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Biomedical subjects

M Marmor

Publications and source records attributed to M Marmor.

At least 19 recordsLinked to original sources
PubMed2000

HIV incidence among injection drug users in New York City, 1992-1997: evidence for a declining epidemic.

OBJECTIVES: We assessed recent (1992-1997) HIV incidence in the large HIV epidemic among injection drug users in New York City. METHODS: Data were compiled from 10 separate studies (N = 4979), including 6 cohort studies, 2 "repeat service user" studies, and 2 analyses of voluntary HIV testing and counseling services within drug treatment programs. RESULTS: In the 10 studies, 52 seroconversions were found in 6344 person-years at risk. The observed incidence rates among the 10 studies were all within a narrow range, from 0 per 100 person-years at risk to 2.96 per 100 person-years at risk. In 9 of the 10 studies, the observed incidence rate was less than 2 per 100 person-years at risk. The weighted average incidence rate was 0.7 per 100 person-years at risk. CONCLUSIONS: The recent incidence rate in New York City is quite low for a high-seroprevalence population of injection drug users. The very large HIV epidemic among injection drug users in New York City appears to have entered a "declining phase," characterized by low incidence and declining prevalence. The data suggest that very large high-seroprevalence HIV epidemics may be "reversed."

Adult↗
PubMed1999

Correlates of condom failure in a sexually active cohort of men who have sex with men.

Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure.

Adult↗
PubMed1999

Non-injection substance use correlates with risky sex among men having sex with men: data from HIVNET.

Associations between substance use and sexual behavior were examined among 3220 seronegative men who have sex with men (MSM) in a HIV vaccine preparedness study. Relationships between current and past substance use and current sexual risk were evaluated using crude odds ratios and logistic regression to adjust for confounding variables. Heroin and injection drug use were uncommon (< 2%). Substances most often used were alcohol (89%), marijuana (49%), nitrite inhalants (29%), amphetamines or similarly acting stimulants (21%), cocaine 14% and hallucinogens (14%). Increased adjusted odds for unprotected sex were significantly associated with current heavy alcohol use (OR 1.66; CI 1.18, 2.33), past alcohol problems (OR 1.25; CI 1.05, 1.48), and current drug use (OR 1.26; CI 1.08, 1.48). When associations with specific drugs and nitrite inhalants were examined separately, current use of cocaine and other stimulants (OR 1.25; CI 1.01, 1.55), hallucinogens (OR 1.40; CI 1.10, 1.77), and nitrite inhalants (some (OR 1.61; CI 1.35, 1.92); heavy (OR 2.18; CI 1.48, 3.20)), were independently associated with unprotected sex. Those with past drug use or past heavy alcohol use but not currently using demonstrated no increase in sexual risk, suggesting an important role for substance-focused interventions in risk reduction efforts among MSM.

AIDS Vaccines↗
PubMed1998

Readiness of high-risk populations in the HIV Network for Prevention Trials to participate in HIV vaccine efficacy trials in the United States.

OBJECTIVE: To determine the willingness of populations at high risk of HIV-1 infection to participate in HIV vaccine efficacy trials, determine factors influencing decision-making, and evaluate knowledge levels of vaccine trial concepts. DESIGN: Cross-sectional study. METHODS: HIV-1-negative homosexual men, male and female injecting drug users and non-injecting women at heterosexual risk were recruited in eight cities in the United States (n=4892). RESULTS: A substantial proportion of the study population (77%) would definitely (27%) or probably (50%) be willing to participate in a randomized vaccine efficacy trial. Increased willingness was associated with high-risk behaviors, lower education level, being uninsured or covered by public insurance, and not having been in a previous vaccine preparedness study. Altruism and a desire for protection from the vaccine were major motivators for participation. Major concerns included positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible problems with insurance or foreign travel. Baseline knowledge of vaccine trial concepts was low. CONCLUSIONS: It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials. A variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for participation.

AIDS Vaccines↗
PubMed1998

Declining seroprevalence in a very large HIV epidemic: injecting drug users in New York City, 1991 to 1996.

