Streptococcal

Arch Facial Plast Surg, 2001 Oct-Dec, 3(4), 277 - 9
Group A streptococcal fasciitis after submental tumescent liposuction; Beeson WH et al.; Tumescent liposuction is a procedure with a good safety record . Local infection is rare but can result in devastating consequences . We report a rare case of group A streptococcal fasciitis complicating tumescent liposuction and highlight the importance of early diagnosis and treatment of this condition . A 62-year-old woman presented 8 days after submental liposuction and a platysmal plication procedure with signs and symptoms of cervical fasciitis . Microbiological analysis confirmed a group A streptococcal infection . By using early aggressive medical and surgical treatments, the disease was arrested before the onset of any necrotizing process . A high index of suspicion is required to make an early diagnosis of this potentially disfiguring and life-threatening infection.

Pediatrics, 2001 Nov, 108(5), 1094 - 8
Early-onset neonatal sepsis in the era of group B streptococcal prevention; Baltimore RS et al.; OBJECTIVE: To determine whether intrapartum antibiotic prophylaxis for neonatal group B streptococcal (GBS) disease has resulted in an increased rate of non-GBS or antibiotic-resistant early-onset invasive neonatal disease . METHODS: Maternal and infant chart review of all infants with bacteria other than GBS isolated from blood or spinal fluid in 1996 through 1999 in 19 hospitals (representing 81% of in-state births to state residents) throughout Connecticut . Suspected cases were identified through clinical microbiology laboratory records or through International Classification of Diseases, Ninth Revision codes when microbiology records were incomplete . RESULTS: Ninety-four cases of non-GBS early-onset sepsis or meningitis were detected between 1996 and 1999 . The rate of GBS-related early-onset infection (days 0-6 of life) dropped from 0.61/1000 to 0.23/1000 births, but the annual rate of non-GBS sepsis remained steady, ranging from 0.65 to 0.68/1000 during the surveillance period . There was an increase in the proportion of Escherichia coli infections that were ampicillin resistant between 1996 and 1998, but the proportion decreased . in 1999 CONCLUSION: There was no increase in the incidence of non-GBS early-onset neonatal infections between 1996 and 1999 . Fluctuations in the annual incidence of E coli infections, including ampicillin-resistant infections, suggest the need for continuation of surveillance in Connecticut and expansion to monitor larger populations.

J Neuroimmunol, 2001 Nov 1, 120(1-2), 146 - 51
Progress toward analysis of D8/17 binding to B cells in children with obsessive compulsive disorder and/or chronic tic disorder; Murphy TK et al.; BACKGROUND: Previous research has suggested that a subgroup of children with obsessive compulsive disorder (OCD) have neuropsychiatric sequelae of streptococcal pharyngitis, similar to that seen in the neurological manifestation of rheumatic fever (RF) . Monoclonal antibody D8/17 demonstrates increased binding to B cells in patients with RF and in patients with neuropsychiatric disorders using immunofluorescent microscopy . OBJECTIVE: The aim of this study was to determine if an earlier immunofluorescent microscopy study of monoclonal antibody D8/17 in childhood-onset OCD and/or chronic tic disorder (CTD) could be replicated using the more objective method of flow cytometric analysis . METHOD: D8/17 binding to B cells was determined in patients with OCD and or CTD (N=32), and healthy controls (N=12) by flow cytometric analysis . RESULTS: Subjects with OCD/CTD showed increased mean cell binding (26.0%) of monoclonal antibody compared with healthy controls (9.1%) (p<0.001) . When using the threshold of greater than 19% binding (95% upper confidence interval) as a measure of positivity, 65.6% of patients compared with 8.3% of controls showed increased antibody binding to B cells (p=0.01) . CONCLUSIONS: Although this study reports positive results, many methodological issues will need to be addressed before generalized use of assay for diagnostic purposes.

Biol Psychiatry, 2001 Oct 15, 50(8), 566 - 77
Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders; Morshed SA et al.; BACKGROUND: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection . METHODS: To test this hypothesis, we looked for the presence ot total and IgG antibodies against neural, nuclear, cytoskeletal and streptococcal epitopes using indirect immunofluorescent assays and Western blot techniques in three patient groups: TS (n = 81), SC (n = 27), and a group of autoimmune disorders (n = 52) and in normal controls (n = 67) . Subjects were ranked after titrations of autoantibodies from 0 to 227 according to their level of immunoreactivity . RESULTS: TS patients had a significantly higher mean rank for total antineural and antinuclear antibodies, as well as antistreptolysin O titers . However, among children and adolescents, only the total antinuclear antibodies were increased in TS patients compared to age matched controls . Compared to SC patients, TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, significantly lower IgG class anticytoskeletal antibodies, and a significantly higher rank for total antinuclear antibodies . Compared to a mixed group of autoimmune disorders, the TS patients had a significantly lower mean rank for total and IgG class antineural antibodies, total and IgG class antinuclear antibodies, IgG class anticytoskeletal antibodies, and a significantly higher rank for antistreptococcal antibodies . CONCLUSIONS: TS patients had significantly higher levels of total antineural and antinuclear antibodies than did controls . Their relation to IgG class antineural and antinuclear antibodies, markers for prior streptococcal infection, and other clinical characteristics, especially chronological age, was equivocal.

Vaccine, 2001 Nov 12, 20(3-4), 370 - 6
Preclinical evaluation of group B streptococcal polysaccharide conjugate vaccines prepared with a modified diphtheria toxin and a recombinant duck hepatitis B core antigen; Paoletti LC et al.; An effective vaccine against group B streptococcal (GBS) disease will undoubtedly include capsular polysaccharides (CPSs) from each of the five serotypes prevalent in the United States individually coupled to immunogenic proteins . This formulation may require the use of two or more different protein carriers . We preclinically examined the potential of two proteins to serve as effective carriers for GBS type III CPS . Recombinant duck hepatitis B core antigen (rdHBcAg), a particulate protein of viral origin, and a newly mutated form of diphtheria toxin (DTm) were covalently and directly coupled to purified type III CPS by reductive amination . Seventy-seven of 79 (97%) newborn pups born to mouse dams actively vaccinated with type III CPS-rdHBcAg conjugate survived GBS type III challenge, whereas none of the pups born to dams that received an uncoupled mixture of type III CPS and rdHBcAg or saline survived . Likewise, 64 (98%) of 65 pups born to dams vaccinated with type III CPS-DTm conjugate survived challenge, in sharp contrast to no survivors among the pups born to dams vaccinated with an uncoupled mixture of type III CPS and DTm . The presence of type III CPS-specific IgG in serum from dams correlated with pup survival in groups that received a conjugate vaccine, and this serum was opsonically active in vitro against GBS type III . In addition, carrier-specific IgG was also measured in serum from vaccinated mice . These data suggest that the rdHBcAg and DTm may be effective carriers for GBS CPSs.

J Laryngol Otol, 2001 Oct, 115(10), 792 - 5
Nasopharyngeal endoscopy adds to reliability of clinical diagnosis of infectious mononucleosis; Weber R et al.; Frequently, the clinical picture in the oropharynx alone does not lend itself to a reliable differentiation between acute pharyngotonsillitis in infectious mononucleosis and a streptococcal inflammation . Such a differentiation, however, is essential for the indication of antibiotic therapy . Therefore, it was the aim of the present study to investigate whether or not endoscopic verification of larger-than-normal lymphatic tissue with fibrinous membranes in the nasopharynx would enhance the reliability of diagnosis . Fifty hospitalized patients exhibiting the clinical picture of acute pharyngotonsillitis were examined for the following parameters: nasopharyngeal endoscopy, determination of glutamine-oxaloacetic transaminase (GOT), glutamine-pyruvic transaminase (GPT), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), leucocytes and haemogram, antibodies to viral capsid antigen (VCA)-IgM, Epstein-Barr virus nuclear antigen (EBNA), and cytomegalovirus (CMV) . In 24 patients with acute tonsillitis/peritonsillar abscess, and in 26 patients with infectious mononucleosis, the total leucocyte count in the blood and the blood/erythrocyte sedimentation rate were comparable . Atypical lymphocytes or absolute lymphocytosis were not seen in acute tonsillitis, but were found in 88.5 per cent of patients with infectious mononucleosis . Elevated transaminase levels were noted in 77 (GOT) and 88.5 per cent (GPT) of patients with infectious mononucleosis, and in acute tonsillitis in 4.2 (GOT) and 12.5 per cent (GPT) of patients . The CRP was higher than normal in 91.7 per cent of patients with acute tonsillitis, and in 57.7 of patients with infectious mononucleosis . In none of the patients with acute tonsillitis was lymphatic tissue with fibrinous membranes seen in the nasopharyngeal cavity . In contrast, nasopharyngeal endoscopy in infectious mononucleosis was positive in 24 out of 26 patients . Hence, the sensitivity was 92.3 per cent, the specificity 100 per cent, and the prediction value for a positive test turned out to be 1 . Endoscopy of the nasopharngeal cavity employed as a simple and supplementary procedure adds to the reliability of diagnosis of infectious mononucleosis.

FASEB J, 2001 Nov, 15(13), 2524 - 6 Epub 2001 Sep 17.
Monovalent fusion proteins of IgE mimotopes are safe for therapy of type I allergy; Ganglberger E et al.; By screening phage display random peptide libraries with purified immunoglobulin E (IgE) from birch pollen-allergic patients, we previously defined peptides mimicking natural IgE epitopes (mimotopes) of the major birch pollen allergen Bet v 1 . The present study aimed to define a monovalent carrier for the IgE mimotopes to induce protective antibodies directed to the IgE epitopes, suitable for mimotope-specific therapy . We expressed the selected mimotopes as fusion proteins together with streptococcal albumin binding protein (ABP) . The fusion proteins were recognized specifically by anti-Bet v 1 human IgE, which demonstrated that the mimotopes fused to ABP resemble the natural IgE epitope . Bet v 1-specific IgG was induced by immunization of BALB/c mice with fusion proteins . These IgG antibodies could inhibit IgE binding to Bet v 1 . Skin testing of Bet v 1 allergic mice showed that the ABP mimotope constructs did not elicit type I skin reactions, although they possess IgE binding structures . Our data suggest that IgE mimotopes are safe for epitope-specific immunotherapy of sensitized individuals, when presented in a monovalent form . Therefore, ABP-fused mimotopes are promising candidates for a new type of immunotherapy based on the precise induction of blocking antibodies.

J Am Acad Dermatol, 2001 Nov, 45(5), 770 - 2
Varicella complicated by group A streptococcal facial cellulitis; Santos-Juanes J et al.; An increase has been recently noted in the incidence of life-threatening group A beta-hemolytic streptococcal (GABHS) infections in children recovering from varicella . We report our experience with a patient who required pediatric intensive care unit admission because of a serious GABHS infection 1 week after the onset of varicella . Emergency physicians must look for this complication in patients with varicella remaining abnormally febrile and presenting unusual manifestations.

J Microbiol Immunol Infect, 2001 Sep, 34(3), 195 - 200
Characteristics of group A streptococcal bacteremia with comparison between children and adults; Huang YC et al.; This retrospective study aimed to compare the characteristics of group A streptococcal bacteremia in children and adults . A total of 76 (12 children and 64 adults) patients with group A streptococcal bacteremia treated from October 1995 through September 2000 at the Linko Chang Gung Memorial Hospital were included . The mean age was 47.6 years (range, 12 days-90 years) . Forty-four (57.9%) patients had predisposing medical conditions . Malignant cancer (23.7%) and diabetes (22.4%) were the 2 most common conditions, which occurred only in adults . Two (16.7%) children had chickenpox associated with secondary group A streptococcal bacteremia . Skin and soft tissue infection (60.5%) was the most common clinical manifestation . The mortality rate related to group A streptococcal bacteremia was 25% . Twelve patients met the criteria of streptococcal toxic shock syndrome and 6 (50%) were children (p<0.05) . Despite immediate and aggressive treatment, mortality due to streptococcal toxic shock syndrome was 66.7% . The incidence of streptococcal toxic shock syndrome was much higher in children (50%) than in adults (9.4%) . Early diagnosis of invasive group A streptococcal infections and streptococcal toxic shock syndrome requires awareness of the presentations and a high level of suspicion . For fulminant group A streptococcal infection, a combination of a beta-lactam antibiotic plus clindamycin and/or adjuvant therapy with intravenous immunoglobulin is recommended.

Acta Trop, 2001 Oct 22, 80(2), 163 - 8
Tonsillar actinomycosis: a clinicopathological study; Bhargava D et al.; Actinomycosis has been known to involve virtually every anatomic site in the body . Although actinomycosis has been identified in resected tonsils, its possible role in adeno-tonsillar disease has received little attention . A clinicopathological study of 302 patients who had adeno-tonsillar surgery is presented . Tonsillar actinomycosis was present in 86 (28.5%) patients . The statistical analysis revealed a significant association (P<0.0001) of actinomycosis and tonsillar hypertrophy (56.8%) compared to only 10.3% in the recurrent tonsillitis group . A statistically significant association (P<0.0001) of tonsillar actinomycosis and sickle cell anaemia, beta thalassaemia, bronchial asthma and beta haemolytic streptococcal infections was also seen . This data supports a predisposition of the above conditions to tonsillar actinomycosis and adeno-tonsillar hypertrophy and a possible etiopathologic role of this organism in adeno-tonsillar hypertrophy and disease . Although the clinical association of actinomycosis and tonsillar hypertrophy and beta haemolytic streptococcal infection has been described before the association of actinomycosis with sickle cell anaemia, beta thalassaemia and bronchial asthma is being observed for the first time in literature.

Infect Immun, 2001 Nov, 69(11), 6696 - 701
Effects of alum adjuvant or a booster dose on immunogenicity during clinical trials of group B streptococcal type III conjugate vaccines; Paoletti LC et al.; Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular polysaccharide (CPS)-protein conjugate vaccines in healthy adults have demonstrated their safety and improved immunogenicity compared with uncoupled CPSs . Two recent trials sought to determine (i) whether adsorption of conjugate vaccine to aluminum hydroxide would improve immunogenicity and (ii) whether the CPS-specific immunoglobulin G (IgG) response could be boosted by administration of a second dose . Adsorption of GBS type III CPS-tetanus toxoid (III-TT) conjugate vaccine to alum did not improve the immune response to a 12.5-microg dose in healthy adult recipients . Four weeks after vaccination, the geometric mean antibody concentrations (GMCs) for the 15 recipients of III-TT with or without alum were 3.3 and 3.6 microg/ml, respectively . In the second trial, 36 healthy adults vaccinated previously with GBS III-TT conjugate were given a second 12.5-microg dose 21 months later . At 4 weeks after the second dose, the GMCs of type III CPS-specific IgG were similar to those measured 4 weeks after the primary vaccination, suggesting a lack of a booster response . However, 8 (22%) of the 36 participants who had undetectable III CPS-specific IgG (<0.05 microg/ml) before the first dose of III-TT conjugate exhibited a booster response to the second dose, with a fourfold-greater GMC of type III CPS-specific IgG than after the initial immunization . These results suggest that prior natural exposure to type III GBS or a related antigen may be responsible for the brisk IgG response to CPS noted in most adults after vaccination . However, a second dose of GBS III-TT conjugate vaccine may be required for adults whose initial CPS-specific IgG concentrations are very low and would also restore the initial peak-specific III CPS-IgG in responders to previous vaccination.

Klin Med (Mosk), 2001, 79(8), 47 - 50
{Evolutionary trends in symptoms of acute glomerulonephritis in adult population of the Novosibirsk region}; Movchan EA et al.; Acute glomerulonephritis (AGN) trends in the last 3 decades in the Novosibirsk Region have been analysed basing on the data from 308 AGN case histories . The results of the analysis demonstrate that AGN occurs not often but with stable rate . It is encountered more frequently in young men . The last decade is characterized by higher morbidity after streptococcal infection, high percentage of women at reproductive age, aggravation of the clinical course with marked edemas, severe arterial hypertension, renal dysfunction (acute renal failure in 10.4%), cases of left ventricular failure (5.2%) and eclampsia (1.7%) not registered earlier.

Structure (Camb), 2001 Aug, 9(8), 679 - 87
Complex between Peptostreptococcus magnus protein L and a human antibody reveals structural convergence in the interaction modes of Fab binding proteins; Graille M et al.; BACKGROUND: Peptostreptococcus magnus protein L (PpL) is a multidomain, bacterial surface protein whose presence correlates with virulence . It consists of up to five homologous immunoglobulin binding domains that interact with the variable (VL) regions of kappa light chains found on two thirds of mammalian antibodies . RESULTS: We refined the crystal structure of the complex between a human antibody Fab fragment (2A2) and a single PpL domain (61 residues) to 2.7 A . The asymmetric unit contains two Fab molecules sandwiching a single PpL domain, which contacts similar VL framework regions of two light chains via independent interfaces . The residues contacted on VL are remote from the hypervariable loops . One PpL-Vkappa interface agrees with previous biochemical data, while the second is novel . Site-directed mutagenesis and analytical-centrifugation studies suggest that the two PpL binding sites have markedly different affinities for VL . The PpL residues in both interactions are well conserved among different Peptostreptococcus magnus strains . The Fab contact positions identified in the complex explain the high specificity of PpL for antibodies with kappa rather than lambda chains . CONCLUSIONS: The PpL-Fab complex shows the first interaction of a bacterial virulence factor with a Fab light chain outside the conventional combining site . Structural comparison with two other bacterial proteins interacting with the Fab heavy chain shows that PpL, structurally homologous to streptococcal SpG domains, shares with the latter a similar binding mode . These two bacterial surface proteins interact with their respective immunoglobulin regions through a similar beta zipper interaction.

Arch Pediatr, 2001 Sep, 8 Suppl 4, 769s - 775s
{Staphylococcal and streptococcal pediatric toxic syndrome from 1998 to 2000 . Data from the National Center for Staphylococcal Toxemia}; Lina G et al.; The clinical and microbial settings of staphylococcal and streptococcal toxemia in pediatric patients were investigated by the French National Reference Center for Staphylococcal Toxemia . From 1998 to 2000, the number of cases was low in regard to the usual putative incidence of these toxemia; this low incidence was probably linked to the passive collection of cases . The most significant finding was the evidence of skin infections as the source of the majorities of staphylococcal toxic shock syndrome and staphylococcal scarlet fever as described for streptococcal toxic shock syndrome or nosocomial suppurative infections . Moreover, most of scalded skin syndrome were from pediatric patients and were exceptional in adults . For other syndromes, no significant original findings were observed.

Int Immunol, 2001 Oct, 13(10), 1335 - 43
Antibody levels to the class I and II epitopes of the M protein and myosin are related to group A streptococcal exposure in endemic populations; Brandt ER et al.; Rheumatic fever (RF)/rheumatic heart disease (RHD) and post-streptococcal glomerulonephritis are thought to be autoimmune diseases, and follow group A streptococcal (GAS) infection . Different GAS M types have been associated with rheumatogenicity or nephritogenicity and categorized into either of two distinct classes (I or II) based on amino acid sequences present within the repeat region ('C' repeats) of the M protein . Sera from ARF patients have previously been shown to contain elevated levels of antibodies to the class I-specific epitope and myosin with the class I-specific antibodies also being cross-reactive to myosin, suggesting a disease association . This study shows that immunoreactivity of the class I-specific peptide and myosin does not differ between controls and acute RF (ARF)/RHD in populations that are highly endemic for GAS, raising the possibility that the association is related to GAS exposure, not the presence of ARF/RHD . Peptide inhibition studies suggest that the class I epitope may be conformational and residue 10 of the peptide is critical for antibody binding . We demonstrate that correlation of antibody levels between the class I and II epitope is due to class II-specific antibodies recognizing a common epitope with class I which is contained within the sequence RDL-ASRE . Our results suggest that antibody prevalence to class I and II epitopes and myosin is associated with GAS exposure, and that antibodies to these epitopes are not an indicator of disease nor a pathogenic factor in endemic populations.

Harefuah, 2001 Sep, 140(9), 810 - 2, 896
{Overuse of antibiotics with upper respiratory tract infections in a primary care clinic}; Cohen AD et al.; In the majority of cases upper respiratory tract infections (URI's) are caused by viruses . Nonetheless, in many instances, patients with URI's are over-treated with antibiotics . In order to evaluate the use of antibiotic therapy in patients with URI's, we recorded medications prescribed for URI's in 394 young adults seeking care in a primary care clinic . The following parameters were assessed: rhinnorhea, cough, sore throat, dysphagia, tonsillar exudates, tonsillar enlargement and cervical lymphadenopathy . Throat cultures were taken from all the patients . RESULTS: Antibiotic therapy was prescribed for 99 of the 370 patients (26.8%) with URI's and negative throat cultures . Among these patients, a high prevalence of the following findings was evident: tonsillar enlargement (66.7%), tonsillar exudates (48.5%), cervical lymphadenopathy (42.4%), lack of rhinorrhea (40.4%), lack of cough (32.0%) and fever (31.3%) . CONCLUSIONS: Excess antibiotic therapy was prescribed for patients with URI's . Possible explanations are: clinical findings that suggest a diagnosis of follicular tonsillitis, early antibiotic treatment that is not based on throat cultures or antigen detection tests, and multiple treating physicians . RECOMMENDATIONS: We recommend that in cases of patients with URI's, antibiotics should not be prescribed unless diagnosis of a streptococcal infection is supported by results of throat cultures or antigen detection tests . Furthermore, in primary care clinics with a number of physicians, treatment should guarantee appropriate medical follow-up.

Anesth Analg, 2001 Oct, 93(4), 986 - 90
Epidural labor analgesia and neonatal sepsis evaluation rate: a quality improvement study; Kaul B et al.; Labor epidural analgesia (LEA) is allegedly associated with maternal fever and an increase in the newborn sepsis work-up (SWU) rate . In this study, we evaluated whether LEA causes an increase in the SWU rate compared with a Control group given parenteral narcotics for labor pain . Maternal and neonatal data were collected prospectively for a continuous quality improvement database . Odds ratios were calculated by using multiple logistic regression for various triggers for SWU in the neonate . Of the 1177 primiparous women and their neonates studied, 922 women received LEA and 255 women received parenteral analgesics . A small but statistically significant increase in maternal and neonatal temperatures occurred in parturients receiving LEA . The SWU rates were 7.5% in the LEA group and 9.4% in the Controls (not significant) . Triggers identified for SWU were birth weight (odds ratio = 116, P = 0.000), gestational age (odds ratio = 86.6, P = 0.000), meconium aspiration and respiratory distress requiring intubation (odds ratio = 8.6, P = 0.000), hypothermia at birth (odds ratio = 7.1, P = 0.001), maternal Group B beta-hemolytic streptococcal colonization (odds ratio = 6, P = 0.000), and preeclampsia or hypertension (odds ratio = 3.5, P = 0.03) . There was no association between LEA and SWU . IMPLICATIONS: Although it has been suggested that epidural analgesia for labor contributes to an increase in neonatal sepsis work-up (SWU), this retrospective analysis shows that epidural analgesia is not associated with an increase in SWU . The factors that were found to contribute to SWU included low birth weight, low gestational age, meconium aspiration or respiratory distress at birth, hypothermia at birth, maternal group B beta-hemolytic colonization, and preeclampsia or hypertension.

Microbiol Res, 2001, 156(2), 133 - 8
Isolation and characterization of enterocin BC25 and occurrence of the entA gene among ruminal gram-positive cocci; Morovsky M et al.; Enterocin BC25, a bacteriocin produced by Enterococcus faecium BC25 isolated from the rumen of cow was purified to homogeneity and sequenced . Twenty amino acids were identified in the peptide chain (TTHSGKYYGNGVYCT-KNKCT), identical to the N-terminal sequence of enterocin A . The DNA sequence of the enterocin BC25 structural gene and putative immunity protein exhibited high similarity to the entA gene . The occurrence of a 726 bp amplicon containing the enterocin A structural gene was studied among gram-positive ruminal cocci by PCR . Our results showed wide occurrence of the entA structural gene among ruminal enterococcal and streptococcal bacterial strains tested, and indicate variable ability to express bacteriocin production and resistance.

Lakartidningen, 2001 Aug 22, 98(34), 3545 - 9
{Rheumatic fever behind acute chorea in a young girl . A case report}; Malmborg P et al.; This article presents the case of a 13-year old girl who was admitted to the emergency department because of rapidly evolving, seriously disabling impairments in movement and speech . Investigation led to the conclusion that her problems were caused by Sydenham's chorea as a manifestation of rheumatic fever . A neuropsychiatric examination performed one year after the onset of disease revealed a hitherto unknown mild mental retardation . The case description is followed by a clinical update on rheumatic fever focusing on cerebral manifestations . The theories concerning the existence of PANDAS--an autoimmune neuropsychiatric disorder following streptococcal infections, distinct from rheumatic fever--are presented.

Laryngoscope, 2001 Sep, 111(9), 1515 - 9
Pediatric autoimmune neuropsychiatric disorders and streptococcal infections: role of otolaryngologist; Orvidas LJ et al.; OBJECTIVE: To increase awareness and understanding of the putative role of streptococcal infection in the development of neuropsychiatric disorders in children and to discuss therapeutic options in this group of patients . METHODS: Case illustration and literature review . RESULTS: Two siblings, one with obsessive-compulsive disorder (OCD) and one with a tic disorder, had tonsillectomy for recurrent streptococcal pharyngitis . At the latest follow-up visit (11 mo postoperatively), both patients exhibited significant improvement in their psychiatric illnesses . We discuss these cases as well as the diagnosis, pathophysiology, and treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) . CONCLUSION: PANDAS is an active area of research investigating the relationship between streptococcal infections and the development of obsessive-compulsive disorder or tic disorders (or both) in children . The etiopathogenesis of PANDAS is thought to reflect autoimmune mechanisms and involvement of the basal ganglia of susceptible hosts . Because otolaryngologists evaluate a large portion of pediatric patients with recurrent streptococcal pharyngitis, it is important to be aware of this association and to manage these patients appropriately.

Laryngoscope, 2001 Aug, 111(8), 1413 - 22
Surgical management of retropharyngeal space infections in children; Kirse DJ et al.; OBJECTIVE: To study the perioperative management strategies in a large group of pediatric patients undergoing surgical therapy for suppurative adenitis of the parapharyngeal and retropharyngeal spaces . STUDY DESIGN: Retrospective analysis of all patients treated surgically from January 1, 1989, to December 31, 1998, in a tertiary care pediatric hospital . METHODS: Charts were reviewed for demographic data, duration and nature of symptoms, radiological workup, surgical approach, complications, duration of medical therapy and antibiotic choice, and bacteriological findings . Computed tomography (CT) results were correlated to surgical findings . RESULTS: A dramatic increase in the incidence of deep neck space infection was seen during the study period; this increase was congruent with the increase in culture-positive group A beta-hemolytic streptococcal abscesses . More than two-thirds of the patients were boys with the peak incidence being in the 3- to 5-year-old group . The duration of symptoms before presentation was less than might be expected, especially in the younger age groups . Seventy of 73 children were treated with a transoral approach . Sixty-eight of 73 were successfully treated with one operative intervention . Irregularity of the abscess wall was found to be a stronger predictor of the presence of pus than the presence of ring enhancement . CONCLUSIONS: The current study represents the largest series of pediatric retropharyngeal abscesses in the modern medical literature . Changes in the disease process and in management from the first half of the century to today are reviewed, and recommendations for optimal management presented . The data in this series support a transoral approach to these abscesses unless there is extension lateral to the great vessels.

Protein Sci, 2001 Oct, 10(10), 2138 - 9
Heparin binding by the HIV-1 tat protein transduction domain; Hakansson S et al.; The protein transduction domain from the HIV-1 tat protein (termed PTD-tat) has been fused to the C-terminus of a model cargo protein, the IgG binding domain of streptococcal protein G . We demonstrate that PG-Ctat (PTD-tat fused to the C-terminus of protein G) binds to a heparin affinity column . PG-Ctat binds with relatively high affinity, as shown by its elution at 1.6 M NaCl . The heparin binding properties of PTD-tat are consistent with the idea that heparan sulfate, an analog of heparin found at the cell surface, plays a role in the translocation of PTD-tat fusions . We suggest that the heparin-binding properties of PTD-tat can be exploited for purification of PTD-tat fusions in the absence of affinity tags.

J Immunol, 2001 Oct 1, 167(7), 3870 - 7
Isolated hypervariable regions derived from streptococcal M proteins specifically bind human C4b-binding protein: implications for antigenic variation; Morfeldt E et al.; Antigenic variation in microbial surface proteins represents an apparent paradox, because the variable region must retain an important function, while exhibiting extensive immunological variability . We studied this problem for a group of streptococcal M proteins in which the approximately 50-residue hypervariable regions (HVRs) show essentially no residue identity but nevertheless bind the same ligand, the human complement regulator C4b-binding protein (C4BP) . Synthetic peptides derived from different HVRs were found to retain the ability to bind C4BP, implying that the HVR corresponds to a distinct ligand-binding domain that can be studied in isolated form . This finding allowed direct characterization of the ligand-binding properties of isolated HVRs and permitted comparisons between different HVRs in the absence of conserved parts of the M proteins . Affinity chromatography of human serum on immobilized peptides showed that they bound C4BP with high specificity and inhibition experiments indicated that different peptides bound to the same site in C4BP . Different C4BP-binding peptides did not exhibit any immunological cross-reactivity, but structural analysis suggested that they have similar folds . These data show that the HVR of streptococcal M protein can exhibit extreme variability in sequence and immunological properties while retaining a highly specific ligand-binding function.

Curr Rheumatol Rep, 2001 Oct, 3(5), 445 - 52
Rheumatic fever; Rullan E et al.; Rheumatic fever is a multisystem inflammatory disease that occurs as a delayed sequel to group A streptococcal pharyngitis . It is less common than it was 50 years ago but is still a major cause of heart disease in developing areas of the world . The relationship between the site of infection, the type of causative organism, and susceptibility of the host is essential in the development of the disease . Its major clinical manifestations include carditis, migratory polyarthritis, chorea, erythema marginatum, and subcutaneous nodules . It can manifest as an acute febrile illness consisting of migratory polyarthritis involving the large joints, as carditis and valvulitis, or as Sydenham's chorea with involvement of the central nervous system . The disorder in its milder form resolves itself without sequelae . Carditis is the condition most associated with increased mortality and morbidity and may be fatal in its severe forms . Penicillin is the most appropriate primary and secondary prophylaxis . Anti- inflammatory agents provide symptomatic relief but do not prevent rheumatic heart disease.

Curr Rheumatol Rep, 2001 Oct, 3(5), 363 - 4
Clinical trials for post-streptococcal reactive arthritis; Lehman TJ et al.; Post-streptococcal reactive arthritis is a frequently observed entity that has an uncertain relationship with acute rheumatic fever . Although different criteria have been suggested for delineating these two conditions, none have been validated . In the absence of a clear definition, it has been impossible for investigators to carry out meaningful studies . Some children who were initially labeled as having post-streptococcal reactive arthritis later suffered from carditis and definite rheumatic fever with subsequent streptococcal infections . Some physicians now recommend that all children with post-streptococcal reactive arthritis receive penicillin prophylaxis . However, the proper duration of treatment and appropriate guidelines for patient selection have not been determined . It will be impossible to answer these questions until collaborative efforts are made to accurately define this illness and then begin a careful analysis of its etiopathogenesis and natural history . In the interim, each physician must evaluate the potential risks and benefits of penicillin prophylaxis in view of the risk of rheumatic fever in the community.

Proteins, 2001 Nov 1, 45(2), 144 - 58
Protein molecular dynamics with the generalized Born/ACE solvent model; Calimet N et al.; Implicit solvent models are increasingly important for the study of proteins in aqueous solution . Here, the generalized Born (GB) solvent polarization model as implemented in the analytical ACE potential {Schaefer and Karplus (1996) J Phys Chem 100:1578} is used to perform molecular dynamics simulations of two small, homologous proteins: the immunoglobulin-binding domain of streptococcal protein G and the Ras binding domain of Raf . Several model parameterizations are compared through more than 60 ns of simulation . Results are compared with two simpler solvent models-an accessible surface area model and a distant-dependent dielectric model, with finite-difference Poisson calculations, with existing explicit solvent simulations, and with experimental data . The simpler models yield stable but distorted structures . The best GB/ACE implementation uses a set of atomic Voronoi volumes reported recently, obtained by averaging over a large database of crystallographic protein structures . A 20% reduction is applied to the volumes, compensating in an average sense for an excessive de-screening of individual charges inherent in the ACE self-energy and for an undersolvation of dipolar groups inherent in the GB screening function . This GB/ACE parameterization yields stable trajectories on the 0.5-1-ns time scale that deviate moderately (approximately 1.5-2.5 A) from the X-ray structure, reproduce approximately the surface distribution of charged, polar, and hydrophobic groups, and reproduce accurately backbone flexibility as measured by amide NMR-order parameters . Over longer time scales (1.5-3 ns), some of the protein G runs escape from the native energy basin and deviate strongly (3 A) from the native structure . The conformations sampled during the transition out of the native energy basin are overstabilized by the GB/ACE solvation model, as compared with a numerical treatment of the full dielectric continuum model .

Neurol Med Chir (Tokyo), 2001 Aug, 41(8), 387 - 92
Adoptive immunotherapy for malignant brain tumors using human peripheral blood mononuclear cells activated by the Streptococcal preparation OK-432; Hirotsu T et al.; Adoptive immunotherapy using OK-432-activated mononuclear cells (OK-MCs) offers cell-mediated and cytokine-mediated pathways for antitumor activity . The effectiveness of direct intratumoral administration of OK-MCs via a catheter/reservoir system was studied in patients with malignant brain tumors . Seventeen patients, 12 with malignant glioma, four with metastatic adenocarcinoma, and one with primary sarcoma of the brain, were treated by OK-MC therapy (1.0 to 11.2 x 10(7) cells/person) between June 1989 and April 1999 . The OK-MC therapy was given to patients with tumors progressing despite previous cytoreductive surgery, radiation, or chemotherapy . Adverse effects seen after the therapy were fever in 10 patients, seizure in two patients, and hypotension in one patient . Evaluation by computed tomography or magnetic resonance imaging revealed that seven patients showed no change including three with minor response, and 10 showed progressive disease . Adoptive immunotherapy using OK-MC was safe and well tolerated, but the therapeutic potential is limited.

Rheumatology (Oxford), 2001 Sep, 40(9), 978 - 87
Suppression of chronic streptococcal cell wall-induced arthritis in Lewis rats by liposomal clodronate; Richards PJ et al.; OBJECTIVES: To investigate the role of macrophages in the pathogenesis of chronic streptococcal cell wall (SCW)-induced arthritis using liposomal clodronate . METHODS: Female Lewis rats with SCW-induced arthritis received a single intravenous injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) 10 days post-arthritis induction . RESULTS: SUVc significantly suppressed the development of chronic SCW-induced arthritis for up to 26 days after treatment . At this time point, ED1(+) macrophages were significantly depleted in the liver and ankle joints, although splenic macrophage numbers were not significantly different from control groups . Macrophage elimination induced a significant reduction in local levels of interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha) and matrix metalloproteinase-9 (MMP-9) from ankle joints . CONCLUSIONS: Macrophage elimination by SUVc inhibits local production of IL-1beta, IL-6, TNFalpha and MMP-9, and the pathogenesis of inflammatory arthritis.

Trop Anim Health Prod, 2001 Oct, 33(5), 355 - 65
An outbreak of respiratory disease complex in sheep in Central Ethiopia; Tibbo M et al.; An investigation was carried out into an outbreak of respiratory disease complex (RDC) in 3641 Menz and Awassi x Menz cross sheep in Central Ethiopia between 1998 and 1999 by clinical, serological, microbiological, post-mortem and histopathological examinations . The monthly incidence of RDC varied from 2.8% to 4.0% and the prevalence was as high as 17% . The case fatality rate was 18%, despite culling of sick sheep . Over 76% of the morbidity occurred in adults, followed by 19% among weaners . Similarly, 62% of the mortality was in adults . However, 27% of the mortality occurred in lambs despite the low morbidity in the group . Significant breed and age differences were seen in the morbidity and mortality rates (p < 0.05) . Clinical signs, gross and microscopic lesions and serological and bacteriological examinations showed an interplay of several causes of the RDC, including pestes des petits ruminants (PPR) (72.3%, serologically confirmed), lung worms, maedi-visna, bacterial bronchopneumonia (staphylococcal and streptococcal), enzootic pneumonia and some fungal infections . Cold temperatures, which may be as low as -8.5 degrees C at night, are major predisposing factors along with managemental stresses . Vaccination of animals with a homologous PPR vaccine appeared to decrease dramatically the occurrence of the disease, showing that PPR played an important role in the outbreak . Several of the pathogens do not appear to be individually capable of causing the respiratory disease . Appropriate strategies for the prevention of RDC are suggested.

J Infect, 2001 Apr, 42(3), 195 - 200
Toxic shock-like syndrome with flu-like prodrome: a possible role of 'enhancing tissue focus' for streptococcal toxic shock; Hirose Y et al.; We describe three patients with invasive group A streptococcal infection, admitted during the 3 months between November 1996 and February 1997 . All patients were previously healthy Japanese women who developed a profound shock, with a rapidly fatal outcome, after experiencing flu-like symptoms . All cases conformed to the case definition of toxic shock-like syndrome (TSLS).Currently, the pathogenic mechanism of TSLS remains unclear . Known microbial virulence factors can not sufficiently explain the occurrence of TSLS, and it has been generally considered that host factors may be contributory . On pathological examination, each patient had one organ or tissue that was most severely involved: Case 1 a non-penetrating trauma; Case 2 a pregnant uterus; and Case 3 a pulmonary lesion reminiscent of lymphocytic interstitial pneumonia . On the basis of clinicopathological features of these cases, we propose that the coexistence of 'enhancing tissue focus' may be one of host factors for the progression of TSLS in patients infected with non-invasive GAS .

Brain Res, 2001 Sep 14, 913(1), 95 - 105
Serum cleaved Tau protein and neurobehavioral battery of tests as markers of brain injury in experimental bacterial meningitis; Irazuzta JE et al.; Brain injury due to bacterial meningitis affects multiple areas of the brain with a heterogeneous distribution generating a challenge to assess severity . Tau proteins are microtubular binding proteins localized in the axonal compartment of neurons . Brain injury releases cleaved Tau proteins (C-tau) into the extracellular space where they are transported to the cerebral spinal fluid . We hypothesized that C-tau crosses the blood-brain barrier during inflammation and that it can be detected in serum . The correlation between serum C-tau levels and the extent of the meningitic insult was examined . Furthermore, we studied whether the use of a subset of neurobehavioral tasks can assess the extent of brain injury after meningitis . The tests were chosen primarily for their ability to detect deficits in the acoustic system, low brain, reflexive responding, as well as for impaired motor coordination and the higher brain functions of learning and memory . A rat model of group B streptococcal meningitis with variable severity was utilized . At five days after bacterial inoculation followed by antibiotic therapy neurobehavioral tests were performed and serum C-tau and histologic samples of the brain were obtained . Our study shows that during meningitis C-tau appears in serum and reflects the extent of neurologic damage . Neurobehavioral performance was altered after bacterial meningitis and could be correlated with histologic and biochemical markers of neurologic sequelae . We conclude that serum C-tau and a composite of neurobehavioral tests could become useful markers for assessing the severity of neurological damage in experimental bacterial meningitis.

Br J Dermatol, 2001 Aug, 145(2), 280 - 4
The importance of serum creatine phosphokinase level in the early diagnosis, and as a prognostic factor, of Vibrio vulnificus infection; Nakafusa J et al.; BACKGROUND: Vibrio vulnificus infection causes rapidly progressive skin lesions and sepsis in compromised hosts with liver cirrhosis, and is often fatal . Early diagnosis and rapid treatment are important . OBJECTIVES: To clarify the characteristics of V . vulnificus infection that distinguish it from other cutaneous and soft-tissue bacterial infections and to confirm that serum creatine phosphokinase (CPK) levels are useful in early diagnosis, and are a prognostic factor for, V . vulnificus infection . METHODS: We analysed the clinical and laboratory findings (especially serum CPK levels) in eight patients with V . vulnificus infection who were treated at the Saga Medical School Hospital between January 1989 and December 1999 . RESULTS: All eight patients had liver dysfunction and typical skin manifestations . Six had eaten raw seafood before onset . Seven patients had initial skin manifestations in their legs or feet and eventually died, despite prompt therapy in the intensive care unit . CPK levels of six of these seven patients were already elevated at their initial presentation . Only one patient, with skin manifestations solely on his left hand, showed and maintained a normal CPK level and survived . In 23 patients with cutaneous and soft-tissue infections (10 with necrotizing fasciitis, three with erysipelas, 10 with cellulitis), only three patients with necrotizing fasciitis and streptococcal toxic shock syndrome (STSS) showed CPK elevation . CONCLUSIONS: A high level of serum CPK in cutaneous or soft-tissue bacterial infection is considered useful for an early diagnosis of V . vulnificus infection and STSS . A history of eating raw seafood, underlying liver disease and multiple lesions suggest a diagnosis of V . vulnificus infection, rather than STSS.

