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Biomedical subjects

J D Klausner

Publications and source records attributed to J D Klausner.

35 records · Page 2Linked to original sources
PubMed1999

Thalidomide stimulates T cell responses and interleukin 12 production in HIV-infected patients.

We performed a placebo-controlled study to evaluate the effects of immunomodulatory treatment with thalidomide on HIV levels, TNF-alpha levels, and immune status of 31 HIV-infected individuals, after temporary suppression of viral replication with antiretroviral drugs. Treatment with a combination of zidovudine and lamivudine (ZDV/LMV) for 14 days resulted in a median decline in plasma viremia of 1.94 log10 RNA equivalents/ml. After discontinuation of ZDV/LMV, thalidomide therapy (200 mg/day for 4 weeks) did not retard the prompt return of HIV titers to the pretreatment levels, and had no effect on plasma levels of TNF-alpha. In contrast, thalidomide treatment resulted in significant immune stimulation. We observed increased levels of plasma soluble IL-2 receptor, soluble CD8 antigen, and IL-12 (p < 0.01 for all parameters), as well as increased cutaneous delayed-type hypersensitivity reactions to recall antigens (p < 0.01) in thalidomide-treated patients. These changes were associated with a median increase in HIV titer of 0.2 log10 RNA equivalents/ml in the thalidomide-treated group (p < 0.05), which resolved after stopping the drug. Further studies were performed in vitro to elucidate the mechanism of thalidomide-induced immune stimulation. When purified T cells from HIV-infected individuals were stimulated by immobilized anti-CD3 in the presence of thalidomide, a costimulatory effect of the drug was observed, resulting in increased production of IL-2 and IFN-gamma, and increased T cell-proliferative responses. Further experiments showed that thalidomide increased IL-12 production by antigen-presenting cells in a T cell-dependent manner. Our findings suggest a potential application for thalidomide as a novel immune adjuvant in HIV disease.

Adult↗
PubMed1999

Correlates of gonococcal infection and of antimicrobial-resistant Neisseria gonorrhoeae among female sex workers, Republic of the Philippines, 1996-1997.

From 1994 to 1997, the proportion of Neisseria gonorrhoeae highly resistant to ciprofloxacin (MIC >/=4 microg/mL) increased substantially among female sex workers (FSWs) in the Philippines. Among 1499 Filipina FSWs, we evaluated factors associated with gonococcal infection and with gonococcal antimicrobial resistance. By multivariate analysis, gonococcal infection was associated with sex with a new client, self-prescribed prophylactic antimicrobial use, work in a brothel, and inconsistent condom use and was negatively associated with registration status and vaginal hygiene practices. Factors associated with ciprofloxacin-resistant gonococci included: marital status, living alone, duration of sex work, and clinic site. Further, gonococci highly resistant to ciprofloxacin were isolated from 10 (11.5%) of 87 FSWs reporting self-prescribed antimicrobial use versus 44 (3.4%) of 1295 reporting no antimicrobial use (P<.001). Self-prescribed prophylactic antimicrobial use and inconsistent condom use could be important factors in the continued emergence of gonococcal antimicrobial resistance in the Philippines.

Adult↗
PubMed1999

Outbreak of Stenotrophomonas maltophilia bacteremia among patients undergoing bone marrow transplantation: association with faulty replacement of handwashing soap.

Using molecular typing methods, we confirmed an outbreak of Stenotrophomonas maltophilia among bone marrow transplant patients. The likely source was a healthcare worker who may have washed with moisturizer instead of soap between patients. Hospital epidemiologists need to go beyond antibiograms when evaluating outbreaks and be vigilant about all aspects of hand washing.

Anti-Bacterial Agents↗
PubMed1999

Investigation of a suspected outbreak of vaginal trichomoniasis among female inmates.

BACKGROUND AND OBJECTIVES: Female inmates have high rates of sexually transmitted diseases (STDs), and many incarcerated women and jail providers believe STDs are acquired within the jail. We investigated a suspected outbreak of trichomoniasis among female inmates and described the epidemiology of trichomonas infection. GOALS OF THIS STUDY: To determine the likelihood of within-jail acquisition of trichomoniasis. STUDY DESIGN: Retrospective chart review of gynecologic visits to the jail medical clinic and comparison of trichomoniasis surveillance data over a 6-year time period. RESULTS: The minimum prevalence of trichomoniasis infection among 450 female inmates presenting to the medical clinic for gynecologic evaluation was 37%. Most infections were diagnosed early after incarceration, no woman developed a new infection after adequate treatment, and there was no clustering of cases by time or location. CONCLUSION: There was no evidence to support within-jail acquisition of trichomoniasis. The high rate of trichomoniasis and other STDs among incarcerated women warrant more comprehensive jail-based STD screening programs.

