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Biomedical subjects

S Cohn

Publications and source records attributed to S Cohn.

At least 37 records · Page 2Linked to original sources
PubMed1997

Incidence and risk factors for hepatitis C among injection drug users in Baltimore, Maryland.

Between 1988 and 1996, the incidence of and risk factors for hepatitis C virus (HCV) infection were studied in a cohort of injection drug users in Baltimore, Maryland. By second-generation antibody testing of stored serum samples, 142 participants were found to be susceptible to HCV at the time they entered the study. After a median follow-up of 6.5 years, 43 participants (30.3%) developed antibodies to HCV (anti-HCV). The overall incidence was 6.4 cases per 100 person-years, but a substantial decline in the annual incidence rate was observed after the first 2 years (1988 to 1990, 13.4/100 person-years; 1991 to 1996, 2.3/100 person-years [P = 0.0001 for trend]). Participants who acknowledged active drug use, especially those who acknowledged frequent use and sharing of drug paraphernalia, were at increased risk of HCV infection. However, high-risk sexual practices were not associated with HCV seroconversion. Efforts to reduce HCV infection must be focused on curbing drug use and especially on the sharing of needles and drug paraphernalia.

Adult↗
PubMed1997

Comparison of PCR and hybrid capture methods for detection of human papillomavirus in injection drug-using women at high risk of human immunodeficiency virus infection.

We compared Hybrid Capture, a new technique for detection of human papillomaviruses (HPV), with a PCR assay based on L1 consensus primers. By both methods, the HPV prevalence was higher in human immunodeficiency virus (HIV)-positive women than in HIV-negative women. PCR had a higher sensitivity (0.89 versus 0.48) but lower specificity (0.43 versus 0.93) for detection of Pap smear abnormalities, compared to Hybrid Capture. The higher intensity of hybridization signal by PCR was related to higher estimates of viral load by Hybrid Capture.

DNA, Viral↗
PubMed1997

HIV infection and cognition in intravenous drug users: long-term follow-up.

A cohort of 185 HIV-infected injection drug users (IDUs) and seronegative controls was followed with semiannual neuropsychological assessments for up to 4.5 years. Changes in cognitive performance over time were evaluated, and results of seronegative controls were used to adjust for level of education and practice effects. The effects of duration of follow-up, decline in CD4+ count, development of clinical symptoms, antiretroviral use, and diagnosis of AIDS on changes in neuropsychological performance over time were assessed with regression models using the generalized estimating equation approach. Improvement in performance over time, consistent with practice effects, was observed for all measures. The only subtest for which the magnitude of the practice effects was mildly attenuated relative to the seronegative controls was Grooved Pegboard, dominant hand. After adjusting for disease progression and antiretroviral therapy use, none of the time trends for the neuropsychological test scores were significant, suggesting no decline in performance of the seropositive patients relative to the seronegative controls. With development of clinical symptoms, there was a trend in the direction of declining performance. For subjects reporting two or more symptoms but not using antiretroviral therapy, the trend was not significant, whereas having two or more symptoms and using antiretroviral therapy was associated with significantly worse performance on tests of psychomotor speed and memory. With development of AIDS, a significant decline in performance was observed on measures of motor and psychomotor speed as well as memory. There is thus no evidence to suggest that HIV infection in the context of chronic drug and alcohol use significantly alters the frequency or rate of progression of cognitive symptoms. These findings suggest that the natural history of cognitive changes secondary to HIV infection is similar among HIV-infected IDUs and other risk groups such as homosexual/bisexual men.

Adult↗
PubMed1996

Differences in the incidence of hepatitis B and human immunodeficiency virus infections among injecting drug users.

