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Biomedical subjects

R S Klein

Publications and source records attributed to R S Klein.

At least 19 recordsLinked to original sources
PubMed1996

Effect of Mycobacterium tuberculosis on HIV replication. Role of immune activation.

The prevalence of Mycobacterium tuberculosis (MTB) has increased worldwide, in part due to the HIV epidemic. Epidemiology data have demonstrated that HIV-infected individuals are more susceptible to MTB disease, which may lead to an acceleration in the progression of HIV disease. The purpose of this study was to determine whether MTB modulates HIV infection in vivo and to delineate the mechanisms involved by using in vitro model systems. Plasma viral load was measured in HIV-infected individuals before, during, and after the development of MTB disease; a 5- to 160-fold increase in viral replication was observed during the acute phase of MTB disease. In order to evaluate the mechanisms involved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-infected individuals. The data demonstrated that MTB induced HIV replication in CD8+ T cell-depleted lymphocytes from HIV-infected individuals with a history of purified protein derivative (PPD) positivity but not in those who were PPD negative; this induction of HIV replication correlated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from healthy donors with a history of PPD positivity, but not in PBMC from PPD-negative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of responding T cells.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Factors associated with unrecognized HIV-1 infection in an inner-city emergency department.

STUDY OBJECTIVE: To determine the prevalence of and risk factors associated with unrecognized HIV-1 infection among medical patients presenting to an inner-city emergency department. METHODS: We conducted anonymous HIV-1 testing in subjects interviewed for risk behaviors and knowledge of HIV status at an inner-city ED in the Bronx, New York. Our subjects were consecutive adult medical patients in noncritical condition (N = 1,744) who were evaluated by three physicians providing primary emergency care. Each patient was given a structured interview for demographic characteristics, risk behaviors, and knowledge of HIV status. Excess serum, drawn for clinical purposes, was linked without identifiers to responses and tested for antibodies to HIV-1. In subjects who denied HIV infection, we tested associations with seropositivity using univariate analyses and logistic-regression techniques (multivariate). RESULTS: Of the 1,744 patients interviewed, 656 (37.6%) reported HIV risk behaviors. Of 970 tested for HIV-1 antibodies, 125 (12.9%) were seropositive. The prevalence of HIV-1 infection among those who denied known infection was 4.0% (35 of 875). In the multivariate model, independent predictors of unrecognized HIV-1 infection were age 35 to 44 years, crack cocaine use, history of syphilis, and ED diagnosis of an infection not necessarily related to HIV infection. Unrecognized HIV-1 infection was more likely among patients admitted to the hospital, but 21 of the 35 with unrecognized infection (60%) were not admitted and in 9(25.7%) no risk factors were identified. CONCLUSION: More than one third of patients who visited one inner-city ED acknowledged HIV risk behaviors. One quarter of patients with unrecognized HIV-1 infection reported no identifiable risk factors. Easily accessible HIV counseling and testing should be considered in EDs in areas serving persons at risk for HIV infection.

Adolescent↗
PubMed1996

An international collaborative study of the effects of coinfection with human T-lymphotropic virus type II on human immunodeficiency virus type 1 disease progression in injection drug users.

To determine whether human T-lymphotropic virus (HTLV) type II coinfection affects progression of human immunodeficiency virus type 1 (HIV) infection, longitudinal data on 370 HIV-infected injection drug users (IDUs) with known HIV seroconversion dates from four cohort studies were pooled. HTLV infection was determined by EIA and confirmed and typed by Western blot. Proportional hazards models were used to determine whether HTLV-II infection was associated with AIDS or AIDS-related mortality. Regression analyses were used to compare declines in CD4 cell percents in singly and dually infected persons. Of 370 IDUs, 61 (16%) were HTLV-II-coinfected. During follow-up, 43 (12%) developed and 24 (6%) died of AIDS. HTLV-II coinfection was not associated with progression to AIDS (relative hazard [RH], .82; 95% confidence interval [CI], 0.34-1.94]) or AIDS mortality (RH, 1.69; 95% CI, 0.62-4.60). Rates of decline in CD4 cell percent were similar in singly and dually infected IDUs. These results suggest that HTLV-II does not affect the progression of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Lack of association of induration size with HIV infection among drug users reacting to tuberculin.