Adult↗
PubMed1999

Elimination and reintroduction of primary and secondary syphilis.

OBJECTIVES: This study was conducted to define factors associated with the epidemic spread, elimination, and reintroduction of primary and secondary syphilis in King County, Washington, from 1987 through 1998. METHODS: Reports of primary and secondary syphilis in King County from 1987 through 1998 were reviewed retrospectively. RESULTS: During the epidemic spread of syphilis, only 15.8% of cases were imported. A total of 24.0% of patients reported cocaine use, and 18.3% of female patients reported having commercial sex. During the elimination of syphilis, significantly higher percentages of cases were imported and lower percentages of patients reported cocaine use or female commercial sex. During the reintroduction of syphilis in 1997-1998, 68% of patients were men who reported sex with men; of this 68%, 66% were sero-positive for HIV. Most men reporting sex with men were 30 years or older and recruited many anonymous partners. CONCLUSIONS: As syphilis wanes, local control must focus on outbreaks following its reintroduction. Resurgence of syphilis among men reporting sex with men recapitulates the epidemiology of syphilis before the historical advent of AIDS, warranting immediate attention to this problem.

Adult↗
PubMed1998

Enhanced control of an outbreak of Mycoplasma pneumoniae pneumonia with azithromycin prophylaxis.

There are currently no recommended epidemic-control measures for Mycoplasma pneumoniae pneumonia outbreaks in closed communities. Previous studies have suggested the usefulness of chemoprophylaxis administered to close contacts of case-patients. To evaluate the effectiveness of various epidemic-control measures during an institutional outbreak, an observational study was undertaken during a very large outbreak of M. pneumoniae pneumonia at a facility for developmentally disabled residents (n = 142 cases). Control measures evaluated included no control, standard epidemic-control measures, and targeted azithromycin prophylaxis (500 mg on day 1, 250 mg/day on days 2-5) plus standard epidemic-control measures. The combined use of azithromycin prophylaxis and standard epidemic-control measures was associated with a significant reduction in the secondary attack rate. This study suggests that the addition of antibiotic prophylaxis to standard epidemic-control measures can be useful during institutional outbreaks of M. pneumoniae pneumonia.

Adolescent↗
PubMed1998

Risk factors for repeated gonococcal infections: San Francisco, 1990-1992.

Gonococcal (GC) infections are very common and are sustained by a core group of persons who often have repeated GC infections. Identifying individual risk factors for repeated GC infection is essential so that infection control programs can develop better strategies for decreasing the incidence of GC infection. A case-control study among high-risk persons found that being African American, having previous chlamydia infection, and having less than a high-school education were associated with repeated GC infections. Remarkably, measures of sexual behavior and access to health care were not associated with repeated GC infections. These findings suggest that among high-risk persons, the community prevalence of GC infection is more important in predicting risk for repeated GC infections than individual behavior. Interventions should include continued use of resources in high-prevalence communities and better understanding of the roles social and economic discrimination play in the risk for GC infections.

Adolescent↗
PubMed1996

The effect of thalidomide on the pathogenesis of human immunodeficiency virus type 1 and M. tuberculosis infection.

Tumor necrosis factor alpha (TNF-alpha), a cytokine produced during the host defense against infection, is associated with fevers, weakness, and progressive weight loss. Thalidomide inhibits the synthesis of TNF-alpha both in vitro and in vivo and may have clinical usefulness. We therefore initiated a pilot study of thalidomide treatment in patients with human immunodeficiency virus type 1 (HIV-1)-associated wasting with or without concomitant infection with tuberculosis. Thirty-nine patients were randomly allocated to treatment with either thalidomide or placebo in a double-blind manner for 21 days. Thirty-two patients completed the study. In patients with concomitant HIV-1 and tuberculosis infections, thalidomide therapy was associated with a reduction in both plasma TNF-alpha levels and HIV-1 levels. No significant reduction in either TNF-alpha or HIV- 1 levels was observed in patients with HIV-1 infection only. During the study period, patients receiving thalidomide treatment (n=16) showed a significant weight gain (mean +/- SEM: 6.5 +/- 1.2%; p<0.02) relative to placebo-treated patients (n=16). Patients with simultaneous HIV-1 and tuberculosis infections experienced a higher mean weight gain during thalidomide treatment than the group of patients with HIV-1 infection only. The results of this pilot study suggest that thalidomide may have a clinical role in enhancing weight gain and possibly reducing TNF-alpha and HIV-1 levels in patients with HIV-1 and concomitant mycobacterial infections.