Br J Dermatol, 2001 Aug, 145(2), 245 - 51
Contrasting patterns of streptococcal superantigen-induced T-cell proliferation in guttate vs . chronic plaque psoriasis; Davison SC et al.; BACKGROUND: Streptococcal infection is strongly associated with guttate psoriasis (GP) and may also exacerbate chronic plaque psoriasis (CPP), possibly through the release of superantigenic toxins . OBJECTIVES: To investigate superantigen-induced generation of cutaneous lymphocyte associated antigen (CLA) -positive lymphocytes in GP compared with CPP . METHODS: Peripheral blood lymphocyte (PBL) expression of CLA and T-cell receptor Vbeta chain was assessed in patients with CPP and with active and resolved GP . Expression of superantigen-reactive Vbeta families was compared with in vitro superantigen-induced peripheral blood mononuclear cell (PBMC) proliferation . RESULTS: Peripheral blood mononuclear cells from patients with active GP showed a twofold increased proliferation after stimulation with streptococcal pyogenic toxins A and streptococcal pyogenic toxins C compared with controls (P < 0.01), whereas the response to the staphylococcal toxins and mitogenic stimulation was the same in all groups . Peripheral blood lymphocytes (PBL) from patients with active GP showed increased use of the superantigen-reactive families Vbeta2 (P < 0.01) and Vbeta17 (P < 0.05), which was not evident in the other patient groups or controls . This pattern of Vbeta expression was only observed in CLA-positive T cells . Furthermore, there was a positive correlation between Vbeta2 expression and enhanced proliferation after stimulation with SPEA (r = 0.82, P < 0.01) and SPEC (r = 0.74, P < 0.05) in active GP . CONCLUSIONS: This study supports the concept that streptococcal infection precipitates acute GP at least in part through superantigen driven generation of Vbeta-restricted CLA-positive skin homing lymphocytes, whereas we could find no evidence for a similar mechanism occurring in the maintenance of stable CPP.

Nurse Pract, 2001 Aug, 26(8), 34, 37 - 42, 44-7; quiz 48-9
Identifying poststreptococcal glomerulonephritis; Lang MM et al.; Expedient antimicrobial treatment of group A beta-hemolytic streptococcal tonsillopharyngitis prevents suppurative complications and rheumatic fever; however, timely therapy does not prevent acute poststreptococcal glomerulonephritis . Acute poststreptococcal glomerulonephritis is the most common form of postinfectious glomerulonephritis and a leading cause of acute and chronic renal failure in childhood . This article discusses clinical presentation, diagnostic workup, treatment, and prevention of poststreptococcal glomerulonephritis in adults and children in the primary care setting.

Int J Med Inform, 2001 Sep, 63(1-2), 31 - 40
Generation of an intelligent medical system, using a real database, to diagnose bacterial infection in hospitalized patients; Cundell DR et al.; The initial diagnosis of bacterial infections in the absence of laboratory microbiological data requires physicians to use clinical algorithms based on symptoms, patient history and infection site . Optimization of such algorithms would be achieved by including as many variables associated with bacterial infection as possible . Demographic data are easily available and frequently used to sub-group human populations . A prospective investigation was, therefore, undertaken to examine the influence of demographic variables on bacterial infection rates, using data obtained from 173 patients presenting to Albert Einstein Medical Center . Data was randomly selected from 149 of these patients and used to generate fuzzy rules to model an intelligent medical system . To test the accuracy of this system at determining bacterial infection, based solely on demographic data, the program was given the remaining 24 patients' information . All 18 patients with either streptococcal, staphylococcal or Escherichia coli infections were correctly diagnosed . Non-E.coli GNR were misdiagnosed as E . coli infections in two patients resulting in an overall prediction rate for the 24 patients of 91.66% . This study suggests that the direct correlation of demographic variables with a predisposition to bacterial infection allow the design of an intelligent medical system, which shows great future potential as a diagnostic tool for all physicians.

J Biol Chem, 2001 Oct 26, 276(43), 39832 - 5 Epub 2001 Aug 21.
Functional molecular mass of a vertebrate hyaluronan synthase as determined by radiation inactivation analysis; Pummill PE et al.; Hyaluronan (HA), a linear polysaccharide composed of N-acetylglucosamine-glucuronic acid repeats, is found in the extracellular matrix of vertebrate tissues as well as the capsule of several pathogenic bacteria . The HA synthases (HASs) are dual-action glycosyltransferases that catalyze the addition of two different sugars from UDP-linked precursors to the growing HA chain . The prototypical vertebrate hyaluronan synthase, xlHAS1 (or DG42) from Xenopus laevis, is a 588-residue membrane protein . Recently, the streptococcal enzyme was found to function as a monomer of protein with approximately 16 lipid molecules . The vertebrate enzymes are larger than the streptococcal enzymes; based on the vertebrate HAS deduced amino acid sequence, two additional membrane-associated regions at the carboxyl terminus are predicted . We have utilized radiation inactivation to measure the target size of yeast-derived recombinant xlHAS1 . The target size of HAS activity was confirmed using two internal standards . First, samples were spiked with glucose-6-phosphate dehydrogenase, an enzyme of known molecular weight . Second, parallel samples of native xlHAS1 and a xlHAS1-green fluorescent protein fusion (833 residues) were compared; substantial confidence was gained by using this novel internal standard . Our test also corroborated the basic tenets of radiation inactivation theory . We found that the vertebrate HAS protein functions catalytically as a monomer.

Arch Dis Child, 2001 Sep, 85(3), 223 - 7
Rheumatic fever in a high incidence population: the importance of monoarthritis and low grade fever; Carapetis JR et al.; AIMS: To describe the clinical features of rheumatic fever and to assess the Jones criteria in a population and setting similar to that in many developing countries . METHODS: The charts of 555 cases of confirmed acute rheumatic fever in 367 patients (97% Aboriginal) and more than 200 possible rheumatic fever cases from the tropical "Top End" of Australia's Northern Territory were reviewed retrospectively . RESULTS: Most clinical features were similar to classic descriptions . However, monoarthritis occurred in 17% of confirmed non-chorea cases and 35% of unconfirmed cases, including up to 27 in whom the diagnosis was missed because monoarthritis is not a major manifestation . Only 71% and 25% of confirmed non-chorea cases would have had fever using cut off values of 38 degrees C and 39 degrees C, respectively . In 17% of confirmed non-chorea cases, anti-DNase B titres were raised but antistreptolysin O titres were normal . Although features of recurrences tended to correlate with initial episodes, there were numerous exceptions . CONCLUSIONS: Monoarthritis and low grade fever are important manifestations of rheumatic fever in this population . Streptococcal serology results may support a possible role for pyoderma in rheumatic fever pathogenesis . When recurrences of rheumatic fever are common, the absence of carditis at the first episode does not reliably predict the absence of carditis with recurrences.

Mt Sinai J Med, 2001 Sep-Oct, 68(4-5), 336 - 8
Cutaneous polyarteritis nodosa after streptococcal necrotizing fasciitis; Stein RH et al.; Polyarteritis nodosa (PAN) is a necrotizing arteritis of small and medium-sized vessels . It may present with hypertension and/or renal insufficiency . Peripheral neuropathy, myopathy, joint pains, testicular pain, and ischemic myalgias may also be seen . Gastrointestinal involvement may lead to gangrene of the bowel, peritonitis, perforation, intra-abdominal hemorrhage, and pancreatitis . The cutaneous manifestations include tender subcutaneous nodules grouped along the course of superficial arteries of the lower extremities, with or without an overlying livedo reticularis . Although multisystem involvement is characteristic, sometimes only one organ or system may be involved . Associations with viral hepatitis (both B and C) and streptococcal infection have been established for PAN . Recurrent strep infections of the upper respiratory tract, streptococcal glomerulonephritis and rheumatic fever have previously been linked to PAN . This report extends the spectrum of associated streptococcal infections to include necrotizing fasciitis.

BJOG, 2001 Aug, 108(8), 840 - 7
Choosing a strategy to prevent neonatal early-onset group B streptococcal sepsis: economic evaluation; Stan CM et al.; OBJECTIVE: To determine the most appropriate strategy to prevent neonatal streptococcal sepsis in a setting with a low incidence of the disease . DESIGN: Decision analysis and economic evaluation . SETTING: Geneva University Hospitals, Switzerland . POPULATION: Pregnant women at 35-37 weeks of gestation and in labour . METHODS: Local data and data from the literature were used in a decision analysis to compare the current policy of antibiotic administration at Geneva University Hospitals with the recommended preventive strategies . MAIN OUTCOME MEASURES: Number of episodes of sepsis averted; cost and number needed to treat to prevent one episode of sepsis; and proportion of women receiving antibiotics during labour . RESULTS: Compared with the current policy, the risk factors strategy would prevent 69 streptococcal sepsis per million deliveries and the screening strategy would prevent 102 cases of sepsis per million deliveries . Cost per averted sepsis case would be 60 pounds, 700 and 473 pounds, 600, respectively . The number needed to treat to prevent one sepsis would be 1,087 with a risk factors strategy and 1,029 with a screening strategy . Preventive strategies would increase the proportion of women receiving antibiotics during labour from 6% with the current policy, to 13.5% and 16.5% respectively . CONCLUSIONS: Preventive strategies are more effective than the current policy, but imply increased hospital costs and a notable increase in the proportion of women receiving antibiotics during labour, which may be unjustified in a low incidence setting.

Horm Res, 2001, 55(2), 77 - 80
Frasier syndrome with childhood-onset renal failure; Buzi F et al.; BACKGROUND: The Wilms' tumour 1 (WT1) gene encodes a protein which is believed to exert transcriptional and tumour-suppressor activities . Mutations of this gene have occasionally been associated with Wilms' tumour (<15% of cases) and, more consistently, with three syndromes characterized by urogenital abnormalities (WAGR, Denys-Drash and Frasier syndrome) . SUBJECT/METHOD: A 25-year-old phenotypic female with a 46,XY karyotype presented with amenorrhoea . An ultrasound scan showed streak gonads and a rudimentary uterus . The patient had a history of post-streptococcal glomerulonephrosis, when aged 4 years, which had rapidly progressed to kidney failure, requiring transplantation at age 8 . RESULT: Frasier syndrome was suspected and confirmed by genetic analysis . In fact, direct sequencing of the PCR product of the intron 9 donor splice site revealed a substitution of guanine for adenine in position +5 . CONCLUSION: Besides being one of the few Frasier syndrome cases to be genetically characterized, this case is interesting because of the unusually early-onset renal failure .

Folia Microbiol (Praha), 2001, 46(1), 61 - 2
Bacteriocins of ruminal bacteria; Morovsky M et al.; Similar sequences of distribution of structural genes encoding enterocin A (isolated from the ruminal strain E . faecium BC25) and enterolysin A (isolated from the ruminal amylolytic strain S . bovis II/1) were demonstrated by PCR using oligonucleotide primers specific for these bacteriocins within the ruminal enterococcal and streptococcal strains . Variable occurrence of these bacteriocins was found within the populations of Gram-positive ruminal cocci.

Infect Immun, 2001 Sep, 69(9), 5345 - 51
T-cell reactivity against streptococcal antigens in the periphery mirrors reactivity of heart-infiltrating T lymphocytes in rheumatic heart disease patients; Guilherme L et al.; T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD) . We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD . The role of HLA class II molecules in the presentation of M5 peptides was also evaluated . We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients . Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls . The M5 peptide encompassing residues 81 to 96 {M5(81-96) peptide} was most frequently recognized by PBMC from HLA-DR7+ DR53+ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81-103) region . Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD . The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue . Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.

Arch Pediatr, 2001 Jul, 8(7), 700 - 6
{Treatment of acute group A beta-hemolytic streptococcal tonsillitis in children with a 5-day course of josamycin}; Portier H et al.; MATERIAL AND METHODS: In this randomized open study, 325 children aged two to 15 years with acute tonsillitis and a positive test of GA beta H streptococcal antigen were treated with josamycin 50 mg.kg-1.day-1 b.i.d for 5 days, or penicillin 50,000 to 100,000 IU/day t.i.d for 10 days . Clinical assessments and throat cultures for GA beta HS isolation were performed at the inclusion visit (V1), at the end of treatment visit (V2: day 12 for all patients) and at the follow-up visit (V3: day 30) . In case of positive GA beta HS culture, the bacterial DNA by RFLP was performed to differentiate between the persistence (presence of original strain at V2), relapse (eradication at V2 and acquisition of same strain at V3) and reinfection (eradication at V2 and acquisition of different strain at V3) . RESULTS: Two hundred and twenty-three patients were included in the bacteriological and clinical criteria per protocol analysis . At V2, eradication rates were comparable: 82% in josamycin and 80% in penicillin patients; clinical cure rates were 90% and 89% . At V3, relapse of GAS assessed only on clinically and bacteriologically cured patients at V2 occurred in 12% of josamycin patients and 12.8% of penicillin patients . Tolerance was good; 14% and 10% of josamycin and penicillin patients respectively experienced an adverse event . CONCLUSION: In this non-inferiority study, the efficacy of a 5-day course of josamycin is comparable to reference treatment in GA beta HS tonsillitis in children.

Jpn J Thorac Cardiovasc Surg, 2001 Jun, 49(6), 373 - 6
Mitral valve replacement through right thoracotomy after coronary arterial bypass grafting with functioning conduits; Wakiyama H et al.; A 67-year-old man who had undergone coronary artery bypass grafting 3 years previously suffered from severe mitral regurgitation associated with Streptococcal infective endocarditis . He was placed in New York Heart Association functional class III . Preoperative angiography demonstrated good opacification of all 3 conduits implanted in the previous operation . We replaced the mitral valve through an anterolateral right thoracotomy, approaching the mitral valve as an alternative to redoing sternotomy to minimize potential injury to patent grafts . His postoperative course was uneventful . After a 1-month course of antibiotics, the patient was discharged as New York Heart Association class II and at present, 3 months after discharge, is doing well . This approach is an effective alternative to redoing sternotomy for mitral valve operation, especially in patients undergoing a previous coronary arterial bypass grafting via median sternotomy.

Vojnosanit Pregl, 2001 Mar-Apr, 58(2), 161 - 6
{Acute post-streptococcal glomerulonephritis in adults--corticosteroid therapy, yes or no?}; Jovanovic D et al.; The aim of this study was to investigate the influence of the corticosteroid therapy on the development and prognosis of proststreptococcal glomerulonephritis (PSGN) in the period of five years . The investigation included a group of 54 patients who were in the acute phase of poststreptococcal glomerulonephritis (PSGN) when they were 18-22 years old . Corticosteroids were administered per os with the starting dose of 0.5 mg/kg bm, and the dose was subsequently decreased by 5 mg every 10 days to 20 mg/per day within 8 weeks of therapy . We have treated ten patients and all were with severe clinical manifestations of the disease (acute renal failure, oliguria, edemas, hypertension) and severe histopathologic (HP) finding of kidney tissue on the initial biopsy . On the basis of clinical parameters, HP changes on the repeated biopsy of the kidney and five years follow-up, we have concluded that the remission of the disease was achieved in patients who had received corticosteroid therapy . Clinical findings were confirmed by PH findings of repeated biopsies with less expressed residues of the disease . Corticosteroid therapy should be administered in adult patients who are in the acute phase of the disease, with clinical and HP severe form of PSGN, since the risk for the further progress of more serious sequelae of the disease is significantly decreased.

Pediatr Int, 2001 Aug, 43(4), 364 - 7
Prognosis of acute poststreptococcal glomerulonephritis (APSGN) is excellent in children, when adequately diagnosed; Kasahara T et al.; BACKGROUND: Recently, the prognosis of acute poststreptococcal glomerulonephritis (APSGN) has been reported as improved, compared with the results of previous studies . In an attempt to clarify this, we analyzed the clinical course of patients with APSGN . METHODS: A total of 220 children with acute nephritic syndrome were treated in the affiliated hospitals of our department, between January 1988 and December 1997 . Among them, 138 children who were diagnosed with APSGN according to the presence of hematuria, transient hypocomplementemia and evidence of group A beta-hemolytic streptococcal infection, were studied . RESULTS: Serum creatinine and blood urea nitrogen levels at onset were 0.5 +/- 0.2 mg/dL and 20 +/-12 mg/dL, respectively . There were no patients with renal dysfunction (serum creatinine level > or = 1.5 mg/dL), but one patient with nephrotic syndrome . Blood pressure was well controlled in all patients and there were no patients with persistent hypertension . Serum complement levels were normalized within 12 weeks (100%), hematuria disappeared within 4 years (100%) and proteinuria disappeared within 3 years (100%) from the onset . CONCLUSIONS: These data indicate that the prognosis of APSGN during childhood is excellent, when adequately diagnosed and treated.

J Rheumatol, 2001 Jul, 28(7), 1681 - 8
Acute rheumatic fever and poststreptococcal reactive arthritis: diagnostic and treatment practices of pediatric subspecialists in Canada; Birdi N et al.; OBJECTIVE: We conducted a survey of pediatric specialists in rheumatology, cardiology, and infectious diseases to ascertain present Canadian clinical practice with respect to diagnosis and treatment of acute rheumatic fever (ARF) and poststreptococcal reactive arthritis (PSReA), and to determine what variables influence the decision for or against prophylaxis in these cases . METHODS: A questionnaire comprising 6 clinical case scenarios of acute arthritis occurring after recent streptococcal pharyngitis was sent to members of the Canadian Pediatric Rheumatology Association, and to heads of divisions of pediatric cardiology and pediatric infectious diseases at the 16 university affiliated centers across Canada . RESULTS: There is considerable variability with respect to diagnosis in cases of ReA following group A streptococcal (GAS) infection both within and across specialties . There is extensive variability regarding the decision to provide prophylaxis in cases designated as ARF or PSReA . Findings indicated that physicians are most comfortable prescribing antibiotic prophylaxis in the presence of clear cardiac risk and are less inclined to such intervention for patients diagnosed with PSReA . When prophylaxis was recommended for cases of PSReA, the majority of respondents prescribed longer term courses of antibiotics . CONCLUSION: The lack of observed consistency in diagnosis and treatment in cases of reactive arthritis post-GAS infection likely reflects the lack of universally accepted criteria for diagnosis of PSReA and insufficient longterm data regarding carditis risk within this population . There is a need for clear definitions and treatment guidelines to allow greater consistency in clinical practice across pediatric specialties.

Ann Pharm Fr, 2001 Jul, 59(4), 246 - 77
{The worldwide challenges of "new" or reemerging communicable diseases at the dawn of the 21st century}; Werner GH; In the first part of this review, AIDS, prion diseases, Hantavirus and arbovirus infections, Ebola hemorrhagic fever, legionellosis, hepatitis C, enterotoxigenic Escherichia coli infections, Lyme disease, tuberculosis have provided alarming examples of emerging or reemerging infectious diseases . In this second part, the stress is placed on the reemergence of diphtheria and of serious streptococcal infections, on bartonelloses, Chlamydia infections, fungal infections, while malaria and cholera are still prevalent in several areas . The increasing resistance of too many pathogens to antimicrobial agents is a major source of concern, directly related to the challenge of nosocomial infections . An infectious cause has been demonstrated (or strongly suspected) for various diseases and the scope of infectiology keeps widening, while the threat of bioterrorism cannot be neglected . The causes of the emergence or reemergence of infectious diseases are multiple and diverse, often in direct relation with human activities (population migrations, changes in husbandry or farming practices, worldwide exchanges of goods and foods, inadequate uses of antibiotics) but also with climatic variations in several areas . The challenge represented by this unexpected comeback of infections to the forefront of human and animal pathology can only be met with a significant improvement of hygienic practices, cessation of certain dangerous behaviors and also, of course, with the development of novel antimicrobial molecules (acting on original targets) as well as of a whole series of new specific vaccines.

Epidemiol Infect, 2001 Jun, 126(3), 365 - 72
Acute poststreptococcal glomerulonephritis: public health implications of recent clusters in New South Wales and epidemiology of hospital admissions; Muscatello DJ et al.; Acute poststreptococcal glomerulonephritis (APSGN) is an inflammatory kidney condition that can complicate Group A streptococcal infections . Two clusters of APSGN occurred recently in New South Wales (NSW), Australia; one in a rural town in December 1999 and the other in a Sydney suburb in January 2000 . We interviewed carers of the affected children but found no common exposures except three of the Sydney cases were cousins in frequent contact . To assess the probability of these clusters occurring, we analysed hospital admissions for acute glomerulonephritis, as a proxy for APSGN in younger patients . The incidence of acute glomerulonephritis in NSW during 1989/90-1997/8 in residents aged under 20 years was 2.2/100000/year (95% CI 2.0-2.5) . Incidence was highest in children aged 5-9 years, boys and Aboriginal children . We found no evidence for other clusters during that period . The recent clusters highlight the continued potential for unexpected future outbreaks of APSGN.

Int J Neuropsychopharmacol, 2001 Jun, 4(2), 191 - 8
Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS); Leonard HL et al.; The evidence to date, both published and unpublished, which addresses the validity of the proposed unique subgroup of children with early and abrupt onset of obsessive--compulsive disorder (OCD) and/or tic disorders subsequent to streptococcal infections was reviewed . The aetiology of OCD and tic disorders is unknown, although it appears that both disorders may arise from a variety of genetic and environmental factors . Post-streptococcal autoimmunity has been postulated as one possible mechanism for some . The acronym PANDAS (for paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections) has been given to a subgroup of paediatric patients who meet five inclusionary criteria: presence of OCD and/or tic disorder, pre-pubertal symptom onset, sudden onset or episodic course of symptoms, temporal association between streptococcal infections and neuropsychiatric symptom exacerbations, and associated neurological abnormalities . The proposed model of pathophysiology provides for several unique treatment strategies, including the use of antibiotic prophylaxis to prevent streptococcal-triggered exacerbations, and the use of immunomodulatory interventions (such as intravenous immunoglobulin or therapeutic plasma exchange) in the treatment severe neuropsychiatric symptoms . For the latter study group, long-term (2--5 yr) follow-up revealed continued symptom improvement for the majority of patients, particularly when antibiotic prophylaxis had been effective in preventing recurrent streptococcal infections . In addition, the episodic nature of the subgroup's illness provides for opportunities to study brain structure and function during health and disease, as well as allowing for investigations of the aetiologic role of anti-neuronal antibodies and neuroimmune dysfunction in both OCD and tic disorders . Although much research remains to be done, an increasing body of evidence provides support for the postulate that OCD and tic disorders may arise from post-streptococcal autoimmunity . The unique clinical characteristics of the PANDAS subgroup, the presence of volumetric changes in the basal ganglia, and the dramatic response to immunomodulatory treatments, suggest that symptoms arise from a combination of local, regional and systemic dysfunction . Ongoing research is directed at understanding the nature of the abnormal immune response, as well as identifying at-risk children, in order to provide for novel strategies of prevention and treatment.

Pediatr Nephrol, 2001 Jul, 16(7), 598 - 600
Recurrence of acute poststreptococcal glomerulonephritis; Watanabe T et al.; Recurrence of acute poststreptococcal glomerulonephritis (APSGN) is a rare phenomenon . We present an 8-year-old boy with a second episode of APSGN 12 months following a complete clinical recovery from his initial attack . Renal histology, obtained from renal biopsies of the patient during the second attack, showed diffuse endocapillary proliferation, granular deposition of C3, IgG, IgA, and fibrinogen along capillary walls, and subepithelial electron-dense deposits . A new streptococcal cytoplasmic antigen (nephritis-associated plasmin receptor protein, NAP1r), which was recently identified as the pathogenic antigen in APSGN, was detected in the glomeruli of an early kidney biopsy specimen from the patient during the second attack of APSGN, using fluorescein isothiocyanate-labeled rabbit anti-NAP1r . However, antibodies against NAP1r, examined by Western blotting, were not present in sera from the patient . These results suggest that recurrence of APSGN in some patients may be caused by an absence of a natural immune response to NAP1r.

Vaccine, 2001 Jul 20, 19(30), 4143 - 52
A novel bipolar mode of attachment to aluminium-containing adjuvants by BBG2Na, a recombinant subunit hRSV vaccine; Dagouassat N et al.; Human respiratory syncytial virus (hRSV) is a major pathogen responsible for bronchiolitis and severe pulmonary disease in very young children, immunodeficient patients and the elderly . BBG2Na, a recombinant chimeric protein produced in Escherichia coli, is a promising subunit vaccine candidate against this respiratory pathogen, composed of G2Na, the central domain of RSV G glycoprotein, and BB, an albumin binding domain of streptococcal protein G . BBG2Na has a basic isoelectric point (pI 9.3) and as expected, is strongly adsorbed by aluminium phosphate (AP) . Surprisingly, BBG2Na is also strongly adsorbed by aluminium hydroxide (AH), which normally binds molecules with acidic isoelectric points . This behaviour was unexpected according to the well established adsorption model of Hem and co-workers . Our observations may be explained by the bipolar two-domain structure of the BBG2Na chimera which is not reflected by the global basic isoelectric point of the whole protein: the BB domain has an acidic isoelectric point (pI 5.5) and the G2Na domain a highly basic one (pI 10.0) . Importantly, formulation in either aluminium salt resulted in equally high immunogenicity and protective efficacy against RSV in mice . From a physicochemical point of view, this unique property of BBG2Na makes it eminently suitable for combination to either paediatric or elderly multivalent AH- or AP-containing vaccines already in the market or in development.

J Am Chem Soc, 2001 Jan 31, 123(4), 526 - 33
Synthesis of peptides and proteins without cysteine residues by native chemical ligation combined with desulfurization; Yan LZ et al.; The highly chemoselective reaction between unprotected peptides bearing an N-terminal Cys residue and a C-terminal thioester enables the total and semi-synthesis of complex polypeptides . Here we extend the utility of this native chemical ligation approach to non-cysteine containing peptides . Since alanine is a common amino acid in proteins, ligation at this residue would be of great utility . To achieve this goal, a specific alanine residue in the parent protein is replaced with cysteine to facilitate synthesis by native chemical ligation . Following ligation, selective desulfurization of the resulting unprotected polypeptide product with H(2)/metal reagents converts the cysteine residue to alanine . This approach, which provides a general method to prepare alanyl proteins from their cysteinyl forms, can be used to chemically synthesize a variety of polypeptides, as demonstrated by the total chemical syntheses of the cyclic antibiotic microcin J25, the 56-amino acid streptococcal protein G B1 domain, and a variant of the 110-amino acid ribonuclease, barnase.

Fam Med, 2001 Jul-Aug, 33(7), 516 - 21
Use of a template to improve documentation and coding; Rose EA et al.; BACKGROUND AND OBJECTIVES: Accurate assignment of evaluation and management (E&M) codes is a challenge for physicians . Having guidelines close at hand during patient visits might improve appropriateness and accuracy of E&M coding . We developed a template based on a clinical prediction rule for group A beta-hemolytic streptococcal (GABHS) pharyngitis to improve documentation and coding decisions . METHODS: Fifty office visits for sore throat were documented using templates and were compared with 50 sore throat visits that were documented using progress notes . We counted history and physical examination items and compared the level of service charged to the level of service supported by the note . RESULTS: Significantly more history of present illness and physical examination items were recorded on templates . Decisions related to treatment for patients with a low probability of GABHS were also improved by the templates . Templates had no effect on billing and coding errors . CONCLUSIONS: The template resulted in more-thorough documentation but had no effect on coding and billing errors relative to progress notes.

Eye, 2001 Jun, 15(Pt 3), 390 - 5
Structure and composition of drusen associated with glomerulonephritis: implications for the role of complement activation in drusen biogenesis; Mullins RF et al.; PURPOSE: The ocular fundi of many patients with membranoproliferative glomerulonephritis type II (MPGN-II) are characterised by the presence of deposits within Bruch's membrane that resemble drusen, hallmark lesions associated with age-related macular degeneration (AMD) . Glomerulonephritis (GN)-associated drusen appear at a younger age, however, than do drusen in individuals with AMD . In light of recent evidence that immune-mediated events participate in drusen biogenesis and AMD, we examined the structure and composition of drusen in eyes obtained from human donors with two distinct glomerulopathies, both of which involve complement deposition within glomeruli . These features were compared with those of drusen from patients with clinically documented AMD . METHODS: Eyes obtained from two human human donors diagnosed with membranous and post-streptococcal GN, respectively, were analysed histochemically, immunohistochemically and ultrastructurally . RESULTS: Subretinal pigment epithelial (RPE) deposits in both types of GN are numerous and indistinguishable, both structurally and compositionally, from drusen in donors with AMD . GN-associated drusen exhibit sudanophilia, bind filipin, and react with antibodies directed against vitronectin, complement C5 and C5b-9 complexes, TIMP-3 and amyloid P component . Drusen from the membranous GN donor, but not the post-streptococcal GN donor, reacted with peanut agglutinin and antibodies directed against MHC class II antigens and IgG . The ultrastructural characteristics of these deposits were also identical with those of AMD-associated drusen . CONCLUSIONS: The composition and structure of ocular drusen associated with membranous and post-streptococcal/segmental GN are generally similar to those of drusen in individuals with AMD . In view of the recent data supporting the involvement of complement activation in drusen biogenesis and the pathobiology of AMD, further studies of the biological relationships between AMD and diseases associated with complement activation are warranted.

Am J Health Syst Pharm, 2001 Jun 15, 58(12), 1133 - 8
Economic burden of influenza-like illness in long-term-care facilities; Carroll NV et al.; Direct medical costs and medically related transportation costs incurred by patients in long-term-care facilities (LTCFs) as a result of influenza-like illness (ILI) were studied . The study was conducted from the payer's perspective . Charts were reviewed retrospectively for all patients who were residents of four Richmond, Virginia, LTCFs between January 1 and May 31, 1999 . Consultant pharmacists gathered data on patient demographics, ILI status, vaccination for influenza and streptococcal pneumonia, diagnosis of asthma or chronic obstructive pulmonary disease, and utilization of health care services related to ILI . Services included the use of antimicrobials, antivirals, and respiratory drugs; emergency room visits; diagnostic tests; hospitalizations; and medically related transportation . Costs were based on average wholesale prices (for drugs) and Medicare or Medicaid reimbursement rates . Data were collected for 551 patients . Of these, 112 patients had been diagnosed with 128 cases of ILI during the study period . Twenty-two patients with ILI had 28 visits to emergency rooms, and 30 patients with ILI had 36 hospitalizations . The mean +/- S.D . cost per case of ILI was $1341 +/- $2063; inpatient hospital costs accounted for 84% of this amount . Centers for Disease Control and Prevention criteria for ILI provided a lower incidence of ILI and, consequently, a lower mean +/- S.D . cost of $968 +/- $1806 per case . ILI in patients in four LTCFs in Richmond, Virginia, generated substantial costs, the bulk of which resulted from hospitalization . A substantial percentage of the patients apparently were not immunized.

Infect Immun, 2001 Aug, 69(8), 4988 - 95
Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a streptococcal isolates in vivo; Kazmi SU et al.; The streptococcal pyrogenic exotoxins (Spes) play a central role in the pathogenesis of invasive group A streptococcal (GAS) infections . The majority of recent invasive GAS infections have been caused by an M1T1 strain that harbors the genes for several streptococcal superantigens, including speA, speB, speF, speG, and smeZ . However, considerable variation in the expression of Spe proteins among clonal M1 isolates has been found, and many of the speA-positive M1 strains do not produce detectable amounts of SpeA in vitro . This study was designed to test the hypothesis that speA gene expression can be induced in vivo . A mouse infection chamber model that allows sequential sampling of GAS isolates at various time points postinfection was developed and used to monitor the kinetics of Spe production in vivo . Micropore Teflon diffusion chambers were implanted subcutaneously in BALB/c mice, and after 3 weeks the pores became sealed with connective tissue and sterile fluid containing a white blood cell infiltrate accumulated inside the infection chambers . Representative clonal M1T1 isolates expressing no detectable SpeA were inoculated into the implanted chambers, and the expression of SpeA in the aspirated aliquots of the chamber fluid was analyzed on successive days postinfection . Expression of SpeA was detected in the chamber fluid as early as days 3 to 5 postinfection in most animals, with a significant increase in expression by day 7 in all infected mice . Isolates recovered from the chamber and grown in vitro continued to produce SpeA even after 21 passages in vitro, suggesting stable switch on of the speA gene . A temporal relation between the upregulation of SpeA expression and the downregulation of SpeB expression was observed in vivo . These data suggest that in vivo host and/or environmental signals induced speA gene expression and suppressed speB gene expression . This underscores the role of the host-pathogen interaction in regulating the expression of streptococcal virulence factors in vivo . The model described here should facilitate such studies.

Medicina (B Aires), 2000, 60(6), 953 - 5
{Streptococcal infection, acute kidney failure and interstitial nephritis}; Faurie RE et al.; The relationship between streptococcal infection and renal disease has been object of multiple studies . Streptococcal infection may induce acute glomerulonephritis or interstitial nephritis . We report a patient with a streptococcal infection who developed acute renal failure . The renal biopsy showed an acute interstitial nephritis, with an interstitium infiltrate with a significant number of eosinophils . We review the causes of acute renal failure associated with streptococcal infection, specially acute interstitial nephritis.

Obstet Gynecol, 2001 Jul, 98(1), 7 - 13
Group B streptococcal disease prevention practices of obstetrician-gynecologists; Watt JP et al.; OBJECTIVE: To describe group B streptococcal (GBS) disease prevention practices of obstetrician-gynecologists . METHODS: We surveyed 1019 ACOG Fellows-the 419 members of the Collaborative Ambulatory Research Network (CARN) and 600 randomly selected non-CARN Fellows . RESULTS: There were 601 eligible respondents . More than 95% in both the CARN and the non-CARN groups reported adopting one of three GBS prevention strategies . The most commonly reported strategy was a combination approach not described in the consensus guidelines . The second most common strategy was the screening-based strategy; the risk-based strategy was third . Most respondents provided GBS information to all prenatal patients, but those using a risk-based strategy and those in solo practice were less likely to do so . Less than 60% in each group used penicillin as their first choice for GBS prophylaxis . More than 20% in each group who routinely screened for GBS did not collect both vaginal and rectal cultures . Respondents rated ACOG publications as the most important influence on their GBS prevention approach . CONCLUSION: Almost all ACOG Fellows have adopted a GBS prevention strategy . The importance of providing GBS prevention information to all patients, use of penicillin, and collection of both vaginal and rectal cultures should be reinforced.

J Mol Biol, 2001 Jul 6, 310(2), 403 - 17
Plasmid transcriptional repressor CopG oligomerises to render helical superstructures unbound and in complexes with oligonucleotides; Costa M et al.; CopG is a 45 amino acid residue transcriptional repressor involved in the copy number control of the streptococcal plasmid pMV158 . To do so, it binds to a DNA operator that contains a 13 bp pseudosymmetric DNA element . Binding of CopG to its operator results in repression, at the transcriptional level, of its own synthesis and that of the initiator of replication protein, RepB . Biochemical experiments have shown that CopG co-operatively associates to its target DNA at low protein:DNA ratios, completely protecting four helical turns on the same face of the double helix in both directions from the inverted repeat that constitutes the CopG primary target . This has been correlated with a CopG-mediated DNA bend of about 100 degrees . Here, we show that binding of CopG to DNA fragments containing the inverted repeat just at one end led to nucleation of the protein initiating from the inverted repeat . Nucleation extended to the entire fragment, with CopG-DNA contacts occurring on the same face of the DNA helix . The protein, the prototype for a family of homologous plasmid repressors, displays a homodimeric ribbon-helix-helix arrangement . It polymerises within the unbound crystal to render a continuous right-handed protein superhelix of homodimers, around which a bound double-stranded (ds) DNA could wrap . We have solved the crystal structure of CopG in complex with a 22 bp dsDNA oligonucleotide encompassing the cognate pseudosymmetric element . In the crystal, one protein tetramer binds at one face of the DNA with two parallel beta-ribbons inserted into the major groove . The DNA is bent about 50 degrees under compression of both major and minor grooves . A continuous right-handed complex helix made up mainly by protein-protein and some protein-DNA interactions is observed . The protein-protein interactions involve regions similar to those observed in the oligomerisation of the native crystals and those employed to set up the functional tetramer . A previously solved complex structure of the protein with a 19 bp dsDNA had unveiled a left-handed helical superstructure just made up by DNA interactions .

Am J Perinatol, 2001 May, 18(3), 147 - 9
Spontaneous rupture of the liver presenting as scrotal bruising; Vachharajani A et al.; We describe a case of spontaneous rupture of the liver in a neonate, presenting with features consistent with testicular torsion . Ruptured liver has been well described in neonates following birth trauma, coagulation defects, and Group B Streptococcal infection . The etiology in our case remains undefined.

Clin Chim Acta, 2001 Jun, 308(1-2), 155 - 61
Lipid peroxidation, osmotic fragility and antioxidant status in children with acute post-streptococcal glomerulonephritis; Devasena T et al.; Plasma and erythrocyte samples from acute post-streptococcal glomerulonephritis (APSGN) children and control children were enrolled in this study . Lipid peroxidation (LPO), measured in terms of thiobarbituric acid-reactive substances (TBARS) was found to be significantly increased in plasma and RBCs of APSGN children (P<0.05) than in control children . Osmotic fragility of erythrocytes was examined . RBCs of APSGN patients were found to be osmotically more sensitive towards hypotonic saline (50% hemolysis at 7 g/l saline) when compared to control RBCs (50% hemolysis at 4 g/l saline) . The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were significantly lowered (P<0.05) in APSGN RBCs when compared to control RBCs . Plasma ascorbic acid, reduced glutathione (GSH), RBC ascorbic acid, GSH and RBC total sulphydryl content (TSH) were significantly depleted in APSGN children relative to controls . The susceptibility of RBCs of APSGN children to lipid peroxidation was confirmed in this study.

Clin Exp Rheumatol, 2001 May-Jun, 19(3), 349 - 51
Severe abdominal involvement as the initial manifestation of cutaneous polyarteritis nodosa in a young girl; Falcini F et al.; We report a young girl who developed ingravescent intestinal symptoms as the first manifestation of cutaneous polyarteritis nodosa (PAN) while the typical skin nodules developed later during the disease course . Cutaneous PAN predominantly affects children and presents with crops of painful skin nodules in the medial aspect of the foot, often preceded by sore throat . Visceral manifestations including gut involvement are commonly associated with the classical form of PAN while they are rarely reported in the cutaneous form . In our patient the severity of the abdominal symptoms required a laparoscopy, which revealed diffuse erythematosus swelling of the intestine on the serosal side . The administration of penicillin and steroids was followed by a dramatic improvement in the disease course . Chronic anterior uveitis developed 4 months after the disease onset and responded to local treatment . At a 2-year follow-up the girl is in good condition under prophylaxis with benzathine-penicillin with no recurrence of the illness . Our case confirms that cutaneous PAN is often related to streptococcal infection, and suggests that ASO titers should be determined in children with vasculitides to ensure a timely diagnosis and treatment of the condition if present.

Rev Argent Microbiol, 2001 Jan-Mar, 33(1), 28 - 35
Influence of bacterial factors on proliferation of bovine mammary epithelial cells; Calvinho LF et al.; Effects of bovine mastitis pathogen virulence factors on mammary epithelial cell function are not clearly understood . In this study, the effect of streptococcal lipoteichoic acid (LTA), streptokinase, and Escherichia coli lipopolysaccharide (LPS) on proliferation of a primary bovine mammary epithelial cell culture (BTE) and on an established bovine mammary epithelial cell line (MAC-T) was evaluated . Mammary epithelial cells were cultured in the presence of bacterial virulence factors for 48 h at 37 degrees C . BTE cell proliferation was inhibited by streptococcal LTA at 8 and 16 micrograms/ml whereas MAC-T cell proliferation was reduced significantly by concentrations of LTA > or = 2 micrograms/ml . Streptokinase had no effect on proliferation of either MAC-T or BTE cells and LPS inhibited proliferation of BTE but not of MAC-T cells . Effect of LTA and LPS on mammary epithelial cell proliferation could be relevant during the periparturient period when mammary glands are markedly susceptible to new intramammary infection and when mammary epithelial cells undergo extensive proliferation, differentiation and synthesis of milk components.

Inflammation, 2001 Jun, 25(3), 137 - 44
Hypothermia attenuates beta1 integrin expression on extravasated neutrophils in an animal model of meningitis; Rowin ME et al.; Brain injury in meningitis occurs in part as a consequence of leukocyte migration and activation . Leukocyte integrins are pivotal in the inflammatory response by mediating adhesion to vascular endothelium and extracellular matrix proteins . We have demonstrated that moderate hypothermia early in the course of meningitis decreases leukocyte sequestration within the brain parenchyma . This study examines whether hypothermia alters neutrophil integrin expression in a rabbit model of bacterial meningitis . Prior to the induction of meningitis, peripheral blood samples were obtained and the neutrophils isolated . Sixteen hours after inducing group B streptococcal meningitis, animals were treated with antibiotics, i.v . fluids, and mechanically ventilated . Animals were randomized to hypothermia (32-33 degrees C) or normothermia conditions . After 10 hours of hypothermia or normothermia, neutrophils were isolated from the blood and cerebral spinal fluid (CSF), stained for beta1 and beta2 integrins, and analyzed using flow cytometry . Cerebral spinal fluid neutrophil beta1 integrin expression was significantly decreased in hypothermic animals . Beta-1 integrins can assume a higher affinity or "activated" state following inflammatory stimulation . Expression of "activated" beta1 integrins was also significantly decreased in hypothermic animals . Beta2 CSF neutrophil integrin expression was decreased in hypothermic animals, but failed to reach significance . These data suggest hypothermia may attenuate extravasated leukocyte expression of both total and "activated" beta1 integrins.