OBJECTIVES: This study assessed recent trends in HIV seroprevalence among injecting drug users in New York City. METHODS: We analyzed temporal trends in HIV seroprevalence from 1991 through 1996 in 5 studies of injecting drug users recruited from a detoxification program, a methadone maintenance program, research storefronts in the Lower East Side and Harlem areas, and a citywide network of sexually transmitted disease clinics. A total of 11,334 serum samples were tested. RESULTS: From 1991 through 1996, HIV seroprevalence declined substantially among subjects in all 5 studies: from 53% to 36% in the detoxification program, from 45% to 29% in the methadone program, from 44% to 22% at the Lower East Side storefront, from 48% to 21% at the Harlem storefront, and from 30% to 21% in the sexually transmitted disease clinics (all P < .002 by chi 2 tests for trend). CONCLUSIONS: The reductions in HIV seroprevalence seen among injecting drug users in New York City from 1991 through 1996 indicate a new phase in this large HIV epidemic. Potential explanatory factors include the loss of HIV-seropositive individuals through disability and death and lower rates of risk behavior leading to low HIV incidence.

Adult↗
PubMed1997

"Why I am not infected with HIV": implications for long-term HIV risk reduction and HIV vaccine trials.

OBJECTIVE: To describe beliefs about remaining HIV-seronegative in injecting drug users in two high-seroprevalence cities, and to consider implications of these beliefs for ongoing risk reduction efforts and for HIV vaccine efficacy trials. DESIGN: Cross-sectional survey with open- and closed-ended questions. SUBJECTS: 58 HIV-seronegative injecting drug users participating in HIV vaccine preparation cohort studies in New York City, New York, U.S.A., and Bangkok, Thailand. MAJOR FINDINGS: Large majorities of subjects in Bangkok (90%) and in New York (89%) believed their "own efforts" to practice safer injection methods and safer sex were very important in avoiding HIV infection. More Bangkok subjects (30%) believed that they would "probably" become infected with HIV in the future than New York subjects (4%). Three percent of Bangkok subjects and 70% of New York subjects believed "having an immune system strong enough to avoid becoming infected with HIV despite exposure to the virus" was very important in avoiding HIV infection. This belief in New York subjects was associated with having previously engaged in high-risk behaviors (i.e., sharing injection equipment, unprotected sex, or both) with partners known to be HIV-seropositive. CONCLUSIONS: Risk reduction programming for high-HIV-seroprevalence populations and within HIV vaccine trials should address not only specific HIV risk behaviors, but also the complex belief systems about avoiding HIV infection that develop within such groups. The person's "own efforts/self-efficacy" appears to be central in the psychology of risk reduction. Members of some high-risk populations may overestimate greatly the frequency of any possible natural immunity to becoming infected with HIV. Prevention programs for these populations will need to address explicitly the probabilistic nature of HIV transmission.

AIDS Vaccines↗
PubMed1997

Reexamination of human T cell lymphotropic virus (HTLV-I/II) prevalence.

In the United States, blood donors are being screened for infection with human T cell lymphotropic viruses I and II (HTLV-I/II) by serologic means, which detect antibodies to the structural proteins of these viruses. Because patients with mycosis fungoides (MF) usually do not have such antibodies even though their cells harbor HTLV-I Tax and/or pol proviral sequences, it was questioned whether the prevalence of HTLV infection among healthy blood donors may also be underestimated by current means of testing. To examine this possibility, a study on specimens of relatives of mycosis fungoides patients (MFR) was begun. In addition, to collect data more expeditiously, a cohort of former injection drug users (IDUs) was tested by routine serologic methods, as well as by PCR/Southern blot analysis for Tax, pol, and gag proviral sequences and Western blot analysis for antibodies to the Tax gene product. To date, 6/8 MFRs and 42/81 (51.8%) of HIV-negative IDUs proved to be positive for HTLV, whereas routine serology identified none of the MFR and only 18/81 (22.2%) of the IDUs. Among the latter test subjects, the incidence of HTLV-I also proved to be 10 times higher than expected. Therefore, it is likely that among healthy blood donors infection with HTLV-I/II is more prevalent than is currently assumed. Since Tax is the transforming sequence of HTLV-I/II, testing for Tax sequences and antibodies to its gene product may be desirable in blood transfusion and tissue donor facilities.

