium levels and the activity of protein kinase C (r = 0.71, p < 0.05) . Unlike the situation in patients with rheumatic fever, T cells in TA showed no stimulation in response to streptococcal antigens . The low level of cAMP (1.12 +/- 0.169 pmoles/million cells) compared with that of controls (1.4 +/- 0.03) further supports the role of PKC-calcium in the T cell activation process . These findings suggest activation of the PKC-calcium pathway in TA.

J Clin Microbiol, 1995 May, 33(5), 1399 - 401
Identity of streptococcal blood isolates and oral isolates from two patients with infective endocarditis; Fiehn NE et al.; The purpose of this study was to isolate streptococcal strains from the oral cavities of streptococcal endocarditis patients and compare these strains biochemically and genetically with the corresponding streptococcal blood isolates . Total identity was observed between the blood and oral cavity isolates from the two patients studied.

Curr Opin Rheumatol, 1995 May, 7(3), 201 - 5
Animal models in rheumatoid arthritis; Houri JM et al.; Two new models for the study of rheumatoid arthritis have been established . SCID (severe combined immunodeficient) mice implanted with human synovial tissues and human HLA-DR4-CD4 transgenic mice represent novel and important approaches to the use of animal models in pathogenetic studies . New studies of streptococcal cell wall arthritis in rats demonstrated that beta 1 integrin-mediated cell-matrix interactions are involved in the induction and perpetuation of inflammatory synovitis and that systemic administration of interleukin-4 selectively suppresses established synovitis, presumably by effects on monocyte function . The importance of nitric oxide as a mediator of synovial inflammation was confirmed in the adjuvant-induced model of rheumatoid arthritis . In the collagen-induced arthritis model, interesting new data have implicated gamma delta T cells in the pathogenesis of arthritis, and the antineoplastic drug taxol was shown to have anti-inflammatory effects.

S D J Med, 1995 May, 48(5), 149 - 53
Group B streptococcal infections in the perinatal period: current approaches; Watson WJ et al.; Group B streptococcal (GBS) infection in the neonate is the most common infectious cause of perinatal morbidity and mortality . There is much confusion in the literature regarding screening and treatment for this disease . The authors review recent literature on perinatal GBS infection and present their clinical opinions in favor of routine screening during pregnancy . Treatment protocols for the GBS positive mother, as well as the infant delivered of a GBS positive mother are considered.

Clin Exp Rheumatol, 1995 May-Jun, 13(3), 321 - 5
Yersinia-associated arthritis in rats: effect of 65 kDa heat shock protein, bovine serum albumin and incomplete Freund's adjuvant; Gripenberg-Lerche C et al.; OBJECTIVE . We have previously shown that the microbial load of rats has a significant effect on their susceptibility to Yersinia-associated arthritis . In this study our aim was to see whether mycobacterial 65 kDa heat shock protein (hsp) could induce the same suppressive effect in experimental Yersinia-associated arthritis as has been reported for arthritides induced by adjuvant, pristane, or streptococcal cell walls (SCW) . METHODS . Arthritis was induced by the intravenous injection of Yersinia enterocolitica 0:8 into Lewis rats . Hsp, bovine serum albumin (BSA) or NaCl, administered in incomplete Freund's adjuvant (IFA), was given subcutaneously on day -5 or +5 with regard to the bacterial inoculation . RESULTS . Mycobacterial hsp given in IFA on day -5 significantly suppressed the development of arthritis . However, a similar suppression was observed with BSA or NaCl given in IFA . CONCLUSION . These results, together with those known from the effect of microbial load, suggest that susceptibility to Yersinia-associated arthritis is easily affected by external factors.

Am J Med, 1995 Apr 24, 98(4A), 15S - 23S; discussion 23S-24S
Erythema migrans and early Lyme disease; Nadelman RB et al.; Erythema migrans (EM) must be distinguished from other entities including streptococcal and staphylococcal cellulitis, hypersensitivity reactions to arthropod bites, plant dermatitis, tinea, and granuloma annulare . Although EM lesions may be pruritic or painful, these complaints are generally mild . Central clearing may be absent in > 50% of patients . Multiple lesions, formerly present in 50% of U.S . patients, now occur in approximately 20% . EM develops days to 1 month after a tick bite (median 7-10 days), and lesion diameter increases with duration . Most patients have associated complaints, with fatigue (54%), myalgia (44%), arthralgia (44%), headache (42%), and fever and/or chills (39%) being the most common . Respiratory and gastrointestinal complaints are infrequent . Symptoms may begin prior to the onset of, concomitant with, or after resolution of the rash . The incidence of viral-like illness due to Lyme disease without EM is unknown . Antibodies to Borrelia burgdorferi are absent in up to 50% of patients at presentation, with initial seropositivity most likely in those with EM of longer duration . The vast majority of patients will become seropositive within the first month of illness, even with treatment . Although there is evidence that B . burgdorferi can spread to the blood and central nervous system soon after onset of infection, oral therapy is highly effective in preventing objective extracutaneous complications of Lyme disease . The most appropriate choice, route of administration, and duration of therapy require further study . Because of variations in the etiologic agent between North America and Europe, comparisons of disease manifestations, treatment, and prognosis of Lyme disease must be made cautiously.

Microb Drug Resist, 1995 Spring, 1(1), 29 - 34
Genetics and molecular biology of beta-lactam-resistant pneumococci; Coffey TJ et al.; Penicillin-resistant pneumococci have been reported with increasing frequency in recent years . Isolates with high-level resistance are now found in many countries, and in some countries they constitute a substantial proportion of all isolates . A worrying development is the recent emergence of pneumococci with high-level resistance to third-generation cephalosporins . Resistance to beta-lactam antibiotics in pneumococci is due entirely to the development of altered forms of the high-molecular-weight penicillin-binding proteins (PBPs) that have decreased affinity for the antibiotics . High-level resistance to third-generation cephalosporins has occurred by the development of altered forms of PBP1a and 2x, whereas high-level penicillin resistance additionally requires alterations of PBP2b . Altered PBPs are encoded by mosaic genes that have emerged by recombinational events between the pbp genes of pneumococci and their homologs in closely related streptococcal species . Horizontal gene transfer, presumably mediated by genetic transformation, has also resulted in the dissemination of altered pbp genes, and possibly capsular biosynthetic genes, between different pneumococcal lineages to produce new resistant clones.

Am J Med Sci, 1995 Apr, 309(4), 226 - 8
Case report: steroid sparing effect of intravenous gamma globulin in a child with necrotizing vasculitis; Gedalia A et al.; This article reports the case of a boy aged 2 years 6 months, who had fever, arthritis, and necrotizing cutaneous vasculitis . Evaluation revealed no evidence of direct infectious causes . However, high anti-streptolysin and streptozyme titers during the acute phase support the possibility that streptococcal infection played an important role in the pathogenesis of this disease . The patient's condition improved significantly with the administration of prednisone . However, several attempts to diminish the prednisone dose resulted in relapses . Subsequently, the prednisone was successfully tapered and discontinued after intravenous gamma globulin administration . It is recommended that intravenous gamma globulin should be considered before immunosuppressive therapy in the treatment of necrotizing vasculitis.

Can J Anaesth, 1995 Apr, 42(4), 330 - 4
Maternal death following epidural anaesthesia for caesarean section delivery in a patient with unsuspected sepsis; Morgan PJ; Sepsis in the parturient may be difficult to recognize in light of the physiological changes associated with pregnancy . The purposes of this report are to highlight the signs and symptoms which indicate an underlying septic process and the management of these patients in the peripartum period . This 32-yr-old GII PI woman with twin gestation presented at 36 wk in labour . Her temperature was 35.3 degrees C, she was normotensive and had a normal white blood cell count . After epidural anaesthesia was administered for Caesarean section, she became apnoeic, pulseless and unresponsive . Despite aggressive cardiopulmonary resuscitation, neither she nor her twin babies survived . Post mortem blood work revealed a considerable left shift of her white blood count (> 60% bands) and an anion gap acidosis . Autopsy revealed evidence of widespread Group A beta-haemolytic streptococcal sepsis . Diagnosis of sepsis in the parturient involves assessment of the patient's temperature, WBC and differential and acid-base status . Evaluation of the intravascular volume must precede anaesthetic intervention . Epidural anaesthesia may be considered in the labouring and Caesarean section patient who has been fluid-resuscitated . Emergency operative delivery may result in cardiovascular compromise in the patient with severe sepsis.

Arch Dis Child, 1995 Apr, 72(4), 308 - 11
Evidence for a superantigen mediated process in Kawasaki disease; Curtis N et al.; The clinical, pathological, and immunological similarities between Kawasaki disease and the staphylococcal and streptococcal toxic shock syndromes suggest that a superantigen toxin may be involved in the pathogenesis of the disease . The V beta repertoire of peripheral blood mononuclear cells from 21 children with Kawasaki disease, 28 children with other illnesses, and 22 healthy controls were examined using monoclonal antibodies to V beta 2, 5, 8, 12, and 19 . The mean percentage of V beta 2 expressing T cells in the patients with Kawasaki disease was increased when compared with healthy controls or children with other illnesses . The mean percentages of V beta 5, 8, 12, and 19 expressing T cells were also increased in the patients with Kawasaki disease compared with healthy controls, but were not increased when compared with children with other illnesses . The selective use of V beta 2 supports the hypothesis that a superantigen is involved in the pathogenesis of Kawasaki disease.

Am J Clin Pathol, 1995 Apr, 103(4), 396 - 9
Comparison of nephelometric and hemolytic techniques for determination of antistreptolysin O antibodies; Pacifico L et al.; The sensitivity of a newly devised nephelometric method for determining antistreptolysin O antibodies was compared with the hemolytic inhibition assay . Three hundred-thirty single serum samples from children with and without evidence of group A streptococcal infection were analyzed by the two techniques . The nephelometric method results correlated well with those of the reference test (concordance: r = 0.88) . Furthermore, 134 pairs of acute and convalescent phase sera from patients with culture-proven GAS infection and 50 pairs from children who served as control subjects were examined . The nephelometric assay was more sensitive in detecting significant ASO antibody rises than the hemolytic assay . The automated nephelometric method appears to be a much simpler and sensitive procedure for testing ASO antibodies.

Crit Care Med, 1995 Apr, 23(4), 705 - 14
Effects of inhibition of endothelium-derived relaxation factor on hemodynamics and oxygen utilization during group B streptococcal sepsis in piglets; Meadow W et al.; OBJECTIVE: To determine the effects of the inhibition of endothelium-derived relaxation factor in an animal model of neonatal group B streptococcal sepsis . DESIGN: Comparison of three experimental protocols: a) N-nitro-L-arginine; b) group B streptococcal; and c) group B streptococcal/N-nitro-L-arginine . SUBJECTS: Piglets, 1 to 2 wks old . INTERVENTIONS: Endothelium-derived relaxation factor inhibition was produced in nonseptic piglets by the infusion of a competitive inhibitor of nitric oxide synthase, N-nitro-L-arginine, at 30 mg/kg (N-nitro-L-arginine protocol; n = 6) . Human group B streptococcal sepsis was modeled in piglets by the continuous infusion of live group B streptococcal organisms at approximately 5 x 10(9) organisms/kg cumulative dose (group B streptococcal protocol; n = 8) . Endothelium-derived relaxation factor inhibition during a group B streptococcal sepsis was produced by N-nitro-L-arginine infusion during continuing group B streptococcal infusion (group B streptococcal/N-nitro-L-arginine protocol; n = 7) . MEASUREMENTS AND MAIN RESULTS: Both N-nitro-L-arginine and group B streptococcal infusion significantly increased systemic and pulmonary vascular resistance and decreased cardiac output and oxygen delivery . N-nitro-L-arginine differed from group B streptococcal infusions in its effects on systemic blood pressure (BP) (N-nitro-L-arginine increased BP while group B streptococcal infusions did not), and pulmonary/systemic vascular resistance ratio (group B streptococcal infusions increased pulmonary/systemic vascular resistance ratio more than N-nitro-L-arginine did) . The group B streptococcal/N-nitro-L-arginine group differed significantly from piglets receiving continued group B streptococcal infusion without N-nitro-L-arginine in cardiac output (significantly lower in group B streptococcal/N-nitro-L-arginine), oxygen delivery (significantly lower in group B streptococcal/N-nitro-L-arginine), and pulmonary vascular resistance (significantly higher in group B streptococcal/N-nitro-L-arginine) . CONCLUSIONS: Group B streptococcal sepsis in human newborns and in animal models of human newborns is characterized by a hemodynamic constellation of "cold shock"--increased vascular resistance and reduced systemic blood flow . Endothelium-derived relaxation factor inhibition during group B streptococcal sepsis in piglets exacerbated many of the adverse hemodynamic consequences of group B streptococcal infusion . We speculate that endothelium-derived relaxation factor inhibition has no foreseeable therapeutic role in neonatal septic shock.

J Infect Dis, 1995 Apr, 171(4), 879 - 84
Immunogenicity and protective activity in animals of a type V group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine; Wessels MR et al.; The recent recognition of type V strains as a frequent cause of group B streptococcal (GBS) infection in both infants and adults prompted investigation of an effective vaccine against these organisms . Purified GBS type V polysaccharide was covalently linked to tetanus toxoid to form a type V polysaccharide-tetanus toxoid conjugate vaccine . The conjugate elicited type V polysaccharide-specific IgG antibodies in rabbits, while unconjugated type V polysaccharide did not . Conjugate-induced rabbit antibodies were opsonic in vitro and protected mice against challenge with type V GBS . Efficacy of the conjugate vaccine also was demonstrated in a maternal vaccination/neonatal challenge model in mice . A GBS type V polysaccharide-tetanus toxoid conjugate is an effective immunogen in animal models and may be a useful component for inclusion in a multivalent GBS vaccine for human use.

Drugs Aging, 1995 Apr, 6(4), 293 - 300
Group B streptococcal infection in older patients . Spectrum of disease and management strategies; Farley MM; Group B streptococcal infection has recently been recognised as an important and apparently increasingly common cause of invasive disease in nonpregnant adults . The annual incidence of invasive disease has been estimated at 4.4 per 100,000 nonpregnant adults and is highest among adults over 60 years of age . The most common clinical diagnoses include skin and soft-tissue infections, bacteraemia with no identified source, osteomyelitis, urosepsis and pneumonia . Other important but less common infections include peritonitis, infectious arthritis, meningitis and endocarditis . The majority of adults with group B streptococcal infections have underlying diseases including diabetes mellitus, malignant neoplasms and liver disease . Nosocomial infection and polymicrobial bacteraemia occur in a significant proportion of patients with invasive group B streptococcal disease . Mortality from invasive disease is particularly high in the elderly . For treatment of serious group B streptococcal infections, high doses of benzylpenicillin (penicillin G) are recommended because of the somewhat higher minimal inhibitory concentrations . In addition to parenteral antibiotic therapy surgical management may be required for successful treatment, particularly in the case of soft-tissue or bone infection . Invasive group B streptococcal infection is a major problem in elderly adults and those with chronic diseases, and efforts should be made to identify and treat such infections early . Future approaches may include vaccine prevention of serious group B streptococcal infection in adults at highest risk.

Immunopharmacology, 1995 Apr, 29(3), 235 - 43
Curative treatments of murine Colon26 solid tumors by immunochemotherapy with G-CSF and OK-432; Kudo C et al.; In order to study the clinical usefulness of biological response modifiers (BRMs) in eliminating malignant solid tumors, we have investigated the effect of various combination therapies on the murine Colon26 solid tumor model . When the tumor-bearing mice were treated with chemotherapeutics, G-CSF and OK-432 (streptococcal preparation), the tumors completely disappeared from all of the treated mice . When these survivors were rechallenged with Colon26 tumor cells on Day 120, all of them survived without showing any sign of recurrence or metastases . The results indicate that mice with malignant solid tumors, which can not be cured using chemotherapeutics alone, may be completely healed with a combination immuno-chemotherapy . During the course of this combination therapy, study, it was found that there was a clear positive correlation between immunosuppressive acidic protein (IAP) levels and tumor sizes . Suppressor macrophages (sM phi) which produce IAP were found to be decreased in bone marrow and spleen of treated mice . This suggests that the combination therapy may make the mice recover from a suppressed immune state caused by sM phi . In conclusion, the combination therapy with chemotherapeutics and BRMs could cure the solid tumor-bearing mice very effectively through not only synergistic direct tumor cell destruction but also indirect immunomodulation of the host.

Hosp Pract (Off Ed), 1995 Mar 15, 30(3), 80 - 3
Penicillin for streptococcal pharyngitis: has anything changed?
Stollerman GH.
It used to be simple: A single IM injection or 10 days of oral therapy would cure the sore throat and prevent rheumatic fever . Post-treatment carriage of group A does not seem to be adequate reason to switch strategies today.