Drugs, 2001, 61(6), 747 - 61
Fluoroquinolones: place in ocular therapy; Smith A et al.; The fluoroquinolones have become widely used antibacterial agents in the treatment of ocular infections, with topical, intravitreal and systemic routes of administration being used . In general, fluoroquinolones (such as ciprofloxacin, ofloxacin, lomefloxacin and norfloxacin) have good activity against gram-negative and gram-positive bacteria . Therapeutic concentrations are achieved in the cornea after topical administration so that the fluoroqinolones have largely replaced combination therapy for the treatment of bacterial keratitis . However, a second line agent is needed when resistance is likely, such as in disease caused by streptococcal species . Reversal of resistance to quinolones may not occur with withdrawal of the antibacterial . This stresses the importance of prudent prescribing to reduce the occurrence of resistance to quinolones . When used in therapeutic topical dosages, corneal toxicity does not occur . Similarly, retinal toxicity is not seen when fluoroquinolones are used at therapeutic dosages, systemically or topically . Corneal precipitation occurs, particularly with ciprofloxacin and to a lesser extent norfloxacin, but does not appear to interfere with healing . In the treatment of endophthalmitis there is reasonable penetration of systemic fluoroquinolones into the vitreous but sufficiently high concentrations to reach the minimum inhibitory concentration for 90% of isolates (MIC90) of all important micro-organisms may not be guaranteed . Systemic administration may be useful for prophylaxis after ocular trauma.

Int J Antimicrob Agents, 2001 Jun, 17(6), 439 - 42
The role of beta-lactamase producing bacteria and bacterial interference in streptococcal tonsillitis; Brook I; The causes of penicillin failure in eradicating group A beta-haemolytic streptococcal pharyngo-tonsillitis are described . The mechanisms accounting for the failure include the presence in the tonsils of beta-lactamase producing bacteria and the absence of bacterial interference . The use of antimicrobials that can overcome and modulate these two phenomena and achieve better cure of the infection is described.

Pediatrics, 2001 May, 107(5), 1181 - 3
A family cluster of streptococcal toxic shock syndrome in children: clinical implication and epidemiological investigation; Huang YC et al.; BACKGROUND: Most invasive group A streptococcal (GAS) disease occurs sporadically . Reports of family clusters of these infections are scanty, and most invasive disease occurs in adults . We describe a family cluster of streptococcal toxic shock syndrome (STSS) involving 3 children and present the results of an epidemiologic investigation . PATIENTS AND METHODS: During a 16-day period, 3 children in a family developed STSS with an interval of 7 and 9 days, respectively, between the onset of disease . Cases 2 and 3 had GAS isolated from blood culture . Case 2 was fatal . Pharyngeal culture survey of the family members and schoolchildren was conducted . Antibiogram, serotyping, detection of exotoxin genes, and random amplified polymorphic DNA patterns of the disease strains and survey strains were examined . RESULTS: One of 15 family members sampled-the sister of the index case-and 7 (5.6%) of 125 schoolchildren sampled had GAS isolated from pharyngeal cultures . Of the 10 strains examined, 2 isolates from the patients, 1 from the sister of index case, and 2 from the classmates of case 2 (the fatal case) had an identical pattern of both genotype and phenotype . CONCLUSION: We describe a family cluster of STSS involving 3 children caused by a single clone and provide additional data regarding invasive GAS infection subsequent to household contact . Additional studies should be conducted in conjunction with surveillance to define better the magnitude of risk in household contacts and to identify settings in which subsequent infections may occur.

Pediatrics, 2001 May, 107(5), 1108 - 15
Invasive group A streptococcal infection and nonsteroidal antiinflammatory drug use among children with primary varicella; Lesko SM et al.; OBJECTIONS: To test the hypothesis that nonsteroidal antiinflammatory drug use increases the risk of necrotizing soft tissue infections and, secondarily, all invasive group A streptococcal (GAS) infections in children with primary varicella infection . METHODS: We conducted a prospective, multicenter case-control study among children <19 years old . Cases were children hospitalized with primary varicella complicated by invasive GAS infection or necrotizing soft tissue infection identified by a network of 45 pediatric infectious disease specialists located throughout the United States . Controls were children with uncomplicated primary varicella residing in the same communities as the cases . Data on medical history, clinical features of the varicella infection, signs and symptoms of infectious complications, and medication use were collected by structured telephone interviews . Univariate and multivariate matched odds ratios were calculated using conditional logistic regression . RESULTS: Between June 1996 and September 1998, 52 cases of invasive GAS infection, including 21 with necrotizing soft tissue infection, and 172 controls with uncomplicated primary varicella were enrolled . Risk of invasive GAS infection was increased among children who were nonwhite (multivariate odds ratio {OR} 3.8, 95% confidence interval {CI}: 1.4-11), living in low-income households (OR 5.1, 95% CI: 1.7-15), exposed to varicella at home (OR 6.4, 95% CI: 2.6-16), or had a persistent high fever (OR 9.6, 95% CI: 2.8-33) . Antipyretic regimen was associated with several measures of varicella illness severity among the controls . The risk of necrotizing soft tissue infection was not associated with the use of ibuprofen before the development of signs or symptoms of this complication (OR 1.3, 95% CI: 0.33-5.3) . Risk of any invasive GAS infection was increased among children who had received ibuprofen (OR 3.9, 95% CI: 1.3-12), but not acetaminophen (OR 1.2, 95% CI: 0.50-3.0) . However, there was no evidence of increasing risk with increasing duration of ibuprofen use . Subgroup analyses revealed that the risk of invasive GAS infection was increased only among children who had received both acetaminophen and ibuprofen . CONCLUSIONS: These data do not support the hypothesis that nonsteroidal antiinflammatory drugs, or ibuprofen in particular, increase the risk of necrotizing GAS infections . A statistically significant association was observed between nonnecrotizing invasive GAS infection and ibuprofen use; however, because of potential confounding, the meaning of this unexpected result is unclear . Nonetheless, these data suggest that parents use ibuprofen or ibuprofen together with acetaminophen to treat high fever and severe illness, which seems to identify children at high risk for invasive GAS infection.

Posit Aware, 1998 Jan-Feb, 9(1), 43 - 4
Latest opportunistic infection prevention guidelines; D'Amico R; AIDS: Although people with HIV are living longer than ever before, they continue to suffer from infections that are associated with low T4-cell counts . The U.S . Public Health Service (PHS) and the Infectious Diseases Society of America (IDSA) have updated the guidelines for preventing opportunistic infections, including their positions on when prophylaxis is indicated . Summaries are given for preventing the following infections: cytomegalovirus (CMV), cryptosporidiosis, fungal infections, human papillomavirus (HPV), herpes-related infections, mycobacterium avium complex (MAC), pneumocystis carinii pneumonia (PCP), streptococcal pneumonia, toxoplasmosis, and tuberculosis .

Posit Aware, 1996 Jan-Feb, 7(1), 16 - 7
Early intervention and prevention options; Multifocal streptococcal pyomyositis complicated by acute compartment syndrome: case report; Department of Orthopaedics, Leeds General Infirmary, Leeds, UKA 5-year-old girl sought treatment for pyrexia of unknown origin . Despite prompt surgical drainage of a streptococcal septic arthritis of the ankle joint, her condition deteriorated . Multifocal pyomyositis was subsequently diagnosed . This was complicated by acute compartment syndrome in three extremities . With aggressive surgical and medical management, the child made a complete recovery . Orthopaedic clinicians in nontropical areas must familiarize themselves with this rare, potentially life-threatening, but eminently curable disease.

Am J Obstet Gynecol, 2001 May, 184(6), 1204 - 10
The effectiveness of risk-based intrapartum chemoprophylaxis for the prevention of early-onset neonatal group B streptococcal disease; Lin FY et al.; OBJECTIVE: Our purpose was to evaluate the effectiveness of a risk-based intrapartum antibiotic prophylaxis strategy for the prevention of early-onset neonatal group B streptococcal disease . STUDY DESIGN: Cases and controls were selected from infants born to women with one or more risk factors: preterm labor or rupture of membranes, prolonged rupture of membranes (>18 hours), fever during labor, or previous child with group B streptococcal disease . Cases were matched with controls by birth hospital and gestational age . Data abstracted from medical records were analyzed to estimate the effectiveness of intrapartum antibiotic prophylaxis . RESULTS: We analyzed data from 109 cases and 207 controls . Nineteen (17%) case versus 69 (33%) control mothers received an acceptable regimen of intrapartum antibiotic prophylaxis . In adjusted analyses, the effectiveness of intrapartum antibiotic prophylaxis was 86% (95% confidence interval, 66%-94%) . When the first dose of antibiotics was given > or =2 hours before delivery, the effectiveness increased to 89% (95% confidence interval, 70%-96%); when it was given within 2 hours of delivery, the effectiveness was 71% (95% confidence interval, -8%-92%) . Effectiveness was lowest in mothers with intrapartum fever (72%, 95% confidence interval, -9%-93%) . On the basis of a 70% prevalence of maternal risk factors expected among cases in the absence of intrapartum antibiotic prophylaxis, we estimate that the risk-based strategy could reduce early-onset group B streptococcal disease by 60% . CONCLUSIONS: The risk-based approach to intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease . To achieve the maximum preventive effect, the first dose of antibiotics should be administered at least 2 hours before delivery.

Infect Immun, 2001 Jun, 69(6), 4072 - 8
Induction of autoimmune valvular heart disease by recombinant streptococcal m protein; Quinn A et al.; Rheumatic heart disease is an autoimmune sequela of group A streptococcal infection . Previous studies have established that streptococcal M protein is structurally and immunologically similar to cardiac myosin, a well-known mediator of inflammatory heart disease . In this study, we investigated the hypothesis that streptococcal M protein could produce inflammatory valvular heart lesions similar to those seen in rheumatic fever (RF) . Fifty percent (3 of 6) of Lewis rats immunized with recombinant type 6 streptococcal M protein (rM6) developed valvulitis as well as focal lesions of myocarditis . Valvular lesions initiated at the valve surface endothelium spread into the valve . Anitschkow cells and verruca-like lesions were present . T cells from rM6-immunized rats proliferated in the presence of purified cardiac myosin, but not skeletal myosin . A T-cell line produced from rM6-treated rats proliferated in the presence of cardiac myosin and rM6 protein . The study demonstrates that the Lewis rat is a model of valvular heart disease and that streptococcal M protein can induce an autoimmune cell-mediated immune attack on the heart valve in an animal model . The data support the hypothesis that a bacterial antigen can break immune tolerance in vivo, an important concept in autoimmunity.

Pediatrics, 1998 Jan, 101(1 Pt 1), 136 - 40
American Academy of Pediatrics . Committee on Infectious Diseases . Severe invasive group A streptococcal infections: a subject review; American Academy of Pediatrics . Committee on Infectious Diseases; The course of severe invasive group A beta-hemolytic streptococcal (GABHS) infections is often precipitous, requiring prompt diagnosis and rapid initiation of appropriate therapy . Therefore, physicians must have a high index of suspicion of this disease, particularly in patients at increased risk (e.g., those with varicella or diabetes mellitus) . Although a relationship between the use of nonsteroidal antiinflammatory drugs and severe invasive GABHS infections has been suggested, at present data on which to base a clinical decision about the use or restriction of nonsteroidal antiinflammatory drugs in children with varicella are insufficient . When necrotizing fasciitis is suspected, prompt surgical drainage, debridement, fasciotomy, or amputation often is necessary . Many experts recommend intravenously administered penicillin G and clindamycin for the treatment of invasive GABHS infections on the basis of animal studies . Some evidence exists that intravenous immunoglobulin given in addition to appropriate antimicrobial and surgical therapy may be beneficial . Although chemoprophylaxis for household contacts of persons with invasive GABHS infections has been considered by some experts, the limited available data indicate that the risk of secondary cases is low (2.9 per 1000) and data about the effectiveness of any drug are insufficient to make recommendations . Because of the low risk of secondary cases of invasive GABHS infections in schools or child care facilities, chemoprophylaxis is not indicated in these settings . Routine immunization of all healthy children against varicella is recommended and is an effective means to decrease the risk of invasive GABHS infections.

Psychoanal Study Child, 2000, 55, 87 - 110
Gustav Mahler's choice . A note on adolescence, genius, and psychosomatics; Garcia EE; At a time of crisis in his marital life, Gustav Mahler met with Freud . After the meeting with Freud, Mahler's spirits and sexual potency were restored, and his attitude toward his wife changed remarkably . However, these changes were accompanied by an apparent loss of the ability to compose: there is no evidence that Mahler wrote any new music between the summer of 1910, when he saw Freud, and May of 1911, when he died from complications of streptococcal endocarditis . Mahler in effect had chosen human love over artistic creativity . An analysis of the encounter and its effects on the composer's artistic capabilities raises questions about the psychology of genius, adolescent trauma, and psychosomatics.

J Autoimmun, 2001 May, 16(3), 363 - 7
Heart-directed autoimmunity: the case of rheumatic fever; Guilherme L et al.; Molecular mimicry was proposed as a potential mechanism for streptococcal sequelae leading to rheumatic fever (RF) and rheumatic heart disease (RHD) . CD4(+)infiltrating T cells are able to recognize streptococcal M peptides and heart tissue proteins . We analyzed the M5 peptide- and heart-specific responses, cytokine profile and T cell receptor (TCR) BV usage from peripheral and heart-infiltrating T cell lines and clones from patients across the clinical spectrum of ARF/RHD . The patient with ARF displayed a higher frequency of mitral valve infiltrating T cell clones reactive against M5: 1-25, 81-103 and 163-177 regions and several valve-derived proteins than the post-RF and chronic RHD patient (67%; 20% and 27%, respectively) . The presence of oligoclonal BV families indicative of oligoclonal T cell expansion among mitral valve-derived T cell lines was increased in the chronic RHD patient . Furthermore, mitral valve T cell lines from all patients produced significant amounts of inflammatory cytokines interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNFalpha) in response to M5(81-96) peptide, with the highest production attained by the chronic RHD patient . These data are consistent with an important role for M5 peptide and host antigen-driven, T1-type CD4(+)T cells in the pathogenesis of RHD and heart lesion progression after recurrence of the streptococcal infection .

An Esp Pediatr, 2001 May, 54(5), 506 - 9
{Childhood cutaneous polyarteritis nodosa}; Nunez Giralda A et al.; Cutaneous polyarteritis nodosa is a form of polyarteritis nodosa . It is a rare disease in children and is characterized by its benign and chronic course . There is no evidence of hypertension or organ dysfunction . The aim of this study was to present a case of cutaneous polyarteritis nodosa and to review the literature . We describe the case of a 3-year-old male child with multiple, red, painful, edematous nodules of the extremities and trunk . Dermatologic findings were accompanied by fever and arthritis . Laboratory findings showed an acute phase response associated with raised antistreptolysin titer . Diagnosis was based on biopsy of the affected skin lesion in which necrotizing arteritis of the lower dermis with neutrophilic and eosinophilic infiltrates was found . The patient responded well to corticosteroid therapy . The evaluation of children with cutaneous polyarteritis nodosa should include laboratory studies to detect streptococcal infection.

Gan To Kagaku Ryoho, 2001 Apr, 28(4), 461 - 6
{Cancer immunotherapy in head and neck region}; Eura M; There is no one common immunotherapy for the treatment of head and neck cancer (H&N cancer) . A streptococcal agent, OK-432, which is classified as a biological response modifier (BRM), is occasionally used by means of local administration for recurrent H&N cancer, and the response rate is approximately 18% . In regard to specific immunotherapy, a murine monoclonal antibody (named mAb 225) against the epidermal growth factor receptor (FGFR) that is frequently overexpressed in H&N cancer has been produced in the U.S.A . Furthermore, to obviate human anti-mouse antibody responses, a chimeric human-to-murine version of mAb 225 (C225) was developed by exchanging the constant regions of mAb 225 to counterparts in human immune globulin . Phase I clinical trials of C225 in the U.S.A . demonstrated that treatment with C225 was well tolerated and that C225 given in combination with cisplatin has biologic activity . On the other hand, many tumor antigens recognized by cytotoxic T lymphocytes (CTL) have been identified from a variety of malignant tumors and some of them, including the MAGE-3 antigen, are frequently expressed in H&N cancer . We identified an MAGE-3-derived epitope recognized by HLA-A24-restricted CTL from peripheral blood mononuclear cells (PBMC) . In contrast we failed to generate CTL specific for MAGE-3+/HLA-A24+ tumors from PBMC in any of 5 HLA-A24+ cancer patients whose tumors expressed the MAGE-3 gene . Therefore, we did not apply MAGE-3-derived CTL epitope in clinical uses such as peptide vaccine and peptide pulsed dendritic cell infusion for H&N cancer.

Ann Dermatol Venereol, 2001 Mar, 128(3 Pt 2), 368 - 75
{Primary and secondary prevention for erysipelas}; Becq-Giraudon B; Erysipelas is a bacterial infection of the deepest skin layer . Predisposing factors are systemic and/or local . Main systemic factors are alcoholism, diabetes and immunodeficiency . The main local factors are an Athlete's foot (tineapedis), venous or lymphatic stasis, prosthetic surgery of the knee, and a past history of saphenous phlebectomy, lymphadenectomy, or irradiation . Such predisposing factors account for the predominance of erysipelas in the lower limbs and for the frequency of recurrence . The prevention of recurrence is stressed by all authors, and would associate correct treatment of the disease, treatment of venous and lymphatic stasis and/or wounds . A preventive antibiotic treatment should be proposed to patients with multiple predisposing factors and frequent recurrence, by using prolonged therapy with Macrolides or Penicillin . Primary prevention could concern local and/or systemic predisposing factors; however its efficacy and necessity has yet to be demonstrated . The usefulness of nosopharyngeal streptococcal carriage eradication and/or vaccination has not demonstrated either.

Ann Dermatol Venereol, 2001 Mar, 128(3 Pt 2), 348 - 51
{Should NSAID/corticoids be considered when treating erysipelas?}; Jaussaud R et al.; Using non-steroidal anti-inflammatory drugs (NSAID) in association with a suitable antibiotherapy in the treatment of erysipelas, is still being largely discussed in medical publications . When compared to other fields of medicine, here their use might be justified by their ability to reduce local inflammation processes, to relieve patients more quickly, and to prevent potential sequels due to an inflammatory process . Numerous reports have suggested an association between the use of NSAID and the progression of an invasive streptococcal infection, particularly necrotizing fasciitis . The exact mechanism is still unclear . No controlled survey (NSAID versus placebo) checking the efficiency and the safety of these treatments is currently available . Only one comparative study showed a gain of one single day for prednisolone The prednisolone-treated patients had a shorter median length of hospital stay (5 days vs . 6) than the placebo-treated ones . The median treatment time with intravenous antibiotics, in the placebo group, was 1 day longer than in the prednisolone group . The occurrence of side effects was not higher in the prednisolone group . If this currently available data is not sufficient to establish a relationship between severe infectious complications and the use of NSAID, one should be cautious when using them to treat erysipelas, since their efficiency has not been positively proved.

Semin Respir Infect, 2001 Mar, 16(1), 67 - 75
Antibody treatment of lower respiratory tract infections; Skerrett SJ; Antibody treatment of lower respiratory infection has a long history of success and is receiving renewed interest . A variety of polyclonal and monoclonal preparations are clinically available . Although used primarily for infection prophylaxis, these agents have limited applications in the treatment of established infections . Immune serum was the first effective treatment for pneumococcal pneumonia . Although long-supplanted by the advent of antibiotics, passive immunotherapy for pneumococcal and other infections is being revisited in an era of increasing antibiotic resistance and growing numbers of immunocompromised individuals . Limited clinical evidence supports the use of immune globulins in the treatment of pertussis and severe streptococcal infection . Bone marrow transplant recipients with lower respiratory infections caused by cytomegalovirus or respiratory syncytial virus also may benefit by adjunctive treatment with immune globulins . Additional indications for antibody treatment of respiratory infection may develop with further investigation.

Scand J Infect Dis, 2001, 33(3), 179 - 81
Clinical characteristics of Group G streptococcal bacteremia in Taiwan; Yang SP et al.; The results of this retrospective study showed that Group G streptococcal bacteremia was an acute febrile disease with low mortality . Most patients were > 60 y old but there was a strong association between age < 60 y and malignancy . Cases clustered in summer and the most common port of entry was the skin.

J Midwifery Womens Health, 2001 Jan-Feb, 46(1), 17 - 23
Group B streptococcal (GBS) disease screening and treatment during pregnancy: nurse-midwives' consistency with 1996 CDC recommendations; Bloom KC et al.; OBJECTIVE: In 1998, the screening and treatment practices of certified nurse-midwives (CNMs) for group B streptococcal (GBS) infection during pregnancy were studied and evaluated for their consistency with the 1996 perinatal GBS prevention guidelines of the Centers for Disease Control and Prevention (CDC) . METHODOLOGY: Five hundred thirty-nine surveys were completed by CNMs attending the 1998 American College of Nurse-Midwives' Convention . Of these, 502 (94.7%) reported a practice policy for GBS prophylaxis . RESULTS: The Culture-Based Approach was used by 66.7% and the Obstetrical Risk Factor Approach by 28% . Most (69%) reported using multiple culture sites, most commonly the proximal vagina and anorectal area (33.2%), followed by the distal vagina and anorectal area (26.7%), and the anorectal area and proximal and distal vagina (7.1%) . Most CNMs (92.5%) reported treating GBS intrapartally, with penicillin the most frequently reported antimicrobial (55.0%) used, and most (94.2%) reporting treatment through labor until birth . CONCLUSION: Overall, GBS prophylaxis practices among survey respondents comply with 1996 CDC recommendations; however, GBS screening practices show room for improvement and the need for continuing education that emphasizes the CDC guidelines, updates as they become available, and other new literature about the topic . In addition, heightened awareness among all perinatal providers is needed with respect to CDC guidelines, especially as they pertain to variations in culture sites, identification of risk categories, and the selection of appropriate antimicrobial treatment agents.

Mol Immunol, 2000 Oct, 37(15), 901 - 13
Molecular analysis of cross-reactive anti-myosin/anti-streptococcal mouse monoclonal antibodies; Mertens NM et al.; Nucleotide sequences of VH- and VL-genes of anti-myosin/anti-streptococcal monoclonal antibodies (mAbs) were analyzed and compared with their highly detailed antigen binding reactivities . Antigen-specificities of the cross-reactive mAbs included myosin, streptococcal M-protein, actin, keratin, N-acetyl-beta-D-glucosamine, vimentin, DNA, tropomyosin, troponin, and laminin as previously described . After nucleotide sequence analysis, homology indicated that some of the V gene sequences aligned with antibodies recognizing gangliosides and blood group antigens glycophorin M and N . Therefore, mAb reactivity with gangliosides and glycophorin M and N was identified . The cross-reactive mAbs utilized a heterogeneous group of germline V-heavy genes comprised of nine J558-, four 7183- and two Q52-family VH-genes . Germline V-light genes utilized by the mAbs included six Vkappa4/5-, three Vkappa8-, two Vkappa10-, three Vkappa19- and one Vkappa23-family VL-genes . No preferential VH/VL-chains correlated with any of the 12 different antigen reactivities, even for mAbs with nearly identical cross-reactivities . However, we did find that the cross-reactive mAb germline genes within a V gene family shared more homology among themselves than with other germline genes within their V gene families, suggesting convergent mutation . Cross-reactive mAbs with the highest relative avidity for myosin were found in the VH7183 family which contained two cytotoxic mAbs . Antibodies with V gene sequences most homologous to those of our cross-reactive anti-myosin/anti-streptococcal mAbs had specificities for laminin, DNA, carbohydrates, or blood group antigens and were reported to cause autoimmune disease in mice.

Ann Emerg Med, 2001 Apr, 37(4), 377 - 81
Critical evaluation of a CLIA-waived streptococcal antigen detection test in the emergency department; Roosevelt GE et al.; STUDY OBJECTIVE: We compare the performance of a Clinical Laboratory Improvement Amendments (CLIA)-waived antigen detection test (ADT) analyzed in the emergency department and a CLIA moderately complex ADT performed in the hospital microbiology laboratory . METHODS: Samples from throat swabs were obtained using a double-headed Culturette II (Becton Dickinson Medical Systems, Sparks, MD) from a consecutive sample of 322 patients 3 years or older who presented to the ED of a university-affiliated pediatric referral hospital with the complaint of sore throat during 1998 . One swab was transported to the microbiology laboratory and analyzed using a CLIA moderately complex ADT; negative results were confirmed using sheep blood agar culture . The second swab remained in the ED where a nurse conducted a CLIA-waived ADT . The accepted standard for documentation of group A beta-hemolytic streptococcal (GABHS) infection was either a positive moderately complex ADT or culture result . The time of specimen collection, as well as the time the ED results and microbiology laboratory results were available to treating physicians, were recorded . Main outcome measures were concordance (kappa statistic), sensitivity, and turnaround time (Mann-Whitney U test) . RESULTS: Three hundred twenty-two patients (mean age 7.5 years) had both ADTs performed . One hundred one (31%) patients had documented GABHS in the microbiology laboratory; 83 (82%) had a positive ADT result in the microbiology laboratory, and 18 (18%) had a positive culture result after a negative moderately complex ADT result . In 299 patients or 93% (95% confidence interval {CI} 90.8%, 95.8%) of patients, the waived ADT and the moderately complex ADT results were concordant (kappa 0.82; 95% CI 0.78, 0.86; P <.001) . The sensitivity of the waived ADT was 80%; the sensitivity of the moderately complex ADT approximated 82% (difference of 2%; 95%CI -3%, 7%) . The median times from swab specimen collection to availability of ADT results were 10 minutes (range 3 to 37 minutes) for the waived ADT and 35 minutes (range 5 to 162 minutes) for the moderately complex ADT (P <.001) with a difference of 25 minutes (95% CI 22.4, 27.6 minutes) . CONCLUSION: In this study, an ED CLIA-waived rapid streptococcal throat test performed as well as its equivalent CLIA-regulated laboratory test . Further, the ED test provided results more rapidly than the laboratory test . Our results also validate previous work that negative rapid throat test results in pediatric patients in the ED should be confirmed by standard throat culture.

Eur J Dermatol, 2001 Mar-Apr, 11(2), 117 - 9
Juvenile generalized circinate pustular psoriasis treated with oral cyclosporin A; Wollina U et al.; We report on a 17-year-old boy presenting with relapsing generalized circinate pustular psoriasis exacerbated by streptococcal angina . Because of the severe course in his case, we started systemic treatment with cyclosporin A and corticosteroids . Corticosteroids could easily be tapered down . Cyclosporin A maintenance therapy was realized with 100 mg/day (1.6 mg per kg body weight and day) . Side effects were a temporary increase in blood pressure during initiation with 200 mg cyclosporin A/day . After dose reduction no side effects were seen . The pustular lesions disappeared and the PASI score decreased from 40.7 to 4.8 . The treatment was found to be well tolerated and effective.

Allergol Immunopathol (Madr), 2000 Nov-Dec, 28(6), 307 - 9
The inverse association between serum anti-streptolysin-O titers and the frequency of exacerbations of asthma in childhood; Nuhoglu Y et al.; BACKGROUND: The decline in infections in childhood may contribute to the rising severity and prevalence of atopic disorders in developed countries . Support for this hypothesis has been obtained from findings of an inverse association between tuberculin responses and atopy and from findings of high prevalence of asthma in certain islands with low prevalence of respiratory infections . With this regard, we investigated the association between serum anti-streptolysin-O (ASO) titers and the frequency of exacerbations of asthma in childhood . METHODS: Thirty atopic asthmatic children who has no sign of upper respiratory tract infection at the time of presentation or during the previous two months were included in the study . Serum ASO titer was measured as an indicator of past streptococcal upper respiratory tract infections . ASO titer > or = 200 Todd units was accepted as positive . RESULTS: A statistically significant association is found between high anti-streptolysin-O titers and decreased number of exacerbations in those children . CONCLUSIONS: Our data suggests that streptococcal infections might be a factor attenuating asthma in childhood.

Am J Med Sci, 2001 Mar, 321(3), 173 - 7
Poststreptococcal reactive arthritis in adults: long-term follow-up; Iglesias-Gamarra A et al.; BACKGROUND: Poststreptococcal reactive arthritis (PSReA) is a recognized inflammatory articular syndrome that follows group A streptococcal infection in persons not fulfilling the Jones criteria for the diagnosis of acute rheumatic fever . Characteristic features include nonmigratory arthritis, lack of response to aspirin or nonsteroidal anti-inflammatory agents, and the presence of extra-articular manifestations, including vasculitis and glomerulonephritis . Whether or not patients with PSReA develop carditis is a point of contention . METHODS: We analyzed the clinical features, laboratory findings, response to therapy, and outcome in patients diagnosed with PSReA between 1983 and 1998 and observed through April 2000 . All patients were contacted, reexamined, and repeat antistreptolysin, rheumatoid factor, C3 and C4 complement components, and echocardiograms were performed . RESULTS: Seventeen patients (4 men and 13 women) were included . All were of low socioeconomic status . All patients had acute severe arthritis that began shortly after a sore throat episode . Extra-articular involvement including tenosynovitis, vasculitis, and glomerulonephritis was relatively common . More importantly, none exhibited clinical and/or echocardiographic evidence of cardiac involvement . Longterm antibiotic therapy was not given . CONCLUSION: Cardiac involvement did not occur in this group of patients with PSReA . Prolonged prophylactic antibiotic therapy may not be required for adult patients presenting with PSReA.

Ann N Y Acad Sci, 2000, 917, 825 - 34
Perturbations of arginine vasopressin secretion during inflammatory stress . Pathophysiologic implications; Chikanza IC et al.; Pro-inflammatory cytokines, such as interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha), released from inflammatory foci, can activate the hypothalamus to produce corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) . These hypothalamic peptides in synergy increase ACTH production by the pituitary gland and hence corticosteroid (CS) secretion by the adrenal cortices . CS dampens inflammation . The pituitary also produces prolactin (PRL), which is pro-inflammatory, and macrophage inhibitory factor (MIF), which by counteracting the anti-inflammatory and immunosuppressive effects of CS, is pro-inflammatory . Lewis rats develop a variety of induced-autoimmune inflammatory conditions, such as streptococcal cell wall arthritis, whereas the histocompatible F344 Fisher rats are resistant to this condition . Lewis rats have a defective hypothalamic-pituitary adrenal (HPA) response to a variety of hypothalamic stimuli, but have augmented systemic secretion of AVP . Patients with rheumatoid arthritis (RA) have deficient CS with exaggerated PRL responses to inflammatory stimuli . Within inflammatory foci, CRH is pro-inflammatory . AVP, which augments autologous mixed lymphocyte reactions, can replace the IL-2 requirement for gamma IFN production by T cells via V1a receptors, and potentiates primary antibody responses, is also pro-inflammatory . Lewis rats have significantly high plasma levels, hypothalamic content, and in vitro release of AVP in comparison to the inflammatory disease-resistant Fischer rats . Immunoneutralization of AVP attenuates inflammatory responses . In Sprague-Dawley rats, AVP potentiates PRL secretion . Preliminary studies in patients with RA have shown that the circulating levels of AVP are significantly increased, which might be a compensatory response to low CS levels or a result of elevated levels of IL-6 in these patients but could nevertheless contribute to rheumatoid inflammation . A similar observation has been made in patients with ankylosing spondylitis.

Ann N Y Acad Sci, 2000, 917, 784 - 96
Susceptibility to autoimmune disease and drug addiction in inbred rats . Are there mechanistic factors in common related to abnormalities in hypothalamic-pituitary-adrenal axis and stress response function?
Wilder RL, Griffiths MM, Cannon GW, Caspi R, Remmers EF.
DA and LEW inbred rats are extraordinarily susceptible to a wide range of experimental autoimmune diseases . These diseases include rheumatoid arthritis models such as collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA), multiple sclerosis models such as myelin-basic-protein (MBP)-induced experimental autoimmune encephalomyelitis (MBP-EAE), and autoimmune uveitis models such as retinal S antigen (SAG) and interphotoreceptor-retinoid-binding-protein (IRBP)-induced experimental autoimmune uveitis (SAG-EAU and IRBP-EAU, respectively) . DA and LEW rats are also addiction-prone to various drugs of abuse, such as cocaine . Moreover, they exhibit a variety of behavioral and biochemical characteristics that appear to be related to their susceptibility to addiction . By contrast, F344 and BN rats show quite different phenotypes . They are relatively resistant to CIA, AIA, MBP-EAE, SAG-EAU, and IRBP-EAU, and they are relatively resistant to addiction . Interestingly, both DA and LEW rats, in contrast to F344 and BN rats, have abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function . For example, circadian production of corticosteroids is very abnormal in DA and LEW rats; that is, they exhibit minimal circadian variation in corticosterone levels . Since corticosteroids potentially have significant influences on immune function and autoimmune disease susceptibility and may also influence sensitivity to drugs of abuse, we have begun to dissect genetic control of these various phenotypic differences, focusing initially on the regulation of autoimmune disease expression . Using genomewide scanning techniques involving F2 crosses of DA x F344 (CIA and AIA), DA x BN (CIA), and LEW x F344 {IRBP-EAU and streptococcal-cell-wall arthritis (SCWA)}, we have identified, to date, 14 genomic regions {quantitative trait loci (QTL)} that regulate disease expression in these crosses . Development and analysis of QTL-congenic rats involving these loci are in progress and should permit us to address the relationships among autoimmune disease susceptibility, drug addiction, and HPA axis and stress response function . These initial data, however, indicate that the genetic control of the autoimmune disease traits is highly complex.

Protein Sci, 2001 Feb, 10(2), 450 - 4
Designed protein G core variants fold to native-like structures: sequence selection by ORBIT tolerates variation in backbone specification; Ross SA et al.; The solution structures of two computationally designed core variants of the beta 1 domain of streptococcal protein G (G beta 1) were solved by (1)H NMR methods to assess the robustness of amino acid sequence selection by the ORBIT protein design package under changes in protein backbone specification . One variant has mutations at three of 10 core positions and corresponds to minimal perturbations of the native G beta 1 backbone . The other, with mutations at six of 10 positions, was calculated for a backbone in which the separation between G beta 1's alpha-helix and beta-sheet was increased by 15% relative to native G beta 1 . Exchange broadening of some resonances and the complete absence of others in spectra of the sixfold mutant bespeak conformational heterogeneity in this protein . The NMR data were sufficiently abundant, however, to generate structures of similar, moderately high quality for both variants . Both proteins adopt backbone structures similar to their target folds . Moreover, the sequence selection algorithm successfully predicted all core chi(1) angles in both variants, five of six chi(2) angles in the threefold mutant and four of seven chi(2) angles in the sixfold mutant . We conclude that ORBIT calculates sequences that fold specifically to a geometry close to the template, even when the template is moderately perturbed relative to a naturally occurring structure . There are apparently limits to the size of acceptable perturbations: In this study, the larger perturbation led to undesired dynamic behavior.

Vestn Ross Akad Med Nauk, 2001, (1), 7 - 11
{Stages and results of Epidemiology Department activities}; Pokrovskii VI et al.; The paper sums up the activities of Department of Epidemiology of Medical Prophylaxis Faculty, I . M . Setchenov Moscow Medical Academy, in the 70 years of its existence . The Department plays the leading role in training specialists for sanitary and epidemiological service of the country . The main research, training, and methodological works in this speciality were prepared by the Department staff members, who prepared curricula for pre- and postgraduate training . For many years the department has been the methodological center in epidemiology training . Trends of research at the Department are concentrated on the pressing problems of general and special epidemiology . Due to activities of the department staff, epidemiological aspects have been studied and fundamentals of prevention and liquidation of many infectious diseases in the country have been formulated: enteric and streptococcal infections, typhus, tularemia, diphtheria, etc . Problems of epidemiological geography, including nosogeography, territorial and republican epidemiology have been investigated . Functioning of parasitic systems and mechanisms of epidemic process in some infections have been characterized with due regard for modern theoretical, methodological, and organization base of epidemiology . The data were used for developing new basis and organization forms of epidemiological surveillance of infectious diseases.

Bioorg Med Chem, 2001 Feb, 9(2), 537 - 54
The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy; Mclay LM et al.; RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes . An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA) . RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM) . It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg) . At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens . The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability . The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies.

Masui, 2001 Feb, 50(2), 154 - 9
{Perioperative management of three patients with streptococcal toxic shock syndrome}; Nakaigawa Y et al.; We report the perioperative management of three patients with streptococcal toxic shock syndrome (STSS) caused by group A streptococcal infection . Three of two patients survived but one patient died from multiple organ dysfunction in spite of vigorous treatments . These patients required the treatments including administration of antibiotics, circulatory and respiratory care, surgical debridement, anticoagulant therapy for disseminated intravascular coagulation and hemofiltration . The early diagnosis and surgical intervention play a key role in the successful management of this syndrome because it has a rapid course and frequent fatal outcome . The anesthetic management of these patients should be targeted to maintain perfusion of the vital organs and to control the blood clotting disorders.

Acta Derm Venereol, 2000 Nov-Dec, 80(6), 404 - 6
Investigation of cytomegalovirus and human herpes viruses 6 and 7 as possible causative antigens in psoriasis; Kirby B et al.; Psoriasis is probably a T-cell-mediated autoimmune disease . Infectious models of autoimmune diseases have been proposed and in psoriasis, it has been suggested that there may be molecular mimicry between streptococcal antigens and epidermal keratins . The immunological profile of stable psoriasis plaques suggests, however, that viral antigens may be important . We investigated, using polymerase chain reaction techniques, whether DNA from either cytomegalovirus (CMV) or human herpes viruses (HHV) 6 and 7 is present in the skin of patients (n = 10) with chronic plaque psoriasis . We also investigated 29 patients for the presence of serum IgG to CMV . We found no evidence of CMV or HHV 7 DNA in psoriasis plaques although DNA for HHV 6 was detected in both involved and uninvolved skin in 1 out of 10 patients . There was no statistically significant increase in prior CMV infection, as assessed by the presence or absence of serum IgG to CMV, in psoriasis, compared to our local population . Although there is circumstantial evidence that viral antigens may be important in the pathogenesis of psoriasis we found no evidence to link infection with CMV or HHV 6 and 7 with subsequent development of chronic plaque psoriasis.

Microbiology, 2001 Mar, 147(Pt 3), 757 - 62
The electrophoretic softness of the surface of Staphylococcus epidermidis cells grown in a liquid medium and on a solid agar; Kiers PJ et al.; Many Staphylococcus epidermidis strains possess capsule or slime layers and consequently the staphylococcal cell surface should be regarded as a soft, polyelectrolyte layer allowing electrophoretic fluid flow through a layer of fixed charges . The presence of such a soft layer decreases the energy barrier due to electrostatic repulsion in the interaction of the organisms with negatively charged substrata {Morisaki, H., Nagai, S., Ohshima, H., Ikemoto, E . & Kogure, K . (1999), MICROBIOLOGY: 145, 2797-2802} and hence plays an important role in their adhesion . In this paper, the authors compare the electrophoretic softness and amount of fixed charge in the outer cell surface layers of 20 S . epidermidis strains, grown in a liquid medium or on a solid agar, as determined from the dependencies of their electrophoretic mobilities upon the ionic strength of a suspending fluid . Most of the staphylococcal cell surfaces were relatively soft, with a mean cell surface softness (1/lambda) for strains grown in liquid medium of 1.7+/-0.6 nm (standard deviation over all 20 strains) which is soft by comparison with a completely bald, peptidoglycan-rich streptococcal cell surface (1/lambda=0.7 nm) . When the staphylococcal strains were grown on solid agar, the cell surface softness of 17 of the 20 strains increased, sometimes by a factor of two . On average for 20 strains, the cell surface softness increased significantly (P:<0.05, Student's t-test) to 2.8+/-1.8 nm . The amount of fixed charge in the outer cell surface layer was -28+/-9 mM for bacteria grown in liquid medium and -24+/-12 mM for bacteria grown on agar . A soft, highly negatively charged polyelectrolyte layer was inferred by microelectrophoresis for all the staphylococcal cell surfaces, regardless of whether staining had indicated the presence of a capsule or slime layer.

Stomatologiia (Mosk), 2001, 80(1), 55 - 7
{Use of immunotherapy with bacterial allergens in the combined treatment of periodontitis}; Khitrov VIu et al.; Bacterial allergens were used in the treatment of patients with chronic generalized slight and medium severe periodontitis . The allergens were used for hyposensitization or immunostimulation, depending on skin reactions to staphylococcal, streptococcal, and Escherichia coli allergens . Positive shifts in nonspecific immunity were attained; bacterial sensitization decreased, which indicates the treatment efficiency.

Acta Derm Venereol Suppl (Stockh), 2000, (211), 17 - 8
Subclinical microbial infection in patients with chronic plaque psoriasis; Bartenjev I et al.; Epidemiological evidence implicates bacterial infection as a common triggering stimulus for psoriasis . Recent studies suggest that continuing, subclinical streptococcal and staphylococcal infections might be responsible not only for relapse of acute guttate psoriasis but also for a new episode of chronic plaque psoriasis . In this study 195 patients suffering from a severe form of chronic plaque psoriasis hospitalized between 1996 and 1998 were examined . The presence of subclinical microbial infection of the upper respiratory tract was studied by the cultivation of pathogens from this area . Patients with other provoking factors, such as a positive history of taking any drugs that may exacerbate psoriasis, endocrine and metabolic factors, alcohol abuse, trauma, dental focus and clinically evident bacterial infection, were excluded . Subclinical streptococcal and/or staphylococcal infections were detected in 68% of tested patients and in only 11% of the control group . The results of this study indicate that subclinical bacterial infections of the upper respiratory tract may be an important factor in provoking a new relapse of chronic plaque psoriasis . Searching for, and eliminating, microbial infections could be of importance in the treatment of psoriasis.