Smaller tuberculin test induration sizes suggest eligibility for tuberculosis chemoprophylaxis in HIV-seropositive than in HIV-seronegative persons. To determine whether human immunodeficiency virus (HIV) infection is associated with induration size among tuberculin reactors, a cross-sectional study of HIV-seropositive and -seronegative drug users was performed. Twenty-four of 160 (15%) HIV-seropositive and 68 of 284 (24%) HIV-seronegative patients had reactions to purified protein derivative (PPD) of > or = 2 mm (OR = 0.56, 95% CI 0.32 to 0.96). However, the prevalence of tuberculin reactivity was equal among nonanergic subjects with and without HIV infection. Median induration size was similar among HIV-seropositive (20.5 mm) and -seronegative (17.5 mm) reactors. Thus, although HIV-seropositive patients were less likely, due to cutaneous anergy, to be PPD reactors, induration size was not associated with HIV infection among reactors. Although using a reduced cutpoint to determine suitability of chemoprophylaxis in HIV-seropositive persons may be prudent, the logical assumption that the loss of specificity this entails is accompanied by an increase in sensitivity for detecting Mycobacterium tuberculosis infection remains to be proved.

AIDS-Related Opportunistic Infections↗
PubMed1996

A prospective study of syphilis and HIV infection among injection drug users receiving methadone in the Bronx, NY.

OBJECTIVES: The purpose of this study was to assess the relationship between syphilis and human immunodeficiency virus (HIV) infection in injection drug users. METHODS: A 6-year prospective study of 790 injection drug users receiving methadone maintenance treatment in the Bronx, NY, was conducted. RESULTS: Sixteen percent (4/25) of HIV-seroconverting patients, 4.8% (16/335) of prevalent HIV-seropositive patients, and 3.5% (15/430) of persistently HIV-seronegative patients was diagnosed with syphilis. Incidence rates for early syphilis (cases per 1000 person-years) were 15.9 for HIV-seroconverting patients, 8.9 for prevalent HIV-seropositive patients, and 2.9 for persistently HIV-seronegative patients. Early syphilis incidence was higher among women than men (8.4 vs 3.2 cases per 1000 person-years). Independent risks for early syphilis included multiple sex partners, HIV seroconversion, paid sex, and young age. All HIV seroconverters with syphilis were female. CONCLUSIONS: Diagnosis of syphilis in drug-using women reflects high-risk sexual activity and is associated with acquiring HIV infection. Interventions to reduce the risk of sexually acquired infections are urgently needed among female drug users.

Adolescent↗
PubMed1995

Heroin use during methadone maintenance treatment: the importance of methadone dose and cocaine use.

OBJECTIVES: The purpose of this study was to examine factors associated with heroin use during methadone maintenance treatment. METHODS: Logistic regression statistical models were used to examine data obtained in a cross-sectional sample of 652 methadone patients. RESULTS: Heroin use during the 3 months prior to interview was shown to be greatest among (1) patients maintained on methadone dosages of less than 70 mg/day (adjusted odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.3, 3.4) and (2) patients who used cocaine during treatment (adjusted OR = 5.9, 95% CI = 3.8, 9.1). These results were independent of treatment duration, treatment compliance, alcohol use, and socioeconomic factors. Cocaine users were more likely than nonusers of cocaine to use heroin at all methadone dosage levels. CONCLUSIONS: This study confirms and extends past research showing high-dose methadone maintenance to be important to heroin abstinence. Further investigation of the independent association between heroin use and cocaine use is needed.

Adult↗
PubMed1995

Stress, coping, and attitudes toward HIV treatment in injecting drug users: a qualitative study.

An exploratory study was conducted with 27 injecting drug users (IDUs) on psychosocial factors (stress, coping reactions, and attitudes toward HIV illness and treatment) which are relevant to treatment acceptance and adherence. A semi-structured interview was used to collect qualitative data in a sample of 13 seropositive and 14 seronegative subjects. The results indicated a range of HIV-specific stressors such as social stigma, uncertainty about the future, disclosure of seropositive status, and monitoring of HIV illness. Seeking of social support, relapse to substance abuse, and mental disengagement were the most common coping reactions reported by the sample; there was a lack of behavioral, problem-focused responses. The study also provided descriptive information on attitudes toward HIV treatment, including fatalism, optimism (hope and control), and ambivalence regarding treatment efficacy. Clinical implications and suggestions for future research are discussed.

Adaptation, Psychological↗
PubMed1994

Risk of genital human papillomavirus infection in women with human immunodeficiency virus-induced immunosuppression.

