The National Institutes of Health: an institute on the move. A conversation with the director of the NIEHS.
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Environmental Exposure↗
Biomedical subjects
David Schwartz
Publications and source records attributed to David Schwartz.
Association between sciatica and microbial infection: true infection or culture contamination?
STUDY DESIGN: Discs were cultured during discectomy from patients with back pain, sciatica, and radiologic evidence of disc herniation causing nerve root compression. OBJECTIVE: To investigate the claim of culpability of bacteria in causing the local inflammatory process seen in patients with disc herniation and radiculopathy. SUMMARY OF BACKGROUND DATA: Bacteria have been cultured from intervertebral discs of patients with sciatica. An infectious etiology for sciatica could have a dramatic effect on treatment options for this common problem. METHODS: To minimize the risk of contamination, the surgeon performed processing and culturing procedures intraoperatively under stringent sterile conditions. Immediately following disc excision, the specimens were divided into 4 pieces, and cultured in various aerobic and anaerobic culture mediums that were incubated for 2 weeks. RESULTS: The 120 specimens from 30 patients underwent bacterial culture growth: 116 were sterile, an 4 aerobic cultures (2 patients) grew coagulase-negative staphylococci, suggestive of contamination. CONCLUSIONS: These results refute the hypothesis that microbial infection plays a role in the pathogenesis of sciatica. It is possible that bacterial growth from discs reported in previous studies was at least partly related to contamination, which we painstakingly avoided by application of rigorous aseptic techniques.
Adult↗
Epitope enhancement of a CD4 HIV epitope toward the development of the next generation HIV vaccine.
Virus-specific CD4+ T cell help and CD8+ cytotoxic T cell responses are critical for maintenance of effective immunity in chronic viral infections. The importance of CD4+ T cells has been documented in HIV infection. To investigate whether a stronger CD4+ T cell response can be induced by modifications to enhance the T1 epitope, the first CD4+ T cell epitope discovered in HIV-1-gp120, we developed a T1-specific CD4+ T cell line from a healthy volunteer immunized with a canarypox vector expressing gp120 and boosted with recombinant gp120. This T1-specific CD4+ T cell line was restricted to DR13, which is common in U.S. Caucasians and African-Americans and very frequent in Africans. Peptides with certain amino acid substitutions in key positions induced enhanced specific CD4+ T cell proliferative responses at lower peptide concentration than the original epitope. This relatively conserved CD4 epitope improved by the epitope enhancement strategy could be a component of a more effective second generation vaccine construct for HIV infection.
AIDS Vaccines↗
Popularity, social acceptance, and aggression in adolescent peer groups: links with academic performance and school attendance.
This article reports a short-term longitudinal study focusing on popularity and social acceptance as predictors of academic engagement for a sample of 342 adolescents (approximate average age of 14). These youths were followed for 4 consecutive semesters. Popularity, social acceptance, and aggression were assessed with a peer nomination inventory, and data on academic engagement were obtained from school records. For adolescents who were highly aggressive, increases in popularity were associated with increases in unexplained absences and decreases in grade point average. Conversely, changes in social acceptance were not predictive of changes in grade point average or unexplained absences. These results highlight the importance of multidimensional conceptualizations of social standing for research on school adjustment during adolescence and emphasize the potential risks associated with popularity.
Achievement↗
Enterococcal bacteraemia: epidemiological, microbiological, clinical and prognostic characteristics, and the impact of high level gentamicin resistance.
Enterococci are increasingly common nosocomial pathogens that can cause serious infections and often acquire antibiotic resistance. This study focused on the epidemiological, microbiological and clinical characteristics of enterococcal bacteraemia with special attention to the impact of high level gentamicin resistance (HLGR) on prognosis. 117 cases of enterococcal bacteraemia constituted 8% of all bacteraemic episodes during the y 2002. The most common source of infection was the urinary tract, more than half of the episodes were polymicrobial and the vast majority of cases was healthcare-associated. 50 of 117 isolates (43%) were resistant to gentamicin. Infection-related mortality (22 of 117, 19%) was associated with 2 independent variables in multivariate analysis: severity-of-illness score (OR=39.6, p<0.00001) and HLGR (OR=6.4, p=0.006). It was concluded that HLGR adversely affects the outcome of bacteraemic enterococcal infection.
Adult↗
Plasmid-mediated imipenem-hydrolyzing enzyme KPC-2 among multiple carbapenem-resistant Escherichia coli clones in Israel.