Structure, 1995 Mar 15, 3(3), 265 - 78
Crystal structure of the C2 fragment of streptococcal protein G in complex with the Fc domain of human IgG; Sauer-Eriksson AE et al.; BACKGROUND: Streptococcal protein G comprises two or three domains that bind to the constant Fc region of most mammalian immunoglobulin Gs (IgGs) . Protein G is functionally related to staphylococcal protein A, with which it shares neither sequence nor structural homology . RESULTS: To understand the competitive binding of these two proteins to the Fc region, the crystal structure of a single Ig-binding domain of streptococcal protein G was determined at 3.5 A resolution in complex with the Fc fragment of human IgG and compared with the structures of protein A:Fc and protein G:Fab complexes . Protein G binds to the interface between the second and third heavy chain constant domains of Fc, which is roughly the same binding site used by protein A . Protein G comprises one alpha-helix packed onto a four-stranded beta-sheet . Residues from protein G that are involved in binding are situated within the C-terminal part of the alpha-helix, the N-terminal part of the third beta-strand and the loop region connecting these two structural elements . The identified Fc-binding region of protein G agrees well with both biochemical and NMR spectroscopic data . However, the Fc-binding helices of protein G and protein A are not superimposable . CONCLUSIONS: Protein G and protein A have developed different strategies for binding to Fc . The protein G:Fc complex involves mainly charged and polar contacts, whereas protein A and Fc are held together through non-specific hydrophobic interactions and a few polar interactions . Several residues of Fc are involved in both the protein G:Fc and the protein A:Fc interaction, which explains the competitive binding of the two proteins . The apparent differences in their Fc-binding activities result from additional unique interactions.

South Med J, 1995 Mar, 88(3), 350 - 1
Group B streptococcal vertebral osteomyelitis with bacteremia; Ganapathy ME et al.; Group B streptococcal vertebral osteomyelitis is rare in adults . Osteomyelitis due to this organism is in general related to contiguous infections, recent surgery, or peripheral vascular disease . All reported cases of group B streptococcal vertebral osteomyelitis, however, have had no association with these predisposing factors and have usually been presumed to be of hematogenous origin, though bacteremia has never been demonstrated . Here we describe a 45-year-old intravenous drug abuser who had vertebral osteomyelitis and bacteremia . We conclude that the vertebral osteomyelitis in this patient was hematogenous, as shown by bacteremia, and most likely resulted from intravenous needle use.

J Bacteriol, 1995 Mar, 177(6), 1470 - 6
Cell surface display of recombinant proteins on Staphylococcus carnosus; Samuelson P et al.; A novel expression system for surface display of heterologous proteins on Staphylococcus carnosus cells has been developed . Taking advantage of the promoter and secretion signals, including a propeptide region, from the lipase gene of Staphylococcus hyicus and the cell wall-spanning and membrane-binding region of protein A from Staphylococcus aureus, efficient surface display of an 80-amino-acid peptide from a malaria blood stage antigen could be achieved . A serum albumin binding protein from streptococcal protein G was used both as a general reporter molecule and to increase the accessibility of the surface-displayed proteins . Immunoblotting, immunogold staining, and immunofluorescence on intact recombinant S . carnosus cells verified the presence of the propeptide, the malaria antigen, and the albumin-binding reporter protein on the bacterial surface . For the first time, fluorescence-activated cell sorting was used to analyze the presence of surface-displayed hybrid receptors on gram-positive bacteria.

J Exp Med, 1995 Mar 1, 181(3), 943 - 52
Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis; Anderton SM et al.; Lewis rats are susceptible to several forms of experimental arthritis-induced using heat-killed Mycobacterium tuberculosis (adjuvant arthritis, or AA), streptococcal cell walls, collagen type II, and the lipoidal amine CP20961 . Prior immunization with the mycobacterial 65-kD heat shock protein (hsp65) was reported to protect against AA, and other athritis models not using M . tuberculosis, via a T cell-mediated mechanism . Hsp65 shares 48% amino acid identity with mammalian hsp60, which is expressed at elevated levels in inflamed synovia . Several studies have reported cross-reactive T cell recognition of mycobacterial hsp65 and self hsp60 in arthritic and normal individuals . We previously described nine major histocompatibility complex class II-restricted epitopes in mycobacterial hsp65 recognized by Lewis rat T cells . Of these only one, covering the 256-270 sequence, primed for cross-reactive T cell responses to the corresponding region of rat hsp60 . Here we have tested each hsp65 epitope for protective activity by immunizing rats with synthetic peptides . A peptide containing the 256-270 epitope, which induced cross-reactive T cells, was the only one able to confer protection against AA . Similarly, administration of a T cell line specific for this epitope protected against AA . Preimmunization with the 256-270 epitope induced T cells that responded to heat-shocked syngeneic antigen-presenting cells, and also protected against CP20961-induced arthritis, indicating that activation of T cells, recognizing an epitope in self hsp60 can protect against arthritis induced without mycobacteria . Therefore, in contrast to the accepted concept that cross-reactive T cell recognition of foreign and self antigens might induce aggressive autoimmune disease, we propose that cross-reactivity between bacterial and self hsp60 might also be used to maintain a protective self-reactive T cell population . This discovery might have important implications for understanding T cell-mediated regulation of inflammation.

Curr Opin Cardiol, 1995 Mar, 10(2), 150 - 4
New developments in infective endocarditis; Murphy JG et al.; Endocarditis as seen today differs significantly from that outlined by Sir William Osler in his famous Gulstonian lectures in 1885 . The median age of the patients has increased; the spectrum of predisposing cardiac lesions has changed; more cases are due to unusual organisms, including gram-negative bacteria and fungi; and more cases present acutely and the classic findings of late endocarditis are seldom seen . Endocarditis was untreatable and uniformly fatal in 1885 . Although continued advances in medical and surgical therapy have significantly increased survival, the recent appearance of multiresistant organisms in some cases is reminiscent of the Osler era . Recent advances in the diagnosis and management of endocarditis include the identification of a specific Staphylococcus aureus receptor protein on endothelial cells, better imaging of the cardiac structures using transesophageal echocardiography, improvement in clinical diagnostic criteria and surgical techniques, and the use of outpatient oral antibiotics for penicillin-sensitive streptococcal endocarditis.

Clin Pediatr (Phila), 1995 Mar, 34(3), 122 - 7
Impact on empiric treatment of group A streptococcal pharyngitis using an optical immunoassay; Harris R et al.; The potential impact of using a rapid diagnostic test (Strep A OIA) on detection and treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in a large-volume pediatric and adolescent clinic was examined . Of 519 swabs processed for both culture and the OIA test, 114 were culture-positive for GABHS compared with 133 positive by the OIA test, for an agreement of 94% . OIA test sensitivity compared with culture was 96%, and specificity was 94% . Forty-seven percent of all study patients were empirically placed on antibiotics . In-clinic OIA testing could have reduced inappropriate therapy and been a cost-effective alternative to culture.

Br J Haematol, 1995 Mar, 89(3), 610 - 4
Severe autoimmune protein S deficiency in a boy with idiopathic purpura fulminans; Bergmann F et al.; Idiopathic purpura fulminans usually occurs in young children and is frequently preceded by a preparatory viral or bacterial infection . Following a severe streptococcal pharyngitis, an 8-year-old boy developed purpura fulminans with disseminated intravascular coagulation and severe protein S deficiency (total antigen < 0.05 u/ml) . Despite generous plasma infusions, skin necrosis progressed rapidly into compartment syndrome which required fasciotomy and skin grafting and resulted in the loss of three digits of the right foot . Total protein S remained low for over a month despite plasma supplementation and complete normalization of protein C levels . A polyclonal anti-protein S IgG was demonstrated in the patient's plasma, which decreased to 25% of baseline titre after 1 month and was undetectable 6 months after purpura fulminans, when plasma protein S had returned to normal . Transient, isolated and severe deficiencies of protein S have been reported in patients with idiopathic purpura fulminans and a previous preparatory infection . Autoimmune protein S deficiency may play a key role in the aetiopathogenesis of idiopathic purpura fulminans.

Klin Lab Diagn, 1995 Mar-Apr, (2), 26 - 9
{The determination of antistreptokinase by an immunoenzyme method}; Shemanova GF et al.; The sensitivity of enzyme immunoassay (EIA) of antistreptokinase, a new method for its measurements, is 10 times higher than the sensitivity of the prototype method . EIA is more sensitive than the prototype method, the incorrectness of the latter being ruled out; endogenous substrates, patients's blood fibrinogen and plasminogen, are used, whose concentrations vary in streptococcal diseases . Effects of nonspecific blood proteinase which, together with streptokinase, may cause a proteolytic effect, on the results of analysis are also ruled out . Microquantities of blood serum are needed for EIA of streptokinase, whereas at least 2 ml of plasma is required for the prototype test . The suggested method is more informative, since it detects the diagnostic titers in a wider range, vs . the prototype technique, and is more diagnostically valuable in comparison with other tests for the diagnosis of streptococcal infection, detection of antistreptolysin 0 and antihyaluronidase.

Am Fam Physician, 1995 Feb 15, 51(3), 625 - 30
New cutaneous manifestations of systemic diseases; Khorenian SD et al.; In recent years, especially with the advent of acquired immunodeficiency syndrome, new skin disorders associated with systemic disease have been described in the literature . Eosinophilic folliculitis and pruritic papules of human immunodeficiency virus (HIV) infection are clinically similar lesions that respond to phototherapy . Bacillary angiomatosis, another HIV-related skin disease that is caused by a pleomorphic gram-negative organism, resembles Kaposi's sarcoma clinically but is curable if treated early with antibiotics . Toxic strep syndrome, a scarlatiniform, desquamative eruption associated with hypotension, fever and multiorgan system dysfunction, is caused by group A streptococcal soft tissue infection . Paraneoplastic pemphigus, a recently characterized autoimmune vesicular eruption, produces painful mucocutaneous ulcerations in patients with an occult neoplasm, such as chronic lymphocytic leukemia or malignant lymphoma.

Am Fam Physician, 1995 Feb 1, 51(2), 401 - 4
St . Anthony's Fire: diagnosis and management of erysipelas; Bratton RL et al.; Erysipelas, a beta-hemolytic streptococcal infection of the skin and subcutaneous tissue, was once a common disease but nearly disappeared after the advent of antibiotics . In the past few years, however, the incidence of erysipelas has been increasing . At particular risk for infection are young patients, elderly patients and immunocompromised patients . The diagnosis is confirmed by the typical appearance of erythema and fever, constitutional symptoms and laboratory findings indicative of streptococcal infection . Penicillin and close follow-up can prevent significant morbidity and possible mortality . The prognosis for patients with erysipelas is excellent.

Int Arch Allergy Immunol, 1995 Feb, 106(2), 163 - 5
IFN-gamma-stimulated human vascular endothelial cells function as accessory cells for superantigen-induced TNF production in human T cells; Imanishi K et al.; In the presence of IFN-gamma-stimulated vascular endothelial cells which have acquired HLA class II molecules, T cells produced tumor necrosis factors (TNF-alpha and TNF-beta) and IL-2 in response to stimulation with streptococcal pyrogenic exotoxin A.

Ann Rheum Dis, 1995 Feb, 54(2), 134 - 6
Benign cutaneous polyarteritis nodosa in children below 10 years of age--a clinical experience; Kumar L et al.; OBJECTIVE--To report 10 children younger than 10 years of age with benign cutaneous polyarteritis nodosa (BCPAN) . METHODS--Ten children aged 1.25-10 years (mean 4.7 years; M:F = 7:3) were admitted with an unusual vasculitis . The clinical features, laboratory investigations, treatment and follow up data were analysed . RESULTS--Clinical features of these patients included: fever (10), peripheral gangrene (eight), livido reticularis (four), ulceration, nodules and vesiculobullous lesions alone or in combination (10), black necrotic patches over limbs and trunk (three), and arthralgia or swelling of large joints (seven) . Cryoglobulinaemia was transient in three children, lasting for eight months in one of them . Histopathology of the skin lesions revealed vasculitis of small and occasionally medium sized blood vessels in nine of the 10 children . Possible association of BCPAN was noted with diphtheria-pertussistetanus immunisation (one), drugs (two), streptococcal infection (two), wasp sting (one), and falciparum malaria (one) . The clinical course was interspersed with remissions and exacerbations . Response to corticosteroids alone occurred in seven patients, while three children needed cytotoxic drugs in addition . In a follow up of 5.6 years (mean) no evidence of systemic involvement was noted . CONCLUSIONS--A rare form of vasculitis, BCPAN, is reported in children . The features that distinguished our patients from those reported earlier were onset in the first decade of life and higher incidence of peripheral gangrene.

J Med Assoc Thai, 1995 Feb, 78(2), 72 - 5
Etiology of erythema nodosum; Puavilai S et al.; One hundred patients with biopsy-proven erythema nodosum were studied at Ramathibodi Hospital from 1982 to 1992 to find out the etiology of this disease . Eighty-eight were females while twelve were males, with an age range from 6 to 72 years old (mean, 31 years old) . Abnormal laboratory findings in these patients included elevation of erythrocyte sedimentation rate (76.9%), increase anti-streptolysin-O titer (10.7%), abnormal chest roentgenogram (16.7%), positive tuberculin test (50%) . The cause of erythema nodosum is still unknown in a large group of patients, and it was found only in twenty-eight patients (28%) . Twelve patients had tuberculosis, seven had history of antibiotic administration, six probably had streptococcal infection and the other three had Behcet's disease.

Ned Tijdschr Geneeskd, 1995 Jan 21, 139(3), 134 - 7
{Acute rheumatic fever in a 33-year-old man}; van den Bergh PJ et al.; In a 33-year-old man with an abnormal ECG three weeks after an episode of a sore throat, laboratory investigations revealed signs of a recent streptococcal infection . Mitral valvular and aortic valvular regurgitation were confirmed by echocardiography . The diagnosis of acute rheumatic fever was established according to the Jones criteria.

Structure, 1995 Jan 15, 3(1), 79 - 85
Model for the complex between protein G and an antibody Fc fragment in solution; Kato K et al.; BACKGROUND: Streptococcal protein G and staphylococcal protein A are bacterial antibody-binding proteins, widely used as immunological tools, whose antibody-binding domains are structurally quite different . The binding of protein G to Fc fragments is competitive with respect to protein A, suggesting that the binding sites for protein A and protein G on Fc overlap, notwithstanding the fact that they lack sequence or structural similarity . RESULTS: To resolve this issue, the residues involved in the interaction between an IgG-binding domain of protein G (domain II) and the Fc fragment of mouse IgG2a have been identified by use of 13C and 15N NMR . Binding of protein G domain II selectively perturbed resonances from residues between the CH2 and CH3 domains of Fc, whereas in domain II the residues affected are primarily those on the alpha-helix and the third strand of the beta-sheet . This information was used, together with the structures of the two uncomplexed proteins, to construct a model of the complex, using Monte Carlo minimization techniques . In this model, the alpha-helix of protein G lies in the same position as helix 1 of protein A in the crystal structure of the protein A:Fc complex, but its orientation differs from the latter by 180 degrees . CONCLUSIONS: The interactions of the bacterial antibody-binding proteins with their 'target' immunoglobulins involve a very versatile set of protein-protein interactions . First, the IgG-binding domains of protein A and protein G have quite different three-dimensional structures, but bind to sites on the Fc fragment that overlap extensively . Secondly, protein G employs two quite different regions of its surface to bind to the Fab and Fc regions of IgG.

J Immunol, 1995 Jan 15, 154(2), 851 - 60
Activation of human monocytes by streptococcal rhamnose glucose polymers is mediated by CD14 antigen, and mannan binding protein inhibits TNF-alpha release; Soell M et al.; The present work was initiated to define mechanisms that account for the binding on human monocytes of streptococcal cell wall polysaccharides formed by rhamnose glucose polymers (RGPs), and subsequent stimulatory activities . We show here that RGPs bind to and stimulate human monocytes to produce TNF-alpha in a dose-dependent manner . To detect cell surface RGPs binding proteins, intact monocytes were biotinylated before lysis with Nonidet P-40 and solubilized proteins were incubated with RGPs Affi-Prep beads . One major membrane protein of 55 kDa was specifically detected and identified as CD14 because it reacted with anti-CD14 mAbs . Furthermore, anti-CD14 mAbs were able to perform a dose-dependent inhibition of RGPs binding, and suppressed TNF-alpha release from RGPs-stimulated monocytes . Moreover, we demonstrated that RGPs also bind to CD11b; however, this binding is not implicated in synthesis of TNF-alpha . Interestingly, RGPs binding to monocytes was enhanced by human normal serum (HNS) whereas HNS inhibits the TNF-alpha-stimulating activity of RGPs . Western blotting analysis of HNS proteins purified on RGPs Affi-prep beads revealed three specific bands of 75, 55, and 32 kDa reactive with anti-C3 Abs, anti-CD14 mAbs (TUK4), and anti-human mannan binding protein (hMBP)-derived peptide IgG, respectively . These results suggest that C3, soluble CD14, and hMBP form complexes that are probably active in enhancing the binding of RGPs to monocytes . Additional studies have shown that hMBP that recognizes RGPs prevents, unlike the LPS binding protein, TNF-alpha release by inhibiting the binding of RGPs to CD14 Ag . By incubating cells with a constant amount of RGPs-hMBP complexes in the presence or absence of increasing concentrations of C1q, we also demonstrated that C1q receptor mediates the binding and probably the uptake of RGPs-hMBP complexes by human monocytes.

Yale J Biol Med, 1995 Jan-Apr, 68(1-2), 1 - 6
Group B streptococcal meningitis presenting as stroke in a nondebilitated man; Klassen H et al.; An unusual case of group B streptococcal meningitis in an adult is described . The evidence presented suggests that early vascular involvement during the meningitic process resulted in cerebral infarction, thereby explaining the patient's sudden deterioration and atypical presentation.