Both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) type 1 seroconversions have been considered as outcome measures to evaluate the effectiveness of needle exchange programs. To assess the relationships between incident HBV and HIV infections among injecting drug users (IDUs), seroconversions were prospectively studied among a cohort of 240 HBV- and HIV- seronegative IDUs. The incidence of HBV seroconversion declined from 24.41/100 person-years in 1988 to 0 seroconversions in 1992. In contrast, HIV seroconversion rates varied little from the overall rate of 3.29/100 person-years. HBV seroconversion predicted subsequent HIV seroconversion among male IDUs (relative incidence [RI]= 4.23) but not among female IDUs (RI=0.86). Because of different transmission dynamics, HBV seroconversion probably has limited utility as a surrogate outcome measure for incident HIV. However, HBV seroconversion itself is an appropriate and important outcome measure for evaluation of prevention programs among IDUs.

Adult↗
PubMed1996

Effect of human immunodeficiency virus on hepatitis C virus infection among injecting drug users.

To assess the effect of human immunodeficiency virus (HIV) immunosuppression on ongoing hepatitis C virus (HCV) infection, CD4 lymphocyte counts and serum concentrations of HCV RNA, HIV RNA, and alanine aminotransferase (ALT) were evaluated among members of a cohort of injecting drug users (IDUs). With 100 participants randomly selected at various stages of HIV-related immunosuppression, serum HCV RNA concentrations increased with age (P = .007) and were higher in HIV-positive IDUs with 201-500 (P = .026) and 51-200 (P = .004) CD4 cells/mL than in HIV-negative participants. Among 27 HCV-infected IDUs who acquired HIV infection, serum HCV RNA concentrations varied between semiannual visits by a mean of 0.45 logs, increasing by 0.60 logs after HIV seroconversion (P < .0001), by 0.12 logs each subsequent year (P = .006), and by 0.36 logs per log increase in CD4 cells (P = .01). Serum ALT levels were similar between HIV-positive (40.1 IU/mL) and HIV-negative (45.4 IU/mL) patients (P > .10). While HIV infection and possibly HIV progression are associated with increased HCV RNA levels, other factors appear to affect biochemical and virologic markers of HCV infection in some dually infected persons.

Adolescent↗
PubMed1996

Effects of anesthesia based on large versus small doses of fentanyl on natural killer cell cytotoxicity in the perioperative period.

Surgical stress and general anesthesia suppress immune functions, including natural killer cell cytotoxicity (NKCC). This suppression could be attributable, at least in part, to opiates. We have previously shown that large-dose fentanyl administration suppressed NKCC in rats. The present study sought to compare the effects of two anesthetic protocols, based on large- (LDFA) versus small (SDFA)-dose fentanyl anesthesia on NKCC in the perioperative period. Forty patients were included in this study; half were assigned to each protocol of anesthesia. In each anesthetic group, half the patients were undergoing surgery for malignant diseases, and half for benign conditions. Blood samples were collected during the perioperative period. NKCC was assessed using the chromium release assay. Initially, both types of anesthesia similarly suppressed NKCC, with a peak effect 24 h after surgery. The two types of anesthesia, however, differed in the rate of recovery of NKCC suppression. By the second postoperative day, NKCC returned to control values in the SDFA patients, whereas NKCC was still significantly suppressed after LDFA. These results indicate that LDFA causes prolonged suppression of NK cell function. Whether this suppression might have a long-term impact on the overall outcome, especially in cancer patients, remains to be determined.

Adult↗
PubMed1996

Human immunodeficiency virus infection and infective endocarditis among injecting drug users.

Human immunodeficiency virus (HIV) infection and infective endocarditis are serious complications of injection drug use. To determine whether HIV infection may increase the risk of endocarditis beyond that associated with drug injection, we performed a nested case-control study among injecting drug users taking part in an ongoing cohort. We identified 26 participants with infective endocarditis between cohort enrollment (in 1988-1989) and June 1992, through reviews of medical records and death certificates. We matched each endocarditis case with up to five controls (N = 120) on enrollment date, race/ethnicity, and follow-up time. Data were taken from baseline and from the one follow-up visit: the last visit before the endocarditis occurred for cases and the closest visit (+/- 3 months) for controls. We used conditional logistic regression to quantify the association between HIV serostatus at follow-up and subsequent endocarditis, after adjusting for a history of endocarditis or sepsis before enrollment, injection duration, current injection frequency, and a recent history of abscess at injection sites. Among current injectors at follow-up, the adjusted odds ratio (OR) of developing endocarditis for HIV-seropositive subjects with > or = 350 CD4 cells per microliter, compared with HIV-seronegative subjects, was 2.31 [95% confidence interval (CI) = 0.61-8.78]; the corresponding OR for HIV-seropositive subjects with < 350 CD4 cells per microliter was 8.31 (95% CI = 1.23-56.37). These data indicate that HIV-related immunodeficiency may independently increase the risk of infective endocarditis among injecting drug users.