Carbapenem resistance in Escherichia coli is rare. We report four genetically unrelated carbapenem-resistant E. coli isolates cultured from four patients hospitalized in Tel Aviv Medical Center. PCR, sequencing, and Southern blot analysis identified KPC-2 as the imipenem-hydrolyzing enzyme in all four strains, carried on different plasmids with a possible common origin. This is the first discovery of KPC-2 in E. coli and the first report of this enzyme originating outside the United States.
Carbapenems↗
Clinical and economic impact of bacteremia with extended- spectrum-beta-lactamase-producing Enterobacteriaceae.
We studied outcomes of extended-spectrum beta-lactamase (ESBL) production in Enterobacteriaceae bacteremia. Inpatients with bacteremia caused by ESBL-producing Escherichia coli, Klebsiella spp., or Proteus spp. (cases) were compared with patients with bacteremia caused by non-ESBL producers (controls). Outcomes included mortality, mortality due to infection, length of stay (LOS), delay in appropriate therapy (DAT), discharge to a chronic care facility, and hospital cost. Ninety-nine cases and 99 controls were enrolled. Thirty-five percent of cases died, versus 18% of controls (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3 to 4.7; P=0.01). Thirty percent of cases died due to infection, versus 16% of controls (OR, 2.3; 95% CI, 1.1 to 4.5; P=0.03). The median LOS after bacteremia for cases was 11 days (interquartile range, 5 to 21), versus 5 days for controls (interquartile range, 3 to 9) (P<0.001). DAT occurred in 66% of cases, versus 7% of controls (OR, 25.1; 95% CI, 10.5 to 60.2; P<0.001). Cases were more likely than controls to be discharged to chronic care (52% versus 21%; OR, 4.0; 95% CI, 1.9 to 8.3; P<0.001). The average hospital cost for cases was 65,509 Israeli shekels, versus 23,538 shekels for controls (P<0.001). After adjusting for differences between groups by using multivariable analysis, ESBL production remained a significant predictor of mortality (OR, 3.6; 95% CI, 1.4 to 9.5; P=0.008), increased LOS (1.56-fold; P=0.001), DAT (OR, 25.1; 95% CI, 10.5 to 60.2; P<0.001), and increased cost (1.57-fold; P=0.003). The mean increase in equivalent cost attributable to ESBL production was $9,620. ESBL production was associated with severe adverse outcomes, including higher overall and infection-related mortality, increased LOS, DAT, discharge to chronic care, and higher costs.
Adult↗
Utility of the VITEK 2 Advanced Expert System for identification of extended-spectrum beta-lactamase production in Enterobacter spp.
Forty clinical isolates of Enterobacter spp. were identified as extended-spectrum beta-lactamase (ESBL) producers by disk diffusion. The VITEK 2 Advanced Expert System (AES) identified the ESBL phenotype in only 25 isolates (62.5%), and erroneously reported cephalosporin susceptibility in 11 isolates (28%). Refinements in the AES are required in order to improve ESBL detection in Enterobacter.
Enterobacter↗
Community violence, family conflict, and preschoolers' socioemotional functioning.
This study examined the relations among family conflict, community violence, and young children's socioemotional functioning and explored how children's social cognition and mothers' psychological functioning may mediate the outcomes associated with this exposure. Mothers of 431 Head Start preschoolers completed questionnaires about their family demography, exposure to community violence, family conflict, and children's distress symptoms. Children were administered a social cognition assessment, and teachers rated their behavior. Results showed that mothers' reports of children's co-witnessing of community violence were positively associated with police department crime rates, children's distress symptoms, and teachers' ratings of aggression. A path analysis revealed that children's social awareness and mothers' depressive symptoms partially mediated the effects of community violence and family conflict on outcomes for children.
Adolescent↗
The role of vancomycin in the persistence or recurrence of Staphylococcus aureus bacteraemia.
Persistence and recurrence of Staphylococcus aureus bacteraemia (SAB) have been linked primarily with difficult-to-eradicate foci of infection such as endocarditis, osteomyelitis or abscess formation. Although vancomycin therapy has been suggested as a predictor of relapse of SAB, it has never been shown to be associated with persistent SAB. The purpose of this study was to examine the possible association of vancomycin therapy and persistence of SAB. Two groups of patients were retrospectively studied. One group consisted of 124 patients who completed > or =10 d of appropriate anti-staphylococcal therapy (from among a total of 284 patients with SAB during 2 y, 1997-8). In this group, persistence of SAB (methicillin resistant and susceptible combined) for >3 d while on therapy, occurred in 11 (22%) of 55 vancomycin recipients and in none of 52 cloxacillin recipients (p = 0.002). When calculated for methicillin susceptible SAB alone, the numbers were 3 of 13 vs 0 of 52, respectively (p = 0.007). The second study group included all patients with persistence and/or relapse of SAB while on appropriate anti-staphylococcal therapy during 4 y (1997-2000). In this group, the persistence occurred while on vancomycin therapy, in 32 (94%) of 34 patients with >3 d of persistence of SAB. In the majority of these patients a secondary focus of infection serving as the site of persistence was identified in addition to the primary focus (or portal of entry). It was concluded that vancomycin is inferior to cloxacillin therapy in terminating SAB and therefore may predispose to prolonged bacteraemia and secondary seeding of infection during therapy.