Scand J Rheumatol, 1995, 24(6), 383 - 5
Plasma interleukin-7 (IL-7) and IL-8 concentrations in acute rheumatic fever and chronic rheumatic heart disease; Kutukculer N et al.; Interleukin-7 (IL-7) and IL-8 productions in 25 children with acute rheumatic fever (ARF) and in 15 children with chronic rheumatic heart disease (CRHD) and in 15 children with streptococcal pharyngitis (SP), were investigated in order to determine whether they have a role in the pathogenesis of rheumatic fever . Significantly higher IL-8 levels were found in ARF patients in the clinically active period . IL-7 concentrations remained unchanged during different stages of rheumatic fever . The decrease of elevated IL-8 concentrations within 3 months and normal IL-8 concentrations in patients with CRHD and SP indicate an excessive production of IL-8, probably by cellular infiltrates in the joint throughout the active period of rheumatic disease.

Caries Res, 1995, 29(6), 498 - 506
The effect of milk and kappa casein on streptococcal glucosyltransferase; Vacca-Smith AM et al.; Many dietary components such as carbohydrates, lipids and proteins may be incorporated into the salivary pellicle and thus may affect glucosyltransferase (GTF) activity on pellicle surfaces . The effect of milk on streptococcal GTF activity was determined . Milk, when coated onto buffer-coated hydroxyapatite or saliva-coated hydroxyapatite (sHA), reduced the subsequent adsorption of GTF onto the surfaces . Milk also reduced the expression of enzymatic activity of GTF adsorbed onto sHA . kappa-Casein, when present on the surface of sHA, reduced the adsorption of GTF activity onto sHA, resulting in reduced glucan formation . alpha-Casein had no effect on the adsorption of GTF onto sHA or on subsequent glucan formation . Both milk and kappa-casein reduced activity of the enzyme in solution . The presence of milk and kappa-casein fractions on the surface of sHA and in solution with GTF can clearly modulate glucan formation in vitro.

Med Decis Making, 1995 Jan-Mar, 15(1), 65 - 75
You can lead a horse to water--improving physicians' knowledge of probabilities may not affect their decisions; Poses RM et al.; OBJECTIVES . To determine whether improving physicians' judgments of the probability of streptococcal pharyngitis for patients with sore throats would affect their use of antibiotics and affect the variation in such use . DESIGN: Post-hoc retrospective analysis of data previously collected as part of a controlled trial . SETTINGS . University student health services in Pennsylvania and Nebraska . PATIENTS . Sequential patients with pharyngitis seen before and after the time clinicians received either an experimental educational intervention designed to improve probabilistic diagnostic judgments (at the Pennsylvania site) or a control intervention, a standard lecture (at the Nebraska site) . The clinician-subjects were the primary case physicians practicing at either site . MEASUREMENTS . Clinical variables prospectively recorded by the clinicians, probability assessments, and treatment decisions . RESULTS . At the experimental site, despite marked decreases in clinicians' overestimations of disease probability after the intervention, the proportion of patients prescribed antibiotics showed a trend toward increasing: 100/290 (34.5%) pre-intervention, 90/225 (40%) post-intervention . The intervention did not decrease practice variation between individual doctors . Univariable and multivariable analyses showed no major change in the relationships between clinical variables and treatment decisions after the intervention . At the control site there was no major change in probability judgments or treatment decisions after the intervention . CONCLUSIONS . Teaching physicians to make better judgments of disease probability may not alter their treatment decisions.

Enferm Infecc Microbiol Clin, 1995 Jan, 13(1), 33 - 9
{Beta-lactamase producing bacteria in the pharyngeal flora of patients with acute pharyngitis}; Romero-Vivas J et al.; BACKGROUND: Production of beta-lactamase by normal pharyngeal flora could account for penicillin treatment failure in patients with acute streptococcal pharyngitis . The aim of the present investigation was to study the beta-lactamase-producing bacteria (BLPB) in 58 patients with acute pharyngitis, and to investigate the impact of two antibiotics, amoxycillin vs amoxycillin/clavulanic acid in the pharyngeal microflora . METHODS: Rapid antigen detection tests for S . pyogenes and standard microbiologic cultures were performed on simultaneously obtained throat swabs from each enrolled patient . Patients with group A streptococcal pharyngitis (GASP) were randomized in two groups: patients treated with 10 days of oral amoxycillin (group I), and patients treated with 10 days of oral amoxicyllin/clavulanic acid (group II) . Patients without GASP and without antibiotic treatment were considered as controls (group III) . Cultures were repeated 15 days following the first culture . All of them were processed for aerobic and anaerobic organisms . RESULTS: S . pyogenes was recovered in 25 patients (43.1%) and BLPB were isolated in 64% of the treated patients and in 78% of the non-treated control patients . We observed that the number of patients harboring BLPB did not change significantly in the untreated control group . After treatment we detected a similar increase in the number of patients harboring BLPB in groups I and II . In the present study BLPB were found in more than 70% of the patients and the failure rate was less than 10% . CONCLUSIONS: The results of this study indicate that production of beta-lactamase by pharyngeal organisms does not fully explain the failures of penicillin therapy for acute streptococcal pharyngitis.

J Fla Med Assoc, 1995 Jan, 82(1), 21 - 3
Latex particle agglutination tests on the cerebrospinal fluid . A reappraisal; Rathore MH et al.; Rapid diagnostic tests are often used to identify microbial etiology of infection early . Latex particle agglutination (LPA) tests on the cerebrospinal fluid (CSF) are frequently used for purpose of rapid diagnosis . We evaluated their usefulness in management of patients with suspected meningitis . We also evaluated the cost effectiveness of LPAs during an 11-month period; 1,540 CSF specimens were tested for H . influenzae type b, Group B streptococcal (GBS), N . meningitidis and S . pneumoniae using LPAs . Only 27 were positive . LPAs were useful in management of only the neonates with GBS infection . On the whole, LPAs were very expensive and not cost-effective.

World Health Forum, 1995, 16(1), 47 - 51
Controlling rheumatic heart disease in developing countries; Kumar R; The streptococcal infection that leads to rheumatic heart disease, which accounts for one third to half of the cardiac admissions in developing countries, appears to spread especially rapidly in overcrowded living conditions . Rheumatic fever can be prevented by antibiotic treatment for streptococcal sore throat in children (primary prophylaxis), and its progression towards rheumatic heart disease can also be stopped by antibiotic therapy (secondary prophylaxis) . At present, the most cost-effective control strategy appears to be secondary prophylaxis.

Ann Surg, 1995 Jan, 221(1), 89 - 99
Anticancer chemosensitivity changes between the original and recurrent tumors after successful chemotherapy selected according to the sensitivity assay; Nio Y et al.; OBJECTIVE: The authors compare and characterize the changes in chemosensitivity between the original tumors before chemotherapy and recurrent tumors after responses . SUMMARY BACKGROUND DATA: The drug resistance in clinical chemotherapy appears to be different from that in experimental chemotherapy, and the profile and mechanisms of clinical drug resistance in recurrent tumors, especially after successful chemotherapy has scarcely been studied . METHODS: Applied chemotherapies were selected out of four agents, cisplatin (CDDP), adriamycin (ADR), mitomycin-C (MMC) and 5-fluorouracil (5-FU), singly or in combinations by a DNA synthesis inhibition assay, by which the sensitivity of recurrent tumors was assessed . Responses were defined according to the standard criteria, and successful chemotherapy indicates complete response (CR) or partial response (PR) for solid tumors and complete disappearance for malignant effusion . RESULTS: In 37 patients, the effectiveness of four agents were compared between before chemotherapy and after recurrence, and the response lasted between 2 and 26 months (mean +/- SD, 7.7 +/- 5.5) . The results suggest that locally recurred tumors may become resistant to the agents previously administered; by contrast, distantly recurred tumors may not necessarily become resistant to the agents administered . The recurrent tumors are suggested to be sensitive to the agents as follows: locally recurrent solid tumors, 5-FU; distantly recurrent solid tumors, 5-FU and CDDP; locally recurrent effusion, CDDP; distantly recurrent effusion, ADR . Twenty-three of 37 recurrent tumors were re-treated with chemotherapies selected according to the sensitivity assay, singly or in combination with a biologic response modifier (BRM)--a streptococcal preparation, OK-432, or interferon-alpha . Responses were seen in 1 of 13 solid recurrent tumors and in 6 of 10 recurrent effusions . Responses were seen only when the patients were treated with a combination of chemotherapy and BRM . CONCLUSION: There may be a notable differences in the basic biologic characteristics of tumor cells with respect to local versus distant recurrences, and between effusion versus solid recurrences . Various approaches, including a combination of chemotherapy and BRM, therefore, may have to be applied to overcome these drug resistances in practical chemotherapies for recurrent tumors.

J Infect Dis, 1995 Jan, 171(1), 74 - 84
Selective depletion of V beta-bearing T cells in patients with severe invasive group A streptococcal infections and streptococcal toxic shock syndrome . Ontario Streptococcal Study Project; Watanabe-Ohnishi R et al.; The V beta repertoire of T cells of patients with gram-positive group A streptococcal (GAS) and non-GAS infections was analyzed to seek evidence for the role of superantigens in streptococcal toxic shock syndrome . No evidence of V beta overexpression but a consistent pattern of depletion of V beta 1, V beta 5.1, and V beta 12 was observed in patients with severe GAS infections . This pattern of V beta depletion was not observed in patients with nonsevere GAS infections or with severe non-GAS gram-positive infections . T cells from patients with severe GAS infections showed evidence of apoptosis; no apoptosis was found when there was no evidence of V beta depletion . There was no correlation with streptococcal M or T serotype or known spe genes . The depletion of specific V beta-bearing T cells in patients with severe GAS infections supports the role of a superantigen in these infections . The in vivo pattern of V beta specificity implicates a novel superantigen(s) in this disease.

Bol Asoc Med P R, 1995 Jan-Feb, 87(1-2), 21 - 5
Group B streptococcal disease in pregnancy; Berrios Penalver R; Group B Streptococcal (GBS) infection in the pregnant female represents a challenging and often complex scenario which may cause deleterious effects in the neonate . In this paper we present three case reports of GBS infection in neonates with different outcome . A comprehensive review of the history, microbiology, clinical presentation and therapy guidelines is presented . Early diagnosis and institution of therapy are the most important factors which may have an impact on maternal and neonatal outcome.

Nephrologie, 1995, 16(2), 191 - 201
{Epidemiology of primary glomerulopathies in a French region . Variations as a function of age in patients}; Simon P et al.; Between January 1st, 1976 and December 31st, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years . The prevalence of PGD during a 70-year exposure to risk (10-80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3,8 in 1000 females) . The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females) . The annual incidence of the disease was evaluated separately for 3 consecutive 5-year periods: period A (1976-80), period B (1981-85), and period C (1986-90) . Within each of these 3 periods the number of patients with PGD was 179, 170 and 131 respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000 . The incidence of IgA nephropathy remained the same throughout the 3 periods: 2.6, 3.1 and 2.5 in 100,000 . The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15/100,000) . Acute streptococcal glomerulonephritis virtually disappeared during periods B and C . Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.3 and 0.6 in 100,000) . There was no significant difference between the 3 periods regarding the incidence of other PGD . Incidence of IgA nephropathy was 3 to 4-fold higher in the adult aged from 20 to 60 years than in the elderly . In contrast, membranous nephropathy was 3 fold more frequent in the elderly than in the adult . Therefore only some histopathological forms have a different incidence according to age, but the major information furnished by this study is that the risk of occurrence of a PGD is similar in the population living in the area, whatever the age group (10-19 years: 6.4/10(5) inhabitants, 20-39: 7.1/10(5), 40-59: 8.4/10(5), 60-79: 8.4/10(5)) . Finally, we confirm that the most common PGD going to end stage renal disease was IgA nephropathy, particularly under 60 years of age (0.8/10(5)) . In contrast, membranous nephropathy was a less frequent cause of ESRD (0.2/10(5)).

Acta Clin Belg, 1995, 50(1), 28 - 30
Poststreptococcal reactive arthritis: a form of acute rheumatic fever in adulthood; Verschuren F et al.; We report the case of a middle-aged woman suffering from a relapsing sterile inflammatory arthritis preceded by a streptococcal infection . This observation suggests that streptococcal infection may need to be included in the list of infections known to precipitate reactive arthritis . The clinical presentation of poststreptococcal arthritis in adulthood and its relationship to acute rheumatic fever is discussed.

Adv Pediatr Infect Dis, 1995, 10, 369 - 90
Superantigens and their role in infectious disease; Schafer R et al.; Although the exact mechanisms by which superantigens may contribute to the pathogenesis of diseases are unknown, it seems increasingly likely that they have a role in the induction and pathogenesis of disease . The studies described here demonstrate that in several different diseases either bacterial or viral superantigens can be isolated from patients . There is also a preferential expansion of particular V beta T-cell subsets, which is a common feature of superantigen stimulation . From the work that has been done to date it can be hypothesized that superantigens may act in several ways . They may stimulate and activate T cells that are autoreactive and lead to the induction or exacerbation of autoimmune disease, as in RA . Alternatively, they may lead to the depletion of T-cell subsets based on V beta expression, thereby resulting in the severe reduction in lymphocytes in certain immunodeficiency diseases such as AIDS . But perhaps the most likely contribution of superantigens to disease pathogenesis is seen indirectly by their effect on the immune system-particularly the stimulation of large numbers of T lymphocytes expressing the same V beta domain . Thus it is likely that the direct effect of various T-cell-derived inflammatory mediators (i.e., interleukins and other cytokines) released by these activated T lymphocytes is the primary cause of disease pathology via response to superantigen stimulation . In addition to the diseases discussed here, there are a number of other diseases in which a potential role for superantigens is being studied . These include autoimmune diseases seen after group A streptococcal infections in which the streptococcal M protein has been postulated to act as a superantigen such as scarlet fever, rheumatic heart disease, and poststreptococcal glomerulonephritis . Other diseases being studied include psoriasis, lupus-like disease, and lymphoproliferative diseases (reviewed in Kotzin et al.) . In the coming years the exact role of superantigens and the specific mechanisms by which they contribute to disease should be more clearly defined . Our understanding of these molecules could also lead to new therapies for the treatment of these diseases.

Nippon Jinzo Gakkai Shi, 1995 Jan, 37(1), 7 - 11
{Stimulatory effects of a streptococcal protein, preabsorbing antigen (PA-Ag), on human lymphocytes}; Kusumi Y et al.; The possible role of a streptococcal protein, preabsorbing antigen (PA-Ag), in human cellular immunity was examined by a lymphocyte stimulation test . Lymphocytes were obtained from 12 healthy adult donors who had no history of acute poststreptococcal glomerulonephritis nor of other renal diseases, and from the blood of 4 umbilical cords . In addition to PA-Ag, pre-purified material from ruptured cell supernatant (RCS) was also tested for lymphocyte stimulation, and their time-response relationships were compared to those with stimulation by phytohemagglutinin (PHA), a nonspecific mitogen . Results showed that the lymphocytes of the 12 adult donors proliferated in a dose-dependent manner in response to PA-Ag or RCS stimulation . In the response to these proteins, the peak responsiveness of lymphocyte proliferation was characteristically seen between the 5th and 7th days of cultivation, while it was seen between the 3rd and 5th days in PHA stimulation . Surprisingly, lymphocytes derived from umbilical cord bloods also significantly proliferated in the presence of PA-Ag . These results indicate that PA-Ag stimulates human lymphocytes to proliferate in a different manner than when stimulated by PHA, and the induction of the stimulatory effects is not dependent on antigen-specific response, since it does not require pre-sensitization of the host.

Int J Clin Lab Res, 1995, 25(2), 110 - 5
Specific reactivity of fluorescein isothiocyanate-conjugated separated IgG and IgA from celiac disease sera on human tissues; Volta U et al.; Study of the reaction of celiac disease-related antibodies with human substrates has been hampered by the immunological cross-reactivity between fluorescein isothiocyanate-conjugated anti-human immunoglobulins and immunoglobulins normally present in human tissues . In order to overcome this problem we extracted IgG from 2 celiac disease sera (positive for specific IgG and IgA antibodies) using a genetically engineered recombinant form of streptococcal protein G covalently immobilized on 4% agarose beads . The separated IgG and IgA was conjugated with fluorescein isothiocyanate and used in direct immunofluorescence on 0 blood group human duodenum, liver, and myocardium . Staining of the lamina propria beneath the villous epithelium, the endomysium of smooth muscle layers in the duodenum, and the liver sinusoidal and pericellular myocardial matrix was observed . The reactivity of celiac disease-related antibodies with various human tissues indicates that these antibodies are the result of a systemic immune response directed against all tissues containing matrix proteins.

Acta Microbiol Pol, 1995, 44(1), 63 - 8
The cytotoxic properties of Serpulina hyodysenteriae; Binek M et al.; Examination of colonic enterocytes inoculate with pure culture of S . hyodysenteriae by phase-contrast microscopy revealed that only few spirochaetes adhere to epithelial cells . S . hyodysenteriae was observed to be highly motile, showed corkscrew-like movement which might suggest that bacteria were trying to penetrate and damaged the host cells . The pattern of motility provide evidence of a chemotaxis . Supernatant of S.hyodysenteriae lysate were found to cause CTE in CHO, Vero and PK-15 culture . This support the hypothesis that damage is consistent with the presence of toxin . Inhibition activity of serpulinas hemolysin preparation with streptolysin S inhibitors confirms the suggestion that the mechanism by which S . hyodysenteriae toxin effects the cells seems to be similar to the action of streptococcal toxin S.