CMAJ, 2001 Feb 20, 164(4), 479 - 85
Physicians' prevention practices and incidence of neonatal group B streptococcal disease in 2 Canadian regions; Davies HD et al.; BACKGROUND: The impact of expert guidelines on the prevention of neonatal group B streptococcal (GBS) disease has not been studied in Canada . Our aim was to determine physician practices with regard to this condition before and after publication of Canadian guidelines and to monitor concurrent trends in the incidence of neonatal GBS disease . METHODS: We used repeat cross-sectional surveys, distributed by mail to all family practitioners and obstetricians attending deliveries in Alberta and in the Metropolitan Toronto and Peel region, Ontario, in 1994, 1995 and 1997, to document prevention practices . Audits were conducted for a subset of respondents to confirm reported practices . Population-based surveillance involving all microbiology laboratories in both regions for 1995-1998 was used to document rates of neonatal disease . RESULTS: The overall survey response rates were as follows: for 1994, 1128/1458 (77%); for 1995, 1054/1450 (73%); and for 1997, 1030/1421 (72%) . During 1995 and 1997, significantly more obstetric care providers were screening at least 75% of pregnant women in their practices than had been the case in 1994 (747/916 {82%} and 693/812 {85%} v . 754/981 {77%}; p < 0.001) . The percentage of obstetric care providers who reported practice that conformed completely with any of 3 consensus prevention strategies increased from 10% in 1994 to 29% in 1997 (p < 0.001) . There was a concurrent overall significant decrease in incidence of neonatal GBS disease during the same period . INTERPRETATION: The adoption by Canadian obstetric care providers of neonatal GBS prevention practices recommended by expert groups was slow but improved significantly over time . These findings highlight the difficulties associated with achieving compliance with diverse and frequently changing recommendations . However, the associated incidence of neonatal GBS disease, which was low or declining, suggests that efforts to disseminate current GBS prevention guidelines have been moderately successful.

Kidney Int, 2001 Mar, 59(3), 950 - 8
Streptococcal erythrogenic toxin B induces apoptosis and proliferation in human leukocytes; Viera NT et al.; BACKGROUND: Previous reports have shown the presence of erythrogenic toxin type B (ETB), apoptosis, proliferation, and leukocyte infiltration in biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN) . METHODS: Attempting to correlate the apoptotic and proliferative events with the interaction of ETB or its precursor (ETBP) with leukocytes, mononuclear leukocytes from 12 healthy subjects were cultured with ETB or ETBP to analyze the levels of apoptosis, proliferation, expression of modulatory apoptosis gene products, and oxidative metabolism . After four days of incubation, cells were assessed for apoptosis by morphological criteria, annexin V assay, and terminal deoxy transferase uridine triphosphate nick end-labeling (TUNEL) assay . The expression of regulatory apoptosis genes was assessed by relevant monoclonal antibodies; proliferation was by incorporation of radioactive thymidine; and oxidative metabolism was by oxidation of 2',7'-dichlorofuorescein diacetate to 2',7'-dichlorofuorescein . Neutralization of Fas-L and cysteine protease activity of ETB were performed by incubation of ETB-treated leukocyte cultures with anti-human Fas-L mAb or with E64, respectively . RESULTS: Elevated levels of apoptosis in ETBP/ETB-treated leukocytes were found when compared with controls: morphological criteria (P < 0.01), Annexin V (control, 5.01 +/- 0.61; ETBP, 10.60 +/- 1.98%, P = 0.0005), and TUNEL (control, 12.5 +/- 2.6; ETBP, 20.56 +/- 3.06%, P = 0.001; ETB, 30.69 +/- 5.05%, P = 0.001) . Increased expression of apoptosis was accompanied by increased expression of Fas (control, 20.15 +/- 5.28; ETBP, 43.51 +/- 5.6%, P = 0.03; ETB, 47.16 +/- 5.54%, P = 0.01), Fas ligand (control, 5.64 +/- 2.38; ETBP, 11.66 +/- 3.65%, P = 0.04; ETB, 16.39 +/- 5.05%, P = 0.02) and p53 products (control, 9.22 +/- 3.44; ETBP, 22.82 +/- 5.72%, P = 0.01; ETB, 24.60 +/- 5.20%, P = 0.01) . Treatment of ETB-leukocyte cultures with anti-human Fas-L exhibited 2.2-fold lower apoptosis expression . Treatment with E64 significantly abrogated the apoptotic effect of ETB . There was no increment on leukocyte oxidative metabolism . Mononuclear leukocytes also showed elevated levels of proliferation when treated with different concentrations (from 50 to 6.2 microg/mL) of streptococcal proteins (Stimulation index ranging: ETBP, 5.6 +/- 1.9 to 6.4 +/- 1.9; ETB, 9.9 +/- 2.8 to 13.9 +/- 3.8) . CONCLUSIONS: These results delineate an additional pathway for the pathogenesis of APSGN related to the role of cationic streptococcal ETB or ETBP on the induction of apoptosis and proliferation during the course of the disease.

Vaccine, 2001 Feb 28, 19(15-16), 2118 - 26
Potency of clinical group B streptococcal conjugate vaccines; Paoletti LC; The potency of clinical group B streptococcal (GBS) capsular polysaccharide-protein conjugate vaccines has been assessed with use of a mouse maternal vaccination-neonatal pup challenge model of GBS disease . Two of the three conjugated GBS vaccines bottled as liquid preparations showed a potency reduction from 100% to < or = 50% in 3 years; whereas all six vaccines bottled as lyophilized preparations with sucrose excipient exhibited no loss of potency during the same span of time . A reconstituted GBS conjugate vaccine remained potent and antigenically intact after 31 days' storage at 2-8 degrees C . These data suggest that lyophilization in the presence of sucrose extends the potency of GBS conjugate vaccines.

J Pediatr Surg, 2001 Mar, 36(3), 487 - 92
Predictors of acquiring a nosocomial bloodstream infection on extracorporeal membrane oxygenation; Steiner CK et al.; PURPOSE: The aim of this study was to identify independent predictors of acquiring a nosocomial bloodstream infection (BSI) during extracorporeal membrane oxygenation (ECMO) . METHODS: This retrospective cohort consisted of 202 neonates treated with ECMO from 1989 to 1998 at the author' institution . Data collected included patient demographics, primary and secondary diagnoses, white blood cell counts, antibiotic usage, presence of central lines, operative procedures, and outcome . Surveillance blood cultures were drawn daily from the circuit using sterile technique to identify acquired pathogens . Statistical analyses included logistic regression, Cox proportional regression analysis, and discriminate analysis . RESULTS: There were 1,245 blood cultures drawn on 202 patients (6.2 cultures per patient), and a nosocomial BSI was identified in 7 patients (3.4%) during this 10-year span . These were infections that were neither present nor incubating on admission . Pre-ECMO diagnoses of patients who had a nosocomial BSI while on bypass included group B beta-hemolytic streptococcal sepsis (n = 2), herpes simplex viral sepsis (n = 1), congenital diaphragmatic hernia (n = 2), persistent pulmonary hypertension (n = 1), and congenital heart disease (n = 1) . The median time on ECMO before obtaining a positive culture was 390 hours . The infectious agents responsible for these BSIs included Staphylococcus epidermidis (n = 5), Staphylococcus aureus (n = 1), and Escherichia coli (n = 1) . The major factor associated with acquiring a nosocomial BSI on ECMO was the duration of bypass (391 v 141 hours, P =.002) . Additionally, patients in the BSI group were more likely to have had an arterial catheter in place (16 v 7 days, P =.009) and to have received more screening blood cultures (16 v 6 cultures, P < 001) . White blood cell counts, absolute neutrophil counts, and immature/total (I/T) ratios were not useful in predicting a nosocomial BSI . Of the 31 patients who required ECMO for more than 10 days, 7 (23%) had a positive blood culture, and 5 of these 7 infants (71%) died (P =.03) . CONCLUSIONS: The only predictor of acquiring a nosocomial BSI on ECMO was the duration of support for greater than 10 days . Because classical predictors of infection are unreliable while the patient is on ECMO, the authors suggest that obtaining daily surveillance blood cultures beginning on the tenth day should be performed with prolonged ECMO courses . The authors confirmed previous reports of the association between a prolonged ECMO course and a high mortality rate . However, the authors speculate that, in actuality, the primary diagnosis leads to the prolonged course of support and is the major factor in the infant' demise.

J Bacteriol, 2001 Mar, 183(6), 2101 - 10
Mobilization function of the pBHR1 plasmid, a derivative of the broad-host-range plasmid pBBR1; Szpirer CY et al.; The pBHR1 plasmid is a derivative of the small (2.6-kb), mobilizable broad-host-range plasmid pBBR1, which was isolated from the gram-negative bacterium Bordetella bronchiseptica (R . Antoine and C . Locht, Mol . Microbiol . 6:1785-1799, 1992) . Plasmid pBBR1 consists of two functional cassettes and presents sequence similarities with the transfer origins of several plasmids and mobilizable transposons from gram-positive bacteria . We show that the Mob protein specifically recognizes a 52-bp sequence which contains, in addition to the transfer origin, the promoter of the mob gene . We demonstrate that this gene is autoregulated . The binding of the Mob protein to the 52-bp sequence could thus allow the formation of a protein-DNA complex with a double function: relaxosome formation and mob gene regulation . We show that the Mob protein is a relaxase, and we located the nic site position in vitro . After sequence alignment, the position of the nic site of pBBR1 corresponds with those of the nick sites of the Bacteroides mobilizable transposon Tn4555 and the streptococcal plasmid pMV158 . The oriT of the latter is characteristic of a family of mobilizable plasmids that are found in gram-positive bacteria and that replicate by the rolling-circle mechanism . Plasmid pBBR1 thus appears to be a new member of this group, even though it resides in gram-negative bacteria and does not replicate via a rolling-circle mechanism . In addition, we identified two amino acids of the Mob protein necessary for its activity, and we discuss their involvement in the mobilization mechanism.

Clin Infect Dis, 2001 Jan, 32(1), E9 - 12
Value of standard laboratory tests for the early recognition of group A beta-hemolytic streptococcal necrotizing fasciitis; Simonart T et al.; The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period . Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.

J Am Acad Dermatol, 2001 Mar, 44(3), 433 - 8
Family history of psoriasis, stressful life events, and recent infectious disease are risk factors for a first episode of acute guttate psoriasis: results of a case-control study; Naldi L et al.; BACKGROUND: The association of guttate psoriasis with streptococcal pharyngitis is well accepted . The association of other risk factors is less well defined . OBJECTIVE: We attempted to provide an estimate of the risk for guttate psoriasis associated with a recent infectious disease and to explore other potential risk factors, including family history of psoriasis and psychologic stress . METHODS: This was a case-control study . Cases were patients with a first diagnosis ever of acute guttate psoriasis, made by a dermatologist . Controls were patients newly diagnosed as having dermatologic conditions other than psoriasis and seen in the same outpatient services as the cases . Inclusion of cases and controls was restricted to patients older than 16 years . The Holmes and Rahe Social Readjustment Rating Scale was used to assess stressful life events during the 6 months before diagnosis . A total of 73 cases (median age, 26 years) and 430 controls (median age, 28 years) were included in the analysis . RESULTS: A family history of psoriasis was strongly associated with guttate psoriasis, the multivariate odds ratio being 7.0 (95% confidence interval, 3.7-13.5) for subjects who reported a history of the disease in parents or siblings . Stressful life events were also associated with guttate psoriasis . The multivariate odds ratio was 1.7 (95% confidence interval, 0.8-3.6) for subjects scoring 41 to 100 and 2.6 (95% confidence interval, 1.3-5.2) for those scoring more than 100 on the Holmes and Rahe Scale . The risk increased with the reported history of any infectious disease . The analysis of specific diagnoses documented a high and significant association with acute pharyngitis, the adjusted odds ratio being 7.8 (95% confidence interval, 1.8-32.5) . CONCLUSION: The study confirmed that recent pharyngeal infection is a risk factor for guttate psoriasis . It also documented the strong association between guttate psoriasis and a family history of psoriasis . Finally, the study added evidence to the belief that stressful life events may represent risk factors for the onset of psoriasis . By relying on the clinical diagnosis we possibly underestimate the association of guttate psoriasis with infection.

Cell Microbiol, 2000 Aug, 2(4), 283 - 92
Bacterial determinants of persistent throat colonization and the associated immune response in a primate model of human group A streptococcal pharyngeal infection; Ashbaugh CD et al.; Group A streptococcal (GAS) pharyngitis and the subsequent bacterial colonization of the human throat elicit an immune response that may precipitate acute rheumatic fever in a susceptible host . To study the bacterial determinants that influence throat colonization and induction of humoral immunity, we characterized the behavior of GAS strains in a baboon model . An M-type 3 clinical isolate of GAS typical of strains that cause pharyngitis and invasive infection was recovered from the pharynx of six out of six baboons for at least 6 weeks after oral inoculation . By contrast, an isogenic mutant deficient in M protein failed to colonize most animals or was rapidly cleared . An isogenic mutant deficient in hyaluronic acid capsule colonized five out of six animals, but only persisted in the pharynx for 14-21 days . Colonized animals developed serum antistreptolysin O (SLO) and anti-M protein immunoglobulin (Ig)G . The kinetics of the antibody responses were similar to those seen after human infection . Peak titres increased with the duration of throat carriage . Colonization with GAS prevented recurrent colonization after challenge with the homologous wild-type strain, but not after challenge with a strain of different M protein type . Early clearance of the M protein-deficient strain was associated with increased susceptibility of this strain to phagocytic killing in non-immune serum, whereas clearance of the acapsular strain was associated with increased susceptibility to phagocytic killing in the presence of specific antibody . These studies support critical and distinct effects of the GAS M protein and capsule on throat colonization and induction of humoral immunity in a model that reproduces important features of pharyngeal colonization and immune response following human infection.

Infect Immun, 2001 Mar, 69(3), 1381 - 8
Functional characterization of streptococcal pyrogenic exotoxin J, a novel superantigen; McCormick JK et al.; Streptococcal toxic shock syndrome (STSS) is a highly lethal, acute-onset illness that is a subset of invasive streptococcal disease . The majority of clinical STSS cases have been associated with the pyrogenic toxin superantigens (PTSAgs) streptococcal pyrogenic exotoxin A or C (SPE A or C), although cases have been reported that are not associated with either of these exotoxins . Recent genome sequencing projects have revealed a number of open reading frames that potentially encode proteins with similarity to SPEs A and C and to other PTSAgs . Here, we describe the cloning, expression, purification, and functional characterization of a novel exotoxin termed streptococcal pyrogenic exotoxin J (SPE J) . Purified recombinant SPE J (rSPE J) expressed from Escherichia coli stimulated the expansion of both rabbit splenocytes and human peripheral blood lymphocytes, preferentially expanded human T cells displaying Vbeta2, -3, -12, -14, and -17 on their T-cell receptors, and was active at concentrations as low as 5 x 10(-6) microg/ml . Furthermore, rSPE J induced fevers in rabbits and was lethal in two models of STSS . Biochemically, SPE J had a predicted molecular weight of 24,444 and an isoelectric point of 7.7 and lacked the ability to form the cystine loop structure characteristic of many PTSAgs . SPE J shared 19.6, 47.1, 38.8, 18.1, 19.6, and 24.4% identity with SPEs A, C, G, and H, streptococcal superantigen, and streptococcal mitogenic exotoxin Z-2, respectively, and was immunologically cross-reactive with SPE C . The characterization of a seventh functional streptococcal PTSAg raises important questions relating to the evolution of the streptococcal superantigens.

Clin Infect Dis, 2001 Feb 1, 32(3), 419 - 30 Epub 2001 Jan 26.
Clinical effectiveness and cost-effectiveness of 2 management strategies for infected total hip arthroplasty in the elderly; Fisman DN et al.; Optimal management of infected total hip arthroplasty poses a major challenge to clinicians . Exchange arthroplasty is usually advocated but has high rates of surgical morbidity and is expensive . Debridement with prosthesis retention is associated with less morbidity, but high rates of relapsed infection have been described . To estimate the effectiveness and cost-effectiveness of these 2 strategies among older patients, we used a Markov model to simulate patients' projected lifetime clinical course in hypothetical cohorts of 65-year-old and frail 80-year-old men and women . Initial debridement and retention increased life expectancy 2.2-2.6 quality-adjusted life months and had a favorable cost-effectiveness ratio in all cohorts . Results were most sensitive to the annual rate of relapse after debridement and age at initial diagnosis of infection . In the absence of prospective clinical trials, debridement and retention is a reasonable strategy for treatment of older persons with staphylococcal or streptococcal infection and a nonloosened prosthesis.

J Clin Epidemiol, 2001 Feb, 54(2), 196 - 201
Measuring antibiotic prescribing practices among ambulatory physicians: accuracy of administrative claims data; Maselli JH et al.; To assess the accuracy of administrative claims data for measuring antibiotic prescribing behavior, we conducted a stratified randomized medical record review of office visits by children with pharyngitis, and adults with acute bronchitis, to primary care physicians in Colorado in 1998 . The diagnoses of pharyngitis (n = 422) and acute bronchitis (n = 497) based on administrative data were verified in 83% and 79%, respectively, of medical records . The sensitivity, specificity, and positive predictive value of administrative data in identifying antibiotic treatment for pharyngitis was 68%, 91%, and 90%, respectively, and for bronchitis was 79%, 84% and 98%, respectively . The sensitivity, specificity, and negative predictive value of administrative data in identifying group A streptococcal test ordering for pharyngitis was 71%, 86%, and 30%, respectively . Absence of testing in administrative data (when present in the medical record) was more frequent among visits to physicians associated with a capitated health plan . We conclude that administrative claims data are accurate sources for measuring and profiling antibiotic prescribing practices in ambulatory practice, although they underestimate actual antibiotic treatment decisions by individual physicians . Measuring and profiling antibiotic prescribing behavior in relation to group A streptococcal test utilization may overestimate inappropriate antibiotic treatment by physicians enrolled in capitated contracts.

Immunity, 2001 Jan, 14(1), 93 - 104
Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II; Li Y et al.; MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the alpha chain and a high-affinity, zinc-dependent site on the beta chain . Only the former has been defined crystallographically . We report the structure of streptococcal pyrogenic exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*0101, DRB5*0101) bearing a self-peptide from myelin basic protein (MBP) . SPE-C binds the beta chain through a zinc bridge that links the SAG and class II molecules . Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes . Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition.

J Immunol, 2001 Feb 15, 166(4), 2734 - 40
Selective inhibition of inducible nitric oxide synthase exacerbates erosive joint disease; McCartney-Francis NL et al.; NO is an essential cytotoxic agent in host defense, yet can be autotoxic if overproduced, as evidenced in inflammatory lesions and tissue destruction in experimental arthritis models . Treatment of streptococcal cell wal1-induced arthritis in rats with N:(G)-monomethyl-L-arginine (L-NMMA), a competitive nonspecific inhibitor of both constitutive and inducible isoforms of NO synthase (NOS), prevents intraarticular accumulation of leukocytes, joint swelling, and bone erosion . Because increased inducible NOS (iNOS) expression and NO generation are associated with pathogenesis of chronic inflammation, we investigated whether a selective inhibitor of iNOS, N:-iminoethyl-L-lysine (L-NIL), would have more directed anti-arthritic properties . Whereas both L-NMMA and L-NIL inhibited nitrite production by streptococcal cell wall-stimulated rat mononuclear cells in vitro and systemic treatment of arthritic rats with L-NMMA ablated synovitis, surprisingly L-NIL did not mediate resolution of inflammatory joint lesions . On the contrary, daily administration of L-NIL failed to reduce the acute response and exacerbated the chronic inflammatory response, as reflected by profound tissue destruction and loss of bone and cartilage . Although the number of iNOS-positive cells within the synovium decreased after treatment with L-NIL, immunohistochemical analyses revealed a distinct pattern of endothelial and neuronal NOS expression in the arthritic synovium that was unaffected by the isoform-specific L-NIL treatment . These studies uncover a contribution of the constitutive isoforms of NOS to the evolution of acute and chronic inflammation pathology which may be important in the design of therapeutic agents.

Presse Med, 2000 Dec 2, 29(37), 2028 - 32
{Resistance and new antibiotic strategies . The other new molecules}; Bergogne-Berezin E; ANTI-PNEUMOCOCCAL DRUGS: New fluoroquinolones with different targets than earlier compounds have been found to be active in certain cases of respiratory tract pneumococcal infections . Moxifloxacin, levofloxacin and gatifloxacin have been particularly effective . These new antibiotics can be classed in a new category of "respiratory quinolones" . EFFLUX PUMP INHIBITORS: The bacterial efflux systems are complex resistance mechanisms allowing the bacteria to expulse certain antibiotics belonging to several drug families and thus to develop multiple resistance capacities . A new series of efflux pump inhibitors has been recently synthesized . Associated with an antibiotic (levofloxacin, macrolide) these inhibitors significantly increase antibacterial activity . BACTERIAL WALL INHIBITORS: These compounds target the biosynthesis units of the bacterial walls, inhibiting for example bacterial enzyme Mur A . CYCLIC LIPOPEPTIDES: These include daptomycin which acts on peptidoglycan synthesis in the bacterial wall via a mechanism different from that of glycopeptides . NEW BETA-LACTAMS: Faropenem is a new member of the penem family . Ceftidoren is an oral cephalosporin that gives 64 to 70% cure after 7 to 10 days in cases of acute maxillary sinusitis and 81 to 83% in exacerbations of acute bronchial infections . In streptococcal pharyngitis in adults, ceftidoren produces better eradication (90%) of S . pyogenes than penicillin V (83%) at treatment end.

J Pept Res, 2000 Dec, 56(6), 438 - 45
An internal histidine residue from the bacterial surface protein, PAM, mediates its binding to the kringle-2 domain of human plasminogen; Schenone MM et al.; The determinants of binding of a peptide lacking C-termini-exposed lysine residues to a kringle domain were investigated using an up-regulated lysine binding kringle (K2Pg{C4G/E56D/K72Y}) of plasminogen and a peptide (a1-PAM) with a sequence derived from a surface-exposed M-like streptococcal protein . Significant kringle-induced chemical shifts in a His side-chain of a1-PAM were revealed by two-dimensional NMR . Further studies using isothermal titration calorimetry (ITC) provided support for the involvement of His12 in the peptide/ protein complex . In an effort to screen a1-PAM-derived truncation peptides, a combinatorial mixture, a1deltaa2-PAM{H12X} (where X=Pro, Arg, His, Trp, Lys, Ala, Phe, Asp and Gly), was analyzed using the surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI) platform . The major peptide that remained bound to the surface of the K2Pg{C4G/ E56D/K72Y}-containing chip was that containing His12, corresponding to the wild-type sequence . Minor peaks, representing binding, were obtained for Lys12-, Arg12- and Trp12-containing peptides . Individual peptides containing these amino acids were then examined using ITC and the binding constants obtained correlated with the relative strengths of binding estimated from the SELDI-based screen.

Drugs, 2000 Dec, 60(6), 1289 - 302
Diagnosis of pneumonia and monitoring of infection eradication; Ruiz M et al.; Pneumonia can be classified as community-acquired (CAP) or hospital-acquired (nosocomial) . Both are frequent infections that demand a great amount of medical resources . The diagnosis of CAP is based on clinical signs and the presence of a pulmonary infiltrate visible on chest radiograph . For practical purposes, CAP has been classified as typical, with an acute onset in which the most representative microorganism is Streptococccus pneumoniae, and atypical, with a subacute onset (Mycoplasma pneumoniae) . Nevertheless, so far no studies have clearly demonstrated the utility of this classification in predicting the aetiology . Guidelines on CAP recommend associating the aetiology of CAP with comorbidity, age and severity . The microbiological diagnosis relies mainly on Gram stain and sputum culture, but this technique has disadvantages such as frequent contamination of the sample with oropharyngeal commensal flora, frequent sterile cultures associated with previous antibiotic treatment, and the fact that approximately 40% of patients are not able to expectorate . Other diagnostic techniques such as blood cultures, serological tests and fibreoptic bronchoscopy must be reserved for patients who are hospitalised, especially if they need admission to an intensive care unit . Compared with CAP, nosocomial pneumonia has major diagnostic problems due to the presence of other diseases able to mimic pneumonia and frequent bacterial colonisation of the lower respiratory tract . Most of the diagnostic techniques produce a high percentage of false-negative and false-positive results . This is especially true for ventilator-associated pneumonia . There is controversy over using a comprehensive aetiological work-up based on bronchoscopic techniques or only on quantitative culture of endotracheal aspiration . By contrast, there is consensus about the importance of the adequacy of empirical antibiotic treatment, since mortality rates are higher in patients who are inadequately treated . Once treatment of pneumonia has begun, it must be maintained for 48 to 72 hours because this is the minimum time to evaluate a clinical response . Antibacterial agents have to be adjusted according to microbiological findings . In nonresponding patients, pneumonia-related complications and the presence of multiresistant micro-organisms or non-covered pathogens must be ruled out.

J Pediatr, 2001 Jan, 138(1), 71 - 5
Group A streptococcal infections and tic disorders in an Italian pediatric population; Cardona F et al.; BACKGROUND: The relationship between childhood tic disorders and group A streptococcal (GAS) infections has been recently investigated by several research groups, but no systematic evaluation of laboratory indicators of GAS infections has been provided . OBJECTIVE: The aim of our study was to seek clinical and laboratory evidence of GAS infections in a large population of children affected with tic disorders . STUDY DESIGN: This investigation was a case-control study: 150 consecutive children presenting with tics were investigated for clinical and laboratory signs of streptococcal infections on the occasion of their first neuropsychiatric consultation . To compare the rate of exposition to GAS in a similar population, a control group of 150 children without tic disorders was examined during the same period . RESULTS: In children with tics, mean antistreptolysin O (ASO) titer (434 +/- 338 IU) was significantly higher compared with that of control subjects (155 +/- 126 IU); 38% of the children with tics compared with 2% of the control subjects (P <.001) had ASO titers > or =500 IU . Twenty-six children with tics (17%) had throat cultures positive for GAS, but in all cases, only few colonies per plate were isolated . Among the strains isolated, no prevalent T pattern or M type was observed . In children with tics a positive correlation between ASO titers and severity of tic disorder (measured by the Yale Global Tic Severity Scale) was found . CONCLUSION: Our results suggest that children with tic disorder could be a unique population in which GAS infection, or at least the exposure to streptococcal antigens, is correlated to the neurobehavioral disorder . Moreover, our data indicate a relationship between the severity of tic disorder and the magnitude of the serologic response to GAS antigens.

JAMA, 2000 Dec 13, 284(22), 2912 - 8
The rational clinical examination . Does this patient have strep throat?
Ebell MH, Smith MA, Barry HC, Ives K, Carey M.
CONTEXT: Sore throat is a common complaint, and identifying patients with group A beta-hemolytic streptococcal pharyngitis (strep throat) is an important task for clinicians . Previous reviews have not systematically reviewed and synthesized the evidence . OBJECTIVE: To review the precision and accuracy of the clinical examination in diagnosing strep throat . DATA SOURCE: MEDLINE search for articles about diagnosis of strep throat using history-taking and physical examination . STUDY SELECTION: Large blinded, prospective studies (having > or =300 patients with sore throat) reporting history and physical examination data and using throat culture as the reference standard were included . Of 917 articles identified by the search, 9 met all inclusion criteria . DATA EXTRACTION: Pairs of authors independently reviewed each article and used consensus to resolve discrepancies . DATA SYNTHESIS: The most useful findings for evaluating the likelihood of strep throat are presence of tonsillar exudate, pharyngeal exudate, or exposure to strep throat infection in the previous 2 weeks (positive likelihood ratios, 3.4, 2.1, and 1.9, respectively) and the absence of tender anterior cervical nodes, tonsillar enlargement, or exudate (negative likelihood ratios, 0.60, 0.63, and 0.74, respectively) . No individual element of history-taking or physical examination is accurate enough by itself to rule in or rule out strep throat . Three validated clinical prediction rules are described for adult and pediatric populations . CONCLUSIONS: While no single element of history-taking or physical examination is sufficiently accurate to exclude or diagnose strep throat, a well-validated clinical prediction rule can be useful and can help physicians make more informed use of rapid antigen tests and throat cultures.

Pediatr Infect Dis J, 2000 Dec, 19(12 Suppl), S171 - 3
Comparison of cefdinir and penicillin V in the treatment of pediatric streptococcal tonsillopharyngitis; Pichichero ME et al.; BACKGROUND: Group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis continues to be a prevalent pediatric infectious disease that requires prompt treatment for relief of symptoms and to prevent complications . OBJECTIVE: To compare the efficacy/tolerability of cefdinir and penicillin V in the treatment of pediatric GABHS tonsillopharyngitis as demonstrated in two clinical trials of similar design . DESIGN: Multicenter, randomized, investigator-blinded trials . PATIENTS: Children < or =12 years of age with sore throat, pharyngeal erythema and positive rapid streptococcal antigen test results . INTERVENTION: In Study A patients took cefdinir 7 mg/kg twice daily or 14 mg/kg once daily or penicillin V 10 mg/kg 4 times daily (all regimens for 10 days) . In Study B patients took cefdinir 7 mg/kg twice daily for 5 days or penicillin V 10 mg/kg 4 times daily for 10 days . MEASUREMENTS: Clinical and microbiologic evaluations were conducted at multiple times during and after therapy . RESULTS: Of 1274 patients 1122 were evaluable (679 patients received cefdinir; 443 received penicillin V) . Clinical cure and microbiologic eradication rates were superior in the combined cefdinir treatment groups (94.9 and 92.7%, respectively), whether given once or twice daily for 10 days or twice daily for 5 days, compared with the penicillin treatment group (88.5 and 70.9%, respectively; P<0.001 for both) . Adverse event rates were comparable in the 2 groups . CONCLUSION: Cefdinir is a reliable and well-tolerated drug for the management of GABHS tonsillopharyngitis in children.

Pediatr Infect Dis J, 2000 Dec, 19(12 Suppl), S131 - 40
Evaluating the need, timing and best choice of antibiotic therapy for acute otitis media and tonsillopharyngitis infections in children; Pichichero ME; Deciding whether an antibiotic is necessary, when to begin therapy and selecting an optimal drug is an everyday challenge in clinical practice . In vitro susceptibility testing which determines the minimum concentration necessary for a particular antibiotic to inhibit or kill most strains of a bacterial species and pharmacodynamic modeling are useful but have limitations . The need for antibiotic therapy for acute otitis media (AOM) has been recently questioned . However, explanations for uniformly positive results with many antibiotic and placebo comparative trials include overdiagnosis of AOM at study entry, inclusion of patients with mild or uncomplicated AOM and broad criteria for the definition of clinical success . Recurrent and persistent AOM does not have as favorable a natural history as uncomplicated AOM; children below 2 years of age benefit most from antibiotic therapy . Selecting the best choice among the many antibiotics that can be used to treat AOM has become more complex over the last decade due to escalating antibiotic resistance among the pathogens that cause this infection . Broader spectrum antibiotics such as cefdinir, the newly introduced third generation cephalosporin, have their most prominent use in the treatment of persistent and recurrent AOM . In the early 1950s and 1960s penicillin clearly was the best available agent for the treatment of group A streptococcal (GAS) infections . In the 1970s the situation began to change as cephalosporin antibiotics became available . Superior eradication rates with cephalosporins such as cefdinir have now been well-documented . The leading hypothesis to explain the widening gap in efficacy between penicillin and cephalosporins relates to two major concepts: the presence of copathogens and differential alteration of the normal microbial ecology in the throat as a consequence of the selected therapy . There are positive and negative consequences to early initiation of antibiotic therapy for GAS tonsillopharyngitis . Penicillin has persisting good efficacy in patients older than the age of 12 years and in those who have been ill for >2 days . Shortening therapy for GAS tonsillopharyngitis offers a therapeutic advantage . Cefpodoxime proxetil and cefdinir have a 5-day indication for the treatment of GAS tonsillopharyngitis . Antibiotics with lower side effect profile, infrequent dosing, good palatability in suspension formulation and efficacy with short duration of treatment may lead to better outcomes because noncompliance often results in failed therapy, persistence of infection and morbidity.

J Biomol NMR, 2000 Nov, 18(3), 207 - 16
Pressure alters electronic orbital overlap in hydrogen bonds; Li H et al.; Pressure-induced changes in 3hJ(NC') scalar couplings through hydrogen bonds were investigated in the immunoglobulin binding domain of streptococcal protein G . 1H, 15N and 13C triple-resonance NMR spectroscopy coupled with the on-line high pressure cell technique was used to monitor 3hJ(NC') scalar couplings at 30 and 2000 bar in uniformly labeled 15N and 13C protein isotopes . Both increased and decreased 3hJ(NC') scalar couplings were observed at high pressure . No correlation with secondary structure was apparent . The difference in coupling constants as well as pressure-induced chemical shift data suggests a compaction of the helix ends and an increase of the helix pitch at its center in response to pressure . Our data provides the first direct evidence that the electronic orbital overlap in protein backbone hydrogen bonds is altered by pressure.

Pediatr Emerg Care, 2000 Dec, 16(6), 423 - 5
Congenital penoscrotal lymphedema complicated by sepsis associated with a streptococcal infection; Watanabe T; Congenital lymphedema is a relatively rare disease caused by congenital abnormality of the lymphatic system . Although bacterial infection frequently causes complications with lymphedema, severe sepsis in congenital lymphedema of the genitalia has not yet been reported . We describe a patient with congenital penoscrotal lymphedema complicated by cellulitis, lymphangitis, and severe sepsis associated with a streptococcal infection . This case represents the importance of obtaining a detailed clinical history and physical findings.

Pediatr Emerg Care, 2000 Dec, 16(6), 398 - 400
When choosing injectable penicillin for the treatment of group A beta-hemolytic streptococcal pharyngitis, there is a less painful choice; Bycroft TC et al.; OBJECTIVE: To determine whether injection of patients with Bicillin CR is less painful than injection with Bicillin LA . To discover if Bicillin CR with the addition of procaine, which doubles the volume, causes the injection to be less painful . DESIGN: An experimental, double-blinded crossover design was used for this study . SETTING: University children's and women's tertiary care emergency Department (ED) with an annual pediatric census of 22,000 . PARTICIPANTS: A convenience sample was enrolled from the student body of a large university and house staff, and employees of a 152 bed children's and women's hospital in southern Alabama . The sample size was limited to 50 participants, all of whom completed the study . METHODS: Each participant received two penicillin injections, one Bicillin CR and one Bicillin LA, and rated the pain of the injection immediately after the injection, 1 hour after the injection and 12 hours after the injection . A visual analogue scale was the tool used for measuring the pain . The penicillin injections were randomized using a random number generator . RESULTS: For each of the three periods, comparisons of pain were made between the Bicillin CR versus Bicillin LA injections . Bicillin LA pain score values were consistently higher for all but the 12-hour comparison . These differences were statistically significant (P < 0.008-0.002) . CONCLUSIONS: Injection of Bicillin CR with the addition of procaine to the benzathine penicillin G is statistically significantly less painful than the injection of Bicillin LA without the addition of procaine to the benzathine penicillin G, even though the Bicillin LA is one-half the volume of the Bicillin CR due to the addition of procaine to the Bicillin CR.

Orv Hetil, 2000 Dec 3, 141(49), 2639 - 47
{Importance of professional proposals in the era of broadening antibiotic resistance}; Katona Z et al.; A great degree of neglection has been portrayed on the consideration in two most important professional proposals in 6906 patients of 44 praxis in the basic health care in 1996: 1 . the obviously viral respiratory diseases (including acute bronchitis, ordinarily) was treated in 56% of cases with antibacterial drugs (in 83% of all treatments with broad spectrum antibiotics), and 2 . for patients with Streptococcal infections too broadened spectrum antibiotics for this purpose were undesirably prescribed (in 75.5% of treatments) by physicians . Taking into consideration the suitable efficient ("evidence based") anticausal therapy and professional proposals, as well, in 63.6% of all antibiotic therapy could be avoided by physicians . By all means, these prescribed legion of the aimless, unnecessary and simultaneously too broadened spectrum antibacterial drugs served for the spreading of antibiotic resistance only, and all of them were the results of the neglection of the most important professional proposals . These unnecessary treatments--excluding the increase of resistance or the improper, unsubstantiated raise in hopes of patients--cost too much: the sum of expenses were 49.5% of the cost for antibiotics in Hungary in 1996 (in our estimation) . To measure and examine periodically the quality level of primary infectological care, new quality indicators were appointed by the authors: the attained quality levels of each medical praxis would have to be compared and approached to the desirable level of quality indicators (reflecting the "evidence based" infections care) for the abolition of the unreasonable, expensive and dangerous practice for patients, as well . It appears, that the wide application of the appropriate, "evidence based" anticausal therapy would be reached with control of offered quality (the offered values of the quality indicators) of physicians in primary care, only . The introduction of quality assurance in basic health care needs urgent comprehensive official action.

Mo Med, 2000 Dec, 97(12), 541 - 4
Evaluation of the American Academy of Pediatrics Principles on Management of Common Office Infections in a managed care setting; Hover AR et al.; The American Academy of Pediatrics has outlined principles for management of common office infections . We evaluated the impact of these principles at St . John's Health System . Study design was a pre and post guideline analysis of claims data and a randomized chart review . There was a high baseline compliance present with the AAP recommendations . There was a 33.5% increase in the use of throat cultures or streptococcal agglutination screens for diagnosis of upper respiratory infections (p = .001) and an 86% decrease in the use of sinus films (p < .001) . We conclude that the AAP principles resulted in a significant change in clinical practice.

Rheumatology (Oxford), 2000 Dec, 39(12), 1351 - 6
The diagnostic value of streptococcal serology in early arthritis: a prospective cohort study; Visser H et al.; OBJECTIVE: To evaluate the diagnostic value of streptococcal serology in adult early arthritis patients in discriminating between post-streptococcal reactive arthritis (PSRA) and arthritis with other causes . METHODS: The antistreptolysin-O (ASO) and anti-DNase B tests were performed at baseline in 366 consecutive, newly referred early arthritis patients . After 1 yr of follow-up the patients were classified according to international classification criteria and were evaluated for the presence of persistent arthritis . The outcome measures were the predictive value of streptococcal serology for the diagnosis of PSRA and the ability of this serology to discriminate at the first visit between the self-limiting and persistent forms of arthritis . RESULTS: With a positive serological result, the probability of having PSRA increased from 2 to 9%, whereas the probabilities of having rheumatoid arthritis or undifferentiated arthritis continued to be high (23 and 29%) . The serological tests did not discriminate between the self-limiting and persistent forms of arthritis . The major Jones criteria apart from arthritis were not observed . CONCLUSION: Streptococcal serology has no diagnostic value in adult early arthritis patients in whom major Jones criteria other than arthritis are not present.

J Infect Dis, 2001 Feb 1, 183(3), 507 - 11 Epub 2000 Dec 20.
Pathogenic mechanisms in rheumatic carditis: focus on valvular endothelium; Roberts S et al.; To clarify immune-mediated mechanisms in rheumatic heart disease caused by group A streptococcal infection, valve tissues from rheumatic patients with valvular heart disease who required valve replacement were studied for reactivity with monoclonal anti-CD4 or anti-CD8 monoclonal antibodies or anti-vascular cell adhesion molecule-1 (VCAM-1) . At the valve surface, CD4(+) and CD8(+) T lymphocytes were adherent to valve endothelium and penetrated through the subendothelial layer . T cell extravasation into the valve through the surface valvular endothelium appeared to be an important event in the development of rheumatic heart disease . VCAM-1 was expressed on the valvular endothelium in rheumatic valves . Evidence suggested that the pathogenesis of rheumatic heart disease involved the activation of surface valvular endothelium with the expression of VCAM-1 and the extravasation of CD4(+) and CD8(+) lymphocytes through the activated endothelium into the valve . Lymphocytic infiltration through the valve surface endothelium has not been appreciated as a potential initiating step in disease pathogenesis.

S D J Med, 2000 Dec, 53(12), 527 - 30
Kawasaki disease: a diagnostic challenge; Chatterjee A et al.; Kawasaki disease (KD) is an acute, self-limited, febrile, multi-system vasculitis that predominantly affects the the pediatric population, and is the leading cause of acquired heart disease in children . No etiologic agent for the disease has been identified, there are no diagnostic tests available, and the diagnosis is established by fulfilling a defined set of clinical criteria . We report on a 9-year-old boy who presented initially with symptoms felt to represent a streptococcal infection . He was subsequently shown to meet the criteria for KD, developed cardiac complications of the disease and subsequently demonstrated recovery over a year's period of time . The diagnostic criteria for KD, differential diagnosis, pitfalls in diagnosis, therapeutic recommendations and outcomes are discussed with relevance to this case . Recent print and electronic information sources and references are provided.