Blood Donors↗
PubMed1997

Low serum thiol levels predict shorter times-to-death among HIV-infected injecting drug users.

OBJECTIVES: To investigate whether serum thiol levels are altered by HIV disease, and whether low serum thiols predict time to death among HIV-infected injecting drug users (IDU). DESIGN: A cross-sectional study of serum thiol levels among 13 HIV-seronegative IDU, 116 HIV-seropositive IDU, and 17 HIV-seropositive IDU with a history of AIDS, and a cohort study of the 133 HIV-infected IDU who took part in the cross-sectional study. METHODS: Subjects were recruited from a methadone-maintenance treatment program during 1990-1991. Total serum thiols were determined spectrophotometrically at enrolment; low serum thiols were defined as those with an absorbance at 412 nm < or = 0.46. Deaths through 31 December 1993 were determined from the National Death Index (NDI). Twenty-six HIV-seropositive subjects died during follow up; death certificates, which were obtained for 23 subjects, indicated AIDS or HIV infection for 20. Product-limit estimation was used to calculate survival. Multivariate analyses employed Cox proportional-hazards regression. RESULTS: Analysis of cross-sectional data showed that serum thiols did not differ significantly among HIV-free subjects, HIV-infected subjects, and HIV-infected subjects with a history of AIDS. Cohort analysis, adjusted for age, revealed that persons with those with high serum thiols (relative hazard = 2.83; 95% confidence interval (CI), 1.15, 6.97); a significant interaction between low serum thiols and a history of AIDS was associated with a relative hazard of 5.65 (95% CI, 1.22-2.61). CONCLUSIONS: Among HIV-infected persons, low serum thiols, especially in concert with a history of AIDS, predict mortality risk. These findings support the hypothesis that oxidative stress is critical to the pathogenesis of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Geographic diversity in tuberculosis trends and directly observed therapy, New York City, 1991 to 1994.

The New York City tuberculosis (TB) case rate declined from 1991 to 1994 following more than a decade of increases. The present study investigated TB trends in New York City neighborhoods and their association with neighborhood-specific rates of application of directly observed therapy (DOT). Using Poisson regression models, TB trends in each of New York City's 30 health districts were classified as increasing, decreasing, or stable, as indicated respectively by significant positive, negative, or nonsignificant regression coefficient. Case counts increased in four health districts, decreased in 10, and were stable in 16. Decreasing TB was associated with a higher rate of application of DOT. TB cases among foreign-born persons increased in 12 health districts and were stable in 18, whereas cases among persons born in the United States decreased in 19 and were stable in 11 districts. Among the foreign-born, increasing TB was not associated with a lesser rate of application of DOT. These data provide some support for the role of DOT in containing TB, but also suggest that the application of DOT among foreign-born residents is less effective than among United States-born residents. This may be due to a greater proportion of TB cases among the foreign-born being due to reactivation of TB rather than new infection.

Antitubercular Agents↗
PubMed1996

HIV incidence among injecting drug users in New York City syringe-exchange programmes.

BACKGROUND: There have been no studies showing that participation in programmes which provide legal access to drug-injection equipment leads to individual-level protection against incident HIV infection. We have compared HIV incidence among injecting drug users participating in syringe-exchange programmes in New York City with that among non-participants. METHODS: We used meta-analytic techniques to combine HIV incidence data from injecting drug users in three studies: the Syringe Exchange Evaluation (n = 280), in which multiple interviews and saliva samples were collected from participants at exchange sites; the Vaccine Preparedness initiative cohort (n = 133 continuing exchanges and 188 non-exchangers, in which participants were interviewed and tested for HIV every 3 months; and very-high-seroprevalence cities in the National AIDS Demonstration Research (NADR) programme (n = 1029), in which street-recruited individuals were interviewed and tested for HIV every 6 months. In practice, participants in the NADR study had not used syringe exchanges. FINDINGS: HIV incidence among continuing exchange-users in the Syringe Exchange Evaluation was 1.58 per 100 person-years at risk (95% CI 0.54, 4.65) and among continuing exchange-users in the Vaccine Preparedness Initiative it was 1.38 per 100 person-years at risk (0.23, 4.57). Incidence among non-users of the exchange in the Vaccine Preparedness Initiative was 5.26 per 100 person-years at risk (2.41, 11.49), and in the NADR cities, 6.23 per 100 person-years at risk (4.4, 8.6). In a pooled-data, multivariate proportional-hazards analysis, not using the exchanges was associated with a hazard ratio of 3.35 (95% CI 1.29, 8.65) for incident HIV infection compared with using the exchanges. INTERPRETATION: We observed an individual-level protective effect against HIV infection associated with participation in a syringe-exchange programme. Sterile injection equipment should be legally provided to reduce the risk of HIV infection in persons who inject illicit drugs.