Adult↗
Erythropoietic response to anemia in chronic hepatitis C patients receiving combination pegylated interferon/ribavirin.
OBJECTIVES: In hepatitis C virus (HCV)-infected patients receiving pegylated interferon (PEG-IFN)/ribavirin (RBV) combination therapy, anemia is a well-known side effect. The purpose of this study was to describe the time course and extent of hemoglobin (Hb) changes and the erythropoietic response to PEG-IFN/RBV-induced anemia. METHODS: In this multicenter, observational, 8-wk study, laboratory parameters were measured weekly for 8 wk or until early withdrawal. Primary endpoints included changes in Hb and serum erythropoietin (sEPO) from baseline to week 8; other measures were changes in reticulocytes and RBV dose. The predictive value of baseline factors for maximum Hb decline was assessed. RESULTS: In the 97 evaluable patients, mean Hb decreased from 14.4 +/- 1.4 g/dl (baseline) to 11.9 +/- 1.3 g/dl (week 8). Twenty-one percent of patients withdrew before week 8. The estimated erythropoietic response was lower than that seen in two historic control populations of iron deficiency anemia patients. Mean RBV dose decreased from 986 +/- 190 mg/day (baseline) to 913 +/- 228 mg/day (week 8). Fifty-seven out of 77 (74%) patients who completed the study maintained their initial prescribed RBV dose. Patients maintained on the initial dose of RBV who had a higher baseline Hb and viral load showed a trend toward larger Hb declines. Platelets and white blood cells (WBCs) also declined during the study. CONCLUSIONS: HCV-infected patients receiving PEG-IFN/RBV therapy have reductions in Hb, platelets, and WBCs, possibly due to bone marrow suppression. They also have diminished endogenous sEPO production for their degree of anemia.
Anemia↗
High levels of antimicrobial coresistance among extended-spectrum-beta-lactamase-producing Enterobacteriaceae.
We compared the susceptibility of 312 extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolates with that of 1,216 ESBL nonproducers. Of ESBL producers, 25% were susceptible to gentamicin, 30% to trimethoprim-sulfamethoxazole, 41% to ciprofloxacin, and 60% to piperacillin-tazobactam. ESBL nonproducers were more often susceptible to these agents. ESBL-producing Enterobacteriaceae represent a major source of resistance to various antibiotics.
Cross Infection↗
Evaluation of an accelerated protocol for detection of extended-spectrum beta-lactamase-producing gram-negative bacilli from positive blood cultures.
We evaluated a protocol for the accelerated detection of extended-spectrum beta-lactamases (ESBLs) in gram-negative bloodstream pathogens. Two hundred eighty-three blood culture bottles were subjected to direct ESBL testing by inoculating samples directly from blood culture bottles onto agar plates containing cefotaxime and ceftazidime disks, with and without clavulanate. Standard ESBL testing in accordance with the NCCLS guidelines after subculturing on agar plates was performed in parallel. Results of the direct ESBL testing were reported 2.3 days sooner and were comparable to those of the standard NCCLS method with sensitivity, specificity, and positive and negative predictive values of 100, 98, 94, and 100%, respectively.
Anti-Bacterial Agents↗
Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein.
BACKGROUND: Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus-based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. METHODS: Over the course of 6 months, HIV-1-specific (vCP 205) and rabies (vCP 65) canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. RESULTS: Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1-specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. CONCLUSIONS: Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen.
AIDS Vaccines↗
Right atrial papillary elastoma: an uncommon location.
We present a patient with a right atrial mass, which was detected by transthoracic and transesophageal echocardiography. The patient was asymptomatic on presentation. The mass was subsequently confirmed by gross and microscopic examination to be a papillary fibroelastoma. To the best of our knowledge this is only the fourth such report of this tumor in this location.
Aged↗
The sequence and analysis of Trypanosoma brucei chromosome II.
We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational 'hot' and 'cold' regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.
Animals↗
American Thoracic Society Statement: Occupational contribution to the burden of airway disease.
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Adolescent↗
Mutual antipathies in the peer group as a moderating factor in the association between community violence exposure and psychosocial maladjustment.
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Adjustment Disorders↗