Anticancer Res, 2000 Sep- Oct, 20(5B), 3363 - 73
A combination of cyclosporin-A (CsA) and interferon-gamma (INF-gamma) induces apoptosis in human gastric carcinoma cells; Morisaki T et al.; Modulation of interferon-gamma effect by other drug may enhance its tumor specific activity . The apoptosis inducing effect of interferon-gamma and its modulation by cyclosporin-A or tacrolimus (FK-506) were investigated in in vitro and ex vivo experiments . We found that a combination of cyclosporin-A (CsA) and recombinant interferon-gamma (rIFN-gamma) induced significant apoptosis in all four types of human gastric carcinoma cells tested but not in normal cells such as human peripheral blood mononuclear cells (PBMCs), human omentum-derived mesothelial cells, or human umbilical vein endothelial cells (HUVECs) in vitro . Apoptosis was also induced by a combination of rIFN-gamma with FK-506 but not with rapamycin . Next, the apoptosis-inducing effect of endogenous IFN-gamma combined with cyclosporin-A was examined using clinical samples . A streptococcal preparation, OK-432, was administered intraperitoneally for the management of 12 gastric cancer patients with malignant ascites . None of the gascitic fluids obtained before the OK-432 injection showed detectable IFN-gamma level . The OK-432 injection induced a detectable IFN-gamma production ranging from 6 to 89 pg/mL in ascitic fluids from 9 out of the 12 patients . A combination of CsA with ascitic fluids collected after but not before OK-432 injection induced significant apoptosis in MK-1 cells, a gastric carcinoma cell line . A positive correlation was found between the IFN-gamma level and CsA-induced apoptosis . The CsA-induced apoptosis was also blocked by a specific antibody against human IFN-gamma . These results indicated that both recombinant and endogenous IFN-gamma can induce potent tumor-apoptosis when combined with CsA.

Indian J Pediatr, 2000 Mar, 67(3 Suppl), S11 - 4
Diagnosis of rheumatic fever: current status of Jones Criteria and role of echocardiography; Saxena A; The original Jones Criteria as proposed by Dr . T . Duckett Jones have been modified four times and the updated revised criteria were published in 1992 . According to this latest publication major manifestations are carditis, polyarthritis, chorea, erythema marginatum and subcutaneous nodules . Minor manifestations include fever, arthralgia and laboratory findings of elevated erythrocyte sedimentation rate, C-reactive protein and prolonged PR interval on ECG . For making a diagnosis of acute rheumatic fever, two major, or one major and two minor manifestations must be accompanied by supporting evidence of antecedent group A streptococcal infection in the form of positive throat culture or elevated or rising anti-streptolysin titre . The updated guidelines also highlighted a subgroup of "exceptions to Jones Criteria" for patients with chorea, indolent carditis and previous history of rheumatic fever or "rheumatic heart disease" . Role of echocardiography has not been defined in these modifications but may be important, as clinical detection of soft murmurs may be difficult due to tachycardia . Doppler and color flow mapping is more sensitive in picking up minor digress of valvular regurgitation . Several studies have confirmed that the yield of carditis with valvular regurgitation increased with use of echocardiography in patients with acute rheumatic fever . Also echocardiography is of great help in mixed valve lesions to determine the severity of each lesion . Other abnormalities detected on echocardiography in acute carditis include prolapse of the valve, focal nodular thickening of leaflets and pericardial effusion . Jones Criteria are guidelines to assist the physician and should not be substituted for clinical judgement as strictly following them may result in underdiagnosis of this disease in our country.

J Chemother, 2000 Oct, 12(5), 396 - 405
Clinical and bacteriologic efficacy of amoxycillin b.d . (45 mg/kg/day) versus amoxycillin t.d.s (40 mg/kg/day) in children with group A beta-hemolytic streptococcal tonsillopharyngitis; Aguilar A et al.; This randomized, observer-blind, multicenter, parallel-group study compared the clinical and bacteriologic efficacy and safety of amoxycillin, 45 mg/kg/day b.d . and amoxycillin, 40 mg/kg/day t.d.s . after 7 days of treatment in 517 children with acute bacterial tonsillopharyngitis . At the end of treatment, a successful clinical response was recorded in more than 96% of patients in each of the treatment groups . A similar result was obtained at follow-up . Among those patients who were bacteriologically evaluable at the end of treatment, a successful bacteriologic response was achieved in more than 94% in each treatment group . Both treatments were well tolerated . Drug-related adverse events were recorded in just 12 patients (4.6%) in the b.d . group and six (2.4%) in the t.d.s . group . The study demonstrated that a twice-daily regimen of amoxycillin, 45 mg/kg/day, was as effective and as well tolerated as the standard three-times-daily regimen of amoxycillin, 40 mg/kg/day, in the treatment of acute bacterial tonsillopharyngitis in children.

Nihon Rinsho Meneki Gakkai Kaishi, 1999 Jun, 22(3), 144 - 50
{Cutaneous polyarteritis nodosa associated with streptococcal infection in a child and a review of the literature}; Sasamoto M et al.; Polyarteritis nodosa (PAN) is a multisystem inflammatory disease associated with necrosis of small and medium arteries . It can occur in a systemic form with manifestations in skin, joints, heart, nervous system, gastrointestinal tracts, lungs and kidneys . It is relatively rare in adults and even more in children . It may be divided into a cutaneous form (C-PAN) and a more generalized form (G-PAN) . Usually C-PAN is thought to run a benign course . But some cases were reported to run chronic courses and be diagnosed G-PAN . It has been reported that some adults with PAN are related to HBV infection . On the other hand most children with PAN had upper respiratory infections some with streptococcal infections . We described a 5-year-old boy who was suffering from high fever, joint pain, subcutaneous nodular and livedo reticularis . We diagnosed him C-PAN by examination and clinical course . Anti-streptolysin O (ASO) and anti-streptokinase (ASK) increased and we suspected that C-PAN followed after streptococcal infection . We reviewed the literatures of C-PAN and streptococcal infection in childhood . Streptococcal infection has been implicated by a positive throat swab or an increase in ASO . There were 25 cases (75.7%) which were thought to be related with prior streptococcal infection in 33 cases . We thought that C-PAN may be associated with streptcoccal infection in childhood.

Intensive Care Med, 2000 Oct, 26(10), 1566 - 70
The effect of C1-esterase inhibitor in definite and suspected streptococcal toxic shock syndrome . Report of seven patients; Fronhoffs S et al.; OBJECTIVE: To evaluate the effect of adjunctive C1-esterase inhibitor substitution therapy on clinical characteristics and outcome of patients with streptococcal toxic shock syndrome (TSS) . DESIGN: Observational . SETTING: Medizinische Poliklinik, University of Bonn, Germany . PATIENTS: Seven patients with direct or indirect evidence of streptococcal TSS . INTERVENTION: In addition to conventional and supportive therapy, all patients received 2-3 single doses of C1-esterase inhibitor totaling 6,000-10,000 U within the first 24 h after admission . MEASUREMENTS AND RESULTS: All patients developed fulminant septic shock, multiorgan failure and/or capillary leak syndrome and necrotizing fasciitis within 10-72 h following the onset of first symptoms . Between 1 and 4 days following administration of C1-esterase inhibitor, a marked shift of fluid from extravascular to intravascular compartments took place in all but one patient, accompanied by a transient intra-alveolar lung edema and rapidly decreasing need for adrenergic agents . Six of seven patients survived . CONCLUSIONS: These clinical observations in a small series of patients and the favorable outcome point towards a positive effect of early and high-dose administration of C1-esterase inhibitor as adjunctive therapy in streptococcal TSS . The possible mechanism involved may be the attenuation of capillary leak syndrome (CLS) via early inactivation of complement and contact systems . Controlled studies are needed to establish an improvement of the survival rates of patients with streptococcal TSS following administration of C1-esterase inhibitor.

Br J Dermatol, 2000 Dec, 143(6), 1177 - 82
HLA-C and guttate psoriasis; Mallon E et al.; BACKGROUND: Psoriasis is a heterogeneous disease in its clinical expression . Both genetic and environmental factors are thought to contribute to the pathogenesis of the inflammatory and hyperproliferative components of the typical skin lesions . Predisposing genetic influences include associations with human leucocyte antigens (HLA) of which that with HLA-Cw6 is the strongest . Guttate psoriasis is a specific clinical manifestation of psoriasis frequently associated with group A beta-haemolytic streptococcal throat infection . OBJECTIVES: We set out to determine whether further clinical subdivision of psoriasis is associated with tighter correlation with HLA-C alleles . PATIENTS/METHODS: We determined the HLA-C locus genotype of 29 caucasian patients with guttate psoriasis presenting consecutively with guttate psoriasis associated with a history of a sore throat and/or an antistreptolysin O titre > 200 IU mL-1 . Polymerase chain reaction typing using sequence-specific primers was used to detect all known HLA-C alleles . These data were compared with a control population of 604 random caucasian cadaver donors . RESULTS: All patients (100%) with guttate psoriasis carried the Cw*0602 allele compared with 20% of the control population (odds ratio = infinity; 95% confidence limits 25.00-infinity; Pcorrected < 0.0000002) . CONCLUSIONS: This result is consistent with HLA-Cw*0602 playing a part directly in the pathogenesis of guttate psoriasis.

Infect Immun, 2001 Jan, 69(1), 534 - 7
Group A streptococcal rofA gene is involved in the control of several virulence genes and eukaryotic cell attachment and internalization; Beckert S et al.; The serotype M6 group A streptococcal RofA regulator was previously shown to exert a direct positive control of protein F1 expression and, concomitantly, fibronectin binding . Using a serotype M6 rofA mutant, we demonstrate here that this regulator has a potentially indirect negative influence on the expression of the mga, emm6, pel-sagA, and speA virulence genes . Additionally, the rofA mutant exhibited reduced eukaryotic cell internalization rates in combination with decreased host cell viability.

Infect Immun, 2001 Jan, 69(1), 252 - 61
Recombinant antigen-enterotoxin A2/B chimeric mucosal immunogens differentially enhance antibody responses and B7-dependent costimulation of CD4(+) T cells; Martin M et al.; The ADP-ribosylating enterotoxins, cholera toxin (CT) and the Escherichia coli heat-labile toxin (LT-IIa), have been shown to enhance mucosal and systemic antibody (Ab) responses to coadministered antigens . The purpose of the present study was to compare the ability of the nontoxic A2/B subunits of these toxins, which have distinct targeting properties, to augment the immunogenicity of a genetically coupled protein antigen . Structurally similar chimeric proteins were generated by genetically replacing the toxic A1 subunit of CT or LT-IIa with the saliva-binding region (SBR) from the streptococcal adhesin AgI/II . Intranasal immunization of BALB/c mice with either chimeric protein induced significantly higher plasma and mucosal anti-SBR immunoglobulin A (IgA) and IgG Ab responses than SBR alone . Moreover, compared to SBR-LT-IIaA2/B, SBR-CTA2/B elicited significantly higher levels of plasma IgG1 and salivary IgA anti-SBR Ab responses . Ex vivo and in vitro experiments revealed that SBR-CTA2/B selectively up-regulated B7-2 expression on murine B cells isolated from both the nasal associated lymphoid tissue, cervical lymph nodes, and spleen . In contrast, SBR-LT-IIaA2/B had little effect on B7-1 or B7-2 expression on B220(+), CD11b(+), or CD11c(+) cells . Analysis of the functional costimulatory activity of SBR-CTA2/B-treated B cells revealed a significant enhancement in anti-CD3-stimulated CD4(+) T-cell proliferative responses, and this proliferation was significantly reduced by treatment with anti-B7-2 but not with anti-B7-1 or isotype control Abs . Thus, SBR-CTA2/B and SBR-LT-IIaA2/B exhibit distinct patterns of antibody responses associated with differential effects on B7-2 expression and subsequent costimulatory effects on CD4(+) T cells.

Protein Eng, 2000 Oct, 13(10), 703 - 9
Charge engineering of a protein domain to allow efficient ion-exchange recovery; Graslund T et al.; We have created protein domains with extreme surface charge . These mutated domains allow for ion-exchange chromatography under conditions favourable for selective and efficient capture, using Escherichia coli as a host organism . The staphylococcal protein A-derived domain Z (Zwt) was used as a scaffold when constructing two mutants, Zbasic1 and Zbasic2, with high positive surface charge . Far-ultraviolet circular dichroism measurements showed that they have a secondary structure content comparable to the parental molecule Zwt . Although melting temperatures (Tm) of the engineered domains were lower than that of the wild-type Z domain, both mutants could be produced successfully as intracellular full-length products in E . coli and purified to homogeneity by ion-exchange chromatography . Further studies performed on Zbasic1 and Zbasic2 showed that they were able to bind to a cation exchanger even at pH values in the 9 to 11 range . A gene fusion between Zbasic2 and the acidic human serum albumin binding domain (ABD), derived from streptococcal protein G, was also constructed . The gene product Zbasic2-ABD could be purified using cation-exchange chromatography from a whole cell lysate to more than 90% purity.

J Infect Dis, 2001 Jan 15, 183(2), 247 - 252 Epub 2000 Dec 08.
The free radical scavenger alpha-phenyl-tert-butyl nitrone aggravates hippocampal apoptosis and learning deficits in experimental pneumococcal meningitis; Loeffler JM et al.; The effect of adjuvant therapy with the radical scavenger alpha-phenyl-tert-butyl nitrone (PBN; 100 mg/kg given intraperitoneally every 8 h for 5 days) on brain injury and learning function was evaluated in an infant rat model of pneumococcal meningitis . Meningitis led to cortical necrotic injury (median, 3.97% {range, 0%-38.9%} of the cortex), which was reduced to a median of 0% (range, 0%-30.9%) of the cortex (P<.001) by PBN . However, neuronal apoptosis in the hippocampal dentate gyrus was increased by PBN, compared with that by saline (median score, 1.15 {range, 0.04-1.73} vs . 0.31 {range, 0-0.92}; P<.001) . Learning function 3 weeks after cured infection, as assessed by the Morris water maze, was decreased, compared with that in uninfected control animals (P<.001) . Parallel to the increase in hippocampal apoptosis, PBN further impaired learning in infected animals, compared with that in saline-treated animals (P<.02) . These results contrast with those of an earlier study, in which PBN reduced cortical and hippocampal neuronal injury in group B streptococcal meningitis . Thus, in pneumococcal meningitis, antioxidant therapy with PBN aggravates hippocampal injury and learning deficits.

Rev Port Cardiol, 2000 Sep, 19(9), 921 - 8
{Rheumatic fever--a review of cases}; Rocha P et al.; OBJECTIVE: To analyse clinical presentation of rheumatic fever (RF), with special emphasis on cardiac involvement, electrocardiographic and echocardiographic findings and the outcome of the cases referred to Maria Pia Children's Hospital from January 1990 to September 1999 . METHODS: We retrospectively analyzed the clinical files of all cases referred to pediatric cardiology clinics with the suspicion of acute RF (Group 1) or with rheumatic valvular disease and heart failure (Group 2) . In group 1 we studied the following: age and sex distribution, year of diagnosis, presence of Jones criteria treatment and outcome . In group 2 we analysed provenance, age of initial onset of RF, age of cardiology referral, treatment and outcome . RESULTS: Thirteen cases were identified, 8 in groups 1 and 5 in group 2 . Group 1 included 3 girls and 2 boys, mean age of 10 years . The diagnosis of RF was based in the presence of 2 major and 1 minor manifestation (4/8), 1 major and 2 minor manifestations (1/8) and chorea in 3 cases associated with clinical carditis in one and subclinical carditis in another . Colour Doppler echocardiography showed pathological mitral regurgitation jet in 6 cases, associated with aortic regurgitation in 2 and dilatation of left ventricle in 3 . All were treated with penicillin associated with anti-inflammatory drugs in 5 and haloperidol in 3 . Group 2 included 3 girls and 2 boys, mean age 9.56 years . Four were from African countries (Angola and Guinea), and one came from the north of Portugal . The elapsed time between the initial acute attack and cardiology referral varied from 5 months to 3 years . All presented severe mitral insufficiency associated with aortic and/or tricuspid valve lesions, and heart failure . All five underwent valve surgery . The secondary prophylaxis was recommended in every patient . There was a recurrence in a child who had interrupted chemoprophylaxis . The patients from African countries were lost for follow-up . CONCLUSIONS: RF still remains a problem in present times, with serious cardiac sequela in African countries . Colour Doppler echocardiography is a valuable tool for the detection of pathological valvular regurgitation and subclinical carditis if strict criteria are used . The need for appropriate treatment of streptococcal pharyngitis and secondary prophylaxis is emphasized.

Clin Infect Dis, 2000 Jan, 32(1), E9 - E12
Value of Standard Laboratory Tests for the Early Recognition of Group A beta-Hemolytic Streptococcal Necrotizing Fasciitis; Simonart T et al.; The laboratory data for 17 patients with group A beta-hemolytic streptococcal necrotizing fasciitis (GAS NF) were compared with data for 145 patients hospitalized for cellulitis during the same period . Admission values of C-reactive protein and creatine kinase were higher for patients in the group with GAS NF than for patients in the group with cellulitis (P<.001), suggesting that standard laboratory tests may be useful for the early differential diagnosis of GAS NF and cellulitis.

Int J Med Microbiol, 2000 Oct, 290(6), 543 - 8
Linkage of determinants for streptogramin A, macrolide-lincosamide-streptogramin B, and chloramphenicol resistance on a conjugative plasmid in Enterococcus faecium and dissemination of this cluster among streptogramin-resistant enterococci; Werner G et al.; A new streptogramin A resistance gene, satG (= vatE), has been recently identified in Enterococcus faecium UW1965 (Werner and Witte 1999 . Antimicrob . Agents Chemother . 43: 1813-1814) . Further sequence analysis of this plasmid revealed that vatE is in a cluster together with other resistance genes . The identified ORFs were nearly identical with the already known genes ermB and cat . The ermB fragment exhibited more than 99% identity with a resistance region from the streptococcal plasmid pIP501, whereas the cat fragment also contained a truncated rep gene homologue with more than 99% identity to sequences in small staphylococcal plasmids . The cat-rep and the ermB-vatE segments were linked by an IS1216V insertion sequence widely distributed among enterococci . PCR analysis of additional 76 streptogramin-resistant isolates possessing vatE and ermB revealed a linkage of both genes in 45 isolates (59%); 15 of them with a gene arrangement, cat-repU-IS1216V-ermB-vatE, identical to the reference strain UW1965 . An identical linkage of IS1216V-ermB-vatE was found among isolates from poultry manure, poultry meat, stool samples of humans, and hospital patients indicating a possible spread of the resistance gene cluster via the food chain to humans.

Chemotherapy, 2001, 47 Suppl 1, 24 - 32
Management of endocarditis: outpatient parenteral antibiotic treatment in Argentina; Lopardo G; Patients with infective endocarditis often face lengthy hospitalization for parenteral antibiotic therapy . Efforts to reduce medical costs have led to consideration of outpatient parenteral antibiotic treatment (OPAT) for these patients . However, concerns about outpatient management of complications, particularly congestive heart failure and emboli, exist . In Argentina, carefully selected patients with infective endocarditis, representing a low-risk population, have been successfully treated with OPAT . A retrospective analysis was conducted of 48 such patients . Three delivery models were used: at home with medications given by the visiting nurse, at infusion center, or at home with medications self-administered . Ten patients received OPAT only; 38 were initially hospitalized, then transferred to an OPAT program . Twenty-nine patients had streptococcal disease, 37 out of 48 patients were treated with ceftriaxone . Clinical and microbiologic cure was achieved in all patients . Three patients developed heart failure, 2 prior to starting antibiotic therapy . Four developed emboli, all prior to starting antibiotics . Surgery was required in 5 patients: 2 were treated with OPAT postoperatively and 3 had surgery after antibiotic therapy was completed . OPAT for infective endocarditis is safe in well selected patients.

Curr Infect Dis Rep, 2000 Aug, 2(4), 302 - 307
Immunogenic and Genetic Factors in Rheumatic Fever; Carreno-Manjarrez R et al.; Although rheumatic fever has virtually disappeared in many developed countries, it remains the number one acquired heart disease among children in developing countries . Many hypotheses advanced to explain the pathogenic mechanisms of this disease include the concept of an abnormal humoral and cellular response within the host to streptococcal antigens cross-reacting with mammalian tissues . This report examines the most recent evidence supporting this concept . It emphasizes the importance of the cellular arm of the immune response in cardiac damage, as wall as possible genetic disposition to the disease.

Eur J Immunol, 2000 Nov, 30(11), 3247 - 55
Host variation in cytokine responses to superantigens determine the severity of invasive group A streptococcal infection; Norrby-Teglund A et al.; Cytokines elicited by superantigens have been suggested to play a central role in severe systemic clinical manifestations of gram-positive sepsis . Here we provide evidence for a potent inflammatory cytokine response in acute invasive group A streptococcal infections, and show a direct correlation between the magnitude of this response and the severity of systemic manifestations of the disease . Severe invasive cases suffering from toxic shock and/or necrotizing fasciitis had significantly higher frequencies of IL-2-, IL-6-, and TNF-alpha-producing cells in their circulation as compared to non-severe invasive cases (p=0.05-0.01) . This difference was even more accentuated when severe and non-severe cases infected with a clonal M1T1 strain were compared (p=0.03-0 . 004) . To determine whether host factors were responsible for this difference in magnitude of cytokine responses, paired age- and gender-matched severe and non-severe M1T1 cases (n=8) were tested in vitro during their convalescent phase for immune response to superantigens produced by their infecting isolate . The results showed persistent and inherent differences in the magnitude of proliferative and cytokine responses of severe and non-severe patients to the streptococcal superantigens to which they had been exposed during infection . Thus, the study provides evidence that patients with a propensity to produce higher levels of inflammatory cytokines in response to streptococcal superantigens develop significantly more severe systemic manifestations than patients who have a propensity to produce lower levels of inflammatory cytokines to the same superantigens . We therefore conclude that host factors influence the magnitude of cytokine responses to superantigens and consequently the clinical outcome of the infection.

Am Surg, 2000 Nov, 66(11), 1064 - 6
Nontropical pyomyositis: analysis of eight patients in an urban center; Hossain A et al.; Nontropical pyomyositis is rare and usually associated with immunodeficiency virus (HIV) infection . This study assessed manifestations and response to treatment of nontropical pyomyositis in an area with a high prevalence of HIV seropositivity . We undertook a chart review of eight consecutive patients treated for pyomyositis - primary infection of skeletal muscles - from 1988 through 1998 . All patients complained of myalgia; four (50%) had fever and six (75%) had leukocytosis . Muscles involved were deltoid, quadriceps, gluteus, and psoas . Six (75%) patients had identifiable risk factors for pyomyositis: HIV seropositivity (two), history of intravenous drug abuse (one), chronic paraplegia and malnutrition (one), diabetes and chronic renal failure (one), and leukemia (one) . One patient had had streptococcal pharyngitis previously but was otherwise healthy; another, a 2-year-old, had no evidence of underlying disease . Staphylococcus aureus was the most common organism isolated (50%) . Four patients were treated with incision and drainage plus antibiotics; the remaining four patients were treated with intravenous antibiotics only; all recovered . Nontropical pyomyositis, which is often associated with HIV seropositivity or chronic illness, has a favorable outcome . Treatment can be effective even without surgical intervention.

J Immunol, 2000 Dec 1, 165(11), 6553 - 8
An IFN-gamma-independent proinflammatory role of IL-18 in murine streptococcal cell wall arthritis; Joosten LA et al.; IL-18 is a member of the IL-1 family of proteins that exerts proinflammatory effects . It was formally known as IFN-gamma-inducing factor and is a pivotal cytokine for the development of Th1 responses . Apart from Th1 immune-stimulatory activity, IL-18 induces the production of proinflammatory cytokines such as TNF-alpha and IL-1 in vitro . The goal was to investigate the role of endogenous IL-18 in murine streptococcal cell wall (SCW)-induced arthritis . Furthermore, we investigated whether IL-18 neutralization had an impact on local TNF and IL-1 production . C57BL/6, BALB/c, and IFN-gamma-deficient mice were injected with 2 mg of rabbit anti-murine IL-18 Abs shortly before induction of arthritis by intra-articular injection of 25 microg of SCW fragments into the right knee joint . Suppression of joint swelling was noted on days 1 and 2 of SCW arthritis after blockade of endogenous IL-18 . Analysis of local cytokine concentrations showed that IL-18, TNF-alpha, and IL-1ss levels were decreased . Severe inhibition of chondrocyte proteoglycan synthesis was seen in the vehicle-treated control animals, whereas a reversal of the inhibition of chondrocyte proteoglycan synthesis was found in the anti-IL-18-exposed animals . Blockade of endogenous IL-18 in IFN-gamma-deficient mice showed results similar to those found in wild-type animals, identifying a role for IL-18 that is IFN-gamma independent . The present study indicates that IL-18 is a proinflammatory cytokine during the onset of murine SCW arthritis, and this inflammatory role of IL-18 is IFN-gamma independent.

Antimicrob Agents Chemother, 2000 Dec, 44(12), 3264 - 71
Monotherapy with intravenous followed by oral high-dose ciprofloxacin versus combination therapy with ceftazidime plus amikacin as initial empiric therapy for granulocytopenic patients with fever; Giamarellou H et al.; The aim of the present study was to obtain clinical experience with the use of high-dose ciprofloxacin as monotherapy for the treatment of febrile neutropenia episodes (granulocyte count, <500/mm(3)) compared to a standard regimen and to clarify whether ciprofloxacin administration may be switched to the oral route . In a prospective randomized study ciprofloxacin was given at 400 mg three times a day (t.i.d.) for at least 72 h followed by oral administration at 750 mg twice a day (b.i.d) . That regimen was compared with ceftazidime given intravenously at 2 g t.i.d . plus amikacin given intravenously at 500 mg b.i.d . The frequency of successful clinical response without modification at the end of therapy was almost identical for ciprofloxacin (50% {62 of 124 patients}) compared with that for ceftazidime plus amikacin (50.8% {62 of 122 patients}) in an intent-to-treat analysis; the frequencies were 48.3% (57 of 118 patients) versus 49.6% (56 of 113 patients), respectively, in a per-protocol analysis (P values for one-sided equivalence, 0.0485 and 0.0516, respectively; delta = 10%), with no significant differences among patients with bacteremia and other microbiologically or clinically documented infections and fever of unknown origin . For 82 (66.1%) patients, it was possible to switch from parenteral ciprofloxacin to the oral ciprofloxacin, and the response was successful for 61 (74.4%) patients . The efficacies of the regimens against streptococcal bacteremias were 16.6% (one of six patients) for the ciprofloxacin group and 33.3% (one of three patients) for the combination group (it was not statistically significant), with one breakthrough streptococcal bacteremia observed among the ciprofloxacin-treated patients . Adverse events were mostly self-limited and were observed in 27 (20.6%) ciprofloxacin-treated patients and 26 (19.7%) patients who were receiving the combination . This study demonstrates that high-dose ciprofloxacin given intravenously for at least 3 days and then by the oral route is therapeutically equivalent to the routine regimen of intraveneous ceftazidime plus amikacin even in febrile patients with severe neutropenia (polymorphonuclear leukocyte count, <100 mm(3)) . However, it is very important that before an empirical therapy is chosen each hospital determine bacteriologic predominance and perform resistance surveillance.

Heart Lung, 2000 Nov-Dec, 29(6), 450 - 2
Escherichia coli chest-wall hemorrhagic cellulitis associated with central-line placement; Hansen EA et al.; Cellulitis is a common clinical entity . Hemorrhagic cellulitis is distinctly unusual and is most frequent in compromised hosts . In normal or near normal hosts, hemorrhagic cellulitis may rarely complicate gram-negative sepsis . Usually, hemorrhagic cellulitis occurs below the waist . The differential diagnosis includes invasive streptococcal infection, mixed aerobic and anaerobic infection, gram-negative sepsis, and gross gangrene . We present the first-known case of Escherichia coli chest-wall hemorrhagic cellulitis associated with a central line in a patient with renal failure.

Diabetologia, 2000 Oct, 43(10), 1302 - 8
Streptococcal wall component OK432 restores sensitivity of non-obese diabetic (NOD) thymocytes to apoptotic signals; Decallonne B et al.; AIMS/HYPOTHESIS: The streptococcal wall component, OK432, prevents diabetes in NOD mice and BB rats by elimination of effector cells . Based on the knowledge of a link between autoimmunity and resistance of immune cells to elimination by apoptosis, we investigated whether OK432 treatment restored the sensitivity of NOD lymphocytes to apoptotic signals centrally (thymus) or peripherally (spleen) or both and we examined the pathways for the enhanced apoptosis rate . METHODS: We treated NOD mice with OK432 (0.1 mg/kg i.p . weekly from 21 to 70 days) . Apoptosis was measured by TUNEL 16 h after cyclophosphamide (70 mg/kg) and 24 h after dexamethasone (0.2 mg/mouse) . Real time quantitative RT-PCR was used to investigate changes in gene expression . RESULTS: Thymocyte apoptosis levels after cyclophosphamide were restored by OK432 treatment to levels observed in C57BL/6 mice: in NOD males apoptosis increased from 8 +/- 1% to 18 +/- 5% (p < 0.05) compared with 20 +/- 4% in C57BL/6 males, and in NOD females from 6+/- 2% to 11 +/- 2% (p < 0.05) compared with 12 +/- 2% in C57BL/6 females . The dexamethasone-induced thymocyte apoptosis rate was equally restored by OK432 treatment (58 +/- 4% vs 41 +/- 3% in control males (p < 0.0005) and 39 +/- 5% vs 26 +/- 3% in control females (p < 0.05)} . No change in apoptosis levels was on the contrary observed in splenocytes after OK432 treatment . By RT-PCR analysis of a panel of apoptosis-related genes in thymocytes we showed a down-regulation of anti-apoptotic Bcl-xL and c-myc by OK432 treatment . CONCLUSIONS/INTERPRETATION: Our data suggest that OK432 prevents diabetes in NOD mice by better elimination of effector cells through increased sensitivity to apoptotic signals centrally in the thymus.

Plasmid, 2000 Nov, 44(3), 262 - 74
Genetic and transcriptional analysis of a regulatory region in streptococcal conjugative transposon Tn5252; Srinivas P et al.; In an attempt to increase our understanding of the mechanisms of conjugal transposition among gram-positive bacteria, we analyzed the genetic and structural properties of a 1.2-kb DNA fragment at the left end of the streptococcal conjugative transposon Tn5252 . The sequence data revealed four short open reading frames . Polypeptides likely to correspond to two of these genes were identified . Transcriptional start sites and the promoter sequences of three transfer-related genes in the left terminal region of the element were identified . The deduced amino acid sequence of one of these, ORF3, was found to be similar to that of several prokaryotic transcriptional regulator proteins . Insertion mutagenesis at this locus reduced the transfer of the element by three orders of magnitude . The presence of a multicopy plasmid carrying ORF3 in a donor cell carrying Tn5252 with a mutated copy of ORF3 or an unaltered element also reduced the transfer frequency of the element similarly . Gel mobility shift assays showed that the ORF3 protein was capable of binding to not only other discrete sites at the left end of the element but also its own promoter, suggesting autoregulation . These results indicate that the ORF3 protein is involved in the regulation of the conjugative transposition of the element .

J Perinatol, 2000 Oct-Nov, 20(7), 421 - 6
Neonatal pneumonia: comparison of 4 vs 7 days of antibiotic therapy in term and near-term infants; Engle WD et al.; OBJECTIVE: To compare a 4-day course of antibiotic therapy to a 7-day course in selected term and near-term neonates with pneumonia . METHODS: The diagnosis of pneumonia was made in neonates admitted to the normal Newborn Nursery (NBN) who later had signs of respiratory distress and whose chest radiographs were consistent with pneumonia . Infants were excluded if any of the following was present: moderate or thick meconium-stained amniotic fluid, prior antibiotic therapy > 24 hours, or need for supplemental oxygen > 8 hours . Infants who were asymptomatic after 48 hours of antibiotic therapy were prospectively randomized to a 4-day group (n = 35) or a 7-day group (n = 38) . Infants in the 4-day group were observed in the hospital for 24 hours following cessation of antibiotics and were seen in follow up within several days of discharge . RESULTS: The groups were comparable with regard to demographic factors, duration of rupture of membranes, and incidence of maternal chorioamnionitis . Median postnatal age at the time of identification of respiratory distress symptomatology was 19 hours (range 0.5 to 55 hours) in the 4-day group and 12 hours (range 1 to 72 hours) in the 7-day group . No study infants had a positive blood culture . Mean reduction in length of hospitalization was 2.1 days, with estimated savings of greater than US$700 per shortened hospitalization . Two infants in the 4-day group developed tachypnea during the 24-hour observation period . However, no infants were rehospitalized for sepsis or pneumonia following discharge . With 95% confidence, the true rate of success for the 4-day group was at least 92% . CONCLUSION: Four days of antibiotic therapy plus a 24-hour period of observation for selected cases of neonatal pneumonia appears to be comparable to 7 days of therapy . It is important to note that newborns in our institution receive a single dose of penicillin soon after birth as part of our group B streptococcal sepsis prophylaxis program, and all infants in this study received prophylaxis prior to the onset of respiratory symptoms . Furthermore, only infants who were asymptomatic after 48 hours of antibiotic therapy were included in this study, and a 24-hour observation period at the end of the 4-day course was required . These qualifications should be taken into account before use of this approach is considered, and additional studies are necessary to further establish its safety and benefits.

Arch Otolaryngol Head Neck Surg, 2000 Nov, 126(11), 1359 - 62
Fewer symptoms occur in same-serotype recurrent streptococcal tonsillopharyngitis; Lee LH et al.; BACKGROUND: Most patients with acute rheumatic fever report no antecedent pharyngitis . OBJECTIVE: To determine the clinical and microbiological characteristics of recurrent group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis . DESIGN: Prospective randomized trial . SUBJECTS: Symptoms were recorded and throat cultures were obtained at 4 to 6, 18 to 21, and 32 to 35 days following the start of treatment . A subset of 60 patients with subsequent GABHS episodes occurring were evaluated for a 0.2-or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer to confirm a bona fide recurrence . RESULTS: Sixteen (27%) of 60 patients had recurrent GABHS tonsillopharyngitis of the same serotype that occurred 21 days or longer following the onset of the initial GABHS infection and was associated with a 0.2- or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer, indicating bona fide recurrent infection; these recurrences all occurred within 55 days . Fewer patients with recurrent GABHS pharyngitis of the same serotype had headache (P =.02), sore throat (P =.006), fever (P = . 008), pharyngeal erythema (P<.001), pharyngeal edema (P<.001), pharyngeal exudate (P =.04), and adenitis (P =.03) compared with the initial episode . Chills, stomachache, scarlatina, tonsillar enlargement, and palatal petechiae were similar for both episodes . CONCLUSIONS: Fewer symptoms occur during recurrent GABHS pharyngitis of the same serotype compared with the initial infection . These patients may be less likely to seek physician attention, yet their infections put them at risk for sequelae.

Clin Infect Dis, 2000 Nov, 31(5), 1175 - 82 Epub 2000 Nov 10.
Relative neutralizing activity in polyspecific IgM, IgA, and IgG preparations against group A streptococcal superantigens; Norrby-Teglund A et al.; In this study we compared the ability of different immunoglobulin (Ig) preparations containing IgG, IgM, and/or IgA to neutralize the activity of streptococcal pyrogenic exotoxin A (SpeA) or culture supernatant from a clinical group A streptococcal isolate . All Ig preparations markedly inhibited the mitogenic and cytokine-inducing activity of SpeA and culture supernatant at concentrations of 0.05-0.5 mg/mL, and at 0.5 mg/mL, most caused 95-100% inhibition of both stimuli . A significantly higher (P< or =.05) inhibition of SpeA was achieved by Pentaglobin (IgG, IgM, and IgA) and IgAbulin (IgA and IgG), as compared with pure IgG preparations . IgM- and IgA-enriched preparations had significantly higher inhibitory activity against SpeA than against culture supernatant, whereas the reverse was true for the IgG preparations (P< or =.05) . The data show that IgM and IgA are potent inhibitors of specific streptococcal superantigens . These findings may have implications for the optimization of immunotherapy in invasive streptococcal infections.

Lab Anim, 2000 Oct, 34(4), 423 - 9
Oral buprenorphine is anti-inflammatory and modulates the pathogenesis of streptococcal cell wall polymer-induced arthritis in the Lew/SSN rat; Volker D et al.; This study was carried out to determine an effective regimen for pain management in streptococcal cell wall (SCW)-induced arthritis in female Lew/SSN rats . Forty weanling rats lin 2 groups) were trained to accept disks of jelly as part of their dietary regimen . At 8 weeks of age weighing 150 g, SCW arthritis was induced and sublingual buprenorphine tablets were incorporated into the jelly disks to alleviate the pain of acute arthritis, which developed 24 h post-induction . Group A rats received buprenorphine at a rate of 1 mg/kg 12 hourly . Group B rats received buprenorphine at a rate of 2 mg/kg 12 hourly . Both groups of rats were monitored for symptoms of distress using an adaptation of the Morton and Griffin scale of adverse reactions . Group A rats with severe arthritis required additional subcutaneous (s.c.) injections of buprenorphine to alleviate the adverse effects of arthritis . Group B rats, with twice the dose of buprenorphine did not require additional s.c . injections of buprenorphine . Histological sections of rat hocks indicated that the inflammation was suppressed in Group B rats . We concluded that oral administration of buprenorphine is an effective method of pain management in the pathogenesis of SCW-induced arthritis in Lew/SSN rats . In this model of arthritis, oral buprenorphine has a significant anti-inflammatory effect and appears to modulate the destructive arthritic phase in joints in this animal model of arthritis.

Pediatrics, 2000 Nov, 106(5), 957 - 64; discussion 1135
Surfactant treatment of neonates with respiratory failure and group B streptococcal infection . Members of the Collaborative European Multicenter Study Group; Herting E et al.; OBJECTIVE: Connatal pneumonia caused by group B streptococcal (GBS) infection may be associated with surfactant dysfunction . We investigated the effects of surfactant treatment in term and preterm neonates with GBS infection and respiratory failure, in comparison with corresponding data from a control population of noninfected infants treated with surfactant for respiratory distress syndrome (RDS) . DESIGN/METHODS: The study comprised 118 infants with respiratory failure, clinical and/or laboratory signs of acute inflammatory disease, and GBS infection proven by culture results . They were recruited retrospectively from a database of patients treated with surfactant at 28 neonatology units participating in European multicenter trials (1987-1993) and prospectively from the same units in the following years . A nonrandomized control group of 236 noninfected infants was selected from the same database . The primary parameters evaluated were oxygen requirement, ventilator settings, and incidence of complications . RESULTS: Median birth weight in the GBS study group was 1468 g (25th-75th percentiles: 1015-2170), and median gestational age was 30 (27-33) weeks . Thirty-one percent of the infants weighed >2000 g . Median age at surfactant treatment was 6 hours . The mean initial surfactant dose was 142 mg/kg (standard deviation: 53) . Ninety of the infants were treated with Curosurf (Chiesi Farmaceutici, Parma, Italy), 13 with Survanta (Abboth GmbH, Wiesbaden, Germany), 12 with Alveofact (Dr Karl Thomae GmbH, Biberach, Germany), and 3 with Exosurf (Wellcome GmbH, Burgwedel, Germany) . Within 1 hour of surfactant treatment, median fraction of inspiratory oxygen was reduced from .84 (25th-75th percentiles:.63-1.0) to.50 (.35-.80) . The incidence of complications in the study group (mortality: 30%; pneumothorax: 16%; intracranial hemorrhage: 42%) was high, compared with infants with RDS . CONCLUSIONS: Surfactant therapy improves gas exchange in the majority of patients with GBS pneumonia . The response to surfactant is slower than in infants with RDS, and repeated surfactant doses are often needed . The mortality and morbidity are substantial, considering the relatively high mean birth weight of the treated infants.

Acta Med Okayama, 2000 Oct, 54(5), 217 - 25
Biochemical modulation of 5-fluorouracil with a streptococcal preparation, OK-432, against murine colon-26 carcinoma; Funaki M et al.; Conventional therapy for colorectal carcinoma using 5-fluorouracil (5-FU) has shown limited antitumor action . The purpose of our study was to investigate synergistic antitumor effects of the streptococcal preparation of OK-432 and 5-FU, and to elucidate the mechanisms of interaction between the 2 agents in mice . Biochemical modulation of OK-432 and 5-FU were determined in vivo against colon-26 carcinoma . The concentration of 5-FU and its metabolites, and the activity of thymidylate synthase and thymidine kinase, respectively, were measured using cytosolic extracts of the tumors . Combination treatment with OK-432 produced a significant increase in intratumor 5-FU and 5-FU in RNA (F-RNA) concentrations, increased the thymidylate synthetase inhibition rate, and decreased thymidine kinase activity, as compared with the results observed in the control mice . These additive antitumor effects are obtained by use of the 2 agents; the mechanism of action is considered to be the suppression of both the de novo and the salvage pathway for DNA synthesis, along with the suppression of RNA synthesis.

Arthritis Res, 2000, 2(6), 489 - 503 Epub 2000 Aug 31.
Fc gamma R expression on macrophages is related to severity and chronicity of synovial inflammation and cartilage destruction during experimental immune-complex-mediated arthritis (ICA); Blom AB et al.; STATEMENT OF FINDINGS: We investigated the role of Fc gamma receptors (Fc gamma Rs) on synovial macrophages in immune-complex-mediated arthritis (ICA) . ICA elicited in knee joints of C57BL/6 mice caused a short-lasting, florid inflammation and reversible loss of proteoglycans (PGs), moderate chondrocyte death, and minor erosion of the cartilage . In contrast, when ICA was induced in knee joints of Fc receptor (FcR) gamma-chain(-/-) C57BL/6 mice, which lack functional Fc gamma RI and RIII, inflammation and cartilage destruction were prevented . When ICA was elicited in DBA/1 mice, a very severe, chronic inflammation was observed, and significantly more chondrocyte death and cartilage erosion than in arthritic C57BL/6 mice . The synovial lining and peritoneal macrophages of naive DBA/1 mice expressed a significantly higher level of Fc gamma Rs than was seen in C57BL/6 mice . Moreover, elevated and prolonged expression of IL-1 was found after stimulation of these cells with immune complexes . Zymosan or streptococcal cell walls caused comparable inflammation and only mild cartilage destruction in all strains . We conclude that Fc gamma R expression on synovial macrophages may be related to the severity of synovial inflammation and cartilage destruction during ICA.