Rheumatol Int, 1995, 14(6), 243 - 8
Glycosylation of IgG during potentially arthritogenic lentiviral infections; McCulloch J et al.; Agalactosyl IgG {Gal(0)} was first discovered in patients with rheumatoid arthritis (RA) . However, the proportion of this glycoform is also raised in tuberculosis and leprosy . This has helped reinforce the suggestion that RA may be triggered by a mycobacterium-like slow bacterial infection . On the other hand, arthritis can occur in mycobacterial diseases, so raised Gal(0) could be associated with a tendency to arthritis, rather than with a particular type of infection . Therefore, we wished to find out whether the percentage of Gal(0) {%Gal(0)} is increased in sheep and goats following infection with maedi visna virus or caprine arthritis encephalitis virus (CAEV), both of which can lead to inflammatory synovitis . We found that the normal level of Gal(0) in these species is much lower than in humans . Goats infected with CAEV or Mycobacterium paratuberculosis (used as a control mycobacterial infection) had a significant increase in %Gal(0), though it was still below the level seen in normal humans . Studies by Western blot confirmed the presence of terminal N-acetylglucosamine on heavy chains, and percentages of Gal(0) comparable to those seen in human RA could be generated by exposing goat IgG to streptococcal beta-galactosidase . The rise in %Gal(0) was greatest in members of infected herds that were just starting to manifest arthritis, and tended to be lower in those in which severe carpitis had developed at the time of bleeding, implying the possibility that raise %Gal(0) may be an early or predisposing event for the development of arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

Stomatologiia (Mosk), 1995, 74(3), 29 - 31
{The species composition of the dental plaque on the surface of fillings made from different materials}; Tsarev VN et al.; The present research was aimed at assessment of the quantitative and qualitative composition of oral microflora in cases with different filling material used . Forty-four patients were fitted with 6 types of filling, both traditional and rarely used cliofil (Japan) . Soft dental deposit was collected from the surface of fillings for microbiologic investigation . The results permit a conclusion that composites are preferable in comparison with amalgams and cements, the contamination being 8-9 times lower when they are used . Moreover, macrocomposite fillings were associated with streptococcal contamination, in contrast to other materials, when actinomycetes were mainly isolated.

Acta Haematol, 1995, 94(2), 69 - 73
Viridans streptococcal shock syndrome during bone marrow transplantation; Martino R et al.; Of 320 patients receiving a marrow transplant at the Hospital de Sant Pau between 1986 and 1992, 12% developed viridans streptococcal bacteremia during severe neutropenia . Five of these patients (13%) developed a rapidly progressive fatal shock syndrome characterized by bilateral pulmonary infiltrates, acute respiratory failure (ARDS) and septic shock early in the transplantation course (6 or 7 days posttransplantation) . All patients were transplanted for acute leukemia in remission, and 2 received an allogeneic and 3 an autologous transplant . Four of these subjects were younger than 15 years of age and all had received cyclophosphamide and total body irradiation as conditioning regimen for marrow transplantation . All 5 patients died, and postmortem examinations revealed diffuse pulmonary lesions characteristic of the ARDS . These observations contribute to defining the clinical and pathologic characteristics of this serious complication of intensive anticancer treatment.

J Immunol Methods, 1994 Dec 28, 177(1-2), 151 - 63
On the interaction between single chain Fv antibodies and bacterial immunoglobulin-binding proteins; Akerstrom B et al.; Using four bacterial immunoglobulin-binding proteins, we have analyzed the binding characteristics of a panel of 34 human single chain Fv antibodies, expressed in E . coli and with known specificity and sequence . Several of the single chain Fv antibodies showed affinity for staphylococcal protein A and peptostreptococcal protein L, but not for the streptococcal proteins G or H . The affinity of the binding was higher for protein L (4.5 and 1.4 x 10(9) M-1) than for protein A (7.7 and 6.7 x 10(8) M-1), using the two single chain Fv antibodies displaying the strongest binding activity to these ligands . The binding was shown to be specific by Western blotting, and the single chain Fv antibodies could be purified from crude bacterial culture media by affinity chromatography on protein L- or A-Sepharose . Protein A, which has affinity for the VH domain of the scFv antibodies, was tested against scFv antibodies containing VH1, VH3, VH4 and VH5 domains, and its binding was restricted to approximately half of the scFv antibodies with a VH3 domain . Protein L, which has affinity for the VL domain, was tested against kappa 1, kappa 4, lambda 1, lambda 2 and lambda 3 domains, and it bound all kappa 1 domains, one lambda 2 and one lambda 3 domain . Comparison of the amino acid sequences of binding and non-binding VL domains demonstrated that amino acid residues crucial to the binding of protein L were distributed over a large area outside the hypervariable antigen-binding regions.

J Pediatr, 1994 Dec, 125(6 Pt 1), 931 - 8
Recurrent group B streptococcal infections in infants: clinical and microbiologic aspects; Green PA et al.; OBJECTIVE: To describe the potential for recurrence of group B streptococcal (GBS) infection in infants, using pulsed-field gel electrophoresis as an epidemiologic tool . DESIGN: Retrospective review of cases identified by laboratory records and review of the literature . SETTING: Neonatal nurseries of a county hospital system . METHODS: Retrospective review of infants with second episodes of GBS bacteremia or meningitis . Digestion of chromosomal DNA with the restriction enzyme Sma I and separation of fragments by use of contour-clamped homogeneous electric field . RESULTS: Nine cases of recurrent GBS infection were identified during a 14-year period . Eight of the nine infants were born at 25 to 36 weeks of gestation, and one was born at term . The first episode of invasive GBS infection occurred at a mean age of 10.4 days (median, 3 days; range, 1 to 27 days) . Parenteral antibiotic therapy was administered for a mean of 13.9 days (median, 14 days; range, 10 to 21 days) . Recurrence occurred at a mean age of 42.3 days (median, 48 days; range, 23 to 68 days) . One patient died during the second episode; eight infants survived to discharge home . Of seven sets of isolates analyzed from first and second GBS episodes, five were confirmed to be the same genotypically . CONCLUSION: Recurrence of GBS disease in infants may be associated with the original infecting strain or a second acquired strain.

Circulation, 1994 Dec, 90(6), 2666 - 70
Activation of complement and kinin systems after thrombolytic therapy in patients with acute myocardial infarction . A comparison between streptokinase and recombinant tissue-type plasminogen activator; Agostoni A et al.; BACKGROUND: We have previously shown that treatment with streptokinase induces abrupt complement activation and transient neutropenia in patients with acute myocardial infarction (AMI) . The purpose of this study was to compare the effects of two different thrombolytic agents--streptokinase (SK) and recombinant tissue-type plasminogen activator (rTPA)--on activation of the complement and kinin systems in plasma of patients with AMI . METHODS AND RESULTS: Forty-one patients with AMI who were eligible for thrombolytic therapy were studied . Twenty-three patients were treated with streptokinase (1.5 million IU IV over 60 minutes) and 18 were treated with rTPA (8 with bolus of 10 mg IV, followed by 50 mg infused over 60 minutes and then 40 mg infused over 120 minutes; 10 patients were administered rTPA and heparin according to the accelerated infusion protocol indicated by the GUSTO study) . C4a and C3a were measured by radioimmunoassay, soluble terminal complement components (SC5b-9) and anti-SK IgG antibodies were measured by ELISA . Cleaved high molecular weight kininogen (HK) was quantitated in plasma by SDS-PAGE and immunoblotting analysis . C4a levels were significantly and similarly increased in both groups, whereas the levels of C3a and SC5b-9 after rTPA infusion were only slightly elevated and were significantly lower than after SK . No differences were observed between patients treated with slow or accelerated rTPA regimens . The titer of antibodies to SK was highly correlated with the levels of C3a and SC5b-9, whereas a lesser correlation was observed with C4a . Treatment with rTPA did not induce the transient neutropenia observed after SK infusion . The cleavage products of HK were significantly greater after SK than after rTPA infusion . CONCLUSIONS: Our results show that both thrombolytic agents activate the classic complement pathway and that plasmin could be the common trigger for this phenomenon . A significant activation of the complement common pathway (from C3 to terminal components) was observed only with SK infusion and is attributable to the rapid formation of immunocomplexes between SK and anti-SK antibodies present in plasma as a consequence of previous streptococcal infections . The minimal activation of C5 component of the common pathway explains the absence of leukopenia in patients treated with rTPA . Cleavage of HK, larger after SK than after rTPA infusion, represents a condition enhancing the generation of bradykinin by kallikrein . The recent experimental data that indicate a damaging effect of complement activation on the infarcted zone and the contrasting favorable effect consequent to bradykinin formation raise some questions about the clinical importance of the different biological consequences of SK versus rTPA.

Obstet Gynecol, 1994 Dec, 84(6), 1058 - 9
Is penicillin G a better choice than ampicillin for prophylaxis of neonatal group B streptococcal infections?
Amstey MS, Gibbs RS.
A review of the pharmacokinetics and the narrow spectrum of action of penicillin G favors this antibiotic over ampicillin for the prophylaxis of early neonatal group B streptococcal (GBS) disease . Penicillin G provides good placental transfer and fetal and neonatal tissue levels . Group B streptococcal disease has a narrower range of sensitivities to penicillin G than to ampicillin, and the potential for selecting more resistant organisms may be greater with the broader spectrum of ampicillin than with penicillin G.

Pediatr Res, 1994 Dec, 36(6), 784 - 91
Experimental neonatal group B streptococcal pneumonia: effect of a modified porcine surfactant on bacterial proliferation in ventilated near-term rabbits; Herting E et al.; We studied bacterial proliferation in relation to surfactant treatment in a model of neonatal group B streptococcal (GBS) pneumonia . Surfactant (Curosurf) was isolated from pig lungs with a method preserving only polar lipids and hydrophobic proteins . Near-term rabbit fetuses were ventilated in a body plethysmograph system . At 15 min, a suspension of GBS strain 090 Ia LD (5 mL/kg, concentration approximately 10(9)/mL) was instilled intratracheally . At 30 min, surfactant (n = 12) or sterile saline (n = 13) was administered via the airways (2.5 mL/kg) . A control group (n = 12) received the same volumes of saline . After 5 h the animals were killed, and samples for blood cultures and blood gases were taken from the heart . The left lung was aseptically removed, weighed, homogenized, serially diluted, and cultured on blood agar plates . The results were expressed as mean log10 colony forming units/g lung +/- SD . Compared with animals (n = 12) killed immediately after GBS instillation (8.13 +/- 0.54), there was a significant increase in bacterial numbers in both groups ventilated for 5 h, but values for surfactant-treated animals (8.96 +/- 0.38) were lower than those for animals receiving saline (9.46 +/- 0.50; p < 0.05) . After 5 h, 96% of GBS-infected animals had positive blood cultures . Light microscopic examination of the right lung of GBS-infected animals revealed inflammatory changes that tended to be less prominent in surfactant-treated rabbits . We conclude that intratracheal inoculation of near-term rabbits with GBS resulted in a significant bacterial proliferation during 5 h of ventilation and that bacterial growth was mitigated by treatment with surfactant.

APMIS, 1994 Dec, 102(12), 956 - 9
Toxic shock syndrome related to simultaneous Staphylococcus aureus epiglottic abscess and group A streptococcal pharyngitis with bacteremia; Ejertsen T et al.; A case of toxic shock syndrome (TSS) is reported in which both a TSST-1-producing Staphylococcus aureus strain and a group A beta-hemolytic streptococcal strain (GABHS) were involved . The S . aureus group I strain was isolated from an epiglottic abscess, and the GABHS strain from tonsils and blood cultures . Acute intubation was needed because of obstruction of the airways by swollen and hyperemic mucous membranes in the oro- and hypopharynx together with external edema around the neck . Intravenous therapy with penicillin G was instituted initially on account of GABHS cellulitis and bacteremia . The patient's condition deteriorated during this treatment, and improvement did not occur until drainage and intravenous dicloxacillin therapy was instituted . It is not possible in this case to draw any conclusions as to which of the two organisms caused the TSS or if they were both involved.

Clin Radiol, 1994 Dec, 49(12), 863 - 6
Indium-111 labelled leucocyte uptake in aortitis; Fink AM et al.; Inflammatory conditions of the aorta may present with non-specific clinical features, including unexplained fever . Indium-111 labelled leucocyte imaging may be performed in such patients to look for the presence of occult sepsis or to assess the activity of a known vasculitis . Of approximately 1100 patients to undergo leucocyte scintigraphy for these indications over a 5 year period, three had focal leucocyte uptake in the aorta . The final diagnoses were: (1) periaortitis in Wegener's granulomatosis; (2) aortic dissection in giant cell arteritis; and (3) streptococcal aortitis with impending rupture . In all three cases the uptake was initially not thought to be in the aorta, but in bowel, a paravertebral abscess and in the lumbar spine respectively . Further imaging with CT and MRI led to the correct diagnoses . As the aorta is a rare site of focal leucocyte uptake, errors in image interpretation are likely . The rapid diagnosis of inflammatory conditions of the aorta is essential, however, as they may be life-threatening if unrecognized; therefore awareness of the aorta as a potential site of uptake is important . Urgent referral for further imaging is imperative in these cases as a false or delayed diagnosis may lead to avoidable morbidity and mortality.

Pediatr Nephrol, 1994 Dec, 8(6), 750 - 1
A case report suggesting a common pathogenesis for IgA nephropathy and Henoch-Schönlein purpura; Kaneko K et al.; A 7-year-old boy who had been followed for asymptomatic haematuria and elevated serum IgA levels developed Henoch-Schonlein purpura (HSP) after a streptococcal infection of the tonsils . Findings on renal biopsy were compatible with mild IgA nephropathy (IgAN); tonsillectomy was also performed as he had chronic tonsillitis . This case suggests that there is a common pathogenesis for IgAN and HSP, at least in some patients.

Biochemistry, 1994 Nov 29, 33(47), 14011 - 7
Three-dimensional solution structure of an immunoglobulin light chain-binding domain of protein L . Comparison with the IgG-binding domains of protein G; Wikstrom M et al.; Protein L is a multidomain protein expressed at the surface of some strains of the anaerobic bacterial species Peptostreptococcus magnus . It has affinity for immunoglobulin (Ig) through interaction with framework structures in the variable Ig light chain domain . The Ig-binding activity is located to five homologous repeats called B1-B5 in the N-terminal part of the protein . We have determined the three-dimensional solution structure of the 76 amino acid residue long B1 domain using NMR spectroscopy and distance geometry-restrained simulated annealing . The domain is composed of a 15 amino acid residue long disordered N-terminus followed by a folded portion comprising an alpha-helix packed against a four-stranded beta-sheet . These secondary structural elements are well determined with a backbone atomic root mean square deviation from their mean of 0.54 A . The B domains of protein L show very limited sequence homology to the domains of streptococcal protein G interacting with the heavy chains of IgG . However, despite this fact, and their different binding properties, the fold of the B1 domain was found to be similar to the fold of the IgG-binding protein G domains {Wikstrom, M., Sjobring, U., Kastern, W., Bjorck, L., Drakenberg, T., & Forsen, S . (1993) Biochemistry 32, 3381-3386} . In the present study, the solution structure of the B1 domain enabled a more detailed comparison which can explain the different Ig-binding specificities of these two bacterial surface proteins . Among the differences observed, the alpha-helix orientation is the most striking.(ABSTRACT TRUNCATED AT 250 WORDS)

Ann Allergy, 1994 Nov, 73(5), 435 - 8
Tonsillectomy in a patient with hereditary angioedema after prophylaxis with C1 inhibitor concentrate; Maves KK et al.; BACKGROUND: A 15-year-old young man with a history of recurrent streptococcal pharyngitis and hereditary angioedema presented for tonsillectomy . Preoperative physical examination was normal with the exception of enlarged pharyngeal tonsils with crypts and pustules; there was no evidence of angioedema . Laboratory studies were remarkable for a C4 level of 8 mg/dL (normal 20-50 mg/dL) and C1 inhibitor (C1 INH) level of 4 mg/dL (normal 11-26 mg/dL) . OBJECTIVE: To report the use of C1 INH concentrate as prophylactic treatment for a patient with hereditary angioedema who required tonsillectomy . METHODS: The patient was treated with stanozolol 4 mg po quid and clindamycin 150 mg po tid during the week before the procedure . Two hours prior to surgery, he received 2300 plasma units of intravenous C1-inhibitor (Human) Vapor Heated, IMMUNO (IMMUNO Clinical Research Corporation, New York, NY) . RESULTS: Approximately eight hours after an uncomplicated tonsillectomy, the patient began to experience crampy abdominal pain, typical of his hereditary angioedema . Beginning 22 hours after surgery, he had facial swelling and complained of difficulty swallowing and the sensation of throat swelling . The symptoms resolved over the next eight hours . Serial laboratory examinations revealed: {table: see text} CONCLUSIONS: We believe that the occurrence of abdominal pain, facial swelling, and difficulty swallowing suggests that this patient may have experienced a mild, generalized flare of hereditary angioedema during the postoperative period in spite of prophylactic therapy with both anabolic steroids and C1 INH concentrate . This serves as a reminder that patients with hereditary angioedema require close observation following invasive procedures even after premedication with stanozolol and C1 INH concentrate.