Adult↗
PubMed1996

Alcohol use and T-lymphocyte subsets among injection drug users with HIV-1 infection: a prospective analysis.

OBJECTIVES: Alcohol use is known to alter immune function and has immunosuppressive effects that may modify T-lymphocyte subpopulations. However, there is no clear evidence regarding the relationship of alcohol use with the progression of immunodeficiency in human immunodeficiency virus-type 1 (HIV-1)-seropositive individuals, particularly injection drug users (IDUs). METHODS: Using prospective data from a cohort of IDUs in a study of the natural history of HIV infection, we examined the relationship of alcohol use and changes in T-lymphocyte subsets. Among the 2921 IDUs followed semiannually in outpatient clinics, 188 were documented HIV-1 seroconverters with known time of seroconversion. At each visit, all study participants were interviewed, underwent physical examinations, and had blood drawn for laboratory studies. Alcohol use was measured by reported frequency and quantity of alcoholic beverages. Longitudinal analyses included data for up to 5 years postseroconversion. To formally test the association of alcohol use with change in levels of CD4+ and CD8+ cells subsequent to HIV seroconversion, regression models incorporating autocorrelation structure were applied. RESULTS: Alcohol use was not appreciably related to age, gender, marital status, income, education, or the duration of intravenous drug use. CD4% decreased for all IDUs within the first 5 years after seroconversion, with no significant differences between alcohol categories. CD8% increased for all IDUs, with no significant differences by alcohol category within the first 2 years after seroconversion. However, between 2 to 5 years postseroconversion, there was a statistically significant increase among the heaviest drinkers: CD8% increased 6.9%/year [95% confidence interval (CI): 4.7, 8.0] for the IDUs who reported > 21 drinks/week, 2.4%/year (95% CI: 0.8, 4.0) for IDUs who drank 21 drinks/week or less, and 0.4% (95% CI: -2.1, 2.9) for abstainers. Similar results were obtained for CD4 and CD8 absolute counts. CONCLUSIONS: In this study population of IDUs, CD8% (but not CD4%) is associated with alcohol consumption early after HIV seroconversion. This is the first prospective study to date to assess the relationship of alcohol use with HIV progression from the time of HIV seroconversion among a cohort of IDUs. If confirmed in future investigations, the findings may have significant implications for prevention and early intervention programs aimed at inhibiting disease progression among HIV-positive IDUs.

Adult↗
PubMed1995

Seroepidemiology of hepatitis B virus in a population of injecting drug users. Association with drug injection patterns.

To investigate the epidemiology of hepatitis B virus (HBV) infection among injecting drug users, the authors assessed the prevalence of HBV seromarkers among 2,558 injecting drug users recruited through street outreach in Baltimore, Maryland, in 1988-1989. Eighty percent of the drug users had at least one HBV seromarker. HBV seropositivity was associated with increasing age, duration of injecting drug use, African-American ethnicity, injecting drugs at least once daily, and sharing needles or visiting "shooting galleries" during the previous 11 years, but not with high-risk sexual behaviors or a history of sexually transmitted disease. This finding is possibly due to the relative inefficiency of sexual transmission as compared with parenteral transmission in injecting drug users. In addition, HBV seropositivity was strongly associated with seropositivity for hepatitis C virus and human immunodeficiency virus. The authors conclude that HBV transmission among injecting drug users occurs primarily through the sharing of contaminated drug injecting equipment rather than through sexual relations, and that efforts to prevent HBV infection must target injecting drug users early in their injecting careers.

Adult↗
PubMed1995

Recent infection with human immunodeficiency virus and possible rapid loss of CD4 T lymphocytes.