Pediatr Infect Dis J, 2000 Oct, 19(10), 963 - 7
Short course therapy with cefitbuten versus azithromycin in pediatric streptococcal pharyngitis; Boccazzi A et al.; OBJECTIVE: To compare the safety and efficacy of a short course (5 days) of ceftibuten vs . azithromycin for 3 days for treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis in children . METHODS: A multicenter, open label, prospective, randomized trial in which patients > or =3 to < or =16 years of age with proven GABHS pharyngitis were randomized to receive either once daily ceftibuten for 5 days or azithromycin for 3 days . Patients were evaluated for clinical outcomes and/or for adverse events at days 6 to 8, 13 to 15 and 33 to 35 posttherapy . Microbiologic assessments (pharyngeal cultures) were conducted at baseline and at each follow-up visit . RESULTS: A total of 132 patients in the ceftibuten arm and 116 in the azithromycin arm were enrolled in the safety analysis, whereas 126 and 101, respectively, were enrolled for ceftibuten and azithromycin efficacy evaluation . Clinical success (cure or marked amelioration) at days 6 to 8 was recorded in 98 and 94% in the 2 groups, respectively . In the bacteriologic efficacy analysis at 6 to 8 days, the GABHS strain was eradicated in 76% of the patients treated with ceftibuten and in 76% of those receiving azithromycin . At 33 to 35 days, 84% of the patients in the ceftibuten arm and 71% in the azithromycin arm were GABHS-negative, and bacteriologic relapse was observed in 4 and 7% of the ceftibuten and azithromycin cases, respectively . Both treatments were well-tolerated by all patients . CONCLUSIONS: Ceftibuten and azithromycin allow simple treatment schedules (i.e . once daily administration, short duration of treatment) . The somewhat higher eradication rate recorded after ceftibuten administration is consistent with the overall superior bactericidal activity of beta-lactams compared with macrolides vs . GABHS in vitro.

Lancet, 2000 Oct 21, 356(9239), 1407 - 8
Universal maternal screening for neonatal group B streptococcal disease; Halliday E et al.; Group B streptococcal infection is a leading cause of neonatal morbidity and mortality in the developed world . Data obtained in our region suggest that the incidence in the UK may be higher than previously reported, and together with the results of a pilot study indicate that preventive strategies based on maternal risk factors alone would prevent less than half the cases of neonatal disease.

Protein Sci, 2000 Sep, 9(9), 1651 - 9
Understanding the sequence determinants of conformational switching using protein design; Dalal S et al.; An important goal of protein design is to understand the forces that stabilize a particular fold in preference to alternative folds . Here, we describe an extension of earlier studies in which we successfully designed a stable, native-like helical protein that is 50% identical in sequence to a predominantly beta-sheet protein, the B1 domain of Streptococcal IgG-binding protein G . We report the characteristics of a series of variants of our original design that have even higher sequence identity to the B1 domain . Their properties illustrate the extent to which protein stability and conformation can be modulated through careful manipulation of key amino acid residues . Our results have implications for understanding conformational change phenomena of central biological importance and in probing the malleability of the sequence/structure relationship.

Cancer Immunol Immunother, 2000 Oct, 49(8), 401 - 9
Enhancement of the photodynamic antitumor effect by streptococcal preparation OK-432 in the mouse carcinoma; Uehara M et al.; Biological response modifier antitumor effects are enhanced by the activation of the host defense mechanisms . We have investigated the antitumor effect of photodynamic therapy (PDT) and/or local administration of a biological response modifier, the streptococcal preparation OK-432, on transplanted NR-S1 mouse squamous cell carcinoma . Hematoporphyrin oligomers (20 mg/kg body weight) were used to photosensitize PDT . A pulsed Nd:YAG dye laser, tuned at 630 nm, was used as the light source . The laser power was 15 mJ cm(-2) pulse(-1), and the irradiation time was 40 min . The photosensitizer was injected intraperitoneally 48 h before laser irradiation . Where used, OK-432 was injected into the tumor either 3 h prior to PDT or immediately afterwards . The antitumor effects were evaluated 48 h after each protocol by (a) estimating the area of tumor necrosis (%) in hematoxylin/eosin-stained specimens, and (b) bromodeoxyuridine immunohistochemistry . Furthermore, the tumor sizes were evaluated 3, 7 and 10 days after each protocol, and the survival time after each protocol was evaluated as well . The antitumor effect of PDT was enhanced by administration of OK-432 3 h before PDT, whereas the administration of OK-432 immediately after PDT did not potentiate a PDT antitumor effect . Treatment with OK-432 alone had little effect on tumors . Photodynamic therapy in combination with local administration of OK-432 3 h before PDT is considered to be a useful treatment modality.

FEMS Microbiol Lett, 2000 Nov 1, 192(1), 1 - 7
Evidence for the involvement of bacterial superantigens in psoriasis, atopic dermatitis, and Kawasaki syndrome; Yarwood JM et al.; A growing body of evidence implicates streptococcal and staphylococcal superantigens in the development of psoriasis, atopic dermatitis and Kawasaki syndrome . In each of these illnesses, an abnormal state of immunologic activity is observed . Superantigens, which have a unique ability to activate large numbers of lymphocytes, are likely to contribute to these disorders in a number of ways . The demonstrated activities of bacterial superantigens include increasing the number of circulating lymphocytes, with activation of autoreactive subsets, upregulation of tissue homing receptors on circulating lymphocytes, and local activation of immune cells within affected tissues . Through these and other mechanisms, superantigens have a proven ability to induce high levels of inflammatory cytokines and/or initiate autoimmune responses that contribute to the development of skin and vascular disorders . Though development of the illnesses discussed in this review are highly complex processes, superantigens may well play a critical role in their onset or maintenance . Understanding superantigen function may elucidate potential therapeutic strategies for these disorders.

Am J Obstet Gynecol, 2000 Oct, 183(4), 1003 - 7
The impact of digital cervical examination on expectantly managed preterm rupture of membranes; Alexander JM et al.; OBJECTIVE: The purpose of this study was to examine the effects of digital cervical examination on maternal and neonatal outcomes among women with preterm rupture of membranes . STUDY DESIGN: This analysis includes data from a previously reported trial of antibiotic treatment during expectant management of rupture of membranes at 24 to 32 weeks' gestation in singleton and twin gestations . Patients from both the randomized trial (n = 299 in the antibiotic group and n = 312 in the placebo group) and the observational component (n = 183) are included in this analysis . The groups were divided into those with one (n = 161) or two digital cervical examinations (n = 27) and those with no digital cervical examinations (n = 606) . RESULTS: The gestational ages at enrollment were similar in the two groups (29 +/- 2 weeks' gestation for one or two examinations vs 29 +/- 2 weeks' gestation for no examinations; P =.85) . There were no differences in chorioamnionitis (27% vs 29%; P =.69), endometritis (13% vs 11%; P =.5), or wound infection (0.5% vs 1%; P >.999) between the group with one or two examinations and the no-examination group . Infant outcomes were also similar in the two groups, including early sepsis (6% vs 5%; P =.68), respiratory distress syndrome (51% vs 45%; P =.18), intraventricular hemorrhage (7% vs 7%; P =.67), necrotizing enterocolitis (5% vs 3%; P =.19), and perinatal death (7% vs 5%; P =.45) . A composite outcome made up of these neonatal outcomes was not different (56% vs 48%; P =.10) between the group with one or two examinations and the no-examination group . The time from rupture to delivery was shorter in the digital examination group (median value, 3 vs 5 days; P < . 009) . Multivariable analysis to adjust for antibiotic study group, group B streptococcal culture status, race, and maternal transfer did not modify these results . CONCLUSION: Performance of one or two digital cervical examinations during the course of expectant management of rupture of membranes between 24 and 32 weeks' gestation was associated with shorter latency but did not appear to worsen either maternal or neonatal outcome.

Am J Obstet Gynecol, 2000 Oct, 183(4), 925 - 9
Effectiveness of antenatal corticosteroid administration after preterm premature rupture of the membranes; Vermillion ST et al.; OBJECTIVE: This study was undertaken to determine the effect of antenatal betamethasone administration on the incidences of respiratory distress syndrome, intraventricular hemorrhage, and perinatal infectious morbidity in the setting of preterm premature rupture of membranes . STUDY DESIGN: We performed a nonconcurrent prospective analysis of women with singleton pregnancies who were delivered between 24 and 32 weeks' gestation after preterm premature rupture of membranes . Patients were subdivided into 2 groups according to betamethasone exposure: (1) none (control group) and (2) two 12-mg doses in a 24-hour interval on admission (single-course group) . Patients who received >2 doses of betamethasone were excluded . All patients received broad-spectrum prophylactic antibiotics . Data were analyzed with the Student t test, the chi(2) test, and the Fisher exact test . Multiple logistic regression analyses incorporated multiple variables considered risk factors for respiratory distress syndrome and intraventricular hemorrhage . P <.05 for all 2-tailed tests was considered significant . RESULTS: A total of 362 patients were included, with 203 in the control group and 159 in the single-course group . Patients in these groups were delivered at 31.0 +/- 3.0 and 30.2 +/- 2.7 (mean +/- SD) weeks' gestation, respectively . The groups were similar with respect to selected demographic characteristics, latency until delivery, mode of delivery, birth weight, and maternal group B streptococcal colonization status . Univariate analysis demonstrated significant decreases in the frequencies of both respiratory distress syndrome (odds ratio, 0.31; 95% confidence interval, 0.2-0.5) and grade III/IV intraventricular hemorrhage (odds ratio, 0.14; 95% confidence interval, 0.1-0.6) in the single-course group . The frequencies of early neonatal sepsis, chorioamnionitis, endometritis, and neonatal death were similar between groups . Multiple logistic regression analyses determined that a single course of betamethasone was independently associated with reductions in the frequencies of both respiratory distress syndrome (odds ratio, 0.16; 95% confidence interval, 0.1-0.4) and grade III/IV intraventricular hemorrhage (odds ratio, 0.18; 95% confidence interval, 0.1-0.4) . CONCLUSIONS: A single course of betamethasone administered antenatally to patients with preterm premature rupture of membranes was associated with decreases in the frequencies of both respiratory distress syndrome and advanced grades of intraventricular hemorrhage without any increase in perinatal infectious morbidity.

Brain Res, 2000 Oct 20, 881(1), 88 - 97
Hypothermia as an adjunctive treatment for severe bacterial meningitis; Irazuzta JE et al.; Brain injury due to bacterial meningitis results in a high mortality rate and significant neurologic sequelae in survivors . The objective of this study was to determine if the application of moderate hypothermia shortly after the administration of antibiotics would attenuate the inflammatory response and increase in intracranial pressure that occurs in meningitis . For this study we used a rabbit model of severe Group B streptococcal meningitis . The first component of this study evaluated the effects of hypothermia on blood-brain barrier function and markers of inflammation in meningitic animals . The second part of the study evaluated the effects of hypothermia on intracranial pressure, cerebral perfusion pressure and brain edema . This study demonstrates that the use of hypothermia preserves CSF/serum glucose ratio, decreases CSF protein and nitric oxide and attenuates myeloperoxidase activity in brain tissue . In the second part of this study we show a decrease in intracranial pressure, an improvement in cerebral perfusion pressure and a decrease in cerebral edema in hypothermic meningitic animals . We conclude that in the treatment of severe bacterial meningitis, the application of moderate hypothermia initiated shortly after antibiotic therapy improves short-term physiologic measures associated with brain injury.

Jpn J Thorac Cardiovasc Surg, 2000 Sep, 48(9), 568 - 73
Early surgery for active infective endocarditis; Sasaki Y et al.; OBJECTIVE: The timing of surgery for active infective endocarditis remains controversial . In this report, we have reviewed 26 patients who underwent surgery for active infective native-valve endocarditis between April 1992 and December 1998 . PATIENTS AND METHOD: There were 19 male and 7 female patients (mean age 45 years) . The aortic valve was involved in 8 patients, the mitral valve in 6 patients, tricuspid valve in 2 patients, both aortic and mitral valves in 7 patients, both aortic and tricuspid valve in 2 patients, and both mitral and tricuspid valve in one patient . The most common microorganisms were streptococcal species . Preoperative high New York Heart Association functional class (III and IV) was presented in 20 patients (77%) . Progressive heart failure and the echocardiographic findings of vegetation (larger than 1 cm) were the main operative indications . Emergency or urgent surgery was required in 18 patients (70%) . All patients underwent valve replacement, involving 25 mechanical prosthesis and 8 bioprosthesis . RESULTS: The operative mortality was 7.8% (n = 2) . In the two patients who died, the infection had extended to the deep cardiac tissue and to the cerebral artery . The mean follow-up of the 24 survivors was 33 months (range from 6 to 82 months) . There was no late death and no recurrence of infective endocarditis . CONCLUSION: In case of active infective endocarditis, early surgical intervention is recommended in patients with rapidly progressive cardiac deterioration or vegetation seen on echocardiography.

Clin Nephrol, 2000 Sep, 54(3), 179 - 90
The outcome of acute interstitial nephritis: risk factors for the transition from acute to chronic interstitial nephritis; Schwarz A et al.; BACKGROUND: Acute interstitial nephritis has been known as a complication of mainly streptococcal infection for nearly a century . With the advent of infection control, it became a complication caused by antibiotics and later by other drugs, which might have changed the outcome . To determine risk factors for the development of chronic renal insufficiency, and thus, the transition from acute to chronic interstitial nephritis, we performed a retrospective study of all cases of acute interstitial nephritis found by reviewing 1,068 renal biopsies from 1968 to 1997 . METHODS: Patients with permanent and reversible renal insufficiency after acute interstitial nephritis were compared with respect to the causative event, the symptoms, and the clinical and histological findings . Differences between the groups were calculated by applying bi- and multivariate analysis . RESULTS: Acute interstitial nephritis was found in 6.5% of all biopsies (64 patients with 68 episodes of acute interstitial nephritis); it was infection-induced in 10%, idiopathic in 4%, and drug-induced in 85% of the cases (antibiotics in 13 cases, analgesics in 17, non-steroidal anti-inflammatory drugs (NSAIDs) in 16, diuretics in 5, and various other drugs in 7) . Renal insufficiency was reversible in 69% and permanent in 31% (12% partially reversible, 19% irreversible) . The infection-induced and idiopathic types of acute interstitial nephritis were always reversible . Drug-related acute interstitial nephritis caused permanent renal insufficiency in 36% with a maximum of 56% in NSAID-induced cases . In drug-induced cases, intake of the suspected drug for more than a month prior to diagnosis caused permanent renal insufficiency in 88% and interstitial granuloma in 31% . Multivariate analysis disclosed the following significant features separating the permanent from the reversible renal insufficiency group: patients in the first group had more tubular atrophy in their histology, more chronic use of mixed analgesics and/or NSAIDs, less oliguria or anuria as an acute symptom, fewer antibiotics as causative agents, more interstitial granuloma, more pronounced interstitial cell infiltration in their histology, and more imaging of renal shrinkage . Renal histology had the highest predictive value . CONCLUSION: Today, acute interstitial nephritis is mainly drug-induced . NSAIDs are the most frequent cause of permanent renal insufficiency after acute interstitial nephritis . Clinically, subacute symptoms, a prolonged intake of the suspect drug, and chronic analgesic or NSAID use are related to a more chronic course of interstitial nephritis . In histology, tubular atrophy, interstitial granuloma, and pronounced interstitial cell infiltration indicate chronicity.

Acad Emerg Med, 2000 Oct, 7(10), 1104 - 9
Concordance of clinical findings and clinical judgment in the diagnosis of streptococcal pharyngitis; Nawaz H et al.; OBJECTIVE: It is uncertain how reliably clinicians apply clinical predictors of group A beta hemolytic streptococcal pharyngitis (GABHSP) to form a clinical impression, and how reliably this impression predicts culture results . The objective was to study clinician accuracy in diagnosing GABHSP . METHODS: This was a prospective cohort study, conducted at an urgent care center of a major university . A convenience sample of 218 patients, aged 9-83 years, presenting with sore throat, was enrolled . Symptoms and signs of pharyngitis were documented on a standardized form; the likelihood of GABHSP was plotted on a visual analog scale; and throat culture was obtained . A comparison was then made between the clinical impression on presentation and the throat culture result . RESULTS: Throat cultures were positive for GABHSP in 41 patients (19%) . The probability of GABHSP was related to node size and tenderness, tonsillar exudate and hypertrophy, and pharyngeal erythema (p<0.05); but not throat soreness, degree of fever, or cough . A strong clinical impression of GABHSP (>50% on the visual analog scale) was associated with tonsillar exudate and hypertrophy, tender nodes, and pharyngeal erythema . Together, these four predictors had a sensitivity of 71%, a specificity of 77%, and a positive predictive value of 46% . CONCLUSIONS: Clinicians in this study based their impression of GABHSP on the most reliable symptoms and signs . While a strong clinical suspicion of GABHSP predicted a greater probability of positive culture, the clinicians consistently overestimated the probability of GABHSP . Symptoms and signs predict GABHSP unreliably when used alone; they are helpful in modifying estimates of disease probability to facilitate optimal use of laboratory tests and antibiotics.

Caries Res, 2000 Sep-Oct, 34(5), 380 - 7
Caries prediction by multiple salivary mutans streptococcal counts in caries-free children with different levels of fluoride exposure, oral hygiene and sucrose intake; Petti S et al.; The aims of this study were to assess whether multiple salivary mutans streptococcal (ms) counts have a higher predictive power than a single one, and whether the predictive power of the test is different at different levels of fluoride exposure, oral hygiene and sucrose consumption . Three salivary ms tests were performed at 3-month intervals (positive test: salivary ms >/=5x10(5) cfu/ml) on a sample of 304, initially caries-free, 6- to 7-year-olds . Plaque index was also assessed and the parents filled out a questionnaire concerning sucrose-containing eating events and fluoride exposure . Sensitivity, specificity and Youden's index (J) were used to compare the predictive power . Thirty-six percent of the children developed caries during the 2-year follow-up . The highest J value for a single ms test (the second) was 0.24 (sensitivity 29.1%, specificity 95.4%) . The multiple ms test with the highest J value (0.29) was obtained by the dichotomies 0 vs . 1-3 positive tests (sensitivity 50.0%, specificity 79.9%) and 0-1 vs . 2-3 positive tests (sensitivity 31.8%, specificity 97.4%) . The predictive power of the multiple test was passable for children with low fluoride exposure and high plaque index (sensitivity 57.4%, specificity 93.7%, J 0.51), while it was low for the other groups . Sucrose exposure did not significantly affect the predictive power of the ms test.sion.

Arthritis Rheum, 2000 Sep, 43(9), 2064 - 72
Suppression of streptococcal cell wall-induced arthritis by human chorionic gonadotropin; Song XY et al.; OBJECTIVE: To determine whether human chorionic gonadotropin (HCG) contributes to pregnancy-associated immunosuppression, as observed clinically by an amelioration of symptoms in human autoimmune diseases, including rheumatoid arthritis, during pregnancy . METHODS: Administration of HCG was initiated 2 days prior to an arthritogenic dose of streptococcal cell wall (SCW) in nonpregnant female rats, and the development and severity of SCW-induced arthritis was monitored . Inflammatory mediators, including plasma nitrite/nitrate and cytokine levels, were measured . Inducible nitric oxide synthase (iNOS) protein and cytokine messenger RNA expression in joint tissue were compared between treated and untreated arthritic animals . RESULTS: Systemic administration of HCG resulted in a dose-dependent reduction in the clinical arthritis index . Consistent with the amelioration of clinical symptoms, HCG significantly reduced the inflammatory cell infiltration, pannus formation, and bone and cartilage degradation . Mechanistically, HCG therapy was associated with suppression of the overzealous production of tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-1beta, which contribute to synovial pathology in animals with SCW-induced arthritis . Circulating nitric oxide and the amount of iNOS protein were also reduced . Furthermore, circulating transforming growth factor beta levels were elevated by the HCG, all of which suggest monocytes/macrophages as a potential target . CONCLUSION: These findings indicate that HCG exerts a protective effect in this experimental arthritis model, through modulation of inflammatory mediators.

J Postgrad Med, 2000 Apr-Jun, 46(2), 91 - 3
Scleredema adultorum; Parmar RC et al.; Scleredema adultorum is a rare connective tissue disorder reported usually following streptococcal infection, influenza, measles, and mumps . It has been reported occasionally following trauma and tuberculous lymphadenitis . This is a report of scleredema adultorum developing after chicken pox in an eight-year-old male child . The diagnosis was established by characteristic picture on skin biopsy using special stain . The patient had a benign course and a spontaneous recovery in two weeks . The case has been reported as the first case of scleredema adultorum developing after chicken pox.

Clin Exp Dermatol, 2000 Jul, 25(5), 377 - 80
Erythema nodosum in Singapore; Tay YK; A retrospective study was carried out of all patients presenting with erythema nodosum over a 3-year period (1994-1997) at the National Skin Centre, Singapore . There were 75 patients, aged 4-70 years with a peak (40%) in the 21-30-year-old age group; 65 were female and 10 were male, giving a female to male ratio of 6.5 : 1 . Precipitating factors included viral respiratory tract infections and streptococcal pharyngitis in 20 cases (26%), tuberculosis in two cases (3%), pregnancy in three cases (4%) and miscellaneous conditions: Behcet's syndrome (two cases), gonorrhoea (one case), varicella (one case) and cat-scratch disease (one case) . The cause was unknown in 45 cases (60%) . The pattern of erythema nodosum in Singapore is similar to that reported in the Western literature except that sarcoidosis and inflammatory bowel disease are uncommon associations.

Cancer Immunol Immunother, 2000 Sep, 49(7), 361 - 8
Local injections of OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of Th1-type cytokines and CXC3 chemokines; Tatsugami K et al.; The effect of local injections with streptococcal preparation OK432 on the antitumor effect induced by adoptive immunotherapy (AIT) was investigated . Draining lymph node cells on day 14 after B7-P815 inoculation were used for AIT after in vitro stimulation . AIT on days 7 and 10 showed no effect on the growth of s.c . established P815 mastocytoma, but local injections with OK432 into the tumor sites on days 3, 6 and 9 resulted in a moderate antitumor effect . On the other hand, the combination therapy significantly suppressed tumor growth, and the tumor-bearing mice survived longer than those receiving only one of the treatment modalities . The significant infiltration of CD4+ or CD8+ T cells and multiple necrosis in the tumor sites were observed only when the tumor-bearing mice were treated with the combination therapy . In addition, a transfer experiment using labeled effector cells revealed these infiltrated CD8+ T cells and CD4 T cells to be derived from the donor and the host respectively . More importantly, the combination therapy clearly led to higher expression of the mRNA for Th1-type cytokines and CXC3 chemokines in the tumor sites than resulted from each of the treatment modalities alone . Collectively, these results indicate that local injections with OK432 can help the infiltration of adoptively transferred CD8+ T cells into the tumor sites and synergistically induce the local production of the Th1-type cytokines and CXC3 chemokines.

Proc Soc Exp Biol Med, 2000 Oct, 225(1), 65 - 71
The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo; Cantor JO et al.; This laboratory has previously described a method of preventing air-space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA) . Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers . In the current study, cell-free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight ( approximately 100 kDa) streptococcal HA to prevent elastolysis . Coating the matrices with HA significantly decreased elastolysis (P<0.05) induced by porcine pancreatic elastase (43%), human neutrophil elastase (53%), and human macrophage metalloelastase (80%) . Concomitant in vivo studies examined the ability of an aerosol preparation of the streptococcal HA to prevent experimental emphysema induced by intratracheal administration of porcine pancreatic elastase . As seen with earlier studies involving bovine tracheal HA, a single aerosol exposure significantly decreased elastase-induced airspace enlargement, as measured by the mean linear intercept (107.5 vs 89.6 microm; P < 0 . 05) . Furthermore, repeated exposure to the HA aerosol for 1 month did not reveal any morphological changes in the lung . The results provide further evidence that aerosolized HA may be an effective means of preventing pulmonary emphysema and perhaps other lung diseases that involve elastic fiber injury.

Mol Microbiol, 2000 Sep, 37(6), 1318 - 26
A role for the fibrinogen-binding regions of streptococcal M proteins in phagocytosis resistance; Ringdahl U et al.; All virulent group A streptococcal isolates bind fibrinogen, a property that is closely linked to expression of type-specific antiphagocytic surface molecules designated M proteins . Here we show that although the M proteins from two different strains, M1 and M5, both bind fibrinogen with high affinity, they interact with different regions in the ligand . Moreover, mapping experiments demonstrated that the fibrinogen-binding regions in the M1 and M5 proteins are quite dissimilar at the amino acid sequence level and that they bind to different regions in the plasma protein . In spite of these differences, the fibrinogen-binding regions of M1 and M5 could both be shown to contribute to streptococcal survival in human blood, providing evidence for the distinct function of a plasma protein interaction in bacterial pathogenesis.

Immunopharmacology, 2000 Sep, 49(3), 363 - 76
Induction of Th1-type cytokines by lipoteichoic acid-related preparation isolated from OK-432, a penicillin-killed streptococcal agent; Okamoto M et al.; We have isolated the lipoteichoic acid (LTA)-related molecule (OK-PSA) from OK-432, a streptococcal preparation, by an affinity chromatography on CNBr-activated Sepharose 4B-bound TS-2 monoclonal antibody (mAb) that neutralizes interferon (IFN)-gamma-inducing activity of OK-432 . In in vitro experiments using human peripheral blood mononuclear cells (PBMC), OK-PSA induced IFN-gamma, interleukin (IL)-2, IL-12, IL-18, tumor necrosis factor (TNF)-alpha and TNF-beta that are generally called "Th1-type cytokines" both in protein and in mRNA levels . Furthermore, the neutralizing test using cytokine-specific antibodies demonstrated that IL-18 plays a most significant role for IFN-gamma- and killer cell-inducing ability of OK-PSA among the other cytokines tested . These findings clearly indicated that OK-PSA, an LTA-related molecule, is a main effective component of OK-432, and is a potent inducer of Th1-type cytokines by T cell and natural killer (NK) cell activation mediated by monocytes-derived IL-18, and that it may be a useful immunotherapeutic agent for the patients with malignancies better than original OK-432.

MMW Fortschr Med, 2000 Aug 10, 142(31-32), 36 - 7
{Function of evidence-based medicine in general practice . Case report: streptococcal pharyngitis}; Porzsolt F et al.; A Bavarian country doctor taking part in a course on evidence-based medicine, put the question whether there was any evidence that, in children with confirmed streptococcal infection of the respiratory tract, appropriate antibiotic treatment could reduce the risk of late complications . With the help of the German Institute for Medical Documentation and Information (DIMDI), we undertook a search of the literature, which, however, failed to turn up any information in support of a prophylactic effect of antibiotic treatment in such a case . To avoid jumping to hasty conclusions, however, the consequences that appear to suggest themselves, should be carefully considered . This example points up three major aspects of evidence-based medicine (attitude, tools and facts) that the doctor needs to acquire, and without which modern medicine will not be possible.

Infect Immun, 2000 Oct, 68(10), 5803 - 8
T-Cell-dependent antibody response to the dominant epitope of streptococcal polysaccharide, N-acetyl-glucosamine, is cross-reactive with cardiac myosin; Malkiel S et al.; Autoantibodies against myosin are associated with myocarditis and rheumatic heart disease . In this study, the antigenic cross-reactivity of myosin and N-acetyl-glucosamine (GlcNAc), the dominant epitope of Group A streptococcal polysaccharide, was examined . Six antimyosin monoclonal antibodies (MAbs) derived from mice with cardiac myosin-induced myocarditis were characterized . All MAbs cross-reacted with GlcNAc, mimicking a subset of MAbs derived from rheumatic carditis patients that bind both myosin and streptococcal polysaccharide . Variable (V) region gene usage was diverse, with five of six MAb heavy-chain V regions encoded by distinct members of the J558 family and the sixth encoded by a member of the VGAM3.8 family . Light-chain V-region segments were derived from the Vk1, Vk4/5, Vk10, and Vk21 families . These antimyosin, anti-GlcNac MAbs demonstrated several T-cell-dependent features: they were predominantly immunoglobulin G, were encoded by V-region genes expressed late in development, and displayed somatic mutation . A direct correlation between the extent of somatic mutation and the affinity for myosin was observed . Affinity for GlcNAc also increased with the frequency of mutation, demonstrating that affinity maturation can occur simultaneously for both self antigen and foreign antigen . Based on these observations, we immunized mice with GlcNAc coupled to bovine serum albumin and demonstrated that a T-cell-dependent response to GlcNAc leads to antimyosin reactivity . We speculate that the pathogenic antibody response in rheumatic carditis may reflect the conversion of a T-cell-independent response to GlcNAc to a T-cell-dependent cross-reactive response to GlcNAc and myosin.

Infect Immun, 2000 Oct, 68(10), 5517 - 24
Bacterial immunoglobulin superantigen proteins A and L activate human heart mast cells by interacting with immunoglobulin E; Genovese A et al.; Human heart mast cells (HHMC) have been identified in heart tissue, perivascularly, and in the intima of coronary arteries . In vitro activation of isolated HHMC induces the release of vasoactive and proinflammatory mediators (histamine, tryptase, and cysteinyl leukotriene C(4) {LTC(4)}) . We investigated the effects of several bacterial proteins on HHMC activation in vitro . HHMC released histamine, tryptase, and LTC(4) in response to Staphylococcus aureus Cowan 1 and the immunoglobulin (Ig)-binding protein A, but not to S . aureus Wood 46, which does not synthesize protein A . The effect of protein A was inhibited by preincubation with monoclonal IgM V(H)3(+) . Some strains of Peptostreptococcus magnus express an Ig light chain-binding surface protein called protein L . Such bacteria and soluble protein L stimulated the release of preformed and newly synthesized mediators from HHMC . Preincubation of HHMC with either protein A or protein L resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus or anti-IgE . Monoclonal IgE (kappa chains) blocked protein L-induced release, whereas IgE (lambda chains) had no effect . Streptococcal protein G, formyl-containing tripeptide, and pepstatin A did not activate HHMC . Bacterial products protein A and protein L and intact bacteria (S . aureus and P . magnus) activate HHMC by acting as Ig superantigens.

Oncology (Huntingt), 2000 Aug, 14(8 Suppl 6), 35 - 9
Current issues in the treatment of resistant bloodstream infections; Wade JC; Bloodstream infections cause significant morbidity and mortality for patients with hematologic malignancy . Antimicrobial drugs are the most reliable currently available treatment for infection, but several issues must be considered before choosing the appropriate regimen . Practitioners must be aware of changes in patterns of microbial prevalence and in drug resistance . Current worldwide data indicate a shift to gram-positive pathogens, with coagulase-negative staphylococci being the most common, and enterococcal and viridans group streptococcal species becoming problematic . Antimicrobial resistance continues to rise among these species, and while current drugs and combinations of them are effective in most cases, successful therapy will require the development of new drugs for which resistance has not emerged . Examples of such drugs include the oxazolidinones and glycylcyclines . While antibiotics will continue to be essential treatment for most patients with fever and neutropenia, a judicious reduction of exposure to antimicrobial drugs and enhanced infection control measures are warranted in the face of increasing antimicrobial resistance (e.g., vancomycin-resistant enterococci) . The standard of care for patients who develop fever while neutropenic is empiric, broad-spectrum antibiotics that are modified as needed until fever and infection subside . Several factors, including antibiotic resistance, must be considered in choosing the empiric regimen.

Clin Infect Dis, 2000 Aug, 31(2), 607 - 8
The initial outpatient-physician encounter in group A streptococcal necrotizing fasciitis; Bisno AL et al.; Of 15 patients in whom the diagnosis of streptococcal necrotizing fasciitis was missed at initial outpatient evaluation, 8 died . Although influenza-like and gastrointestinal symptoms were common, the most consistent clinical clue was unrelenting pain out of proportion to the physical findings . Necrotizing fasciitis should be considered in patients presenting with the latter complaint, even if there is only mild or no fever or erythema.

J Am Acad Child Adolesc Psychiatry, 2000 Sep, 39(9), 1120 - 6
Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS); Lougee L et al.; OBJECTIVE: To determine the rates of psychiatric disorders in the first-degree relatives of children with infection-triggered obsessive-compulsive disorder (OCD) and/or tics (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; PANDAS) . METHOD: The probands of this study were 54 children with PANDAS (n = 24 with a primary diagnosis of OCD; n = 30 with a primary diagnosis of a tic disorder) . One hundred fifty-seven first-degree relatives (100 parents {93%} and 57 siblings {100%}) were evaluated for the presence of a tic disorder . One hundred thirty-nine first-degree relatives (100 parents {93%} and 39 of 41 siblings over the age of 6 {95%}) were evaluated with clinical and structured psychiatric interviews to determine the presence of subclinical OCD, OCD, and other DSM-IV Axis I disorders . RESULTS: Twenty-one probands (39%) had at least one first-degree relative with a history of a motor or vocal tic; 6 mothers (11%), 9 fathers (19%), and 8 siblings (16%) received this diagnosis . Fourteen probands (26%) had at least one first-degree relative with OCD; 10 mothers (19%), 5 fathers (11%), and 2 siblings (5%), received this diagnosis . An additional 8 parents (8%) and 3 siblings (8%) met criteria for subclinical OCD . Eleven parents (11%) had obsessive-compulsive personality disorder . CONCLUSIONS: The rates of tic disorders and OCD in first-degree relatives of pediatric probands with PANDAS are higher than those reported in the general population and are similar to those reported previously for tic disorders and OCD . Further study is warranted to determine the nature of the relationship between genetic and environmental factors in PANDAS.

Zentralbl Neurochir, 2000, 61(2), 95 - 102
Intracranial infection after missile brain wound: 15 war cases; Hecimovic I et al.; OBJECTIVES: The present study describes 15 cases of intracranial infections developed in a group of in patients with missile brain wound (MBW), during the war in Croatia in the region of East Slavonia . METHOD: The retrospective study included 88 MBW casualties . There were 11 females and 77 males aged 2-80 years . The projectile penetration of the cranial dura was confirmed and the presence of intracranially retained foreign bodies was evaluated with computerized tomography (CT) in all the patients . The wounded were treated according to the modern recommendations of neurotrauma care . However, we extracted only accessible bone/metallic fragments during intracranial debridement . All intracranial infections were documented by cultures, CT, surgery or autopsy . The mean follow-up period of wounded with intracranial infections was 2.4 years (range, 10 days to 7 years) . RESULTS: Intracranial infection developed in 14 patients (17%) as "early intracranial infections" . Among 14/15 cases, infection developed within the first 8 weeks, and in 1 case 5 months after wounding . We recorded 4 cases of isolated bacterial meningitis, whereas in 9 cases brain abscess had developed . In 6 cases brain abscess was associated with concomitant meningitis and epidural empyema . Local cerebritis developed in one case, as well as subdural empyema with the concomitant meningitis in one case . There were 8 deaths in total of 15 cases . Glasgow Outcome Score 3 was observed in 2 and good outcome in 5/15 cases . The infectious organisms were isolated in 8 cases . Gram-positive bacteria were found in 12 different specimens . Gram-negative bacteria were found in 9 specimens . The most frequently isolated organism was Staphylococcus aureus . beta-hemolytic streptococcal and clostridial infections were not observed . Among the 15 patients with intracranial infection, just one did not have intracranially retained bone and/or metallic fragments . However, among the 73 head injuries without intracranial infections only 10 did not have retained fragments . CSF fistula and/or dehiscence developed in 13/15 patients with intracranial infection . In 67/73 wounded without intracranial infections, wound complications were not registered . CONCLUSIONS: The liberal use of post-contrast CT of the brain within the first 2 months after injury, especially if performed early in the clinical course, can lead to a prompt diagnosis of most of "early intracranial infections" . The surgical procedures in order to prevent wound CSF fistula/dehiscence development are absolutely necessary . The immediate scalp and dural wound repair in case of wound complications are absolutely indicated and if needed, the procedures can be repeated . However, it seems that retained fragments are not responsible for an increased rate of intracranial infection.

Biochemistry, 2000 Sep 19, 39(37), 11216 - 26
Nanosecond dynamics of the single tryptophan reveals multi-state equilibrium unfolding of protein GB1; Tcherkasskaya O et al.; Unfolding of the immunoglobulin binding domain B1 of streptococcal protein G (GB1) was induced by guanidine hydrochloride (GdnHCl) and studied by circular dichroism, steady-state, and time-resolved fluorescence spectroscopy . The fluorescence methods employed the single tryptophan residue of GB1 as an intrinsic reporter . While the transitions monitored by circular dichroism and steady-state fluorescence coincided with each other, the transitions followed by dynamic fluorescence were markedly different . Specifically, fluorescence anisotropy data showed that a relaxation spectrum of tryptophan contained a slow motion with relaxation times of 9 ns in the native state and 4 ns in the unfolded state in 6 M GdnHCl . At intermediate GdnHCl concentrations of 3.8-4.2 M, however, the slow relaxation time increased to 18 ns . The fast nanosecond motion had an average time of 0.8 ns and showed no dependence on the formation of native structure . Overall, dynamic fluorescence revealed two preliminary stages in GB1 folding, which are equated with the formation of local structure in the beta(3)-strand hairpin and the initial collapse . Both stages exist without alpha-helix formation, i . e., before the appearance of any ordered secondary structure detectable by circular dichroism . Another stage in GB1 folding might exist at very low ( approximately 1 M) GdnHCl concentrations.

Folia Microbiol (Praha), 1999, 44(4), 449 - 53
Comparative genetic study of group B streptococcal strains of human and bovine origin; Dmitriev A et al.; The presence and restriction fragment length polymorphism (RFLP) of DNA fragments hybridizing with virulence and "house keeping" gene probes were analyzed for 87 group B streptococcal (GBS) strains of human and bovine origin . Most characteristics obtained for bovine strains were similar when compared with those for human strains . The most significant degree of RFLP was discovered for the sizes of HindIII fragments containing bca gene . Human GBS strains with bac gene, encoding beta antigen with IgA binding capacity, were characterized by almost identical complex hybridization patterns with multiple gene probes . At the same time bac gene was not found among bovine GBS strains . Gene scpB that encodes C5a peptidase in all human GBS strains was detected only in 9 of 39 strains of bovine origin . These two characteristics effectively distinguished bovine GBS strains from GBS strains of human origin.

Probl Tuberk, 2000, (4), 32 - 4
{Endoscopic bronchial care in patients with chronic bronchitis}; Guseinov KhIu; Endoscopic bronchial sanitation was made in 194 patients with an exacerbation of chronic bronchitis . Catarrhal and purulent endobronchitis was endoscopically diagnosed in 121 and 73 patients, respectively . For endoscopic sanitation, therapeutical lavage was used at fiber bronchoscopy . Ringer's solution added by methyluracil and dioxidine was used as a wash liquid . In patients with staphylococcal or streptococcal infection, the bronchial washing was completed by the administration of specific phage preparations . Good and fair effects could be achieved in 97.7 of the treated patients.

Acta Clin Belg, 2000 May-Jun, 55(3), 163 - 9
The use of polyclonal intravenous immunoglobulins in the prevention and treatment of infectious diseases; Lories RJ et al.; In this review we discuss the prevention and treatment of infectious diseases with intravenous immunoglobulins (IVIG) . IVIG can be used to prevent infections in primary as well as in certain secondary immunodeficiencies . We also discuss the use of IVIG in the prevention of CMV-disease after organ or bone marrow transplantation . Besides their use in prevention, IVIG can also be used as an additional therapy in sepsis in neonates, in streptococcal toxic shock syndrome and in CMV-disease after bone marrow or solid organ transplantation . We briefly discuss the different preparations of IVIG that are available in Belgium.

Rev Esp Cardiol, 2000 Sep, 53(9), 1209 - 78
{Guidelines of the Spanish Society of Cardiology on valve heart disease}; Azpitarte J et al.; Valvular heart diseases, which continue to be a major cause of morbidity and mortality world wide, have undergone radical changes since the first valve prostheses were implanted 40 years ago . These changes have been the result of both scientific progress and improved standard of living in developed countries . The availability of penicillin to treat streptococcal pharyngitis and less crowded living conditions have now made rheumatic fever uncommon in these countries . However, other forms of valve impairment have appeared over the past several years . The etiology of some of these valvular diseases remains obscure (e . g . myxomatous mitral valve); others, such as the senile type of calcific aortic valve stenosis, seem to be the price to be paid for the extension of life expectancy . With regard to diagnosis, echocardiography has constituted a formidable tool for visualizing anatomic valve changes, interpreting complex hemodynamic derangements, and evaluating repercussion on the left ventricle . In addition, the iteration of this non-invasive examination has allowed a much better understanding of the natural history of non-severe valvular disease and therefore of the precise timing for surgical intervention, without awaiting, in most cases, the appearance of advanced symptomatology . This has also been possible because of the great advances in cardiac surgery which can be summarised as: a) the improvement in extracorporeal circulation and myocardial preservation techniques; b) the greatly improved biologic and mechanic valve substitutes; c) the introduction of imaginative mitral valve repair procedures, and d) the use of intraoperative transesophageal echocardiography to assess the adequacy of valve repair . At the same time, percutaneous catheter balloon valvuloplasty has emerged as a valid alternative to mitral surgical commissurotomy for mitral stenosis . All these changes, and many more that can not be described in this brief summary, make a review of the management of patients with valve heart disease appropriate.