J Pediatr, 1994 Nov, 125(5 Pt 1), 812 - 6
Long-term outcome of patients with rheumatic fever receiving benzathine penicillin G prophylaxis every three weeks versus every four weeks; Lue HC et al.; OBJECTIVE: To compare the efficacy of injections of 1.2 million units of benzathine penicillin G given every 3 weeks versus every 4 weeks for secondary prevention of rheumatic fever, based on the long-term outcome of patients receiving such prophylaxis . METHODS: A total of 249 consecutive patients with rheumatic fever, randomly assigned to either a 3-week or a 4-week regimen, were examined every 3 to 6 months, and followed for 794 and 775 patient-years, respectively . RESULTS: Compliance with each regimen was comparable: 83 (66.9%) of 124 patients in the 3-week group versus 92 (73.6%) of 125 patients in the 4-week group stayed in the program (p > 0.05) . Streptococcal infections occurred less frequently in those receiving the 3-week regimen: 7.5 versus 12.6 per 100 patient-years (p < 0.01) . Prophylaxis failed in 2 patients receiving the 3-week regimen and in 10 receiving the 4-week regimen (0.25 and 1.29 per 100 patient-years respectively; p = 0.015) . Serum penicillin levels were adequate (> or = 0.02 micrograms/ml) in 100 (56%) of 179 samples obtained 21 days after penicillin injection in the 3-week regimen, and in 51 (33%) of 155 samples obtained 28 days after injection in the 4-week regimen (p < 0.01) . Of 71 patients with mitral regurgitation in the 3-week regimen, 47 (66%) no longer had the murmur; of 87 patients in the 4-week regimen, 40 (46%) no longer had the murmur (p < 0.05) . CONCLUSIONS: This 12-year controlled study indicates that the outcome of patients with rheumatic fever is better with a 3-week than with a 4-week penicillin prophylaxis regimen . Greater emphasis and more widespread use of the 3-week regimen should be recommended.

J Exp Med, 1994 Nov 1, 180(5), 1911 - 20
Human CD4-major histocompatibility complex class II (DQw6) transgenic mice in an endogenous CD4/CD8-deficient background: reconstitution of phenotype and human-restricted function; Yeung RS et al.; To reconstitute the human immune system in mice, transgenic mice expressing human CD4 and human major histocompatibility complex (MHC) class II (DQw6) molecules in an endogenous CD4- and CD8-deficient background (mCD4/8-/-), after homologous recombination, have been generated . We report that expression of human CD4 molecule in mCD4/8-/- mice rescues thymocyte development and completely restores the T cell compartment in peripheral lymphoid organs . Upon vesicular stomatitis virus (VSV) challenge, the reconstituted mature T cell population effectively provide T help to B cells in immunoglobulin class switching from IgM to specific IgG-neutralizing antibodies . Human CD4+DQw6+ double transgenic mice are tolerant to DQw6 and the DQw6 molecule functions in antigen presentation, effectively generating a human MHC class II-restricted T cell response to streptococcal M6C2 peptide . These data show that both the hCD4 and DQw6 molecules are functional in mCD4/8-/- mice, fully and stably reconstituting this limb of the human immune system in mice . This animal model provides a powerful in vivo tool to dissect the human CD4-human class II MHC interaction, especially its role in human autoimmune diseases, superantigen-mediated diseases, and acquired immunodeficiency syndrome (AIDS).

Circulation, 1994 Nov, 90(5 Pt 2), II175 - 82
Aortic valve endocarditis . Determinants of early survival and late morbidity; Aranki SF et al.; BACKGROUND: Aortic valve surgery for endocarditis remains a high-risk procedure . The objective of this study was to analyze the interaction between the various subsets of endocarditis (native, prosthetic, healed, and active), timing of surgery, and their influence on early and late outcomes . METHODS AND RESULTS: During a 20-year period starting January 1972, 200 patients underwent aortic valve replacement for infective endocarditis (age range, 13 to 88 years; median, 53 years) . There were 51 (26%) females, and 109 (55%) were in New York Heart Association functional class IV before surgery . Native valve endocarditis (NVE) and prosthetic valve endocarditis (PVE) were present in 132 (66%) and 68 (34%) patients, respectively . Surgery was required in 120 (60%) during the active phase (AE) and 80 (40%) during the healed phase (HE) of endocarditis . The main indication for surgery in the healed group was progressive congestive heart failure . The indications for the active group were congestive heart failure (68%), continuing active sepsis (70%), echocardiographic vegetation (28%), peripheral emboli (30%), and arrhythmias (13%) . Streptococcal infections predominated in NVE, staphylococcal in PVE and AE; culture-negative endocarditis predominated in the healed group . Isolated aortic valve surgery was performed in 68% of the patients, and concomitant procedures (32%) included mitral valve and coronary bypass procedures . The overall operative mortality (OM) was 12.5% . The OM was 7.5% and 22% for NVE and PVE, respectively (P = .004), and 7% for HE versus 15% for AE (P = .06) . The OM for early PVE was 33% versus 18% for late PVE (P < .05) . Multivariate logistic regression analysis identified PVE and New York Heart Association functional class IV to be independent predictors for early death . Recurrent endocarditis occurred 26 times in 24 patients (11 early, 13 late), with three operative deaths in the early group, all due to residual staphylococcal infections . Freedom from recurrent endocarditis was significantly different between HE (96 +/- 3% and 86 +/- 6% at 5 and 10 years, respectively) and AE (89 +/- 3% and 83 +/- 4%, respectively (P = .02) . Long-term survival for discharged patients was 81 +/- 3% and 63 +/- 5% at 5 and 10 years, respectively, with no significant difference between NVE, PVE, AE, and HE . CONCLUSIONS: These data suggest that for active endocarditis, surgery should be delayed to achieve a healed status provided there is no pressing need for immediate surgery . Patients with staphylococcal endocarditis, particularly on a prosthesis, should be operated on sooner and should be covered with antibiotics for an extended period to prevent recurrent PVE . This study stresses the need for aggressive antibiotic prophylaxis, particularly in the presence of a prosthesis.

Intern Med, 1994 Nov, 33(11), 706 - 9
Purulent meningitis after endoscopic injection sclerotherapy for esophageal varices; Toyoda K et al.; A 57-year-old man with liver cirrhosis developed alpha-hemolytic streptococcal meningitis following endoscopic injection sclerotherapy for esophageal varices . Central nervous system infection is uncommon as a complication of sclerotherapy, however, when such an infection does develop, it is usually intractable . We therefore emphasize the importance of immediate antibiotic therapy right after the onset of inflammatory symptoms in order to prevent the development of undesired infectious complications following sclerotherapy.

Cutis, 1994 Nov, 54(5), 341 - 2
Perianal streptococcal dermatitis: two familial cases; Paradisi M et al.; Two familial cases of perianal streptococcal dermatitis in a 3-year-old girl and her 5-1/2-year-old brother are reported . The clinical features of well-demarcated perianal erythema variably associated with itching, painful defecation with subsequent constipation, rectal bleeding, and proctitis are reviewed, together with suggestions for the best therapy.

Med Microbiol Immunol (Berl), 1994 Nov, 183(5), 239 - 56
Molecular characterization of the cfb gene encoding group B streptococcal CAMP-factor; Podbielski A et al.; An internal fragment of the cfb gene from group B streptococcal (GBS) strain R268 was amplified by polymerase chain reaction (PCR) using degenerate primers with sequences derived from the CAMP-factor amino acid (aa) sequence of GBS strain NCTC8181 {Ruhlmann et al . (1988) FEBS Lett 235:262-266} . After cloning and sequencing this fragment, the remainder of cfb and the adjacent 5' and 3' sequences were amplified by inverted PCR of genomic DNA and directly sequenced from the PCR product . Within the 1560 bp sequenced, a complete cfb gene deviating in two deduced aa residues from the published sequence was identified . In addition, the cfbR268 sequence contained a 29-aa leader peptide . Using primers directed to the 5' and 3' ends of cfb for PCR, a cfb gene of uniform size could be detected in 19 clinical GBS isolates including three phenotypically CAMP-negative strains . Utilizing Northern blot analysis and primer extension assays, the cfbR268 promoter was located and the length of the cfb transcript was assessed at about 1100 bp . In a parallel experiment, no cfb transcript could be detected from the CAMP-negative GBS strain 74-360 . The complete cfbR268 gene and different portions of its 5' and 3' ends were cloned into the plasmid pJLA602 and expressed in E . coli DH5 alpha . The recombinant peptides could be detected by Western immunoblots with polyclonal antiserum . Only the full-sized recombinant CAMP-factor was found to exert co-hemolytic activity in a sheep-blood agar assay . This co-hemolytic activity could be inhibited by anti-CAMP antiserum.

Protein Sci, 1994 Nov, 3(11), 1945 - 52
Fast folding of a prototypic polypeptide: the immunoglobulin binding domain of streptococcal protein G; Kuszewski J et al.; The folding of the small (56 residues) highly stable B1 immunoglobulin binding domain (GB1) of streptococcal protein G has been investigated by quenched-flow deuterium-hydrogen exchange . This system represents a paradigm for the study of protein folding because it exhibits no complicating features superimposed upon the intrinsic properties of the polypeptide chain . Collapse to a semicompact state exhibiting partial order, reflected in protection factors for ND-NH exchange up to 10-fold higher than that expected for a random coil, occurs within the dead time (< or = 1 ms) of the quenched flow apparatus . This is followed by the formation of the fully native state, as monitored by the fractional proton occupancy of 26 backbone amide groups spread throughout the protein, in a single rapid concerted step with a half-life of 5.2 ms at 5 degrees C.

Rev Med Chil, 1994 Nov, 122(11), 1276 - 82
{Anemia associated with acute post streptococcal glomerulonephritis}; Becker A et al.; Thirty-three children with post-streptococcal acute glomerulonephritis, age mean: 8.3 years (range: 6 - 12) were studied prospectively . Mean initial hematocrit (Hct) was 31.6% with 90% showing Hct under the normal lower limit for this age group . Reticulocyte index (RI) was < 0.5 in half of the cases . Serum iron concentration, total iron binding capacity (TIBC) and percentage of transferrin saturation were normal for this age group although 75% of the children had increased serum ferritin levels . At the time of discharge, Hct increased to 35.1% but 44% still had anemia . Hct increased spontaneously for 105 days stabilizing at 38% . Based on Hct changes, 3 groups were defined: Group I (3 individuals): normal upon discharge; Group II (19): partial recovery at discharge, slow recovery stabilizing after 105 days; Group III (11): lower Hct, slower recovery but with RI significantly higher than group II (0.96 vs 0.45 p < 0.01) . Our data suggest that although hemodilution is present in all, it may be considered the solely factor only in 3 cases (Group I) . In group II, evidence of bone marrow depression was indicated by the low RI . On the other hand, the intense anemia that could not be justified only by hemodilution and marrow depression in group III, suggests other pathogenic factors.

Rev Inst Med Trop Sao Paulo, 1994 Nov-Dec, 36(6), 507 - 13
Erythema nodosum: prospective study of 32 cases; Fernandes NC et al.; The results of 32 cases studied lead us to the conclusion that erythema nodosum's investigation routine is very important, once in our retrospective study, the percentage of cases of unknown etiology was 69.4%, and in this prospective study it is 21.8% . In 10 cases (31.2%), more than one causing agent was suspected . Infections (bacterial, helminthic, fungal, by protozoa) were diagnosed in 26 cases, streptococcal infection having predominated (12 cases) . Drugs-dipirone, aspirin, anovulatory--were suspected as causing agents in 13 cases . The association of erythema nodosum and histoplasmosis capsulata is described for the first time in Brazil . We consider erythema nodosum to be a complex syndrome which should be regarded as a manifestation of underlying diseases . The fact that all 32 subjects were women, 26 of them during menacme, suggests that particular hormonal media may favor the action of various processes (infections and drugs), precipitating erythema nodosum's clinical picture.

JAMA, 1994 Oct 19, 272(15), 1183 - 9
Reduction of fever and streptococcal bacteremia in granulocytopenic patients with cancer . A trial of oral penicillin V or placebo combined with pefloxacin . International Antimicrobial Therapy Cooperative Group of the European Organization for Research and Treatment of Cancer; Quantification of superantigen induced IFN-gamma production by computerised image analysis--inhibition of cytokine production and blast transformation by pooled human IgG; Department of Immunology, Arrhenius Laboratories for Natural Sciences, Stockholm University, SwedenA quantitative image analysis technique was developed to assess the cytokine content of immunocytochemically stained cytokine producing cells . Peripheral blood mononuclear cells were stimulated to induce cytokine production with the superantigen streptococcal pyrogenic exotoxin-A . We have developed a method based on indirect immunocytochemistry which identifies IFN-gamma producing cells by a characteristic morphology generated by the accumulation of IFN-gamma in the Golgi organelle . An image analysis technique permitted discrimination between these producer cells and IFN-gamma binding target cells, which showed a different appearance, with staining restricted to the cell surface membrane . A semi-automated routine programme allowed the signal from a video camera to be processed by computerised image analysis methodology . This enabled us to measure the number of cytokine producing cells, the cytokine staining intensity in individual cells and the cell size expressed in actual cell area . The incidence of IFN-gamma producing cells determined by image analysis measurement was compared to results obtained using manual microscopy . Cell size was assessed by the image analysis system as well as by flow cytometry . Administration of pooled human IgG for intravenous use (IVIg) to the superantigen stimulated cells significantly down-regulated IFN-gamma production, both in terms of the numbers of producer cells and in terms of cytokine staining intensity in individual cells . In addition blast transformation of cells was substantially reduced . These effects, mediated by IVIg, were also evident following delayed IVIg administration 24 h after the initial cell stimulation.

J R Army Med Corps, 1994 Oct, 140(3), 141 - 2
Life-threatening streptococcal myonecrosis complicating primary wound closure after pilonidal sinus excision; Panov TA et al.; We describe a case of anaerobic streptococcal myonecrosis as a rare complication after pilonidal sinus excision with primary closure . The recognition of the disease in any patient who has early septic deterioration after a surgical procedure requires aggressive management for survival.

AJR Am J Roentgenol, 1994 Oct, 163(4), 769 - 75
Felix Fleischner Lecture . The traffic of polymorphonuclear leukocytes through pulmonary microvessels in health and disease; Hogg JC; Polymorphonuclear leukocytes (PMN) enter the circulation from the bone marrow and remain within the vascular space unless they become activated and migrate out of the vessels as part of an inflammatory response . This article reviews their behavior in the pulmonary circulation of both healthy and diseased individuals . First, the flow of PMN is compared with that of erythrocytes (RBC) to explain how differences in the traffic of these two cell types result in a concentration of PMN with respect to RBC in pulmonary capillary blood . Second, some recent concepts are presented concerning the role of PMN in the pathogenesis of emphysema, and the hypothesis is discussed that the inhalation of cigarette smoke contributes to the pathogenesis of emphysematous lung destruction by delaying and activating PMN while they travel through lung capillaries . Finally, the example of streptococcal (i.e., pneumococcal) pneumonia is used to illustrate new information as to how PMN adhere to the endothelium and migrate into an inflammatory site in the lung . The effect of this localized inflammatory response on PMN traffic in the surrounding lung also is discussed in relation to the pathogenesis of the generalized lung injury (acute respiratory disease syndrome {ARDS}) that can complicate severe pneumococcal lung infections.

Kansenshogaku Zasshi, 1994 Oct, 68(10), 1229 - 36
{Serotype and antibiotic susceptibility of isolates from children with group A streptococcal infection; observation for 10 years}; Fujita K et al.; Six hundred and seventy isolates from children with group A streptococcal infections from 1981 through 1990 were typed serologically and their antibiotic susceptibilities were determined . Productivity of streptococcal pyrogenic exotoxins was also investigated in some isolates . Four hundred and seventy-nine strains were isolated from patients with pharyngitis, 133 from those with scarlet fever, 35 from those with suppurative infection and 23 from those with non-suppurative disease . With immediate treatment (antibiotics were started at the same day throat swabs were taken) for 10 days, 5.3% of the patients with pharyngitis including scarlet fever had relapses and 13.4% of those patients had recurrences . Of the episodes of recurrences 15.7% were due to the same M serotype strains . Six patients had two episodes of scarlet fever . M type of isolate was different in the first and the second episode of each patient . Pyrogenic exotoxin type was unprecedented in the second episode of 4 out of 6 patients . M-typable and T-typable rates of isolates were 90.7% and 97.3%, respectively . Coincidence between M and T types was 73.3% (83.0% if including strains with the same and mixed T-type) . Prevalent M-serotypes were 12 and 4, but M1, 3, or 28 was the most prevalent type of isolates in certain years . None of the 670 strains was resistant to penicillin G and cephalexin . Resistant rate of isolates to erythromycin and linecomycin was 26.5% in 1981 and 18.4% in 1982 . But a marked decrease has noted since 1983 and only one has been resistant since 1986.(ABSTRACT TRUNCATED AT 250 WORDS)

Arch Ophthalmol, 1994 Oct, 112(10), 1325 - 33
Echographic findings in infectious endophthalmitis; Dacey MP et al.; OBJECTIVE: To correlate the initial echographic findings in eyes with infectious endophthalmitis with the visual prognosis and causative microorganism . DESIGN: A retrospective review of the clinical and standardized ocular echographic findings in eyes with infectious endophthalmitis was performed . SETTING: University-based ophthalmology department . STUDY PARTICIPANTS: One hundred thirty-seven eyes (136 patients) with infectious endophthalmitis that were evaluated by the ocular echography service of the Doheny Eye Institute, Los Angeles, Calif, between January 1, 1981, and December 31, 1992 . RESULTS: Four findings on initial echography were associated with poor initial vision: dense vitreous opacities, retinal detachment, macular detachment, and choroidal detachment . Five findings on initial echography correlated with poor final vision: dense vitreous opacities, vitreous membranes, the presence of retinal detachment, the extent of retinal detachment, and the presence of choroidal detachment . Change (decrease) in vision during the follow-up period was associated with the presence of combined vitreous and subhyaloid opacities, retinal detachment, and choroidal detachment . All eyes with initially clear vitreous on ocular echography had either early streptococcal or culture-negative endophthalmitis . Advanced streptococcal endophthalmitis correlated with the most severe vitreous inflammation, vitreous membranes, and the most extensive posterior vitreous detachment, whereas gram-negative endophthalmitis correlated with choroidal detachment on initial echography . Stepwise logistic regression analysis revealed that the presence of choroidal detachment, not gram-negative microorganisms, was the principal predictor of poor visual outcome in these eyes . CONCLUSION: Ocular echography is a useful method in the clinical evaluation and treatment of infectious endophthalmitis, especially in eyes with opaque media.