This study examined the risk factors for genital human papillomavirus (HPV) infection, including HIV-related immunosuppression as well as demographic and behavioral factors. Subjects were 207 women with known HIV serologic status, the majority of whom were intravenous drug users recruited from a methadone treatment program in the Bronx, New York. A structured questionnaire interview, cervico-vaginal lavage, and CD4 cell measurements were obtained. HPV genomes in the cervico-vaginal cells were detected by Southern-blot hybridization. HPV prevalence was 23% among HIV seronegatives, 45% among HIV seropositives with CD4 percent > 20 and 61% among HIV seropositives with CD4 percent < or = 20. Multivariate analysis identified the following independent risk factors that were significantly associated with HPV positivity: HIV-related immunosuppression, < 35 years of age, and never used oral contraceptive pills. HIV-related immunosuppression was also associated with a stronger Southern-blot signal strength. HIV infection, however, did not increase the susceptibility to HPV infection with the oncogenic types (16, 18, 31, 33 and 35). Women with HIV infection or immunosuppression had a higher prevalence of HPV infection with the oncogenic types, but they also had an increased prevalence of infection with other HPV types as compared to the HIV-seronegative women. The results suggest that HIV-related immunosuppression increases the risk of genital HPV infection and has an effect on HPV replication.

Adult↗
PubMed1994

Risk factors for squamous intraepithelial lesions on Pap smear in women at risk for human immunodeficiency virus infection.

To determine risk factors for squamous intraepithelial lesions (SIL) on Pap smear, 253 women at risk for human immunodeficiency virus (HIV) infection had Pap smear, HIV antibody testing, CD4+ cell measurements, and human papillomavirus (HPV) genome detection by Southern blot hybridization. Associated with SIL (P < .05) on univariate analysis were genital HPV (SIL prevalence in HPV-positive subjects, 36.3%; odds ratio [OR], 9.3; 95% confidence interval [CI], 4.2-20.3) and HIV infection (SIL prevalence in seropositive subjects, 21.9%; OR, 2.5; 95% CI, 1.2-5.1). No demographic or behavioral variables were associated with risk for SIL. Multivariate analyses identified genital HPV infection (OR, 6.78; 95% CI, 2.9-15.7), detection of known high-risk HPV types (OR, 11.8; 95% CI, 4.1-34.1), strong HPV Southern blot signal strength (OR, 10.8; 95% CI, 3.5-33.7), and severe HIV-related immunosuppression (OR, 3.1; 95% CI, 1.04-9.5) as independent risk factors associated with SIL. Thus, severe immunosuppression due to HIV infection increases the risk for SIL mediated by HPV infection.

Adult↗
PubMed1994

Laboratory markers and the risk of developing HIV-1 disease among injecting drug users.

OBJECTIVE: To characterize the progression to HIV-1 disease among injecting drug users (IDU) according to laboratory markers. DESIGN: Prospective study of cohort of HIV-1-seroprevalent IDU, with case-comparison component. METHODS: Different laboratory markers were examined as predictors of progression to HIV-1-associated diseases including AIDS in a cohort of 318 HIV-1-infected IDU. The cohort was enrolled from a methadone treatment program in the Bronx, New York, USA. The independent utility of non-CD4 cell markers was evaluated after adjustment for the association of low CD4 lymphocyte count with AIDS risk. Clinical events in the natural history of HIV-1 were related to changes in levels of two variables related to duration of infection, CD4 lymphocyte count and serum beta 2-microglobulin (beta 2M) concentration. RESULTS: On univariate analysis, AIDS incidence measured from baseline increased with declining CD4 lymphocyte number and percentage, increasing serum beta 2M level, low platelet count, low leukocyte count and p24 antigenemia. Among HIV-1-related outcomes prior to any AIDS diagnosis, the relative risk of pyogenic bacterial infections conferred by these markers was similar to the relative risk of AIDS. For all HIV-1 outcomes, the elevated risk encountered at CD4 lymphocyte number < or = 200 x 10(6)/l was entirely due to the high risk at < or = 150 x 10(6)/l. On multivariate analysis, control for CD4 lymphocyte count eliminated the association of any other marker with increased AIDS hazard. HIV-1-related outcomes tended to occur in this order: multiple constitutional symptoms, oral candidiasis, pyogenic bacterial infections and AIDS. CONCLUSIONS: In HIV-1-infected IDU, several laboratory markers may predict AIDS when analyzed individually. These are not, however, independently related to increased AIDS risk after adjustment for low CD4 lymphocyte count. A CD4 count < or = 150 x 10(6)/l is more strongly related to immediate risk of adverse outcome than a count of 200 x 10(6)/l. A progressive series of clinical events is associated with markers of duration of HIV-1 infection, prior to and including AIDS diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Criteria for the diagnosis of urinary tract infection.