To assess a hypothesized trend that persons recently infected with the human immunodeficiency virus (HIV) may have more rapid declines in absolute CD4 T-lymphocyte (CD4+ cell) counts than those who were HIV-infected in earlier years, sequential CD4+ cell counts in three groups who had definable dates of HIV seroconversion between 1978 and 1992 were reviewed. The CD4+ cell counts examined were from some of the longest extant studies in the United States: 100 homosexual and bisexual men engaged in ongoing observational cohort studies in San Francisco, Denver, and Chicago since 1978 (Group 1); 89 persons in South Carolina infected after 1986 (Group 2); and 155 injecting drug users participating in an observational cohort study in Baltimore since 1988 (Group 3). For all groups, individually and in the aggregate, mean CD4+ cell counts declined rapidly in the first year after HIV infection and then stabilized. However, there was no clear trend for lower (or higher) CD4+ cell counts by fixed time after HIV seroconversion among those seroconverting in recent compared with earlier calendar years. These data do not support a hypothesized trend for more rapid loss of CD4 T lymphocytes--and, by implication, more pathogenic strains of HIV-1--among persons acquiring HIV infection in recent years.

CD4 Lymphocyte Count↗
PubMed1995

Temporal trends of incident human immunodeficiency virus infection in a cohort of injecting drug users in Baltimore, Md.

OBJECTIVE: To measure the temporal trends in the incidence of infection with human immunodeficiency virus in a cohort of injecting drug users in Baltimore, Md, between 1988 and 1992. DESIGN: Study subjects were screened for antibodies to human immunodeficiency virus by enzyme-linked immunosorbent assay and confirmed with Western blot. They were followed up at 6-month intervals with repeated serologic screening and comprehensive interviews for human immunodeficiency virus risk factors. SETTING: Special study clinic. PARTICIPANTS: A cohort of 2960 participants were recruited and screened between February 1988 and March 1989. Recruitment criteria included an age of 18 years or older, a history of illicit drug injection since 1978, and the absence of the acquired immunodeficiency syndrome; subjects were subsequently tested for human immunodeficiency virus antibodies. Most subjects (85%) were not receiving methadone treatment at baseline and were recruited by word of mouth. MAIN OUTCOME MEASURE: Human immunodeficiency virus seroconversion. RESULTS: Of the 2247 seronegative participants at baseline, 1532 were followed up, and 188 (12.3%) had seroconverted by December 1992. The incidence of human immunodeficiency virus infection over time among users declined somewhat, especially among women; the overall incidence was 1.90 per 100 person-semesters, or 3.80% annually. The incidence, adjusted for gender, was higher in younger (< 35 years) than older (> or = 35 years) subjects (relative incidence, 1.75; 95% confidence interval, 1.29 to 2.38) and in women compared with men, adjusted for age (relative incidence, 1.29; 95% confidence interval, 0.95 to 1.80). The relative incidence among active compared with inactive drug users adjusted for age and gender was 1.58 (95% confidence interval, 1.06 to 2.35). CONCLUSIONS: Although the incidence of human immunodeficiency virus infection in this cohort of injecting drug users in Baltimore declined somewhat during the 4 years of follow-up, especially among women, the persistent annual incidence of nearly 4% during 3 1/2 to 4 1/2 years of observation suggests the need for additional strategies for prevention of infection, especially among those who continue injecting drugs. Newer methods of prevention, such as provision of sterile injection equipment, an effective human immunodeficiency virus vaccine, and wider availability of effective treatment or prevention of drug addiction, are urgently needed in these high-risk populations.

Adult↗
PubMed1995

Incidence and risk factors for human T-lymphotropic virus type II seroconversion among injecting drug users in Baltimore, Maryland, U.S.A.