Microbiology, 2000 Sep, 146 ( Pt 9), 2259 - 65
Conjugal transfer of plasmid pMV158: uncoupling of the pMV158 origin of transfer from the mobilization gene mobM, and modulation of pMV158 transfer in Escherichia coli mediated by IncP plasmids; Farias ME et al.; The streptococcal plasmid pMV158 encodes a gene cassette involved in its mobilization by large conjugative plasmids . Two elements compose this region: i) the mobM gene, encoding the MobM protein that initiates transfer, and ii) the origin of transfer, oriT, which is the target of MobM . In vitro, MobM protein introduces a specific nick within the pMV158-oriT region on supercoiled pMV158 DNA . This paper reports the uncoupling of the oriT and the mobM gene, the latter being placed under the control of an inducible promoter . Upon induction, the vector containing pMV158-oriT was transferred in Escherichia coli matings at a moderate frequency whereas, in vitro, purified MobM protein efficiently cleaved the vector harbouring the pMV158-oriT . Transfer of this vector, as well as transfer of pMV158 in E . coli, required the presence of either the IncW R388 or the IncP RP4 plasmids as auxiliary plasmids . Dissection of the functions encoded by RP4 showed that the traG and traF genes were essential for pMV158 mobilization.

Infect Dis Obstet Gynecol, 2000, 8(3-4), 138 - 42
Is antenatal group B streptococcal carriage a predictor of adverse obstetric outcome?
Garland SM, Kelly N, Ugoni AM.
OBJECTIVES: While early-onset neonatal GBS sepsis is positively associated with premature birth and prolonged rupture of membranes, there is debate in the literature as to whether maternal GBS colonization is a predictor of adverse obstetric outcome . This is a critical issue to resolve for appropriate management (expectant vs . interventional management) of the patient presenting with premature rupture of membranes, who has no overt signs of sepsis, but who is colonized with GBS . METHODS: Since 1981 it has been hospital policy to screen all public patients antenatally for genital carriage of GBS by collection of a low vaginal swab at 28-32 weeks . All patients colonized with GBS antenatally are given penicillin as intrapartum chemoprophylaxis . Review of all GBS-colonized antenatal patients for a 12-month period (580 of 4,495 patients) and a randomized (every fourth consecutive antenatal patient) number of noncolonized patients (958) was made . Lower vaginal GBS colonization and other risk factors for preterm delivery were assessed using univariate and multivariate generalized linear modeling . RESULTS: In the study group, the maternal GBS colonization rate was 12.9% . When cofounding variables were controlled in a multivariate analysis, the association between antepartum GBS colonization and preterm labor and preterm rupture of membranes was not significant . CONCLUSION: Maternal antenatal carriage of GBS does not predict preterm labor . Therefore it is appropriate that expectant management occur for a GBS-colonized woman who ruptures her membranes, is not in labor, and has no evidence of sepsis.

J Med Microbiol, 2000 Sep, 49(9), 787 - 91
Comparison of resin-containing BACTEC Plus Aerobic/F* medium with conventional methods for culture of normally sterile body fluids; Sorlin P et al.; The sensitivity of culture in Bactec Plus Aerobic/F* culture vials of body fluids from adult patients at a university hospital was compared with that of conventional culture methods, including enrichment in Schaedler broth . Previous antibiotic therapy was recorded at the time of sampling . Analysis of culture results took account of the clinical significance of isolates and impact on therapy . Of 336 specimens evaluated, 81 (24%) yielded positive cultures, of which 50 cultures (15%) were considered to be clinically significant (yielding 71 isolates) and 31 (9%) were considered contaminated . Of the 71 pathogens, 16 (23%) were isolated in the Bactec system only, whereas 13 (18%) grew in conventional media only; 12 of the latter were strict anaerobes . Among clinically significant positive specimens, 19 (38%) were from patients receiving antibiotic therapy . In 27 cases (8% of all specimens and 54% of significantly positive cultures), the isolation of a pathogen led to modification of therapy . Overall, culture in the Bactec system showed higher sensitivity for the isolation of aerobic micro-organisms than Schaedler broth . Most of the difference was due to a better recovery of Streptococcaceae . Additional pathogens found only in resin-containing Bactec media led to 30% of all culture-influenced modifications of empirical therapy . These data confirm that culture of normally sterile body fluids frequently yields results that are useful for guiding therapy . Although more costly than standard enrichment broth, the resin-containing Bactec Plus Aerobic/F* vial can be advantageous for culture of aerobic pathogens from these specimens, particularly in patients receiving antibiotic therapy.

Postgrad Med J, 2000 Sep, 76(899), 561 - 5
High prevalence of iliofemoral venous thrombosis with severe groin infection among injecting drug users in North East Scotland: successful use of low molecular weight heparin with antibiotics; Mackenzie AR et al.; Injecting drug use, mainly of heroin, currently represents a major public health issue in the North East of Scotland . The recent tendency of the committed injecting drug user to inject into the groin has created novel problems for the Infection Unit.Data are presented on 20 consecutive patients admitted between 1994 and 1999 with iliofemoral venous thromboses, often complicated by severe soft tissue infections and bacteraemia as a result of heroin injection into the femoral vein . Nine had coexistent groin abscesses, four had severe streptococcal soft tissue infection of the right thigh, groin and lower abdomen, and two had coincidental soft tissue infections of the upper limb . Nine were bacteraemic on admission . All of the patients were chronic injecting drug users with a median injection duration of 6.5 years . The 18 patients tested for hepatitis C virus were all seropositive . None of the 14 patients tested was positive for HIV.Seventeen patients were treated with subcutaneous low molecular weight heparin (tinzaparin), three having received intravenous unfractionated heparin initially . The tinzaparin was self administered and given for a median duration of seven weeks . One patient declined to have any treatment . Three months after presentation eight patients were asymptomatic, seven had a persistently swollen leg, and five were lost to follow up . None developed clinically apparent pulmonary embolism after institution of anticoagulant therapy.The management of iliofemoral venous thrombosis in injection drug users is problematic because of poor venous access, non-compliance with prescribed treatment, ongoing injecting behaviour, and coexistent sepsis . It is unlikely that a randomised trial of standard treatment with heparin and warfarin versus low molecular weight heparin alone would be practical in this patient group . These retrospective data indicate that the use of tinzaparin in injecting drug users is feasible and appears to result in satisfactory clinical responses.The possibility of concomitant infection in injecting drug users with venous thrombosis should always be addressed, as it appears to be a common phenomenon . Early drainage of abscesses and antimicrobial chemotherapy, often administered intramuscularly or orally because of lack of peripheral venous access, is central to the appropriate care of these patients.

Neuropediatrics, 2000 Jun, 31(3), 155 - 8
Familial systemic lupus erythematosus and congenital infection-like syndrome; Dale RC et al.; We present two siblings with congenital and progressive encephalopathy associated with systemic lupus erythematosus . The two brothers presented soon after birth with an encephalopathy associated with intracranial calcification (=2), intrauterine growth retardation (= 2), hepatitis (= 1) and thrombocytopenia (= 1), mimicking a congenital virus infection . Within the first year of life both children developed hypocomplementaemia and systemic lupus erythematosus (SLE), the main features of which were a discoid lupus-like rash on the hands and feet and the progressive production of high levels of autoantibodies . Both children were severely handicapped and died in early childhood from streptococcal infections . There are many causes of congenital encephalopathy with intracranial calcification . The early development of systemic lupus in these children suggested that their cerebral disease formed part of an autoimmune process . Complement levels and autoantibody profiles should be considered part of the investigation of a child with congenital infection-like syndrome, particularly when there are progressive dermatological complications.

Immunopharmacol Immunotoxicol, 2000 May, 22(2), 221 - 35
PSK and OK-432-induced immunomodulation of inducible nitric oxide (NO) synthase gene expression in mouse peritoneal polymorphonuclear leukocytes and NO-mediated cytotoxicity; Asai K et al.; We investigated whether PSK (a polysaccharide from the mycelia of Coriolus versicolor) or OK-432 (a streptococcal preparation) can up-regulate inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) production in mouse peritoneal polymorphonuclear leukocytes (PMNs) . Six hrs after intraperitoneal injection of mice with PSK (2,500 microg/mouse) or OK-432 (100 microg/mouse), mouse peritoneal PMNs were restimulated with PSK (500 microg/ml) or OK-432 (10 microg/ml) plus 100 U/ml of mouse interferon-gamma (IFN-gamma) in vitro . Northern blot analysis showed strong synergism between both PSK and OK-432 and IFN-gamma for the induction of iNOS gene expression . NO production by PMNs was increased up to 20 microM (2 microM/10(6) PMNs/24 hrs) as measured by the Griess reagent method when PMNs were restimulated with PSK or OK-432 plus IFN-gamma for 24 hrs, although tumor cell killing was not detected . NO concentrations of more than 80 microM were required for P815 tumor cell killing . These results suggest that PMNs produce NO after stimulation with PSK or OK-432 in combination with IFN-gamma and may regulate the immune system in vivo, although the NO production induced by these agents is insufficient for tumor cell killing in vitro.

J Infect Dis, 2000 Sep, 182(3), 824 - 32 Epub 2000 Aug 17.
Severity of group B streptococcal arthritis is correlated with beta-hemolysin expression; Puliti M et al.; Septic arthritis is a clinical manifestation of group B streptococcal (GBS) infection in neonates and adults . To examine the potential role of GBS beta-hemolysin in joint injury, mice were infected with 2 wild-type strains or with nonhemolytic (NH) or hyperhemolytic (HH) variants derived by transposon mutagenesis . Compared with mice infected with the parent strains, mice infected with the NH mutants had decreased mortality and bacterial proliferation . A reduced LD(50) and a higher microbial load were obtained in mice infected with the HH mutants . Greater degrees of joint inflammation and damage were observed in the HH mutant-infected animals than in those infected with the parental strains . NH mutant-infected mice manifested only a mild and transient arthritis . Systemic and local levels of interleukin-6 mirrored the observed differences in virulence and severity of arthritis . These data support a direct correlation of GBS beta-hemolysin expression with mortality and severity of articular lesions.

Mycoses, 2000, 43(5), 181 - 3
Erysipelas and tinea pedis; Roldan YB et al.; During a 2-year period 30 adults were selected out of a group of patients diagnosed with erysipelas, who, except for tinea pedis, were apparently otherwise healthy patients . Clinical and epidemiological studies were performed to establish how tinea pedis and erysipelas are related . Thirteen of 30 patients with a diagnosis of erysipelas were found to have tinea pedis due to Trichophyton mentagrophytes and Trichophyton rubrum . In seven of the patients (23%) tinea pedis was found to be the unique predisposing factor for erysipelas . Tinea pedis may be a risk factor for streptococcal infections such as erysipelas, mainly in tropical countries, where tinea pedis is a frequent disease.

Am J Obstet Gynecol, 2000 Aug, 183(2), 271 - 6
Amniotic fluid index values after preterm premature rupture of the membranes and subsequent perinatal infection; Vermillion ST et al.; OBJECTIVE: Our purpose was to determine whether an amniotic fluid index (AFI) <5 cm after preterm premature rupture of the membranes is associated with an increased risk of perinatal infection . STUDY DESIGN: We performed a nonconcurrent prospective analysis of 225 singleton pregnancies complicated by preterm premature rupture of the membranes, with delivery between 24 and 32 weeks' gestation . All included patients received 2 doses of betamethasone antenatally, in the first 24 hours after admission, and broad-spectrum antibiotic prophylaxis . Patients were categorized into 2 groups on the basis of a 4-quadrant AFI <5 cm (n = 131) or > or =5 cm (n = 94) . Perinatal outcomes analyzed included latency until delivery, mode of delivery, and frequencies of clinical chorioamnionitis, postpartum endometritis, and culture-proved early neonatal sepsis . Continuous data were evaluated for normal distribution and tested for significance with the Student t test . Categoric data were tested with the chi(2) and Fisher exact tests . Multiple logistic regression analyses were performed with chorioamnionitis, endometritis, and early-onset neonatal sepsis each as the dependent variable in separate analyses . All 2-sided P values <.05 were considered significant . RESULTS: Both groups were similar with respect to selected demographics, gestational age at rupture of the membranes, birth weight, and maternal group B streptococcal colonization . Patients with an AFI <5 cm demonstrated a shorter mean latency until delivery (5.5 +/- 4.0 vs 14.1 +/- 5.2) (mean +/- SD) days (P =.02), greater frequency of amnioinfusion therapy (23.6% vs 5.3%) (P <.001), and cesarean delivery for nonreassuring fetal testing (18.3% vs 4 . 3%) (P =.01) . Multiple logistic regression analysis showed that an AFI <5 cm was the only significant risk factor independently associated with early-onset neonatal sepsis (P =.004) and chorioamnionitis (P =.024) . CONCLUSIONS: An AFI <5 cm after preterm premature rupture of the membranes between 24 and 32 weeks' gestation is associated with an increased risk of perinatal infection and a shorter latency preceding delivery.

Microbiol Immunol, 2000, 44(6), 519 - 23
Sensitive enzyme-linked immunosorbent assays for the detection of bacterial superantigens and antibodies against them in human plasma; Miwa K et al.; Enzyme-linked immunosorbent assays for the quantitation of bacterial superantigens, staphylococcal enterotoxins A, B and C, toxic-shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, were developed . The assays had sensitivity to quantitate these toxins to 1.4, 5.9, 16.3, 2.5 and 4.3 pg/ml, respectively, in a buffer including 50% human plasma . It takes only 150 min to complete the assays after plate preparation . Specificity of the assays agreed with those of reverse latex agglutination assay . We also developed enzyme-linked immunosorbent assays to detect antibodies against these five superantigens . The assays are expected to be significant tools for the study of superantigens in several diseases.

J Paediatr Child Health, 2000 Aug, 36(4), 401 - 2
Acute thrombocytopenia associated with post-streptococcal acute glomerulonephritis; Muguruma T et al.; A case of acute thrombocytopenia associated with post-streptococcal acute glomerulonephritis is described . The patient showed a mild glomerulonephritis and a remarkable increase of platelet-associated immunoglobulin G (PAIgG) . The relation between the mild degree of glomerulonephritis and the high PAIgG value is discussed.

Turk J Pediatr, 2000 Apr-Jun, 42(2), 101 - 4
Poststreptococcal reactive arthritis: clinical course and outcome in 15 patients; Kocak G et al.; Patients with Group A beta-hemolytic streptococcal infection and articular disease, who do not fulfill the modified Jones criteria for diagnosis of acute rheumatic fever (ARF), have been classified as having poststreptococcal reactive arthritis (PSRA) . We reviewed the clinical characteristics, laboratory findings and outcome of 15 patients with PSRA . None of these patients had clinical evidence of carditis . The pattern of joint involvement was variable and included arthritis in five patients and arthralgia in the remaining ten patients . Nine patients were treated with salicylates for one to 16 weeks; the others recovered spontaneously . Usually, the patients with arthralgia responded promptly to salicylates, while the response was poor in patients with arthritis . One patient with monoarthritis developed carditis nine months after his first arthritis attack . Another patient presenting with monoarthritis later had two additional episodes of poststreptococcal reactive arthralgia . It seems there is a wide spectrum of poststreptococcal rheumatic diseases, and patients with PSRA are also at risk for cardiac disease; therefore, prophylactic antibiotic therapy should be considered in these patients.

Protein Sci, 2000 Jul, 9(7), 1382 - 90
HYR, an extracellular module involved in cellular adhesion and related to the immunoglobulin-like fold; Callebaut I et al.; Domains belonging to the immunoglobulin-like fold are responsible for a wide variety of molecular recognition processes . Here we describe a new family of domains, the HYR family, which is predicted to belong to this fold, and which appears to be involved in cellular adhesion . HYR domains were identified in several eukaryotic proteins, often associated with Complement Control Protein (CCP) modules or arranged in multiple copies . Our analysis provides a sequence and structural basis for understanding the role of these domains in interaction mechanisms and leads to further characterization of heretofore undescribed repeated domains with similar folds found in several bacterial proteins involved in enzymatic activities (some chitinases) or in cell surface adhesion (streptococcal C-alpha antigen).

Mol Microbiol, 2000 Aug, 37(3), 492 - 500
Plasmid copy number control: an ever-growing story; del Solar G et al.; Bacterial plasmids maintain their number of copies by negative regulatory systems that adjust the rate of replication per plasmid copy in response to fluctuations in the copy number . Three general classes of regulatory mechanisms have been studied in depth, namely those that involve directly repeated sequences (iterons), those that use only antisense RNAs and those that use a mechanism involving an antisense RNA in combination with a protein . The first class of control mechanism will not be discussed here . Within the second class (the most 'classical' one), exciting insights have been obtained on the molecular basis of the inhibition mechanism that prevents the formation of a long-range RNA structure (pseudoknot), which is an example of an elegant solution reached by some replicons to control their copy number . Among the third class, it is possible to distinguish between (i) cases in which proteins play an auxiliary role; and (ii) cases in which transcriptional repressor proteins play a real regulatory role . This latter type of regulation is relatively new and seems to be widespread among plasmids from Gram-positive bacteria, at least for the rolling circle-replicating plasmids of the pMV158 family and the theta-replicating plasmids of the Inc18 streptococcal family.

Clin Exp Immunol, 2000 Aug, 121(2), 270 - 4
Autoantibodies in the sera of patients with rheumatic heart disease: characterization of myocardial antigens by two-dimensional immunoblotting and N-terminal sequence analysis; Tontsch D et al.; The concept of antigenic mimicry in autoimmune diseases such as rheumatic fever has been under investigation for decades and the range of cross-reactive tissue antigens for streptococcal-induced antibodies identified in rheumatic heart disease is still expanding . To identify heart tissue-reactive antigens which may be implicated in the secondary immunopathogenesis of rheumatic fever, sera from 56 patients with acute rheumatic heart disease were probed in two-dimensional Western blots for reactivity against heart tissue antigens . After two-dimensional immunoblot analysis, proteins were submitted to N-terminal amino acid sequence analysis . This analysis identified creatine kinase, two mitochondrial proteins and, at a low level, various stress proteins as cross-reactive myocardial antigens . Therefore, in addition to myosin, creatine kinase may represent another major antigen for autoreactive antibodies in rheumatic heart disease . Mitochondrial proteins have been implicated in the pathogenesis of inflammatory heart disease for some years, and in this study we have identified two mitochondrial proteins as relevant antigens in rheumatic heart disease.

Clin Ther, 2000 Jun, 22(6), 673 - 84
Short-Course antimicrobial therapy for upper respiratory tract infections; Guay DR; OBJECTIVE: This review examines the issues surrounding short-course antimicrobial therapy of group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis, acute (suppurative) otitis media, and acute sinusitis . BACKGROUND: Accumulating evidence suggests that short-course (ie, < or = 5 days) antimicrobial therapy may have equivalent or superior efficacy compared with traditional longer (10- to 14-day) therapies . RESULTS: In GABHS tonsillopharyngitis, short-course therapy with 6 days of amoxicillin, 4 or 5 days of various cephalosporins, and 5 days of azithromycin (10 mg/kg once daily on all 5 days in pediatric patients) are all reasonable alternatives to traditional 10-day penicillin therapy . In uncomplicated acute (suppurative) otitis media, single-dose intramuscular ceftriaxone or 3- to 5-day short-course oral antimicrobial therapy should be effective in > or = 80% of patients . However, more research is needed in children aged <2 years, since short-course therapy may not be successful in most patients in this population . In sinusitis, most short-course therapy data have involved acute maxillary disease in adult patients . Preliminary results are encouraging, but more study is needed, especially in children . CONCLUSIONS: Cost-containment in antimicrobial therapy should include consideration of short-course therapy in the management of upper respiratory tract infections.

Ann Pharmacother, 2000 Jul-Aug, 34(7-8), 936 - 9
Clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes; Russell NE et al.; OBJECTIVE: To evaluate the utility of clindamycin in the treatment of streptococcal and staphylococcal toxic shock syndromes . DATA SOURCES: Biomedical literature was accessed through MEDLINE (1966-December 1999) . Key terms included clindamycin, streptococcal toxic shock, and staphylococcal toxic shock . DATA SYNTHESIS: Streptococcal and staphylococcal toxic shock syndromes are associated with a high mortality rate . beta-Lactams have been considered the drug of choice for the treatment of these serious infections, with the occasional use of adjunctive clindamycin, although no clinical evidence has been published to support this latter regimen . An evaluation of the information to propose the usefulness of clindamycin was conducted . CONCLUSIONS: Experimental laboratory evidence suggests utility of the adjunctive use of clindamycin in streptococcal and staphylococcal infections complicated by toxin production . Research using animal models comparing clindamycin plus beta-lactams with beta-lactams alone for the treatment of these infections would be useful.

Infect Control Hosp Epidemiol, 2000 Jul, 21(7), 473 - 83
Neonatal group B streptococcal disease: how infection control teams can contribute to prevention efforts; Schrag SJ et al.; Group B streptococcal (GBS) disease is a leading cause of morbidity and mortality among newborns . Many cases of newborn GBS disease can be prevented by the administration of intrapartum antibiotic prophylaxis . Current consensus guidelines for prevention of perinatal GBS disease have led to substantial declines in the incidence of GBS disease occurring in newborns <7 days of age (early-onset disease) . Despite declines in the incidence of early-onset disease, approximately 20% of pregnant women are colonized with GBS at the time of labor and thus have the risk of transmitting the bacteria to their newborns . Consequently, continued and improved implementation of prevention efforts is essential . Infection control teams can contribute uniquely to prevention of perinatal GBS disease by serving as hospital champions of GBS disease prevention . In particular, teams can coordinate with administration and staff to encourage establishment and effective implementation of GBS prevention policies; facilitate improved laboratory processing of prenatal GBS screening specimens; monitor any adverse consequences of increased use of intrapartum antibiotics within the hospital; and investigate GBS cases that occur to determine whether they could have been prevented . By spearheading efforts to improve implementation of perinatal GBS disease prevention at the hospital level, hospital epidemiologists and infection control practitioners can play an important role in reducing the burden of early-onset GBS disease.

J Perinatol, 2000 Jul-Aug, 20(5), 316 - 7
Indicated preterm birth: a possible contribution to group B streptococcal sepsis prophylaxis protocol failures . A case report; Stiller RJ et al.; BACKGROUND: Despite the acceptance of protocols for the prevention of group B streptococcal (GBS) sepsis for the newborn, protocol violations, with subsequent failure to initiate intrapartum antibiotic therapy, occur at many institutions . The causes for GBS prophylaxis protocol violations are not well understood . CASES: We report two cases of indicated preterm birth in which appropriate antibiotic prophylaxis for GBS sepsis was not initiated . CONCLUSION: In the setting of indicated preterm birth, GBS prophylaxis may be overlooked . We suspect that the attention given to the medical or fetal complications of indicated preterm birth may contribute to the omission of GBS sepsis prophylaxis in these situations.

Pediatrics, 2000 Aug, 106(2 Pt 1), 244 - 50
The influence of intrapartum antibiotics on the clinical spectrum of early-onset group B streptococcal infection in term infants; Bromberger P et al.; OBJECTIVE: The use of intrapartum antibiotics to prevent early-onset group B streptococcal (EOGBS) infection has left pediatricians in a quandary about the appropriate evaluation and treatment of infants at risk for this infection . The aim of this study was to determine whether intrapartum antibiotic prophylaxis changed the constellation and timing of onset of clinical signs of group B streptococcal (GBS) infection in term infants . METHODOLOGY: We conducted a retrospective chart review of infants who had EOGBS infection and were born in Southern California Kaiser Permanente Hospitals from 1988 through 1996 . Objective criteria were used to ascertain maternal risk of infection, intrapartum antibiotic prophylaxis, and onset of clinical signs of infection . RESULTS: Three hundred nineteen infants with EOGBS sepsis, bacteremia, or clinically suspected infection were identified from a population of 277 912 live births . Of the 172 term infants with culture-positive infection who had clinical signs of infection, 95% exhibited them in the first 24 hours of life . All of the infants exposed to intrapartum antibiotics became ill within the first 24 hours of life . CONCLUSIONS: Exposure to antibiotics during labor did not change the clinical spectrum of disease or the onset of clinical signs of infection within 24 hours of birth for term infants with EOGBS infection . A 48-hour stay is not required to monitor asymptomatic term infants exposed to intrapartum antibiotics for onset of GBS infection.

Semin Pediatr Neurol, 2000 Jun, 7(2), 103 - 7
Autoimmune mechanisms in movement disorders; Visvanathan K et al.; A number of disorders, including childhood-onset obsessive compulsive disorder (OCD) and Gilles de la Tourette's syndrome (TS), are known to be neurobiological in nature . Both TS and OCD are neuropsychiatric diagnoses that involve congitive and perceptual dysfunction in addition to motor and psychiatric manifestations . The association of the B-cell marker with both Sydenham's chorea and a group of neuropsychiatric disorders, such as OCD, tics, and TS, has been useful as a marker in these diseases . This evidence, coupled with the recent finding of anti-brain antibodies in the sera of these patients, raises a number of interesting questions concerning the pathological mechanisms involved in these diseases . Thus, further molecular characterization of the brain and streptococcal antigens will be crucial to our understanding of the neurophysiological processes involved in these disorders.

Harefuah, 1999 Mar 15, 136(6), 438 - 41, 515
{Knowledge and practice of primary care physicians relating to the treatment of streptococcal pharyngitis}; Leshem S et al.; Knowledge and practice of primary care physicians as to diagnosis and treatment of group A, b-hemolytic streptococcal pharyngitis, and the degree to which they agreed with the medical literature and current clinical guidelines were examined . The study was conducted in a group of 195 general physicians, pediatricians, and family medicine specialists and residents . The data were collected using questionnaires which included personal information and questions relating to b-hemolytic streptococcal pharyngitis and were analyzed by chi-square and t-tests, and logistic regression, as appropriate . A new dependent variable, good clinical practice (GCP), was defined as the total number of correct answers to the questions in the questionnaire . 147 of the 195 eligible physicians returned completed questionnaires, a compliance rate of 76% . 96.6% cited penicillin V as the drug of choice at a daily dosage of 1 g (43.7%) or 2 g (25.4%), for 10 days (90%) . 133 physicians (90%) stated that the goal of penicillin therapy for b-hemolytic streptococcal pharyngitis is to prevent late complications . 116 physicians (82%) cited rheumatic fever as a complication of group A b-hemolytic streptococcal pharyngitis, preventable by appropriate antibiotic therapy . However, only 84 (59%) cited glomerulonephritis as a preventable complication . When the knowledge and attitudes of the respondents was analyzed in terms of the new variable, GCP, a significant association (p < 0.001) was found between physicians' attitudes and variables such as where they had studied medicine, and work seniority . Those with less seniority and or medical graduates of the Americas demonstrated greater knowledge and better clinical judgment than their more senior colleagues and graduates of European and Asian medical schools . Most primary care physicians in northern Israel treat group A b-hemolytic streptococcal pharyngitis as recommended in the medical literature . The level of medical studies in Israel and the Americas and the quality of training of residents in family medicine and pediatrics, have a positive influence on the degree of knowledge of as common a subject as b-hemolytic streptococcal pharyngitis . Emphasis should be placed on continuing medical education among primary care physicians, particularly veteran general physicians and those who studied in European or Asian medical schools.

Pediatr Neurol, 2000 May, 22(5), 380 - 3
Infection: a stimulus for tic disorders; Singer HS et al.; The object of this study was to investigate the potential association of infections, especially group A hemolytic streptococcal infection, with the abrupt onset/exacerbation of tics or obsessive-compulsive behaviors . A structured clinical interview was used to evaluate 80 consecutive children, 5-17 years of age, with a diagnosis of tic disorder . Forty-two patients (53%) described a sudden, explosive onset or worsening of tic symptoms; 15 of these 42 had their exacerbation historically associated with an infection, nine of the 15 specifically with a streptococcal infection . Comparisons between those nine individuals and the remainder of the study population are presented . The results of this study reveal that descriptions of an abrupt tic onset or exacerbation are not uncommon in children with tic disorders; approximately 11% of children with tic disorders described abrupt changes of tic behavior within a 6-week period after a streptococcal infection.

Acta Paediatr Taiwan, 1999 Mar-Apr, 40(2), 83 - 6
Group B Streptococcal infection in neonates: an 11-year review; Ho MY et al.; Group B Streptococcal (GBS) infection is an important cause of infant morbidity and mortality . The purpose of this study is to evaluate the incidence, clinical characteristics, mortality and complications of this infection . From 1985 through 1995, 66 infants with early onset disease (EOD) and 23 infants with late onset disease (LOD) were treated at Mackay Memorial Hospital (MMH) . The occurrence rate of EOD was 3.26-10.08/1000 admissions . The incidence of the disease was 0.11-1.39/1000 live births . Of the 66 EOD infants, 24 (36%) were preterm infants . There were 33 (50%) infants in EOD category with respiratory distress and 40 (60%) infants with sepsis . Among the 23 LOD infants, 3 (13%) were preterm infants . There were 6 (13%) infants in LOD category with respiratory distress and 16 (69%) with sepsis . Nine (13%) EOD infants and 14 (60%) LOD infants had meningitis . Leukopenia occurred in 24 (36%) EOD infants and 5 (21%) LOD infants . Twelve (18%) EOD infants and 9 (39%) LOD infants had a history of prolonged rupture of membrane (PROM) . The mortality rate was 14% in EOD and 4% in LOD infants . Four (17%) LOD infants developed neurological seguelae . Clinically, EOD infants were often premature and prone to develop sepsis, respiratory distress and leukopenia, while LOD often presented with meningitis and sepsis . Our estimated occurrence rate and incidence of EOD were similar to the European estimates . The influence of prenatal measures on EOD and the meaning of PROM on LOD need further evaluation.

Curr Opin Rheumatol, 2000 Jul, 12(4), 306 - 10
Poststreptococcal reactive arthritis; Ayoub EM et al.; The occurrence of an entity designated poststreptococcal reactive arthritis (PSReA) has been highlighted in recent reports . The syndrome was considered part of the spectrum of acute rheumatic fever by some, whereas others stressed the differences between the two diseases . As distinct from acute rheumatic fever, PSReA is characterized by a shorter latency period between the inciting streptococcal infection and the onset of arthritis, a higher frequency of involvement of the small joints and axial skeleton, poor response to aspirin and other nonsteroidal anti-inflammatory drugs, a protracted course of arthritis, a low incidence of carditis, and absence of other major manifestations of acute rheumatic fever . Recent studies have demonstrated an increased frequency of DRB1*01 in patients with PSReA, which contrasts with the increased frequency of DRB1*16 in rheumatic fever . Because 6% of patients with PSReA have been reported to have late onset carditis, it is judicious to recommend that patients with PSReA receive prophylactic antimicrobials for a minimum period of 5 years or until the age of 21 years, whichever is longer.

J Biotechnol, 2000 Jun 23, 80(2), 169 - 78
Stability towards alkaline conditions can be engineered into a protein ligand; Gulich S et al.; One of the problems with a proteinaceous affinity ligand is their sensitivity to alkaline conditions . Here, we show that a simple and straightforward strategy consisting in replacing all asparagine residues with other amino acids can dramatically improve the chemical stability of a protein towards alkaline conditions . As a model, a Streptococcal albumin-binding domain (ABD) was used . The engineered variant showed higher stability towards 0.5 M NaOH, as well as higher thermal stability compared to its native counterpart . This protein engineering approach could potentially also be used for other protein ligands to eliminate the sensitivity to alkaline cleaning-in-place (CIP) conditions.

J Clin Invest, 2000 Jul, 106(2), 217 - 24
Cytotoxic mAb from rheumatic carditis recognizes heart valves and laminin; Galvin JE et al.; Anti-streptococcal antibodies cross-reactive with N-acetyl-betaD-glucosamine (GlcNAc) and myosin are present in the sera of patients with rheumatic fever (RF) . However, their role in tissue injury is not clear . In this study, we show that anti-GlcNAc/anti-myosin mAb 3.B6 from a rheumatic carditis patient was cytotoxic for human endothelial cell lines and reacted with human valvular endothelium and underlying basement membrane . Reactivity of mAb 3.B6 with the valve was inhibited by human cardiac myosin > laminin > GlcNAc . The mAb 3.B6 epitopes were localized in fragments of human cardiac myosin, including heavy meromyosin (HMM), the S1 subfragment, and two light meromyosin (LMM) peptides containing amino acid sequences KEALISSLTRGKLTYTQQ (LMM 1) and SERVQLLHSQNTSLINQK (LMM 33) . A novel feature of mAb 3.B6 was its reactivity with the extracellular matrix protein laminin, which may explain its reactivity with the valve surface . A laminin A-chain peptide (HTQNT) that includes homology to LMM33 inhibited the reactivity of mAb 3.B6 with human valve . These data support the hypothesis that cross-reactive antibodies in rheumatic carditis cause injury at the endothelium and underlying matrix of the valve.

Infect Immun, 2000 Aug, 68(8), 4407 - 15
Identification of a novel gene cluster encoding staphylococcal exotoxin-like proteins: characterization of the prototypic gene and its protein product, SET1; Williams RJ et al.; We report the discovery of a novel genetic locus within Staphylococcus aureus that encodes a cluster of at least five exotoxin-like proteins . Designated the staphylococcal exotoxin-like genes 1 to 5 (set1 to set5), these open reading frames have between 38 and 53% homology to each other . All five proteins contain consensus sequences that are found in staphylococcal and streptococcal exotoxins and toxic shock syndrome toxin 1 (TSST-1) . However, the SETs have only limited overall sequence homology to the enterotoxins and TSST-1 and thus represent a novel family of exotoxin-like proteins . The prototypic gene in this cluster, set1, has been cloned and expressed . Recombinant SET1 stimulated the production of interleukin-1beta, interleukin-6, and tumor necrosis factor alpha by human peripheral blood mononuclear cells . PCR analysis revealed that set1 was distributed among other strains of S . aureus but not in the other staphylococcal species examined . Sequence analysis of the set1 genes from different strains revealed at least three allelic variants . The protein products of these allelic variants displayed a 100-fold difference in their cytokine-inducing potency . The distribution of allelic variants of the set genes among strains of S . aureus may contribute to differences in the pathogenic potential of this bacterium.

Proteins . 2000 Sep 1;40(4):675.
Characterization of the active site of group B streptococcal hyaluronan lyase
Pritchard DG, Trent JO, Li X, Zhang P, Egan ML, Baker JR.
Xin Li was inadvertently dropped from the list of authors for this article . The authors regret this error.

J Surg Res, 2000 Aug, 92(2), 276 - 82
Impaired Kupffer cell function and effect of immunotherapy in obstructive jaundice; Tomioka M et al.; BACKGROUND: Obstructive jaundice is frequently associated with septic complications . This study examined the influence of biliary obstruction on bacterial clearance and translocation . The study focused on the phagocytic and killing activities of Kupffer cells and the preventive effect on bacterial translocation of OK-432, which is a hemolytic streptococcal preparation developed as a biological response modifier . METHODS: To study the mechanism of sepsis in obstructive jaundice, two groups of Wistar rats were examined: rats subjected to common bile duct ligation (CBDL) and rats subjected to a sham operation . Bacterial clearance, organ distribution, hepatic blood flow, and phagocytic function of Kupffer cells were examined . To evaluate the effect of OK-432 on bacterial translocation, rats were divided into three groups: sham operation + phosphate-buffered saline (PBS), CBDL + PBS, and CBDL + OK-432 . RESULTS: In this study, clearance of Escherichia coli . from the peripheral blood in CBDL rats was decreased significantly compared with that in sham-operated rats . Significant decreases in E.coli trapped in the liver and in hepatic blood flow were observed in CBDL rats compared with sham-operated rats . Phagocytic activity and superoxide production of Kupffer cells isolated from CBDL rats were significantly lower than in sham-operated rats . The incidence of bacterial translocation in CBDL rats was increased significantly, and oral administration of OK-432 prevented it . CONCLUSION: The results suggest that susceptibility to infection in obstructive jaundice is due to impaired phagocytic function of Kupffer cells . Furthermore, obstructive jaundice promotes bacterial translocation, and OK-432 may be useful in preventing this translocation .

Protein Sci, 2000 Jun, 9(6), 1177 - 93
The role of backbone conformational heat capacity in protein stability: temperature dependent dynamics of the B1 domain of Streptococcal protein G; Seewald MJ et al.; The contributions of backbone NH group dynamics to the conformational heat capacity of the B1 domain of Streptococcal protein G have been estimated from the temperature dependence of 15N NMR-derived order parameters . Longitudinal (R1) and transverse (R2) relaxation rates, transverse cross-relaxation rates (eta(xy)), and steady state {1H}-15N nuclear Overhauser effects were measured at temperatures of 0, 10, 20, 30, 40, and 50 degrees C for 89-100% of the backbone secondary amide nitrogen nuclei in the B1 domain . The ratio R2/eta(xy) was used to identify nuclei for which conformational exchange makes a significant contribution to R2 . Relaxation data were fit to the extended model-free dynamics formalism, incorporating an axially symmetric molecular rotational diffusion tensor . The temperature dependence of the order parameter (S2) was used to calculate the contribution of each NH group to conformational heat capacity (Cp) and a characteristic temperature (T*), representing the density of conformational energy states accessible to each NH group . The heat capacities of the secondary structure regions of the B1 domain are significantly higher than those of comparable regions of other proteins, whereas the heat capacities of less structured regions are similar to those in other proteins . The higher local heat capacities are estimated to contribute up to approximately 0.8 kJ/mol K to the total heat capacity of the B1 domain, without which the denaturation temperature would be approximately 9 degrees C lower (78 degrees C rather than 87 degrees C) . Thus, variation of backbone conformational heat capacity of native proteins may be a novel mechanism that contributes to high temperature stabilization of proteins.

J Infect Dis, 2000 Jul, 182(1), 168 - 73 Epub 2000 Jun 29.
Invasive disease due to group B streptococcal infection in adults: results from a Canadian, population-based, active laboratory surveillance study--1996 . Sentinel Health Unit Surveillance System Site Coordinators; Tyrrell GJ et al.; In 1996, a population-based surveillance program for invasive adult group B streptococcal (GBS) diseases in Canada was undertaken, to define the epidemiologic and microbiologic characteristics of the disease . Nine public health units across Canada, representing 9.6% of the population, participated in the program . In total, 106 culture-positive cases of invasive adult GBS disease were reported, which represented an incidence rate 4.6 per 100,000 adults (41/100, 000 for pregnant and 4.1/100,000 for nonpregnant adults) . Sixty-two (58.5%) of the 106 cases occurred in females, and, of these, 15 (14 . 2%) were associated with pregnancy . Serotype V was the most common, accounting for 31% of the 90 GBS isolates typed (26.7% of nonpregnant and 4.4% of pregnant cases) . This was followed by serotypes III (19%), Ia (17%), Ib (10%), II (9%), and VII (1%) . Thirteen percent were nontypeable . All isolates were susceptible to penicillin, ampicillin, and vancomycin . Resistance to erythromycin and clindamycin was 6.7% and 4.4%, respectively.

Int Immunol, 2000 Jul, 12(7), 1063 - 74
Molecular evidence for antigen-driven immune responses in cardiac lesions of rheumatic heart disease patients; Guilherme L et al.; Rheumatic heart disease (RHD) is a sequel of post-streptococcal throat infection . Molecular mimicry between streptococcal and heart components has been proposed as the triggering factor of the disease, and CD4(+) T cells have been found predominantly at pathological sites in the heart of RHD patients . These infiltrating T cells are able to recognize streptococcal M protein peptides, involving mainly 1-25, 81-103 and 163-177 N-terminal amino acids residues . In the present work we focused on the TCR beta chain family (TCR BV) usage and the degree of clonality assessed by beta chain complementarity-determining region (CDR)-3 length analysis . We have shown that in chronic RHD patients, TCR BV usage in peripheral blood mononuclear cells (PBMC) paired with heart-infiltrating T cell lines (HIL) is not suggestive of a superantigen effect . Oligoclonal T cell expansions were more frequently observed in HIL than in PBMC . Some major BV expansions were shared between the mitral valve (Miv) and left atrium (LA) T cell lines, but an in-depth analysis of BJ segments usage in these shared expansions as well as nucleotide sequencing of the CDR3 regions suggested that different antigenic peptides could be predominantly recognized in the Miv and the myocardium . Since different antigenic proteins probably are constitutively represented in myocardium and valvular tissue, these findings could suggest a differential epitope recognition at the two lesional heart sites after a common initial bacterial challenge.

Clin Infect Dis, 2000 Jun, 30(6), 961 - 2
Kallikrein-kinin system activation in streptococcal toxic shock syndrome; Sriskandan S et al.; A retrospective analysis of 7 patients with streptococcal toxic shock revealed isolated prolongation of the activated partial thromboplastin time, which returned to normal during recovery . Levels of factor XII were reduced in 2 patients who had single factor assays performed, consistent with activation of the kallikrein-kinin system . We speculate that bradykinin release following activation of the kallikrein-kinin system in streptococcal toxic shock may underlie the features of pain, capillary leaking, and severe hypotension characteristic of this syndrome.