Despite years of clinical experience with urinary tract infection, the criteria for the diagnosis of this common condition are controversial. Accumulating evidence confirms prior suggestions that criteria must be flexible and varied, depending on the clinical syndrome encountered. The combination of pyuria and bacteriuria, with a uropathogen present at a urine colony count level predictive of infection, offers the best way to distinguish infection from contamination of the collected urine specimen. The level of bacteriuria on quantitative urine culture that should be considered significant varies from 10(2) to 10(5) colonies or more per milliliter of urine, depending on the clinical setting.

Colony Count, Microbial↗
PubMed1994

Guanylhydrazones in therapy of Pneumocystis carinii pneumonia in immunosuppressed rats.

Guanylhydrazones are cationic heteroaromatic drugs similar to the diamidines which are effective in the treatment of African trypanosomiasis and pneumocystosis. On the basis of their antitrypanosomal activity, different guanylhydrazones were selected for evaluation in a rat model of Pneumocystis carinii pneumonia. The most active compounds were the 2-(4'-formylphenyl)-1-methylimidazo-[1,2-a] pyridinium guanylhydrazones which, at a dose of 2 mg/kg/day, were about as effective as trimethoprim-sulfamethoxazole at a dose of 50 mg of trimethoprim per kg/day plus 250 mg of sulfamethoxazole per kg/day. The anti-P. carinii activity of these guanylhydrazone derivatives was found with parenteral but not with oral administration. The 1,3-arylene diketone bis(guanylhydrazones) were generally ineffective, although a triacetyl derivative showed some anti-P. carinii activity. Nitroimidazole guanylhydrazone derivatives were also ineffective. Attempts to improve the therapeutic efficacy of the different guanylhydrazones were limited by problems of toxicity. We conclude that some guanylhydrazone derivatives are potent anti-P. carinii drugs and that further studies should be pursued to develop safer compounds and investigate structure-activity relationships.

Animals↗
PubMed1993

Correlates of the rate of decline of CD4+ lymphocytes among injection drug users infected with the human immunodeficiency virus.

Changes in the level of CD4-bearing T-lymphocytes in injection drug users infected with the human immunodeficiency virus were evaluated in a sample of 318 subjects enrolled from a methadone program in the Bronx, New York, from 1985 through 1989. Follow-up continued through 1990. The percentage of CD4+ T-lymphocytes (CD4%) was used to maximize the stability of measurements. The rate of decline of the CD4% was determined using a random-effects assumption, and predictors of rate of decline were evaluated using an autoregressive model. The rate of CD4% decline was approximately 1.2 CD4% lost per 6 months, with a higher rate in recent seroconverters (2.2 CD4% lost). The most important predictors of decline of the CD4% in autoregressive models were current pyogenic bacterial infection (CD4% reduced by 2.75, 95% confidence interval (CI) 0.42-5.08), current report of a second constitutional symptom (CD4% reduced by 2.16, 95% CI 0.03-4.29), and history of bacterial infection (CD4% reduced by 1.49, 95% CI 0.09-2.89; proportion of prior CD4% lost increased by 0.14, 95% CI 0.01-0.27). Oral thrush was not related to an accelerated rate of CD4% decline.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Effects of HIV infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users.

OBJECTIVE: To describe the effects of human immunodeficiency virus (HIV) infection on the serologic manifestations and response to treatment of syphilis in intravenous drug users. DESIGN: Cohort study of intravenous drug users. SETTING: Medical clinic in a hospital-based methadone maintenance treatment program in New York City. PATIENTS: Fifty patients with syphilis, of whom 31 were HIV seropositive and 19 HIV seronegative. MEASUREMENTS: Serologic tests for syphilis and clinical manifestations. RESULTS: Stage of syphilis at presentation was not associated with HIV serologic status. No unusual or fulminant manifestations of early syphilis or neurosyphilis were noted among HIV-seropositive cases. Maximum nontreponemal titers were higher among HIV-seropositive (median, 1:128) than among HIV-seronegative (median, 1:32) patients with syphilis (P = 0.05); this difference was present only among patients with first-episode syphilis. All 26 evaluable, HIV-seropositive patients treated for syphilis responded appropriately, including 13 patients given standard or less-than-standard doses of penicillin. Seven of 43 patients (16%) showed reversion to negative treponemal antibody assay results after treatment for syphilis; this finding was not associated with HIV infection, CD4 count, or stage of syphilis. Low nontreponemal titer was weakly associated with treponemal test reversion. CONCLUSIONS: Infection with HIV did not alter the stage at presentation, clinical course, serologic manifestations, or response to treatment of syphilis in this cohort of intravenous drug users.

Adult↗