To determine the incidence of and risk factors for human T-lymphotropic virus, type II (HTLV-II) seroconversion among injecting drug users (IDUs), specimens from IDUs recruited into the ALIVE Study in 1988/1989 were assayed at baseline for antibody to HTLV with use of enzyme immunoassay and Western blot. Participants were monitored semiannually with venipuncture and interviews. In 1992, the most recent sera of HTLV-negative participants were tested for HTLV with use of enzyme immunoassay and confirmed and typed by Western blot. For positive cases, assays were then performed for all intervening visits to determine the calendar time of seroconversion. Incidence rates were estimated using person-time. Risk factor analysis used a nested case-control design, with up to seven controls per case matched by time of study entry and duration of follow-up. At baseline, 251 HTLV-positive, 22 indeterminate, and 2,574 HTLV-seronegative IDUs were identified. Follow-up of the seronegative IDUs identified 38 seroconverters (all HTLV-II) over 5,813.6 person-years, for a rate of 0.7/100 person-years. Median lag time for seroconversion was 6.8 months. Factors associated with HTLV-II seroconversion included a specific needle-sharing practice called "backloading" within the previous 6 months [odds ratio (OR) = 6.52; 95% confidence interval (CI) = 1.94-21.95] and a baseline history of receiving money for sex (OR = 3.36; 95% CI = 1.32-8.57). Of those with more than one sex partner in the past 6 months, women were more likely than men to seroconvert (OR = 5.77; 95% CI = 1.33-25.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Vitamin A deficiency and wasting as predictors of mortality in human immunodeficiency virus-infected injection drug users.

A nested case-control study of vitamin A deficiency and wasting as risk factors for mortality from AIDS and infections was done within a large prospective cohort of human immunodeficiency virus (HIV)-infected injection drug users (IDUs). Fifty adult subjects who died from AIDS and infections were matched with 235 controls who survived. Plasma vitamin A, weight, and body mass index were measured. Mean length of follow-up was 2.4 +/- 1.1 years. Vitamin A deficiency occurred in 50% and wasting occurred in 38% of patients in the last visit before death. CD4 cells count < 200/microL, wasting, and vitamin A deficiency were associated with mortality. There was a higher risk of death in HIV-infected subjects with vitamin A deficiency (odds ratio [OR], 4.6; 95% confidence interval [CI], 1.8-11.3) and wasting (OR, 8.8; 95% CI, 2.7-28.2). Vitamin A deficiency and wasting are common during HIV infection and are independent predictors of mortality in HIV-infected IDUs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Correlates of hepatitis C virus infections among injection drug users.

Injection drug users are at high risk for hepatitis C virus (HCV) infection. In Baltimore, Maryland, the prevalence of anti-HCV is greater among injection drug users who are black, human immunodeficiency virus (HIV) infected, have injected longer, have injected more frequently, and have injected cocaine than among other injection drug users. HCV infection occurs quickly after the initiation of injecting illicit drugs, with 78% of study participants anti-HCV positive after 2 years of injecting. The prevalence of anti-HCV among injection drug users does not appear to be related to socioeconomic factors or sexual practices. Some injection drug users remain free of anti-HCV even after years of injecting and serologic evidence of other bloodborne pathogens. Some of these injection drug users have HCV infection, demonstrated by HCV RNA in their sera. However, the basis for viral persistence in the absence of anti-HCV and for the absence of HCV infection in long-term drug users is not known. Further studies are indicated to determine the mechanism or mechanisms for the absence of anti-HCV in persons exposed to the virus, because the biologic basis for this condition may elucidate the elements missing in the immune response of the majority of HCV-exposed persons who acquire persistent infection. In addition, interventions to prevent HCV infections should be applied in populations at risk for injection drug use early or before drug use begins.

Adolescent↗
PubMed1995

A simple modification in operative technique can reduce the incidence of nonanastomotic biliary strictures after orthotopic liver transplantation.