J Perinatol, 2000 Jun, 20(4), 262 - 4
Secondary infection presenting as recurrent pulmonary hypertension; Hintz SR et al.; Primary infection in the neonate, especially group B streptococcal infection, has long been recognized as a cause of persistent pulmonary hypertension of the newborn (PPHN), sometimes requiring treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO) . However, secondary nosocomial infections in the neonatal period have not been widely reported as a cause of severe recurrent pulmonary hypertension (PHTN) . We now present two cases of secondary infection in the neonate leading to significant PHTN . In both cases, the infants presented with PPHN soon after birth, requiring transfer to a level 3 neonatal intensive care unit and treatment with high-frequency oscillatory ventilation and iNO . After successful resolution of the initial PPHN, including extubation to nasal cannula, both infants developed signs of severe recurrent PHTN, leading to reintubation, high-frequency oscillatory ventilation and iNO therapy, and consideration of ECMO . In both cases, blood cultures taken at the time of recurrence of PHTN returned positive, one for Staphylococcus epidermidis, the other for methicillin-resistant Staphylococcus aureus . These unusual cases present the possibility of severe recurrent PHTN requiring iNO or ECMO in the setting of secondary infection . We speculate that these infants, although extubated after their first episodes of PHTN, were at risk for recurrence of PHTN due to continued pulmonary vascular reactivity.

Indian J Pediatr, 2000 Apr, 67(4), 283 - 6
Diagnosis of rheumatic fever: current status of Jones Criteria and role of echocardiography; Saxena A; The original Jones Criteria as proposed by Dr . T . Duckett Jones have been modified four times and the updated revised criteria were published in 1992 . According to this latest publication major manifestations are carditis, polyarthritis, chorea, erythema marginatum and subcutaneous nodules . Minor manifestations include fever, arthralgia and laboratory findings of elevated erythrocyte sedimentation rate, C-reactive protein and prolonged PR interval on ECG . For making a diagnosis of acute rheumatic fever, two major, or one major and two minor manifestations must be accompanied by supporting evidence of antecedent group A streptococcal infection in the form of positive throat culture or elevated or rising anti-streptolysin titre . The updated guidelines also highlighted a subgroup of "exceptions to Jones Criteria" for patients with chorea, indolent carditis and previous history of rheumatic fever or "rheumatic heart disease" . Role of echocardiography has not been defined in these modifications but may be important, as clinical detection of soft murmurs may be difficult due to tachycardia . Doppler and color flow mapping is more sensitive in picking up minor digress of valvular regurgitation . Several studies have confirmed that the yield of carditis with valvular regurgitation increased with use of echocardiography in patients with acute rheumatic fever . Also echocardiography is of great help in mixed valve lesions to determine the severity of each lesion . Other abnormalities detected on echocardiography in acute carditis include prolapse of the valve, focal nodular thickening of leaflets and pericardial effusion . Jones Criteria are guidelines to assist the physician and should not be substituted for clinical judgement as strictly following them may result in underdiagnosis of this disease in our country.

Pediatr Infect Dis J, 2000 Jun, 19(6), 569 - 70
Convenient schedules and short course treatment of acute streptococcal pharyngitis; Tanz RR; A number of options exist for reducing the frequency of antibiotic dosing and shortening the course of treatment of GAS pharyngitis . All oral agents are more costly than oral penicillin and have a broader spectrum of antimicrobial activity . These issues must be weighed against the convenience of these treatment regimens . At this time penicillin remains the drug of choice for acute streptococcal pharyngitis . Oral penicillin V can be given twice daily for 10 days . Intramuscular benzathine penicillin is inexpensive and obviates any concerns about compliance . For penicillin-allergic patients, twice daily erythromycin for 10 days is preferred but azithromycin once a day for 5 days is a reasonable (but expensive) alternative.

Am J Obstet Gynecol, 2000 Jun, 182(6), 1344 - 54
Prevention of early-onset invasive neonatal group B streptococcal disease in a private hospital setting: the superiority of culture-based protocols; Main EK et al.; OBJECTIVE: In a large private tertiary care hospital we compared the two different approaches to group B streptococcal screening and intrapartum chemoprophylaxis suggested by The American College of Obstetricians and Gynecologists, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention: risk factor-based protocol and culture-based protocol . STUDY DESIGN: A 2-year baseline period was followed by sequential prospective observational studies of the impacts of two different group B streptococcal management protocols, 3 years with the risk-based approach and 2 years with the culture-based approach of universal screening at 35 to 37 weeks' gestation . RESULTS: During the baseline period the rate of early-onset group B streptococcal infection was 1 . 1 cases per 1000 births (n = 8 cases per 6829 births) . With the risk-based strategy the rate was also 1.1 cases per 1000 births (15 cases/13,270 births) . After we switched to the culture-based protocol for 2 years, there were no cases of early-onset group B streptococcal infections among 9304 births (P =.001; chi(2) = 10.9) . There were no increases in other early-onset infections or in antibiotic resistance . CONCLUSIONS: In our setting, which included good prenatal care and good communication between laboratories and the hospital, the approach based on maternal culture at 35 to 37 weeks' gestation and treatment during labor of all patients with positive results significantly reduced early-onset group B streptococcal infections without increasing infections from resistant organisms.

Int Arch Allergy Immunol, 2000 May, 122(1), 76 - 84
Dexamethasone and cyclosporin A affect the maturation of monocyte-derived dendritic cells differently; Manome H et al.; In contrast to the confirmed effects of glucocorticoids (GCs) and cyclosporin A (CyA) on T cells, the effects of both agents on antigen-presenting cells (APCs), especially on dendritic cells (DCs), are still poorly understood . In this study, we cultured monocyte-derived DCs (MoDCs) under a variety of stimulations in the presence or absence of these immunosuppressants and compared their effects on the activation of MoDCs by these stimulations . The stimulations used were the following: three bacterial toxins, including lipopolysaccharide (LPS), staphylococcal enterotoxin A (SEA) and streptococcal pyrogenic exotoxin A (SPEA), the combination of IL-1beta and TNF-alpha, and an agonistic anti-CD40 antibody . All of these stimulations increased the expression of CD54, CD83, CD86, and HLA-DR antigen, and the production of TNF-alpha in MoDCs . When MoDCs were treated with dexamethasone (Dex) during the stimulation, Dex significantly suppressed the augmentation of CD86 expression and TNF-alpha production induced by all of these stimulations . In contrast, when MoDCs were treated with CyA, it inhibited only the effects induced by the superantigens, SEA and SPEA, but not that induced by LPS, the combination of cytokines, or anti-CD40 antibody . The augmentation of CD54 or HLA-DR antigen expression was not significantly suppressed by either Dex or by CyA . When we used MoDCs pretreated with each of these stimulations + Dex or + CyA as APCs, however, significant suppression of T cell proliferation was observed only in the case of the pretreatment with IL-1beta/TNF-alpha + Dex . The allogeneic T cell stimulation by MoDCs pretreated with the other combinations did not significantly differ from that treated with the stimulation alone . Our present study succeeded in demonstrating a clear difference between Dex and CyA in the activation of MoDCs . These differences may induce a significant difference in their final immunological responses .

Med J Aust, 2000 Apr 3, 172(7), 317 - 20
Prevention of perinatal group B streptococcal disease: screening practice in public hospitals in Victoria; Connellan M et al.; OBJECTIVES: To survey clinical protocols for prevention of early-onset group B streptococcal disease (EOGBSD) of the newborn in public maternity hospitals . DESIGN: Postal questionnaire with telephone follow-up when required . SETTING: All hospitals that undertook deliveries in public patients in the State of Victoria, November 1997 to January 1998 . RESULTS: The survey was sent to 84 hospitals: 71 responded and 64 met the criteria and provided usable data (76% response rate) . These 64 represented 42,784 births (68% of births in Victoria in 1996) . Most hospitals (62; 97%) undertook actions that would identify and treat pregnant women at risk of EOGBSD . 48 (75%) performed bacteriological screening for maternal GBS carriage, but only 20 of these had a unified protocol . Screening was mostly by low vaginal swab (15 hospitals) and before 30 weeks' gestation (12 hospitals) . Low vaginal swab plus anal swab was used in only one hospital . Bacteriological screening was significantly more common in metropolitan hospitals than in rural hospitals (100% versus 67%; P = 0.007, Fisher's exact test) . Targeting of prophylaxis by recognised risk factors was reported by 59 (92%) hospitals, 45 of which also undertook screening . There was considerable variation in the specific risk factors used . CONCLUSIONS: While there was clearly widespread awareness of EOGBSD in Victorian public hospitals, prevention programs varied considerably . The development of consensus practice guidelines might improve EOGBSD prevention, reducing morbidity, mortality and costs.

J Invest Dermatol, 2000 Jun, 114(6), 1180 - 3
Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism; Kaluza W et al.; Genes encoded on chromosome 6 within the major histocompatibility complex region are thought to play an important role in the pathogenesis of psoriasis . A potential candidate gene is tumor necrosis factor alpha . The tumor necrosis factor alpha promoter contains several polymorphisms including two G-->A transitions at position -308 and -238, which are the most common in Caucasian populations . The TNF238.2 (-238A) allele has been strongly associated with psoriasis . We have investigated the effect of the -238 and -308 variants on transcription of the tumor necrosis factor alpha gene in luciferase reporter gene assays . In addition, peripheral blood mononuclear cells of 47 patients with psoriasis and 43 controls were stimulated with different antigens and mitogens (streptococcal sonicate and superantigen, lipopolysaccharide, phorbol-12-myristate, phytohemagglutinin, CD3 antibodies) and tumor necrosis factor alpha production was measured in supernatants by enzyme-linked immunosorbent assay . The psoriasis-associated tumor necrosis factor alpha promoter allele TNF238.2 showed a significantly decreased transcriptional activity . Peripheral blood mononuclear cells carrying this allele produced significantly less tumor necrosis factor alpha after stimulation with T cell mitogens and streptococcal antigens in comparison to controls . The promoter allele TNF238.2 seems to influence tumor necrosis factor alpha production; a possible role in the pathogenesis of psoriasis has to be further evaluated.

APMIS, 2000 Apr, 108(4), 303 - 12
Emm gene polymorphism among temporally clustered group A streptococcal isolates in western Norway; Mylvaganam H et al.; Nineteen group A streptococcal isolates obtained in western Norway from patients with invasive disease during a period of high morbidity and mortality were examined for clonality and emm gene polymorphism . These isolates belonged to the prevalent serotypes during the outbreak, namely T1, T3 or T6 . Restriction fragment length polymorphism and sequencing of the emm genes were used to compare these isolates with 14 isolates of the same serotype but from non-invasive infections . The restriction analysis did not identify specific invasive clones . The emm genes in three of the four T3 isolates from invasive disease had nucleotide substitutions inducing a charge difference in the N-terminal part of the M protein . The 4 T6 isolates had a longer emm amplicon when compared to 15 isolates from superficial infections and also showed nucleotide substitutions that could induce conformational changes in the hypervariable end of the M protein . Restriction analysis of the emm amplicon of the T6 isolates in order to estimate the number of A- and C-repeats is described . The emm gene sequence served as an epidemiological marker within the serotypes T3 and T6, but the significance of the emm polymorphism displayed by the isolates from invasive disease is uncertain at this stage.

Indian J Pediatr, 2000 Mar, 67(3), 163 - 7
Prophylactic efficiency of 3-weekly benzathine penicillin G in rheumatic fever; Oran B et al.; Benzathine penicillin G (BPG) is effective for secondary prophylaxis of rheumatic fever (RF) . However, interval between injections a remains a controversial matter . In a study population of 74 patients, following the initial diagnosis of RF, 3-weekly BPG (1.2 million units) regimen was started . During the first three-week period, serum penicillin concentrations were examined on the 7th, 14th and 21st days and throat culture done for group-A b hemolytic streptococcal (GABHS) infection . Ten patients (13.5%) at 21st day of injection had low serum penicillin concentration after the first BPG . GABHS was isolated in 5 patients during this period . Although two of these 5 patients had symptoms of respiratory tract infection, according to laboratory data, the other three were accepted as carriers . All 74 patients were then followed-up for rheumatic recurrence (RR) during long-term period (6 to 60 months, mean 25 +/- 5 months) . There was no RR among regular (missing no more than one injection a year) group . We concluded that 3-weekly BPG regimen was satisfactory for secondary prophylaxis in RF, even though serum penicillin level was inadequate during the third week in some of the patients.

Neuropediatrics, 2000 Apr, 31(2), 70 - 4
Unilateral involuntary movement associated with streptococcal infection: neurophysiological investigation; Maegaki Y et al.; Two boys developed rhythmic involuntary movements in the extremities on one side of the body after febrile illness . They also showed behavioral disturbances . In both patients, serum antistreptolysin-O and antistreptokinase titers were elevated in acute illness and decreased a few months later . One patient showed tremorous movement, and the other choreiform movement . In the former, a surface EMG showed short-duration (30 to 60 ms), highly frequent (6 to 8 Hz) and synchronous discharges of multiple muscles, including the antagonists, suggesting myoclonic jerk . In the latter, a surface EMG showed long-duration (0.5 to 1 s), repetitive (about 0.5 Hz) and synchronous or asynchronous discharges of the antagonists, suggesting choreoathetosis . In both patients, giant somatosensory evoked potentials and high-voltage slow EEG activities were observed predominantly in the hemisphere contralateral to the involuntary movement . In the myoclonic patient, long-latency EMG responses were enhanced and cortical potentials preceding the myoclonus were present by jerk-locked back averaging technique . The present data suggest that unilateral rhythmic involuntary movements occur secondary to streptococcal infection . The pathophysiology of the involuntary movements may be associated with sensorimotor cortex hyperexcitability.

Indian J Pediatr, 1996 Jul-Aug, 63(4), 437 - 40
Streptococcal pharyngitis: is penicillin still the drug of choice?
Rajesh KR, Gordon RC.
With the advent of cephalosporins, penicillin appears to have lost some ground for treatment of Acute Group A Beta Hemolytic Streptococcal Pharyngitis . It has been argued for some time now whether penicillin should remain the drug of choice for the management of this infection . Evidence has been presented both in favour and against using penicillin for Group A beta hemolytic streptococcal (GABHS) pharyngotonsillitis . In this commentary, we review the available data in the current literature and conclude that penicillin should still remain the drug of first consideration for GABHS pharyngitis . If penicillin treatments were less effective now, the clinical and bacteriologic failure rates should be on the rise compared to the previous years.

Asia Pac J Public Health, 1999, 11(1), 26 - 9
Rapid streptococcal testing in Vietnamese children with pharyngitis; Finger R et al.; Streptococcal pharyngitis has been a significant public health problem in Vietnam for many years . Accurate diagnosis of the infection, however, has been difficult . We carried out a clinical trial of a rapid streptococcal antigen detection test (Quick-Vue (R) Flex Strep A) on a population of 777 children with pharyngitis seen at the Institute for the Protection of Children's Health (Children's Hospital) in Hanoi, Vietnam . Bacterial culture was performed in parallel with the rapid test on simultaneously obtained throat swab specimens . The rapid test was found to be 89% sensitive and 92% specific (96% in children not on prior antibiotics) compared to culture . The test was also found to be convenient and acceptable to patients and clinicians . A significant benefit of the test is that those children found positive are more likely to be treated with penicillin rather than a broad spectrum antimicrobial, which in turn will reduce the likelihood of resistant infections in the future.

Biochemistry, 2000 May 30, 39(21), 6564 - 71
Role of side-chains in the cooperative beta-hairpin folding of the short C-terminal fragment derived from streptococcal protein G; Kobayashi N et al.; A short C-terminal fragment of immunoglobulin-binding domain of streptococcal protein G is known to form nativelike beta-hairpin at physiological conditions . To understand the cooperative folding of the short peptide, eight Ala-substituted mutants of the fragment were investigated with respect to their structural stabilities by analyzing temperature dependence of NMR signals . On comparison of the obtained thermodynamic parameters, we found that the nonpolar residues Tyr45 and Phe52 and the polar residues Asp46 and Thr49 are crucial for the beta-hairpin folding . The results suggest a strong interaction between the nonpolar side chains that participates in a putative hydrophobic cluster and that the polar side chains form a fairly rigid conformation around the loop (46-51) . We also investigated the complex formation of the mutants with N-terminal fragment at the variety of temperature to get their thermal unfolding profiles and found that the mutations on the residues Asp46 and Thr49 largely destabilized the complexes, while substitution of Asp47 slightly stabilized the complex . From these results, we deduced that both the hydrophobic cluster formation and the rigidity of the loop (46-51) cooperatively stabilize the beta-hairpin structure of the fragment . These interactions which form a stable beta-hairpin may be the initial structural scaffold which is important in the early folding events of the whole domain.

Clin Infect Dis, 1999 Apr, 28(4), 800 - 7
Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study . The Canadian Streptococcal Study Group; Kaul R et al.; Twenty-one consecutive patients with streptococcal toxic shock syndrome (TSS) between December 1994 and April 1995 were treated with a median dose of 2 g of intravenous immunoglobulin (IVIG)/kg (cases) and were compared with 32 patients with streptococcal TSS between 1992 and 1995 who did not receive IVIG therapy (controls) . The outcome measure was 30-day survival . Patient plasma was tested for its ability to inhibit T cell activation induced by the infecting strain . The proportion of cases with 30-day survival was higher than that of the controls with 30-day survival (67% vs . 34%, respectively; P = .02) . Multivariate analysis revealed that IVIG administration and a lower Acute Physiology and Chronic Health Evaluation II score were associated with survival; the odds ratio for survival associated with IVIG therapy was 8.1 (95% confidence interval, 1.6-45; P = .009) . IVIG therapy enhanced the ability of patient plasma to neutralize bacterial mitogenicity and reduced T cell production of interleukin-6 and tumor necrosis factor alpha . IVIG may be an effective adjunctive therapy for streptococcal TSS, possibly because of its ability to neutralize bacterial exotoxins.

Crit Care Med, 2000 Apr, 28(4), 1210 - 6
Use of recruitment maneuvers and high-positive end-expiratory pressure in a patient with acute respiratory distress syndrome; Medoff BD et al.; OBJECTIVE: To present the use of a novel high-pressure recruitment maneuver followed by high levels of positive end-expiratory pressure in a patient with the acute respiratory distress syndrome (ARDS) . DESIGN: Observations in one patient . SETTING: The medical intensive care unit at a tertiary care university teaching hospital . PATIENT: A 32-yr-old woman with severe ARDS secondary to streptococcal sepsis . INTERVENTIONS: The patient had severe gas exchange abnormalities because of acute lung injury and marked lung collapse . Attempts to optimize recruitment based on the inflation pressure-volume (PV) curve were not sufficient to avoid dependent lung collapse . We used a recruitment maneuver using 40 cm H2O of positive end-expiratory pressure (PEEP) and 20 cm H2O of pressure controlled ventilation above PEEP for 2 mins to successfully recruit the lung . The recruitment was maintained with 25 cm H2O of PEEP, which was much higher than the PEEP predicted by the lower inflection point (P(Flex)) of the PV curve . MEASUREMENTS AND MAIN RESULTS: Recruitment was assessed by improvements in oxygenation and by computed tomography of the chest . With the recruitment maneuvers, the patient had a dramatic improvement in gas exchange and we were able to demonstrate nearly complete recruitment of the lung by computed tomography . A PV curve was measured that demonstrated a P(Flex) of 16-18 cm H2O . CONCLUSION: Accumulating data suggest that the maximization and maintenance of lung recruitment may reduce lung parenchymal injury from positive pressure ventilation in ARDS . We demonstrate that in this case PEEP alone was not adequate to recruit the injured lung and that a high-pressure recruitment maneuver was required . After recruitment, high-level PEEP was needed to prevent derecruitment and this level of PEEP was not adequately predicted by the P(Flex) of the PV curve.

Isr Med Assoc J, 2000 Feb, 2(2), 169 - 73
Evaluation of the approach of primary care physicians to the management of streptococcal pharyngotonsillitis . IPROS Network; Erlichman M et al.; BACKGROUND: Streptococcal pharyngotonsillitis remains a common illness in children and can lead to serious complications if left untreated . OBJECTIVE: To evaluate the diagnostic and management approach of a sample of primary care physicians in the largest sick fund in Israel to streptococcal pharyngotonsillitis in children . METHODS: A questionnaire was mailed to all physicians who treat children and are employed by the General Health Services (Kupat Holim Klalit) in the Jerusalem District . The questionnaire included data on demographics, practice type and size, and availability of throat culture and rapid strep test; as well as a description of three hypothetical cases followed by questions relating to their diagnosis and treatment . RESULTS: Of the 188 eligible physicians, 118 (62.5%) responded, including 65 of 89 pediatricians (73%) and 53 of 99 family and general practitioners (53.5%) . Fifty-six physicians (47.4%) had more than 18 years experience, and 82 (70%) completed specialization in Israel . Mean practice size was 950 patients . Fifty-three physicians (43%) worked in Kupat Holim community clinics, 25 (21%) worked independently in private clinics, and 40 (34%) did both . A total of 91 (77%) had access to laboratory facilities for daily throat culture . The time it took for the results to arrive was 48 to 72 hours . For the three clinical scenarios, 90% of the physicians accurately evaluated case A, a 1-year-old with viral pharyngotonsillitis, and 100 (85%) correctly diagnosed case C, a 7-year-old with streptococcal infection . As expected, opinions were divided on case B, a 3-year-old child with uncertain diagnosis . Accordingly, 75 (65.3%) physicians did not recommend treatment for case A, compared to 109 (92.5%) for case C . For case B, 22 (19%) said they would always treat, 43 (36%) would sometimes treat, and 35 (30%) would await the result of the throat culture . For 104 (88%) physicians the antibiotic of choice for case C was penicillin, while only 9 (7.5%) chose amoxicillin . However, the recommended dosage regimens varied from 250 to 500 mg per dose, and from two to four doses daily . For case C, 110 physicians (93%) chose a 10 day duration of treatment . CONCLUSIONS: The primary care physicians in the sample (pediatricians, general practitioners and family physicians) accurately diagnosed viral and streptococcal pharyngotonsillitis . However, there was a lack of uniformity regarding its management in general, and the dosage regimen for penicillin in particular.

Isr Med Assoc J, 2000 Feb, 2(2), 145 - 6
Erythema nodosum in Israeli children; Garty BZ et al.; BACKGROUND: Erythema nodosum, although uncommon in children, is the most frequent form of panniculitis in pediatrics . EN has been associated with various infections and chronic inflammations, and its course varies with age, gender, and racial and geographic factors . There is no information on EN in Israeli children . OBJECTIVES: To examine the clinical course of EN and the conditions with which it is associated in Israeli children . METHODS: We conducted a retrospective study of 24 children with a diagnosis of EN who presented at our Center over a 10 year period (1989-98) . RESULTS: EN was more frequent in females than males (ratio 2:1) due to a cluster of adolescent girls . The mean duration of the skin manifestation was 18 days . The course was benign in all patients . Streptococcal infection was the most common cause (25%), followed by Epstein-Barr virus infection (18%) and inflammatory bowel disease (13%) . In one-third of cases, no specific cause could be identified . Tuberculosis, an important cause of EN in the past, was not found in our patients . CONCLUSIONS: Most cases of EN in Israeli children are related to streptococcal and EBV infections or to chronic inflammatory conditions . Despite the increase in tuberculosis morbidity in Israel during recent years, we found no association of EN and tuberculosis in our study.

Pediatrics . 2000 May;105(5):E60.
Invasive group A streptococcal disease in children and association with varicella-zoster virus infection . Ontario Group A Streptococcal Study Group; Laupland KB et al.; OBJECTIVES: To describe the incidence and clinical features of invasive group A streptococcal (GAS) disease in children in Ontario and determine the risk of invasive GAS infection following chickenpox . METHODS: During 1992-1996, we conducted prospective, active, population-based surveillance for pediatric invasive GAS disease in Ontario, Canada (population: 11 million; 2.5 million children) and reviewed clinical and laboratory records . RESULTS: There were 1.9 cases of invasive GAS disease per 100,000 children per year . Streptococcal toxic shock syndrome (STSS) occurred in 7% of cases and necrotizing fasciitis (NF) in 4% for incidences of.08 and.13 per 100,000 per year, respectively . Case-fatality rates were 56% for STSS, 10% for NF, and 4% overall . The presence of chronic underlying illness other than asthma was associated with death (relative risk {RR}: 11; 95% confidence interval {CI}: 2.4-45) . Fifteen percent of children identified had preceding chickenpox infection, which significantly increased the risk for acquisition of invasive GAS disease (RR: 58; 95% CI: 40-85) . Children with invasive GAS and recent chickenpox were more likely to have NF (RR: 6.3; 95% CI: 1.8-22.3) . CONCLUSIONS: Childhood invasive GAS disease occurs at an incidence similar to the adult population but has a lower rate of STSS and case-fatality . Chickenpox dramatically increases the risk for acquiring invasive GAS disease, and universal chickenpox vaccination could potentially prevent up to 15% of all pediatric invasive GAS disease.

Indian J Pediatr, 1999 Mar-Apr, 66(2), 207 - 14
Asymptomatic hematuria in childhood: a practical approach to evaluation; Wood EG; The differential diagnosis of hematuria with or without proteinuria is extensive, and isolated hematuria is a common problem in children and adolescents . Extensive evaluation is often necessary for the child presenting with macroscopic plus microscopic hematuria including nonglomerular and glomerular etiologies, while children with only isolated microscopic hematuria can generally be followed after baseline evaluation to rule out infection, hypercalciuria, familial hematuria, sickle cell disease, post-streptococcal glomerulonephritis (GN), and structural abnormalities (cysts, stones, obstruction, Wilms tumor) . Children with the combination of hematuria and proteinuria require rapid systematic evaluation, generally including renal biopsy, except in cases where post-streptococcal GN can be clearly documented . Post-streptococcal GN occurs 7-21 days after a streptococcal infection, is associated with an acute fall in C3 levels with return to normal by approximately 8 weeks, rarely causes acute renal failure, and in children has a pattern of gradual resolution of hypertension, hematuria, and proteinuria over a course of 6-12 months.

Indian J Pediatr, 1999 Mar-Apr, 66(2), 199 - 205
Acute glomerulonephritis; Srivastava RN; Acute glomerulonephritis (AGN) manifests with abrupt onset of hematuria, facial edema, hypertension and impairment of renal function . The commonest form of AGN in developing countries is that following a beta hemolytic streptococcal infection where the glomerular injury is mediated by deposition of immune complexes . In the usual patient with moderately severe poststreptococcal AGN (PSAGN) the above-mentioned features are present However, gross or microscopic hematuria may be the only abnormality . A similar picture may occasionally be produced by a variety of infections (when GN is referred to as post-infectious and the mechanism of glomerular damage and the renal histology are similar to that in PSAGN), primary renal glomerular disorders (e.g . membranoproliferative GN, IgA nephropathy), collagen vascular diseases (systemic lupus erythematosus), systemic vasculitis (Henoch Schonlein purpura) and hereditary nephritis and some nonglomerular conditions . PSAGN may also present with one or more of its complications such as profound volume expansion with heart failure and hypertensive encephalopathy . PSAGN resolves rapidly and has an excellent prognosis . Patients with severe renal involvement and life threatening complications need expert supportive management . AGN with associated systemic features or very pronounced azotemia, nonstreptococcal AGN and unresolving GN need prompt, appropriate evaluation that often includes a renal biopsy . If extensive crescentic changes are found (crescentic GN), aggressive immunosuppression will be necessary.

Cochrane Database Syst Rev . 2000;(2):CD001976.
Antistreptococcal interventions for guttate and chronic plaque psoriasis; Owen CM et al.; BACKGROUND: Guttate psoriasis is a distinctive acute form of psoriasis which characteristically occurs in children and young adults . It is closely associated with preceding streptococcal sore throat or tonsillitis . Some authorities have claimed that ordinary (chronic plaque) psoriasis may also be made worse by infection at distant sites . Although many dermatologists have recommended using antibiotics for guttate psoriasis in particular, it is not clear whether they influence the course of either form of psoriasis . Some dermatologists have also recommended tonsillectomy for psoriasis in patients with recurrent streptococcal sore throat . OBJECTIVES: To assess the evidence for effectiveness of antistreptococcal interventions including antibiotics and tonsillectomy in the management of acute guttate and chronic plaque psoriasis . SEARCH STRATEGY: We searched the Cochrane Clinical Trials Register (Cochrane Library, Issue 3, 1999), Medline (1966- September 1999), Embase (1988-September 1999), the Salford Database of Psoriasis Trials (to November 1999) and the European Dermato-Epidemiology Network (EDEN) Psoriasis Trials Database (to November 1999) for terms {STREPTOCOCC* or ANTIBIOTIC* or TONSIL*} and PSORIASIS using the Cochrane Skin Group search strategy . SELECTION CRITERIA: Randomised trials of one or more antistreptococcal interventions in patients with guttate or chronic plaque psoriasis . DATA COLLECTION AND ANALYSIS: Two reviewers independently examined each retrieved trial for eligibility and quality . MAIN RESULTS: The one eligible trial we identified compared the use of two oral antibiotic schedules in 20 psoriasis patients, predominantly of guttate type, who had evidence of beta-haemolytic streptococcal colonisation . Either rifampicin or placebo was added to the end of a standard course of antistreptococcal antibiotic (phenoxymethylpenicillin or erythromycin) . No patient in either arm of the study improved during the observation period . No randomised trials of tonsillectomy for psoriasis were identified . REVIEWER'S CONCLUSIONS: Although it is well known that guttate psoriasis may be precipitated by streptococcal infection, there is no firm evidence to support the use of antibiotics either in the management of established guttate psoriasis or in preventing the development of guttate psoriasis following streptococcal sore throat . Although both antibiotics and tonsillectomy have frequently been advocated for patients with recurrent guttate psoriasis or chronic plaque psoriasis, there is to date no good evidence that either intervention is beneficial.

Clin Exp Immunol, 2000 May, 120(2), 375 - 83
Intra-articular IL-10 gene transfer regulates the expression of collagen-induced arthritis (CIA) in the knee and ipsilateral paw; Lubberts E et al.; We studied the effects of local IL-10 application, introduced by a recombinant human type 5 adenovirus vector, in the mouse knee joint during the early phase of CIA . One intra-articular injection with the IL-10-expressing virus (Ad5E1mIL-10) caused substantial over-expression of IL-10 in the mouse knee joint, using virus dosages which did not induce distracting inflammation . High expression of IL-10 was noted for a few days, being maximal at day 1 . One intra-articular injection of Ad5E1mIL-10 in the knee joints of collagen type II (CII)-immunized mice, before onset of CIA was noted, reduced the incidence of collagen arthritis in that knee . Of high interest, the protective effect of local IL-10 expression by Ad5E1mIL-10 was not restricted to the knee joint alone . The arthritis incidence in the ipsilateral paw was highly suppressed . In contrast, local IL-10 over-expression was not effective when treatment was started after onset of CIA . Further analysis in the acute streptococcal cell wall-induced arthritis model revealed that local IL-10 over-expression markedly suppressed the production of tumour necrosis factor-alpha (TNF-alpha) and IL-1alpha, but had no significant effect on IL-1beta and IL-12 production in the inflamed synovium . These data indicate that local over-expression of IL-10 in the knee joint of mice regulates the expression of collagen arthritis, probably through down-regulation of TNF-alpha.

Psychiatry Res, 2000 Apr 24, 94(1), 43 - 9
Increased anti-streptococcal antibodies in patients with Tourette's syndrome; Muller N et al.; Infection or postinfectious phenomena have been postulated to play a role in the pathogenesis of children afflicted with the typical symptoms of Tourette's syndrome (TS) . We investigated whether an increase of titers of antistreptococcal antibodies can be reproduced in our children with TS, and whether this increase is restricted to children . We examined the titers of two different antistreptococcal antibodies, antistreptolysin (ASL) and anitDNase B, both in children and adults . Titer s of ASO and antiDNase B were measured (1) in 13 children/adolescents suffering from TS and in an aged-matched comparison group;(2) in 23 adult patients, a comparison group of 23 aged-matched controls, and in another group of 17 aged-matched, non-medicated acute schizophrenics . ASO and antiDNase B titers were determined by laser nephelometry using a commercially available kit . Two antistreptococcal cut-off levels were compared (> 250 U/ml and 400 U/ml) . As expected, increases ASO titers (>400 IU/ml) were found in a higher portion of children/adolescents with TS compared to controls . Regarding adults, titers >250 U/ml for both antistreptococcal antigens were found in significantly more TS patients than in schizophrenic patients or healthy control subjects . The mean values of ASO and antiDNase titers were significantly higher in both groups of TS patients compared to control children/adolescents, to the comparison groups of healthy adults and to schizophrenics . No difference in antistreptococcal titers was found between schizophrenics and the group of healthy adults . TS patients exhibited higher antistreptococcal titers than age-matched comparison groups of both children/adolescents and adults using different types of calculation . Our findings support the theory that a postinfectious immune mechanism may play a role in the pathogenesis of TS . The mechanism still needs to be elucidated.

Arch Oral Biol, 2000 Jul, 45(7), 569 - 75
Effects of an anticariogenic casein phosphopeptide on calcium diffusion in streptococcal model dental plaques; Rose RK; Casein phosphopeptides (CPP) stabilize amorphous calcium phosphate (ACP) and may be used to localize ACP in dental plaque, maintaining a state of supersaturation with respect to tooth enamel, reducing demineralization and enhancing remineralization . The aim here was to investigate these effects by measuring the effect of CPP-ACP on calcium diffusion in plaque . Using Dibdin's effusion system, calcium diffusion was measured in streptococcal model plaques . This demonstrated that by providing a large number of possible binding sites for calcium, 0.1% CPP-ACP reduces the calcium diffusion coefficient by about 65% at pH 7 and 35% at pH 5 . Hence, CPP-ACP binds well to plaque, providing a large calcium reservoir within the plaque and slowing diffusion of free calcium . This is likely to restrict mineral loss during a cariogenic episode and provide a potential source of calcium for subsequent remineralization . Overall, once in place, CPP-ACP will restrict the caries process.

J Clin Oncol, 2000 May, 18(9), 1845 - 55
Alpha hemolytic streptococcal infection during intensive treatment for acute myeloid leukemia: a report from the Children's cancer group study CCG-2891; Gamis AS et al.; PURPOSE: Past reports indicate that alpha hemolytic streptococcal (AHS) organisms are a common cause of infection among acute myeloid leukemia (AML) patients . This study was intended to ascertain the population incidence and rate (infections per 100 patient-days of treatment) of AHS and to identify associated risk factors . PATIENTS AND METHODS: Patients (n = 874 with 151,350 days of risk) enrolled on the Children's Cancer Group (CCG) protocol for newly diagnosed AML, CCG-2891, which randomly assigned intensity of induction and intensification, were prospectively evaluated for infectious complications . RESULTS: AHS occurred in 21% of patients, was primarily blood borne (86%), made up 21% of bacteremic infections, and had a recurrent incidence of 31% during subsequent therapy . AHS was more often life-threatening (59%) than other infections (41%) (P = .001) . AHS rates increased with age less than 10 years (odds ratio {OR}, 2.0; P = .007), intensively timed induction (OR, 1.8 to 1.9; P = .02), and high-dose cytarabine intensification (OR, 3.7; P<.0001) . Among all courses, the greatest incidence (19%) and rate (0.41) were associated with the use of high-dose cytarabine . Gastrointestinal toxicity correlated significantly with AHS bacteremia (P<.01) . Infection with AHS resulted in increased hospital days (P =.0001) . Only among bone marrow transplant patients were overall survival (OR, 2.8; P = .0001) and disease-free survival (OR, 2.1; P = .008) decreased after AHS bacteremia . CONCLUSION: This study, the first to prospectively examine AHS incidence among uniformly treated patients in multiple institutions, established that as the intensity of AML therapy has increased, so has the rate of AHS . Young children, those with previous AHS bacteremias, and those receiving high-dose cytarabine are at particularly high risk of AHS bacteremia.

Am J Orthop, 2000 Apr, 29(4), 315 - 9
Massive subperiosteal hemorrhage and femoral shaft osteonecrosis: a complication of tissue plasminogen activator therapy for purpura fulminans; Rodgers WB et al.; We present the case of a child who developed a massive subperiosteal hemorrhage and subsequent osteonecrosis of her right femur after treatment with tissue plasminogen activator for post-varicella streptococcal purpura fulminans . Radiographs showed posteromedial translation of the capital femoral epiphysis on the necrotic shaft, and the hip was immobilized . The femur slowly remodeled and has continued to grow . The child is independently ambulatory with a 2.1-cm leg length discrepancy, a varus deformity of the hip, and a valgus distal femur.

Infect Immun, 2000 May, 68(5), 2880 - 7
Humanized in vivo model for streptococcal impetigo; Scaramuzzino DA et al.; An in vivo model for group A streptococcal (GAS) impetigo was developed, whereby human neonatal foreskin engrafted onto SCID mice was superficially damaged and bacteria were topically applied . Severe infection, indicated by a purulent exudate, could be induced with as few as 1,000 CFU of a virulent strain . Early findings (48 h) showed a loss of stratum corneum and adherence of short chains of gram-positive cocci to the external surface of granular keratinocytes . This was followed by an increasing infiltration of polymorphonuclear leukocytes (neutrophils) of mouse origin, until a thick layer of pus covered an intact epidermis, with massive clumps of cocci accumulated at the outer rim of the pus layer . By 7 days postinoculation, the epidermis was heavily eroded; in some instances, the dermis contained pockets (ulcers) filled with cocci, similar to that observed for ecthyma . Importantly, virulent GAS underwent reproduction, resulting in a net increase in CFU of 20- to 14,000-fold . The majority of emm pattern D strains had a higher gross pathology score than emm pattern A, B, or C (A-C) strains, consistent with epidemiological findings that pattern D strains have a strong tendency to cause impetigo, whereas pattern A-C strains are more likely to cause pharyngitis.

Eur J Oral Sci, 2000 Apr, 108(2), 130 - 5
Superoxide release and superoxide dismutase expression by human gingival fibroblasts; Skaleric U et al.; Oxygen reactive intermediates released from phagocytic cells are important for microbicidal activity, but they may also be harmful to surrounding cells and matrix components at the inflammation site . In different forms of inflammatory periodontal disease, peripheral and crevicular polymorphonuclear leukocytes, as well as mononuclear phagocytes and gingival fibroblasts, are exposed to bacterial cell wall components and cytokines . The aim of this study was to evaluate if some bacterial components and cytokines induce superoxide release and superoxide dismutase (SOD) expression in gingival fibroblasts . Lipopolysaccharide (LPS), streptococcal cell walls (SCW), and formyl-methionyl-leucyl-phenylalanine were found to stimulate O2- release from gingival fibroblasts, which increased when Ca2+ was added . Phorbol myristate acetate, a potent activator of respiratory burst in phagocytes, was found to be a weak stimulator of O2- release in gingival fibroblasts . Of the cytokines tested, tumor necrosis factor (TNF)-alpha was found to activate superoxide release in gingival fibroblasts . Gene expression for manganese superoxide dismutase (MnSOD), but not for copper/zinc superoxide dismutase (CuZnSOD), was demonstrated in fibroblasts exposed to LPS, SCW and TNF-alpha using Northern blot analysis . The production of MnSOD may be protective for these cells . We conclude that bacterial cell wall components and cytokines modulate O2- release by gingival fibroblasts which may contribute to periodontal pathology.

Arch Gen Psychiatry, 2000 Apr, 57(4), 364 - 72
Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders; Peterson BS et al.; BACKGROUND: Previous studies have provided preliminary serological evidence supporting the theory that symptoms of tic disorders or obsessive-compulsive disorder (OCD) may be sequelae of prior streptococcal infection . It is unclear, however, whether previously reported associations with streptococcal infection were obscured by the presence of diagnostic comorbidities . It is also unknown whether streptococcal infection is associated in vivo with anatomical alterations of the brain structures that have been implicated in the pathophysiology of these disorders . METHODS: Antistreptococcal antibody titers were measured in 105 people diagnosed as having CTD, OCD, or attention-deficit/hyperactivity disorder (ADHD) and in 37 community controls without a disorder . Subjects were unselected with regard to their history of streptococcal exposure . Basal ganglia volumes were measured in 113 of these subjects (79 patients and 34 controls) . RESULTS: A DSM-IV diagnosis of ADHD was associated significantly with titers of 2 distinct antistreptococcal antibodies, antistreptolysin O and anti-deoxyribonuclease B . These associations remained significant after controlling for the effects of CTD and OCD comorbidity . No significant association was seen between antibody titers and a diagnosis of either CTD or OCD . When basal ganglia volumes were included in these analyses, the relationships between antibody titers and basal ganglia volumes were significantly different in OCD and ADHD subjects compared with other diagnostic groups . Higher antibody titers in these subjects were associated with larger volumes of the putamen and globus pallidus nuclei . CONCLUSIONS: These findings suggest that the prior reports of an association between antistreptococcal antibodies and either CTD or OCD may have been confounded by the presence of ADHD . They also support the hypothesis that in susceptible persons who have ADHD or OCD, chronic or recurrent streptococcal infections are associated with structural alterations in basal ganglia nuclei.

Curr Opin Pediatr, 2000 Apr, 12(2), 105 - 10
Chemoprophylaxis of early-onset group B streptococcal disease in 1999; Gotoff SP; The evolution of the guidelines for selective intrapartum chemoprophylaxis (SIC) of group B streptococcal early-onset disease is reviewed here . To assess the benefits of the risk-based and culture-based strategies for prevention, observational studies since 1996 are summarized . The effect of chorioamnionitis on group B streptococcal early-onset disease, despite SIC, is emphasized . Optimal management remains controversial, and alternative strategies for the selection of women for chemoprophylaxis and for the management of infants are discussed.

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