Ann Thorac Surg, 1994 Oct, 58(4), 1073 - 7
Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only; Yu VL et al.; The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis . We used a multicenter, prospective, observational study design . Six university teaching hospitals with high volume cardiothoracic surgery participated . Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation . All patients were followed up prospectively for 1 year . Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively . The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%) . Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58% . At 6 months and 12 months, mortality was 46% and 47%, respectively . Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05) . Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis . From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis . Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.

J Am Acad Dermatol, 1994 Oct, 31(4), 561 - 6
Cutaneous polyarteritis nodosa of childhood; Sheth AP et al.; BACKGROUND: The clinical presentation of childhood polyarteritis nodosa (PAN) can range from isolated cutaneous findings to widespread multisystem involvement . Both the systemic and cutaneous forms are known to occur after streptococcal infection . OBJECTIVE: Our purpose was to emphasize the frequent association of childhood cutaneous PAN with antecedent streptococcal infection . METHODS: We discuss four cases of cutaneous PAN that were associated with streptococcal infection and briefly review the pertinent literature . RESULTS: All patients had evidence of preceding streptococcal infection at the onset of their illness . Although mild systemic symptoms were present in all, their course was benign . The use of nonsteroidal antiinflammatory agents or corticosteroids resulted in clinical improvement . Antibiotic therapy was also used in the treatment of these patients . CONCLUSION: In children with PAN, evaluation should include laboratory studies to detect streptococcal infection.

Gen Pharmacol, 1994 Oct, 25(6), 1115 - 22
Inhibition of IL-1 release from human monocytes and suppression of streptococcal cell wall and adjuvant-induced arthritis in rats by an extract of Tripterygium wilfordii Hook; Yu KT et al.; 1 . It was investigated whether an extract of Tripterygium wilfordii Hook f (TW) inhibits IL-1 production by monocytes and suppresses the development of IL-1-dependent arthritis induced in rats with streptococcal cell wall and adjuvant . 2 . TW preferentially inhibited IL-1 alpha and IL-1 beta production by bacterial lipopolysaccharide (LPS)-stimulated human monocytes with IC50 of approximately 1 microgram/ml . 3 . Oral administration of TW dose-dependently suppressed joint swelling and structural damage in streptococcal cell wall-induced arthritis (ED50 = 20 mg/kg/day) and in adjuvant-induced arthritis (ED50 = 46 mg/kg/day for developing and 8 mg/kg/day for established arthritis).

Kidney Int, 1994 Oct, 46(4), 1192 - 8
Epidemiology of primary glomerular diseases in a French region . Variations according to period and age; Simon P et al.; Between January 1, 1976 and December 31, 1990, histological diagnosis of primary glomerular diseases (PGD) was made in 480 patients born and living at the time of diagnosis in a region of France, comprising 410,664 inhabitants, of whom 390,574 were aged from 10 to 80 years . The prevalence of PGD during a 70 year exposure to risk (10 to 80 years of age) was evaluated to 5.7 in 1000 (7.6 in 1000 males and 3.8 in 1000 females) . The most common PGD was IgA nephropathy with a prevalence of 1.9 in 1000 (3.3 in 1000 males, 1 in 1000 females) . The annual incidence of the disease was evaluated separately for three consecutive five-year periods: period A (1976-80), period B (1981-85), and period C (1986-90) . Within each of these three periods the number of patients with PGD was 179, 170 and 131, respectively, and annual incidence was 9.3, 8.8 and 6.7 in 100,000 . The incidence of IgA nephropathy remained the same throughout the three periods: 2.6, 3.1 and 2.5 in 100,000 . The incidence of membranoproliferative glomerulonephritis decreased from 1981 onward (0.9, 0.5 and 0.15 in 100,000), while that of membranous nephropathy increased slightly (1.2, 1.6 and 1.7 in 100,000) . Acute streptococcal glomerulonephritis virtually disappeared during periods B and C . Lipoid nephrosis was less frequent in period C and idiopathic proliferative glomerulonephritis with crescents slightly increased (0.3, 0.4 and 0.6 in 100,000) . There was no significant difference between the three periods regarding the incidence of other PGD.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Pediatr (Phila), 1994 Oct, 33(10), 606 - 10
Scleredema revisited . A poststreptococcal complication; Cron RQ et al.; Scleredema is a rare connective disease which must be differentiated from scleroderma in childhood . Scleredema is characterized by thickening of the dermis of the neck, head, and upper trunk . We report a case of scleredema in an 8-year-old boy with coincident streptococcal colonization . The patient report demonstrates many of the common features of scleredema, including an associated streptococcal infection, a relatively benign presentation of illness, and the characteristic mucopolysaccharide intradermal staining on skin biopsy . The literature on scleredema is reviewed, focusing on the disease course, differential diagnosis, and an overview of the proposed three subgroups of scleredema . The association of scleredema to a prior streptococcal infection is explored, and a proposed autoimmune pathophysiology of the disease, as it relates to streptococcal infection, is presented.

J Infect Dis, 1994 Sep, 170(3), 585 - 91
Relation between low capacity of human sera to inhibit streptococcal mitogens and serious manifestation of disease; Norrby-Teglund A et al.; The proliferative response of lymphocytes induced by a new streptococcal mitogenic factor (MF) and the streptococcal pyrogenic exotoxins (Spe) A and B was determined in sera from 6 healthy persons . Responses were compared to those obtained from reference serum that lacked mitogen-specific ELISA antibodies . The sera showed individual variations in the levels of MF- and Spe-specific antibodies, as determined by ELISA . The experiments showed that most human sera, which contained mitogen-specific antibodies, could neutralize the mitogenicity of the proteins . However, there were sera that contained mitogen-specific antibodies but that did not inhibit the toxin-induced proliferation . Thus, the ELISA antibody titer did not always equal the neutralizing capacity . Sera from 27 patients with group A streptococcal bacteremia had significantly lower neutralizing ability against MF and SpeB than did sera from 25 uncomplicated tonsillitis cases.

Infect Immun, 1994 Sep, 62(9), 3731 - 8
Similar cytokine induction profiles of a novel streptococcal exotoxin, MF, and pyrogenic exotoxins A and B; Norrby-Teglund A et al.; The cytokine production induced by a newly discovered streptococcal exotoxin, MF, and the pyrogenic exotoxins SpeA and SpeB was determined by in vitro stimulation of peripheral blood mononuclear cells (PBMCs) obtained from healthy blood donors . The induction and kinetics of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, gamma interferon, tumor necrosis factor alpha (TNF-alpha), TNF-beta, and granulocyte-macrophage colony-stimulating factor were studied at the single-cell level by use of cytokine-specific monoclonal antibodies and intracellular immunofluorescent juxtanuclear staining . The cytokine-producing cells, with the exception of IL-1-expressing cells, had a characteristic morphology generated by the accumulation of cytokines in the Golgi organelle . MF, SpeA, and SpeB induced a massive gamma interferon and TNF-beta response in 10 to 16% of the PBMCs after 48 to 96 h of cell stimulation . In contrast, IL-2 and TNF-alpha production was detected in only 1 to 3% of the PBMCs . The induction of a lymphocyte TH2 phenotype response, including production of IL-3, IL-4, IL-5, and IL-10, was weak . However, the monokines, IL-1 alpha, IL-1 beta, IL-1 receptor antagonist, and IL-8, were consistently found and gradually produced, peaking at 24 h in approximately 5 to 8% of the PBMCs . MF showed extensive cytokine- and proliferation-inducing capacities equal to those of SpeA and SpeB, which suggests that MF is also a superantigen . A marked interindividual variation could be noted both in the proliferative response and in the cytokine induction of lymphocytes isolated from different individuals, which may be one explanation for the varying clinical severity noticed during group A streptococcal infections.

Obstet Gynecol, 1994 Sep, 84(3), 460 - 2
Prevention of neonatal group B streptococcal infection; Landon MB et al.; The optimal clinical strategy to prevent neonatal group B streptococcal infection has not been established . The Maternal-Fetal Medicine Units Network assessed the feasibility of a randomized clinical trial to compare the effectiveness of two methods of prevention of streptococcal infection . The attack rates of early-onset group B streptococcal disease were estimated for the following: 1) a hypothetical program of universal prenatal screening and selective intrapartum chemoprophylaxis, and 2) a hypothetical program of selective intrapartum chemoprophylaxis based on clinical risk factors . Sample size requirements were calculated for a clinical trial to detect a significant difference in attack rates between the two hypothetical programs . Similar low attack rates using both strategies would require extremely large sample sizes to detect differences between programs . Until a satisfactory, rapid diagnostic test for intrapartum group B streptococcal carrier status is developed and clinical strategies are tested in populations with varying carriage frequencies, institutions will need to individualize their approaches to prevent early-onset neonatal group B streptococcal disease.

Clin Pediatr (Phila), 1994 Sep, 33(9), 542 - 7
Changing pattern of glomerular disease at Beijing Children's Hospital; Zhang Y et al.; Current clinical experience with glomerular disease at a pediatric referral center in Beijing, China, was reviewed . In 1992, renal disorders accounted for 505 of a total 6,885 (7.3%) pediatric medical discharges . Acute glomerulonephritis accounted for 30% of renal diagnoses, while nephrotic syndrome accounted for 28% and Henoch-Schonlein purpura nephritis accounted for 16% of renal disease . Mortality in children with renal disease was 0.4% (two of 505) . All children with acute glomerulonephritis recovered or improved at last follow-up, regardless of the relationship to a streptococcal infection . In children with uncomplicated nephrotic syndrome, 91% had a complete or partial response to corticosteroids . Nephritis developed in 81 of 278 patients with Henoch-Schonlein purpura (29%) . Since 1956, a dramatic decrease in the diagnosis of acute glomerulonephritis has occurred at this pediatric hospital . Nephrotic syndrome, in contrast, has increased from 45.3 cases per year in the 1956-to-1965 decade to 146 cases annually in the period from 1986 to 1992 . Similarly, Henoch-Schonlein purpura has increased from 45.3 cases annually in the 1956-to-1965 period to 238 cases per year in the past 6 years . The incidence of nephritis in patients with Henoch-Schonlein purpura has remained constant at 29% in the past 36 years . These data should be helpful for individuals and institutions who are planning educational or clinical collaborations with pediatric nephrologists in China.

J Emerg Med, 1994 Sep-Oct, 12(5), 665 - 80
Streptococcal pharyngitis: a review of pathophysiology, diagnosis, and management; Kline JA et al.; Pharyngitis is an illness frequently treated by emergency physicians and primary care practitioners . It is the subject of much controversy regarding optimal treatment in the acute care setting . This review discusses pertinent aspects of the pathophysiology, clinical features, diagnosis, and treatment based on available literature . This review is also meant to serve as a bibliographic resource for some of the controversies of this complex topic.

Gan To Kagaku Ryoho, 1994 Sep, 21(13), 2108 - 10
{Skin reaction to OK-432 and its dosage for locoregional administration}; Yamaguchi Y et al.; Establishment of optimal dosage of OK-432, a streptococcal preparation, was studied based on its skin test was studied . Locoregional immunotherapy using OK-432 was conducted for patients with malignant fluids . More OK-432 was administered to patients having a weaker skin reaction to OK-432 and less to those having a stronger one, corresponding to their redness diameter of skin reaction . There was a marked difference in OK-432-skin test among patients . Some patients with malignant fluids having small redness responded to the treatment after a large amount of OK-432, and others were well controlled by a smaller dosage of OK-432 . It is suggested that OK-432-skin test may provide the optimal dosage for local treatment of malignant fluids.

Zh Mikrobiol Epidemiol Immunobiol, 1994 Sep-Oct, (5), 33 - 6
{The manifestations of an epidemic process in a respiratory streptococcal infection among ships' crews under commercial sailing conditions}; Obernikhin IM et al.; Morbidity in respiratory streptococcal infection in 6 ships of the State Fishery Amalgamation "Dal'ryba" during 8 voyages was analyzed . During voyages morbidity rate is determined by sporadic cases, seasonal rises at the time of the voyage and epidemic outbreaks . Spring and summer months constitute the period of risk for seasonal morbidity rises during voyages and epidemic outbreaks at the time of the formation of the crew . The minimal size of the crew in which the activation of the epidemic process took place was 350 persons . In lesser crews (250-300 persons) seasonal rises in morbidity were observed only in the presence of frequent and intensive change-over of crew members.

Eur J Clin Microbiol Infect Dis, 1994 Sep, 13(9), 701 - 10
Use of teicoplanin in community medicine; Wilson AP et al.; Administration of parenteral antibiotics to outpatients is increasingly used to reduce hospital costs, to reduce loss of earnings for the patient and to improve the quality of life in patients requiring prolonged antibiotic treatment . The glycopeptides are required for treatment of infections caused by methicillin resistant staphylococci and some enterococci, or for treatment of patients allergic to beta-lactam agents . For home therapy, teicoplanin has some advantages over vancomycin in that it requires only once-daily bolus administration, does not necessitate monitoring of serum concentrations and offers the choice of intravenous or intramuscular administration . Teicoplanin has been used to complete treatment of endocarditis at home in selected patients, streptococcal disease being the most suitable form of endocarditis for this treatment . In open trials, teicoplanin has been found effective in home therapy of osteomyelitis but, as with other agents, prolonged dosage can be associated with adverse effects . It has also been used for home treatment of infections of the respiratory tract, intravascular catheters and soft tissue . Despite its higher acquisition costs, teicoplanin is to be preferred over vancomycin because of the reduced administration and assay costs and fewer adverse effects.

Immunology, 1994 Sep, 83(1), 107 - 13
Influence of Gm allotype on the IgG subclass response to streptococcal M protein and outer membrane proteins of Moraxella catarrhalis; Carson RT et al.; The IgG antibody response to streptococcal M protein is distributed between the IgG1 and IgG3 subclasses, however individual sera vary with respect to the relative amounts of these two subclasses . The basis of this variation was investigated . Sera were also analysed for IgG subclass antibodies to the outer membrane proteins (OMP) of Moraxella catarrhalis, as these have also been reported to have a major IgG3 component . The mean percentage of IgG3 was higher in the antibody response to OMP and there was less variability between sera for this antigen than was seen for M protein . Non-specific binding of IgG3 in ELISA, which has been reported for some bacterial proteins (including M protein of some serotypes) was excluded as an explanation for the apparent IgG3 bias of these antibodies . The relative amount of IgG3 antibody to the two antigens showed a positive correlation, suggesting that some individuals tended to make a greater IgG3 response to unrelated antigens . Serial bleeds from two individuals maintained a relatively constant subclass profile over several months, suggesting that time since infection did not play a major role in determining the proportion of IgG1 and IgG3 . Gm allotypes for the sera were determined, and found to correlate with both total serum IgG3 concentrations and with IgG subclass composition of specific antibodies . Mean serum IgG3 concentrations were highest in sera typed as Gm(fb/fb) homozygous and lowest in sera typed as Gm(ag/ag) homozygous . Similarly, in the M protein-specific antibodies, the mean percentage of IgG3 was much lower in the Gm(ag/ag) sera than in the Gm(fb/fb) homozygous sera . Sera which typed as Gm(fb/ag) heterozygous were not significantly different from the Gm(fb/fb) homozygous sera for either total serum IgG3 or for M protein-specific IgG3 . Moreover, both Gm(fb/fb) homozygous and Gm(fb/ag) heterozygous sera included samples in which IgG1 was the predominant antibody subclass and the percentage of IgG3 was very low . In contrast to the M protein-specific antibodies, for the OMP-specific antibodies there was no correlation between Gm phenotype and the proportion of IgG3 . The data suggest that Gm allotype may influence the IgG subclass composition of antibody responses to bacterial surface protein, but that other factors are also likely to be involved.