Adult↗
PubMed1996

Weight loss associated with HIV seroconversion among injection-drug users.

To describe symptoms associated with human immunodeficiency virus (HIV) seroconversion, we studied a cohort of 366 injection-drug users (IDUs) with a study design that included recall every 3 months to collect symptom histories using a structured questionnaire. Eleven HIV seroconversions were observed in 621.5 person years at risk (PYAR), equivalent to 1.8 seroconversions/100 PYAR. Cox regression analysis showed age < or = 35 years to be a significant risk factor for HIV seroconversion after controlling for gender, race, and the frequency of drug injection. An embedded case-control analysis then compared symptom histories of HIV seroconverters with those of age-(+/- 5 years) and visit number-matched controls who remained HIV seronegative for > or = 3 months longer than the HIV-seroconverters. Multivariate case-control analysis adjusted for injection frequency yielded significant associations of HIV seroconversion with histories of weight loss > or = 4.5 kg (seven of 11 cases; odds ratio [OR] = 11.6, 95% confidence interval [CI] 3.1, 43.1) and oral ulcers (three of 11 cases; OR = 7.6, 95% CI = 1.2, 48.2) in the 3 months before the subjects' first HIV-seropositive study visit. We conclude that histories of recent symptoms reported by HIV-seroconverting IDUs differ from those reported by non-HIV-seroconverting IDUs, and weight loss may be particularly common among IDUs experiencing primary HIV infection.

Adult↗
PubMed1996

Evaluation of contractile reserve by dobutamine echocardiography: noninvasive estimation of the severity of heart failure.

Functional status in chronic heart failure is evaluated in general by subjective means, such as the New York Heart Association class, or by invasive techniques difficult to use routinely. The aim of this study was to evaluate noninvasively the contractile reserve in cases of heart failure as a means to define the functional status of the patients. Cardiac peak power, a new noninvasively obtained afterload-independent index of contractility, was calculated from online Doppler and central arterial blood pressure estimated noninvasively in 35 patients with heart failure and 10 healthy subjects during dobutamine infusion. Cardiac output increased in all patients to the same extent, without differentiation among the functional classes. Contractile reserve, as assessed by peak power, was found to be a good marker of functional class: it was significantly higher in functional class 1 than in functional classes 2 through 4. A correlation of r = 0.99 and probability of p < 0.001 was found with the functional status. This new, noninvasive contractility index, peak power, allows an objective evaluation of the severity of heart failure.

Aged↗
PubMed1996

Determination of the true prevalence of infection with the human T-cell lymphotropic viruses (HTLV-I/II) may require a combination of biomolecular and serological analyses.

Infection with the human T-cell lymphotropic virus types I and II (HTLV-I/II) usually is determined by tests that detect antibodies to the viral structural proteins. However, recent studies revealed that patients with mycosis fungoides have proviral DNA sequences related to the HTLV transactivating-transforming gene tax, without having antibodies to the virus. These results raised the possibility that the prevalence of HTLV infection in the general population of the United States also may be underestimated. To reassess the prevalence of HTLV-I/II infection effectively, a population at increased risk for infection (i.e., a cohort of injection drug users [IDUs]) was studied. Paired sera and peripheral blood mononuclear cells (PBMCs) from 81 IDUs were subjected to testing by Western blot analysis for antibodies to the viral structural proteins gag and env and by polymerase chain reaction (PCR) Southern analysis to detect gag, pol and tax proviral DNA sequences. Western blot assays showed 1 of 81 IDUs to be positive for HTLV-I, 14 to be positive for antibodies to HTLV-II, and 3 to be HTLV-serotype indeterminate. When whole-cell lysates of PBMCs from these individuals were subjected to PCR and Southern analysis. 39 of 81 were found to have HTLV-related sequences. A total of nine IDUs were found to be infected with HTLV-I, a figure nearly 10 times higher than that estimated by serology alone. Bio-molecular analysis showed HTLV-II-specific proviral sequences in 21 IDUs. Three individuals were seropositive for HTLV-II but lacked PCR evidence of gag, pol and tax sequences. Thus, the overall prevalence of HTLV infection among this cohort was 59% (43 of 81) (i.e., more than twice the frequency predicted by serology, 18 of 81 or 22%). These results indicate that it may be necessary to incorporate biomolecular as well as serological methodologies to identify all persons infected with these retroviruses.