Nonanastomotic strictures after liver transplantations are a source of significant morbidity, often necessitating retransplantation. The purpose of this study was twofold: first to identify features associated with the development of this lesion; second, to make technical modifications that will decrease the incidence of this problem. In the first part of this study, 15 of 131 patients were diagnosed with nonanastomotic biliary stricture. A stepwise logistic-regression analysis associated donor cold ischemic time and dopamine dose with the development of nonanastomotic biliary strictures. All these patients had arterial reconstruction after partial revascularization of the liver with portal venous blood. Because the bile duct receives its blood supply from only the hepatic artery, we hypothesized that the prolonged period of warm ischemia from staged reconstruction of the vascular supply would promote the development of this lesion. In a second part of this study, the stricture rate in 45 patients with simultaneous revascularization using both the hepatic artery and portal vein was compared with that in 83 patients from the first part of this study initially revascularized with portal venous blood. All patients in the second study had grafts preserved using UW solution. Only 1 patient with simultaneous revascularization developed a nonanastomotic biliary stricture. Because we were unable to identify any significant complications related to this method of revascularization, we propose that the hepatic artery and portal vein should be released simultaneously, especially in patients receiving a graft with prolonged storage time.

Adenosine↗
PubMed1994

A pilot study of isotretinoin in the treatment of juvenile chronic myelogenous leukemia.

BACKGROUND: Juvenile chronic myelogenous leukemia (CML) is a rare myeloproliferative disease of infants and young children for which there is no effective therapy other than allogeneic bone marrow transplantation. In vitro, isotretinoin (13-cis-retinoic acid) attenuates both the spontaneous proliferation of leukemic peripheral-blood progenitor cells (granulocyte-macrophage colony-forming units) and their selective hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). We conducted a pilot study to evaluate the clinical efficacy of isotretinoin in juvenile CML. METHODS: To be eligible the patients had to have newly diagnosed untreated disease, leukocytosis with monocytosis, marrow with less than 25 percent blasts, hepatosplenomegaly, no chromosomal abnormalities, and negative viral cultures and antibody titers. Isotretinoin was administered orally in single daily doses of 100 mg per square meter of body-surface area. When possible, patients subsequently underwent bone marrow transplantation. RESULTS: Ten children (median age, 10 months) were enrolled in the study. In all 10 there was spontaneous colony formation of leukemic progenitor cells in vitro. In the eight patients tested there was hypersensitivity to GM-CSF. The only toxic effect of isotretinoin therapy was cheilitis in two patients. Four children had disease progression. Two children had complete responses to isotretinoin (normalization of the white-cell count and disappearance of organomegaly), three had partial responses (more than a 50 percent reduction in the white-cell count and degree of organomegaly), and one had a minimal response (more than a 50 percent reduction in the white-cell count, but a 26 to 50 percent reduction in the degree of organomegaly). The median duration of response was 37 months (range, 6 to 83). Three of the four children who had a complete or partial response and who did not undergo bone marrow transplantation were alive 36 to 83 months after the diagnosis of juvenile CML. The spontaneous colony formation in vitro was reduced in samples from the five patients in whom this factor was reassessed during treatment. There was also a reduction in the hypersensitivity of leukemic progenitor cells to GM-CSF in the two patients retested. CONCLUSIONS: Isotretinoin can induce durable clinical and laboratory responses in patients with juvenile CML.

Child, Preschool↗
PubMed1994

Drug-related behavior change for HIV transmission among American injection drug users.

While high risk drug-related behaviors for human immunodeficiency virus (HIV) transmission among injection drug users (IDUs) are asserted to have declined over time in response to the AIDS epidemic, evidence from longitudinal cohorts has been sparse. In a cohort of 810 IDUs (442 seronegatives and 368 seropositives) in Baltimore, we identified drug-related risk behaviors at four consecutive semi-annual visits. Using robust methods for repeated measurements and multiple logistic regression, we estimated the probabilities of maintaining and reducing risk behaviors according to HIV serostatus and time in the study. Seropositive participants were more likely to maintain lower risk behaviors, and behavior maintenance increased with time in study for both seronegative and seropositive IDUs. Greater risk reduction (towards non-use and not sharing injection equipment) was seen among seropositive IDUs, with behavior change occurring soon after enrollment in the study. While behavior changes have been reported, many active IDUs, especially those still at risk for acquiring HIV infection, have not adequately reduced their risk. Continuing prevention programs and efforts in vaccine development are imperative to reduce the risk of HIV infection among IDUs.

Baltimore↗