Eur J Biochem, 1994 Aug 15, 224(1), 103 - 8
Competitive elution of protein A fusion proteins allows specific recovery under mild conditions; Nilsson J et al.; A novel system is described for mild elution of fusion proteins by competitive elution . The approach is based on displacement of immobilized fusions containing a monovalent IgG-binding staphylococcal protein A fragment (Z) from an IgG-affinity matrix by a divalent fragment fused to a serum-albumin-binding region derived from streptococcal protein G . Using real-time interaction analysis, the binding (K(aff)) to polyclonal human IgG was found to be 3.3 (+/- 0.4) x 10(8) M-1 for divalent ZZ and 2.0 (+/- 0.1) x 10(7) M-1 for monovalent Z . This more than tenfold difference in binding strength ensures a high efficiency in the elution step . The competitor protein can specifically be removed and recovered from the elution mixture by subsequent passage through a human serum albumin(HSA)-affinity column, leaving only the target fusion protein in the flow-through fraction . Here, we show that a recombinant Klenow fragment of DNA polymerase I expressed in Escherichia coli can be recovered with high yield, and retained activity, from a crude bacterial lysate by IgG-affinity chromatography using mild conditions during both binding and elution.

Nippon Ika Daigaku Zasshi, 1994 Aug, 61(4), 306 - 14
{Echocardiographic evaluation of left ventricular hemodynamics in children with post-streptococcal acute glomerulonephritis}; Kamisago M et al.; Left ventricular hemodynamics were studied using M-mode and pulsed doppler echocardiography in 18 cases with post-streptococcal acute glomerulonephritis (PSAGN) during the acute phase . Both the ratio of left atrial to aortic dimension and the end-diastolic volume index increased in the acute phase compared with those in the recovery phase in each case (p < 0.01, p < 0.01) . These results indicated that the increase in the preload was due to hypervolemia . End-systolic wall stress increased in the acute phase (p < 0.01), thereby the afterload was considered to have increased as well . But the value of systemic vascular resistance showed no significant difference in either phase . Therefore it seems the increase of the afterload was due to increasing blood pressure, which was mainly due to hypervolemia . The ratio of end-systolic wall stress to the end-systolic volume index (ESWS/ESVI) was significantly higher in the acute phase (p < 0.01) . Stroke volume index (SI) was also increased in the acute phase (p < 0.01) . The increase in SI was considered to be due to a more prominent increase in both the preload and left ventricular contractility than in the afterload . Left ventricular inflow patterns derived from pulsed doppler echocardiography also suggested a markedly increased preload and an increased afterload in the acute phase . These data showed that in the acute phase of PSAGN, left ventricular preload, contractility and afterload were increased due mainly to hypervolemia.

Br J Cancer, 1994 Aug, 70(2), 233 - 8
Enhancement of in vitro prostaglandin E2 production by mouse fibrosarcoma cells after co-culture with various anti-tumour effector cells; Okada F et al.; We have previously reported that an increase in the production of immunosuppressive prostaglandin E2 by a QR tumour (QR-32) is accompanied by progressive growth of the tumour in syngeneic C57BL/6 mice . In order to determine what kinds of cell and factor(s) enable QR-32 cells to promote PGE2 production, we investigated the amounts of PGE2 in the supernatant of QR-32 cells by co-culturing them with various anti-tumour effector cells . Significantly high levels of PGE2 production were observed when the QR-32 cells were co-cultured with lymphokine-activated killer (LAK) cells, natural killer (NK) cells, polymorphonuclear (PMN) leucocytes and streptococcal preparation (OK432)-activated or resident peritoneal macrophages (activated and resident macrophages) . On the other hand, PGE2 production was not increased when QR-32 cells were co-cultured with cytotoxic T lymphocytes (CTLs) specific to QR-32 cells . The high levels of PGE2 production were partially or totally inhibited by the presence of radical scavengers such as superoxide dismutase (SOD), catalase and mannitol, although the cytotoxicity of LAK cells was not . We also exposed QR-32 cells to human recombinant cytokines and the growth factors which are produced when anti-tumour effector cells come in contact with tumour cells . Significant PGE2 production by QR-32 cells was observed when the cells were treated with interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) (all P < 0.001) . These results suggest that oxygen radicals produced by anti-tumour effector cells and inflammatory cytokines provoke QR-32 cells to produce large amounts of immunosuppressive PGE2.

J Bacteriol, 1994 Aug, 176(16), 5145 - 50
Identification and nucleotide sequence analysis of a transfer-related region in the streptococcal conjugative transposon Tn5252; Kilic AO et al.; To obtain a functional map of Tn5252, a 47.5-kb streptococcal conjugative transposon, a series of defined deletion and insertion mutations were introduced within the transposon . Interruptions at several regions were found to affect the conjugal transposition functions of the element in filter-mating experiments . The nucleotide sequence of the left terminus of Tn5252 showed two open reading frames, ORF1 and ORF2, adjoining the att site . The organization of this region and the structure of the predicted integrase encoded by ORF1 were found to be similar to those of other site-specific recombination systems.

Am J Med Sci, 1994 Aug, 308(2), 110 - 1
Case report: toxic shock syndrome arising from cellulitis; DiTomaso A et al.; Toxic shock syndrome is a febrile, multiorgan illness related to toxins elaborated by staphylococcal or streptococcal infections . In the 1980s, most cases were associated with menstruation . More recently, many cases now are unrelated to menses . In this article, the authors describe a case of a nonmenstruating woman with toxic shock syndrome, associated with cellulitis of her arm . Cultures of the arm grew Staphylococcal aureus, which produced enterotoxin B.

J Clin Microbiol, 1994 Aug, 32(8), 1958 - 62
Comparison of four immunoserologic assays for detection of antibodies to Borrelia burgdorferi in patients with culture-positive erythema migrans; Mitchell PD et al.; In view of the significant sequelae associated with Lyme borreliosis, there is a need for timely and accurate diagnosis of erythema migrans (EM) . Although Borrelia burgdorferi can be cultured from biopsies of EM lesions, immunodiagnostic testing is more widely available . Four immunoserologic methods were studied by using the sera of 51 patients with EM lesions that were culture positive for B . burgdorferi . Nineteen patients had single primary lesions, and thirty-two had multiple secondary lesions . At the time of biopsy, 40 patients, 8 with primary lesions and all patients with secondary lesions, were seropositive by an immunoglobulin M (IgM) indirect fluorescent-antibody (IgM IFA) test (Bion Enterprises) . Twenty-three patients were seropositive by a whole-cell fluorescence enzyme immunoassay (EIA) (BioWhittaker, Inc.), twenty-two were positive by immunoblotting (ViroStat, Inc.), and one was positive by a P39 recombinant EIA (P39 EIA) (General Biometrics, Inc.) . Sera from various patient control groups were tested: rheumatoid arthritis (n = 19), infectious mononucleosis (n = 20), systemic lupus (n = 22), syphilis (n = 13), streptococcal sequelae (n = 20), and healthy subjects (n = 16) . None of these sera reacted with the IgM IFA test or P39 EIA . Fifteen reacted with the fluorescence EIA . We conclude that the IgM IFA test is an effective and reliable assay for the diagnosis of EM, particularly for patients with secondary lesions . Immunoblot, fluorescence EIA, and P39 EIA lack the sensitivity to reliably diagnose EM.

Nippon Kyobu Geka Gakkai Zasshi, 1994 Aug, 42(8), 1193 - 7
{A successful repair of acquired left ventricular-right atrial communication due to infective endocarditis}; Hirai H et al.; A 17-year-old boy, who had suffered from streptococcal infective endocarditis, was referred to our hospital because of the uncontrolled infection and severe right ventricular failure despite 2 months of vigorous antimicrobial therapy . Preoperative two-dimensional and Doppler echocardiography revealed a shunt from the left ventricule or aorta to the right atrium . Both aortic and tricuspid valves had vegetations and severe regurgitations . He underwent an operation because of the persistent infection and worsening heart failure . Intraoperatively, the aortic valve was found to be severely damaged and to have numerous vegetations on both surfaces . The tricuspid valve had multiple vegetations on the atrial surface only, and its annulus was markedly dilated . There was a perforation in the septal leaflet of the tricuspid valve, and an exploration of the focal site disclosed a perimembranous ventricular septal defect (VSD) communicating directly between the left ventricle and right atrium . Aortic and tricuspid valve replacements and patch closure of the VSD were done successfully and his postoperative course was uneventful except for the episode of ventricular tachycardia, torsade de pointes, on the fifth postoperative day.

Immunol Invest, 1994 Aug, 23(4-5), 323 - 35
Preferential binding of cross-reactive group A streptococcal anti-DNA monoclonal antibodies to decondensed human sperm DNA; D'Cruz OJ et al.; Four murine anti-streptococcal monoclonal antibodies (mAbs) that cross-react with human DNA were evaluated by immunofluorescence flow cytometry for their reactivity with condensed and decondensed human sperm nuclei . All 4 anti-DNA mAbs reacted with condensed sperm nuclei . The reactivity of 3 of these mAbs with decondensed sperm nuclei was 13 to 177 times higher than that found with condensed nuclei . Under identical conditions, mAbs to cytoskeletal/cytocontractile proteins lacked reactivity with decondensed sperm nuclei . Binding of monoclonal anti-DNA antibodies to decondensed sperm nuclei was abolished by preincubation with double-stranded DNA . The preferential binding of anti-DNA antibodies to decondensed sperm DNA suggests the utility of decondensed sperm nuclei as the antigenic substrate for screening anti-DNA antibodies by flow cytometry.

J Am Acad Nurse Pract, 1994 Aug, 6(8), 357 - 61
Group B streptococcal disease: a life-threatening infection in the newborn; Gallagher RJ et al.; Group B streptococcal (GBS) disease, a life-threatening infection in newborns in the United States, causes considerable neonatal morbidity and mortality . GBS is also a major source of maternal infection . Screening during pregnancy leads to early identification . Intrapartal treatment of affected mothers can prevent harmful neonatal effects . Implementation of screening and treatment protocols is recommended for the protection of all obstetric and neonatal patients.

Arch Pediatr, 1994 Aug, 1(8), 735 - 7
{Brachial plexus neuropathy following pyogenic cervical adenophlegmon}; Masson P et al.; BACKGROUND--Brachial plexopathy is rare in children; it may follow a non-specific respiratory infection or occur after a specific viral disease or immunization . CASE REPORT--An 8 year-old girl was admitted suffering from presuppurative acute cervical adenitis . She was given penicillin V, netilmicin and corticosteroids . The adenitis gradually resolved over a period of ten days . There was no evidence of a specific bacterial infection . The patient suffered from pain localized to her right shoulder 15 days after admission; this pain was resolved within 3-4 days but was followed by paralysis affecting the upper brachial roots without sensory signs . EMG performed 15 days later showed signs of denervation . Amyotrophy set in rapidly but recovery under physiotherapy was complete 5 months later . CONCLUSION--This plexopathy resembling the Parsonage-Turner syndrome could be allergic in pathogenesis although similar cases after bacterial, possibly streptococcal, infection remain to be confirmed.

J Virol Methods, 1994 Aug, 49(1), 67 - 78
A rapid indirect ELISA for the serogrouping of Australian orbiviruses; Blacksell SD et al.; This communication describes the development and evaluation of a simple and rapid method for the classification of Australian orbiviruses into one of seven established serogroups (i.e . bluetongue, epizootic haemorrhagic disease of deer, Palyam, Eubenangee, Corriparta, Wallal, Warrego) or an 'ungrouped' category . The Australian orbivirus serogrouping ELISA (SG-ELISA) utilised a sodium deoxycholate-treated cell lysate preparation from infected BHK cells which was subsequently probed in an indirect ELISA format with polyclonal antibodies representative of each serogroup . Bound immunoglobulin was detected by the use of a recombinant streptococcal protein G-HRPO conjugate and subsequent reaction with the chromogenic substrate . All reference orbiviruses tested in the SG-ELISA were identified and were in agreement with the serogroups originally designated . Minimal inter-serogroup cross-reactions were observed . One-way cross-reactions were observed between Warrego and Mitchell River viruses.

Thorac Cardiovasc Surg, 1994 Aug, 42(4), 233 - 6
Treatment of postoperative chylothorax by pleurodesis with the streptococcal preparation OK-432; Shimizu J et al.; Of the 2877 patients who underwent chest surgery at our department during the 20-year period between 1973 and 1992, 9 (0.3%) developed postoperative chylothorax . The underlying disease included primary lung cancer in 5 patients, pulmonary metastasis in 1, invasive thymoma in 2, and neuroblastoma of the posterior mediastinum in 1 . For the treatment of chylothorax, the thoracic duct was ligated in 2 patients with a high volume of chylous leakage . In 6 patients treated conservatively, early pleurodesis was attained by injecting 1 to 5 doses (mean: 2.2 doses) of the streptoccal preparation OK-432 intrathoracically; favorable results were achieved . In 1 patient, the diagnosis of chylothorax was delayed because of postoperative pyothorax . This patient developed nutritional deficiency, compromised immunity, and disseminated intravascular coagulation (DIC), which led to death before the chylothorax could be treated . In principle, postoperative chylothorax should be treated conservatively . Favorable results can be expected with the intrathoracic injection of OK-432 beginning at the early postoperative period to achieve pleurodesis, combined with the prevention of nutritional deficiency, electrolyte imbalance, and infection.

J Calif Dent Assoc, 1994 Aug, 22(8), 46 - 8, 50-5
Cephalosporin vs penicillin; Nguyen TT et al.; The correlation between late infection of an orthopedic prosthesis and a dental bacteremia remains controversial . Transient bacteremia does occur after dental treatment, usually involving streptococcal bacteria, but many orthopedic surgeons choose an anti-staphylococcal agent as their prophylactic antibiotic of choice . This article reports the results of a recent survey designed to determine, from orthopedic surgeons, antibiotic premedication coverage and, specifically, the rationale for a chosen regimen for patients having dental surgery . The responses showed no common agreement for the choice of a specific antibiotic and little rationale regarding the need for prophylaxis.

Ann Otol Rhinol Laryngol, 1994 Jul, 103(7), 554 - 7
Peritonsillar abscess: repeated needle aspiration versus incision and drainage; Wolf M et al.; The study evaluates the management of peritonsillar abscess (PTA) by comparing needle aspiration versus incision and drainage of the abscess . Twenty-four of 86 patients treated by needle aspiration underwent a single aspiration, and 38 had 2, 19 had 3, and 5 had 4 aspirations before the abscess resolved . A significant amount of pus, up to 8, 5, and 3 mL, respectively, was detected in the subsequent aspirations . Recurrent PTA was noted in 20 patients (23.26%) . In 9 of these patients (10.47%) the recurrent episode occurred immediately (in less than 1 month) and was considered residual disease . Seventy-four patients were treated by incision and drainage, and none had an immediate recurrence . Only 3 (4.05%) patients developed a late recurrent episode . The difference in the recurrence rate between the two groups is statistically significant . A history of recurrent tonsillitis prior to abscess formation did not show a significant influence on the recurrence rate . A high incidence of streptococcal infections was noted in both groups, with anaerobes detected in only 15% of samples . There was a good response to penicillin-resistant organisms . Although needle aspiration is a tempting modality for treating PTA in community clinics, one should be aware of the risks of a higher incidence of residual and recurrent disease in comparison to incision and drainage, as well as the need for repeated aspirations.

Am J Surg, 1994 Jul, 168(1), 36 - 40
Postoperative immunochemotherapy including streptococcal lysate OK-432 is effective for patients with gastric cancer and serosal invasion; Maehara Y et al.; The effects of postoperative immunochemotherapy including the streptococcal preparation OK-432 on the rate of peritoneal recurrence and survival time after curative resection were studied in 36 patients with gastric cancer . Patients randomized to group B received 18 months of a therapy that is widely used in Japan for patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4 . Patients randomized to group A received the same drugs given to group B plus an intraperitoneal injection of OK-432 on postoperative day 0 and intradermal injections of OK-432 for 18 months at 2-week intervals . There were no differences between the two groups in any known prognostic factor or dose of any drug received, except for OK-432 . There was no difference in the toxicity rates between the groups . The concomitant administration OK-432 and anticancer drugs significantly decreased the rates of peritoneal recurrence and lengthened survival time (P < 0.05).

Eur J Obstet Gynecol Reprod Biol, 1994 Jul, 56(1), 21 - 6
Sensitivity of intrapartum group B streptococcal screening and in vitro comparison of four rapid antigen tests; Adriaanse AH et al.; OBJECTIVES: To evaluate the sensitivity of intrapartum screening for group B streptococcal (GBS) colonization and to compare 4 rapid GBS antigen tests in vitro . DESIGN: Two swabs of the lower vagina of 769 parturients were taken; one swab was cultured, the other was frozen at -70 degrees C until antigen testing with the Group B Strep Test (Quidel) of the culture positive samples was performed . The Quidel test was then compared with 3 other rapid GBS antigen tests in vitro: Wellcogen Strep B (Wellcome Diagnostics), Slidex meningite Strepto B (bioMerieux) and ICON Strep B (Hybritech) . The supernatant of 29 GBS cultures in Todd-Hewitt broth was tested in bacterial concentrations of 10(6), 10(7), and 10(8) Colony-forming Units (CFU)/ml, respectively . RESULTS: Lower vagina GBS carrier rate was 13.4% (103/769) and heavy colonization (growth density 3 and 4 on blood agar plates) was found in 5.2% (40/769) . The Group B Strep Test detected 11% (11/103) of GBS carriers, with a sensitivity for heavy colonization of 25% (10/40) . In vitro none of the tests scored positively with a concentration of 10(6) CFU/ml, while with 10(7) CFU/ml the enzyme immunoassay tests (Quidel, Hybritech) were more sensitive (McNemar test, P < 0.05) than the latex agglutination tests (Wellcome Diagnostics, bioMerieux) . CONCLUSIONS: Although in vitro the enzyme immunoassay tests are more sensitive than the latex agglutination tests, sensitivity in vivo is too low to recommend the use of rapid antigen tests for general screening.