Blotting, Southern↗
PubMed1995

A new methodology for non-invasive clinical assessment of cardiovascular system performance and of ventricular-arterial coupling during stress.

The objective of the study was to develop a non-invasive method for the quantitative evaluation of cardiovascular performance and ventricular-arterial (VA) coupling during varying physiological states. VA-coupling was represented by the ratio between the arterial and ventricular elastances-Ea/Ees. Approximate indices of the relative change of Ees and VA-coupling during stress were developed and tested. These indices can be evaluated directly from non-invasive measurements of ejection fraction values (for VA-coupling) and measurements of stroke volumes and systolic and diastolic arterial pressures (for Ees). Additional relative indices can be evaluated from these data (e.g., stroke work, cardiac output) to yield a complete representation of the cardiovascular response to stress. The present methodology was applied to assess the exercise stress response in healthy subjects (H, n = 8) and in patients with left ventricular dysfunction (n = 24). Left ventricular volumes were determined by nuclear angiography and arterial pressures were measured non-invasively by a new, validated method. Using published data obtained invasively, we found that the relative indices of Ees and VA-coupling showed a high correlation with the invasive ones (r > 0.8, P < 0.01). The patients were subgrouped by their maximal exercise capacitance (P2-50W, P3-75W). At rest, the two patient groups had similar ejection fraction values (45 +/- 15% and 48 +/- 16%), which were significantly different from those of the healthy subjects (66 +/- 7%, P < 0.05). During stress, a larger increase in stroke work and cardiac output was found in the healthy subjects. All three groups showed similar relative increases in Ees and heart rate, but relative Ea increased in P2 and decreased in H, while the opposite was found for the end-diastolic volume. The relative VA-coupling index in P2 was significantly larger than that in P3 and H (P < 0.05). The present non-invasively based indices can be used to quantitatively monitor the individual cardiovascular response to stress testing or drug interventions and to evaluate the importance of VA-coupling in the clinical setting.

Arteries↗
PubMed1995

Progress in identifying clinical relevance of inhibition, stimulation and measurements of poly ADP-ribosylation.

Our laboratory, in collaboration with Oxigene Inc, has been involved in identifying commercially feasible clinical applications of measurement or modulation of ADP-ribosylation as a core technology. For this purpose a pivotal regulatory role for ADP-ribosylation in the repair of DNA lesions leading to cytotoxic as well as mutagenic events has been hypothesized. A new class of DNA repair inhibitors, the N-substituted benzamides, has been identified which can react with radiation to produce reactive intermediates that oxidize thiol amino acids. Their proposed mechanisms of action are two-fold: ie they can interact with radiation: i) to directly enhance DNA damage; and ii) to react with thiols in the zinc finger DNA binding domain of poly ADP-ribosyl transferase to inhibit DNA repair and thereby increase DNA damage. Sensamide, a clinically relevant formulation of metoclopramide which is an N-substituted benzamide, has indicated enhancement of tumor response and survival in patients with inoperable squamous cell carcinoma of the lung when it was administered as a radiosensitizer in a phase I/II trial and compared to historical controls. A mechanism of endogenous regulation of human mononuclear leucocyte ADP-ribosylation has been identified to be HOCl/N-chloramine production via the oxidative burst of phagocytes. HOCl/N-chloramines are potent oxidants of thiol-containing proteins. Quantitative estimation of N-chloramine sensitive plasma thiols has been identified as an effective surrogate measure of leucocyte poly ADPRT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