Adult↗
PubMed1995

Thalidomide treatment reduces tumor necrosis factor alpha production and enhances weight gain in patients with pulmonary tuberculosis.

BACKGROUND: The monocyte-derived cytokine, tumor necrosis factor alpha (TNF alpha), is essential for host immunity, but overproduction of this cytokine may have serious pathologic consequences. Excess TNF alpha produced in pulmonary tuberculosis may cause fevers, weakness, night sweats, necrosis, and progressive weight loss. Thalidomide (alpha-N-phthalimidoglutarimide) has recently been shown to suppress TNF alpha production by human monocytes in vitro and to reduce serum TNF alpha in leprosy patients. We have therefore conducted a two-part placebo-controlled pilot study of thalidomide in patients with active tuberculosis to determine its effects on clinical response, immune reactivity, TNF alpha levels, and weight. MATERIALS AND METHODS: 30 male patients with active tuberculosis, either human immunodeficiency virus type 1 positive (HIV-1+) or HIV-1-, received thalidomide or placebo for single or multiple 14 day cycles. Toxicity of the study drug, delayed type hypersensitivity (DTH), cytokine production, and weight gain were evaluated. RESULTS: Thalidomide treatment was well tolerated, without serious adverse events. The drug did not adversely affect the DTH response to purified protein derivative (PPD), total leukocyte, or differential cell counts. TNF alpha production was significantly reduced during thalidomide treatment while interferon-gamma (IFN gamma) production was enhanced. Daily administration of thalidomide resulted in a significant enhancement of weight gain. CONCLUSIONS: The results indicate that thalidomide is well tolerated by patients receiving anti-tuberculosis therapy. Thalidomide treatment reduces TNF alpha production both in vivo and in vitro and is associated with an accelerated weight gain during the study period.

Adult↗
PubMed1993

Mycobacterium tuberculosis in household contacts of human immunodeficiency virus type 1-seropositive patients with active pulmonary tuberculosis in Kinshasa, Zaire.

Rates of infection with Mycobacterium tuberculosis were compared in Kinshasa, Zaire, in 521 household contacts of 74 human immunodeficiency virus type 1 (HIV-1)-seropositive index patients and in 692 household contacts of 95 HIV-1-seronegative [corrected] index patients with sputum smear-positive pulmonary tuberculosis: No difference was noted between contacts of HIV-1-seropositive and -seronegative patients. The increasing prevalence of M. tuberculosis infection with increasing age was similar in household contacts of seropositive and seronegative patients; by age 16 years, 75% were purified protein derivative-positive. The similarly low rates of M. tuberculosis infection in household contacts of HIV-1-seropositive and -seronegative index patients with sputum smear-positive pulmonary tuberculosis indicates that HIV-1-seropositive patients with pulmonary tuberculosis are not more infectious than HIV-1-seronegative patients with pulmonary tuberculosis.

Adolescent↗
PubMed1992

Clinical correlates of cerebral ventricular enlargement in schizophrenia. Further evidence for frontal lobe disease.

Numerous studies have shown evidence of cerebral ventricular enlargement in schizophrenia and its relationship to severity of clinical symptoms and psychosocial dysfunction. In this large prospective study, 88 noninstitutionalized DSM-III-R schizophrenic patients were administered a CT scan and rated for positive and negative symptomatology and premorbid adjustment. The CT scans from 14 healthy controls were used for comparison of cerebral ventricular measures. Patients had an enlarged ventricle to brain ratio of the anterior portion of the lateral ventricles, the frontal horns, compared with controls. Patients with larger frontal horns had more severe negative symptoms and poorer premorbid childhood adjustment. The area of the main body of the cerebral lateral ventricles, though not elevated in patients, was correlated with the total number of prior hospitalizations. These results support the hypothesis of a structural and functional "frontal" deficit in schizophrenia.

Adolescent↗