Clin Ther, 1994 Jul-Aug, 16(4), 604 - 20; discussion 603
Meta-analysis in the evaluation of treatment for streptococcal pharyngitis: a review; Blumer JL et al.; Penicillin has been first-line therapy for the treatment of streptococcal pharyngitis for more than 40 years . Since the 1980s, there have been a number of reports suggesting that bacteriologic failure rates with penicillin may be rising . A number of alternative therapies have been proposed, including oral cephalosporins . To evaluate the efficacy of these agents, two meta-analyses have recently been performed . In the meta-analysis performed by Pichichero and Margolis, oral cephalosporins were reported to achieve a significantly greater bacteriologic cure rate than penicillin (92% with cephalosporins vs 84% with penicillin, P < 0.0001) when results from 19 studies were analyzed . A separate meta-analysis performed by Deeter et al reported that the oral cephalosporin cefadroxil monohydrate achieved significantly greater bacteriologic cure rates (94.8% cefadroxil vs 87.5% penicillin, P < 0.05) than oral penicillin when 9 trials in 1406 patients with streptococcal pharyngitis were analyzed . A review of 65 studies of the use of penicillin for the treatment of streptococcal pharyngitis has shown that bacteriologic failure rates in the period 1980 to 1993 were approximately 12% to 13%, slightly but not significantly greater than during the period 1953 through 1979 . Oral cephalosporins such as cefadroxil monohydrate provide reasonable alternatives for the treatment of streptococcal pharyngitis.

Bone Marrow Transplant, 1994 Jul, 14(1), 89 - 93
Infection prevention in autologous bone marrow transplantation and the role of protective isolation; Dekker AW et al.; The efficacy of an antimicrobial regimen for prevention of infections was prospectively evaluated in 113 patients undergoing autologous bone marrow transplantation (BMT) . Ciprofloxacin, 500 mg orally twice a day plus antifungal prophylaxis, fluconazole 50 mg once daily plus amphotericin B tablets or suspension and tablets, each 200 mg four times a day, was given . In addition all patients received streptococcal prophylaxis for 10 days after BMT . Documented infections occurred in 39% (44 of 113) of patients and unexplained fever in 27% (30 of 113) . The efficacy of this regimen was reflected in a low mortality rate (3.5%) from infections and in the low need for intravenous amphotericin B (7%) . No benefit of protective isolation was found in 59 patients compared with 54 patients treated without isolation measures.

Clin Infect Dis, 1994 Jul, 19(1), 166 - 8
Group B streptococcal endocarditis involving the tricuspid valve in a 7-month-old infant; Sledge D et al.; To our knowledge, we report the first case of group B streptococcal endocarditis that occurred in an infant after the neonatal period . A large, friable vegetation had destroyed the tricuspid valve and resulted in pulmonary emboli . Surgical resection of the valve was needed to achieve clinical cure of the patient . A review of the English-language literature on older patients with group B streptococcal endocarditis revealed a mortality rate of 60% among patients treated with antimicrobial drugs alone and a mortality rate of 29% among those whose treatment included both surgery and therapy with antimicrobial drugs . Surgical debridement of the valve may be necessary for children with large vegetations, which tend to embolize and thus contribute to the morbidity and mortality associated with group B streptococcal endocarditis.

Mil Med, 1994 Jul, 159(7), 534 - 6
Recurrent erythema nodosum in an aviator; Fabian BG et al.; Erythema nodosum is an uncommon skin eruption frequently associated with underlying infections, systemic diseases, or drug toxicity . We report the case of a 27-year-old aviator with three occurrences of erythema nodosum attributed to streptococcal pharyngitis . We review the causes of erythema nodosum to emphasize the importance of a thorough investigation to rule out serious underlying disease prior to returning an aviator to flight status.

West J Med, 1994 Jun, 160(6), 529 - 33
Management of upper respiratory tract infections by telephone; Jepson S et al.; We surveyed Utah general internists (N = 134) regarding their attitudes toward and practices associated with telephone management of upper respiratory tract infections . The questionnaire contained 3 case vignettes--viral upper respiratory tract infection, streptococcal pharyngitis, and acute infectious epiglottitis--and a series of questions were asked about telephone diagnosis, management preferences (clinic versus telephone), and telephone management practices . The 53 respondents (40%) were able to make important diagnostic distinctions about upper respiratory tract infections from a written vignette . As the likelihood of a complicated or serious condition increased, patients would be appropriately triaged for clinical evaluation . Most internists would make a written record of the telephone conversation . Only 1 internist of the 53 would charge for telephone management.

Mol Microbiol, 1994 Jun, 12(5), 725 - 36
A group A streptococcal Enn protein potentially resulting from intergenomic recombination exhibits atypical immunoglobulin-binding characteristics; Podbielski A et al.; The gene encoding the Enn protein (enn) of the M untypeable group A streptococcal (GAS) strain 64/14 was amplified by polymerase chain reaction, cloned into the expression vector pJLA602 and expressed in Escherichia coli DH5 alpha . Unlike other GAS-Enn proteins, which exhibit IgA-binding activity, the recombinant Enn enn64/14 protein reacted preferentially with human IgG3 . The 1050 bp open reading frame comprising the enn64/14 gene was completely sequenced . The region of the gene encoding the signal peptide and the C-terminus exhibited > 95% homology to corresponding sections of other enn genes . The region of enn64/14 encoding the N-terminus of the mature Enn protein was found to be highly homologous to the corresponding section of the gene encoding the M-like protein of GAS serotype M9 (emmL9) . The recombinant protein encoded by emmL9 was found to react with all four human IgG subclasses . About 30% of the 1152 bp open reading frame of emmL9 encoding the N-terminus was found to display > 90% homology to the corresponding section of enn64/14 but was < 50% homologous in the remainder of the gene sequence . The functional analysis of the subcloned N-terminal section of emmL9 demonstrated a polypeptide exhibiting selective binding to human IgG3 . These findings suggested that enn64/14 was a hybrid gene formed by recombination of an enn gene and an emmL9 gene . The putative recombinational event could have involved a set of flanking 7 bp direct repeats . Since enn64/14 and emmL9 are genes from different phylogenetic lineages of GAS, this report provides evidence that intergenomic recombinations between different types of GAS genes can occur and could lead to hybrid proteins with unique Ig-binding characteristics.

Nippon Sanka Fujinka Gakkai Zasshi, 1994 Jun, 46(6), 497 - 502
{Recent status of group B streptococcal (GBS) infection of newborn in Japan}; Hoshina K et al.; Group B streptococcal (GBS) infections in neonates have been a leading cause of bacterial infections . In many cases the infected neonates and young infants died or sequelae remained . The trend of cases, risk factors and prognosis of this disease have been the subjects of questionnaires for the past 5 years in Japan . The number of cases has increased year by year . Risk factors including amniotic turbidity, chorioamnionitis, premature rupture of membrane and fever during labor were recognized in 58% of early onset (less than 7 days of age) and in 28% of late onset (7 days and more of age) infant disease . Cases of death and remaining sequelae were 63(20.8%) of 303 early onset, 27(39.1%) of 69 late onset and 90(24.2%) out of a total of 372 cases . These results suggested that strategies for the prevention of GBS infections in the newborn are necessary.

J Virol Methods, 1994 Jun, 48(1), 53 - 63
The use of an indirect ELISA with protein G-peroxidase conjugate and a blocking ELISA to demonstrate recent bluetongue infection in sheep; Lunt RA et al.; The humoral immune response of sheep infected with bluetongue virus serotypes 3, 9 and 16 was monitored by plaque inhibition (PI), blocking ELISA (BELISA) and indirect ELISA over a period of 63 days post-infection . Results indicated that testing of a single plasma or serum sample by both a BELISA and an indirect ELISA using a recombinant streptococcal protein G (PrG) peroxidase conjugate enabled an assessment of the proximity of a recent infection based on the failure of PrG to bind ovine IgM class antibodies . When BELISA and indirect ELISA results were expressed as a ratio, values indicative of recent infection (> or = 5) were observed for an average duration of 16.5 days (range 8 to 23 days) following the initial detection of antibody by BELISA . This approach has potential to improve diagnosis of a wide range of virus infections by providing an indicator for the relationship of serological status with a recent infection . However, where reinfection may occur, as with bluetongue virus, alternative methods may be required for definitive diagnosis.

Scand J Urol Nephrol, 1994 Jun, 28(2), 187 - 9
Renal cell carcinoma in a natural remaining kidney after two kidney transplantations . Case report; Jekunen A et al.; A 57-year-old woman with nephropathy following a streptococcal infection had received a kidney transplant in 1980 and 1986 and immunosuppressive treatment since 1980 . Renal cell carcinoma was found in the right native kidney in 1991, with skeletal metastases . Nephrectomy was performed and radiotherapy given . Removal of non-functioning kidneys would prevent development of such cancer.

Mol Microbiol, 1994 Jun, 12(6), 911 - 20
The functional units of a peptostreptococcal protein L; Murphy JP et al.; Protein L is a cell-surface protein from Peptostreptococcus which interacts with immunoglobulin kappa light chains . A gene from Peptostreptococcus strain 3316 coding for protein L and fragments thereof were expressed in Escherichia coli . The peptides were examined for binding to immunoglobulin and serum albumin . The four C units were shown to be responsible for binding to immunoglobulin and the four D units for binding to albumin . This protein L molecule therefore binds to albumin at a site separate from that involved in binding to immunoglobulin . The albumin-binding units have high amino acid sequence identity with the albumin-binding units of streptococcal cell-surface proteins . The gene contains three sites available for internal initiation of translation resulting in three active proteins . The protein L molecule presented in this report was compared with a previously reported protein from Peptostreptococcus strain 312 . The two proteins differ in several respects, including size and the number and types of repeat units.

FEMS Immunol Med Microbiol, 1994 Jun, 9(1), 65 - 76
Streptococcal erythrogenic toxin type C is not a phosphorylated protein . Description of two different purification procedures and investigation of its phosphorylation state; Ozegowski JH et al.; Erythrogenic toxin type C (ETC) from different streptococcal group A strains was successively purified by absorption on phenylsepharose, acidic dialysis of the eluate at 40% saturated ammonium sulphate solution, CM-Sepharose chromatography, finally by immunoaffinity chromatography on monoclonal antibodies . Second, after growing of bacteria in the presence of {32P}orthophosphate to phosphorylate ETC, the ETC was purified with phenylsepharose following immunoaffinity chromatography . The occurrence of phosphoamino acids in the purified ETC was investigated by an immunoassay . No phosphoamino acids could be detected in the ETC molecule . Also after radiolabelling with 32P it was not possible to demonstrate a radioactive signal . The treatment with alkaline phosphatase has no influence on the mitogenicity or position of ETC in isoelectric focusing . The results obtained led to the conclusion that in contrast to the literature, ETC is not a phosphorylated protein.

Clin Immunol Immunopathol, 1994 Jun, 71(3), 273 - 80
Cross-reactivity to proteoglycans in bacterial arthritis: lack of evidence for in vivo role in induction of disease; van de Langerijt AG et al.; Cross-reactivity between bacterial epitopes and cartilage components has been assumed to play a role in the pathology of bacterial-induced arthritis models . In this study, we report prominent proteoglycan (PG) depletion in Safranin-O stained ankle joint sections from collagen-induced arthritic rats . In adjuvant arthritis and streptococcal cell wall-induced arthritis (SCW-A), however, only limited PG degradation was observed . In vitro, PG fractions were able to stimulate T lymphocytes from these arthritic rats . To investigate the contribution of cross-reactivity, Lewis rats were primed with SCW in Freund's incomplete adjuvant (SCW/FIA) . This immunization protocol resulted in in vitro stimulatory responses to the SCW antigens and cartilage PG antigens, but not to joint inflammation per se . Next, papain was injected intraarticularly to create a situation in which a large amount of potential cross-reactive cartilage epitopes are released . Interestingly, no inflammatory reaction could be observed in the papain-injected joints of SCW/FIA-primed rats . These data suggest that cross-reactivity between bacterial epitopes and PG does not seem to be a key element in the onset of joint inflammation in bacterial-induced arthritis . However, it cannot be ruled out that at later time points cross-reactivity will contribute to joint inflammation.

Schweiz Rundsch Med Prax, 1994 May 24, 83(21), 654 - 7
{Necrotizing soft-tissue infections of the extremities}; Kossmann T et al.; The term "Necrotizing soft tissue infections" describes a group of limb- and sometimes lifethreatening infections mostly of the limbs . The necrotizing soft tissue infections are classified, depending on the involved tissue level, microbiology and clinical course: 1 . primarily located in the subcutaneous level and fascia: 1.1 hemolytic streptococcal gangrene, 1.2 necrotizing fasciitis, 1.3 gram-negative, synergistic, necrotizing cellulitis, 1.4 clostridial cellulitis, 1.5 anaerobic nonclostridial-cellulitis; 2 . primary located in the muscle: 2.1 clostridial myonecrosis, 2.2 streptococcal myositis . Between 1989 and 1992 17 patients with necrotizing soft tissue infections were treated at the Department of Surgery, University Hospital of Zurich . Incipient necrotizing soft tissue infections are underestimated easily due to atypical or minor initial signs . The infections may be caused by a variety of bacteria, spread rapidly and can lead to a critical condition . The surgical treatment has to be aggressive with extensive debridement of the affected areas supported by intensive care . Delayed or even omitted surgical treatment, inappropriate therapeutic concepts and incomplete debridement with compromises may have fatal consequences . Repeated debridement as well as amputation of the affected limb is justified to guarantee the patient's survival.

Biochemistry, 1994 May 17, 33(19), 6004 - 14
NMR solution structure of the isolated N-terminal fragment of protein-G B1 domain . Evidence of trifluoroethanol induced native-like beta-hairpin formation; Blanco FJ et al.; The solution structure of the isolated N-terminal fragment of streptococcal protein-G B1 domain has been investigated in H2O and TFE/H2O solution by CD and NMR to gain insight into the possible role that native beta-hairpin secondary structure elements may have in early protein folding steps . The fragment also has been studied under denaturing conditions (6 M urea), and the resulting NMR chemical shifts were used as a reference for the disordered state . On the basis of CD and NMR data, it is concluded that in aqueous solution the fragment is basically flexible, with two local low populated chain bends involving residues 8-9 and 14-15, respectively, in close agreement with secondary structure predictions, a structure that is different from the final folded state of that segment of the protein . The changes in the CD spectrum, the presence of several medium-range NOEs plus two long-range NOEs, and the sign of the H alpha conformational shifts reveal that the addition of TFE facilitates the formation of a set of transient beta-hairpins involving essentially the same residues that form the native beta-hairpin found in the final three-dimensional structure of the B1 domain . The stabilization of native-like structures by TFE is known to occur for helices, but, to our knowledge, this is the first time the stabilization of a native-like beta-hairpin structure by TFE is reported . Since long-range tertiary interactions are absent in the isolated fragment, our results support the idea that, in addition to helices, beta-hairpins may play an active role in directing the protein folding process.

Ophthalmology, 1994 May, 101(5), 832 - 8
Endogenous bacterial endophthalmitis . Report of a ten-year retrospective study; Okada AA et al.; PURPOSE: The purpose of this study is to report the predisposing factors, timing of symptoms, timing of diagnosis, causative organisms, source of infection, and visual outcome in cases of endogenous bacterial endophthalmitis . METHODS: The records of 28 patients with endogenous bacterial endophthalmitis who presented to our combined ophthalmology and medicine services over a 10-year period were reviewed . RESULTS: Ninety percent of the patients had prior medical conditions, including diabetes mellitus, gastrointestinal disorders, hypertension, cardiac disorders, and malignancy . Acute ocular symptoms were the most common reasons why the patient went to the physician (usually an ophthalmologist) rather than systemic symptoms . A correct initial diagnosis was made in 50% of patients, with a delay in diagnosis of 4 days or more in 29% of patients . Organisms were identified in 27 of the 28 patients (96% identification rate), two thirds of which were gram-positive organisms . Streptococcal species were the most common group (32% of patients), although the single most common organism was Staphylococcus aureus (25% of patients) . Sources of infection were identified in 93% of patients, with endocarditis and the gastrointestinal tract being the most common . In the majority of patients, visual outcome was poor . However, six eyes that received intravenous and intravitreal antibiotics, as well as therapeutic vitrectomy, achieved visual acuities of 20/50 or better . CONCLUSION: These results provide a further understanding of the manner of presentation, organisms involved, and sources of infection in endogenous bacterial endophthalmitis . They also suggest that improved outcome may be associated with early initiation of combined medical and surgical treatment.

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