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.

Dilated heart muscle disease associated with HIV infection.

As more effective therapies have produced longer survival times for HIV-infected patients, non-infectious complications of late stage HIV infection such as the development of severe global left ventricular dysfunction (dilated heart muscle disease) have emerged. The demographic and clinical characteristics of HIV-infected patients who develop dilated heart muscle disease as well as potential risk factors are, as yet, poorly characterized. Of 174 patients enrolled in a prospective longitudinal study, a total of nine patients, all with CD4 T cell counts < 200 mm-3, developed symptomatic heart disease (congestive heart failure n = 7, sudden cardiac death n = 1 and cardiac tamponade n = 1); three of these patients developed progressive cardiac dysfunction leading to primary cardiac failure and death. An additional 55 HIV-infected patients referred to our Cardiomyopathy Service were found to have global left ventricular dysfunction, with 84% having New York Heart Association Class III or IV congestive heart failure on presentation. Clinical characteristics associated with severe symptomatic cardiac dysfunction included low CD4 T cell counts, myocarditis associated with non-permissive cardiotropic virus infection on endomyocardial biopsy and persistent elevation of anti-heart antibodies. No relationships to any specific HIV risk factor or opportunistic infection were found. These findings suggest that a severe form of HIV-related dilated heart muscle disease is largely a disease of late stage HIV infection. Virus-related myocarditis and cardiac autoimmunity may play a role in the pathogenesis of progressive cardiac injury. Long-term longitudinal studies of larger HIV-infected cohorts are warranted to identify clinical, behavioral and immunologic risk factors.

Patterns of myocardial cell adhesion molecule expression in human endomyocardial biopsies after cardiac transplantation. Induced ICAM-1 and VCAM-1 related to implantation and rejection.

Conflicting patterns of myocardial cell adhesion molecule expression associated with cardiac rejection have emerged from numerous studies of randomly selected cardiac biopsies. We designed a prospective, longitudinal study which reports both qualitative and quantitative levels of myocardial ICAM-1, VCAM-1, E-selectin, and P-selectin expression in sequential human cardiac allograft biopsies. Intense ICAM-1 and VCAM-1 staining was found in all biopsies during the first three weeks after transplant and coincided with elevated serum levels of troponin T, a sensitive marker of ischemic myocyte injury. Baseline ICAM-1 and VCAM-1 expression returned within three to four weeks, as did serum troponin T levels in all patients who did not develop rejection. All 29 rejection episodes encountered were associated with intense ICAM-1 staining, while 24 of the 29 (83%) had intense VCAM-1 staining. Increased ELAM-1 and CD62 staining was only rarely observed. Persistence of increased ICAM-1 and VCAM-1 staining after treated rejection episodes predicted a recurrent rejection episode within two months (75% positive and 100% negative predictive value). Objective quantitative measurements by radioimmunoassay (RIA) confirmed these patterns of induced ICAM-1 and VCAM-1 expression. Thus, longitudinal monitoring of serial biopsies for myocardial ICAM-1 and VCAM-1 expression could be useful in the early detection of rejection episodes and monitoring the efficacy of immunosuppressive therapy.

Myocarditis and cardiotropic viral infection associated with severe left ventricular dysfunction in late-stage infection with human immunodeficiency virus.

OBJECTIVES: The purpose of this study was to characterize the histologic and immunopathologic results of 37 endomyocardial biopsy samples from patients infected with human immunodeficiency virus type 1 (HIV-1) who were evaluated for unexplained global left ventricular dysfunction. BACKGROUND: Recent studies have identified a growing number of patients infected with HIV-1 who develop unexplained left ventricular dysfunction and congestive heart failure. Myocarditis has been confirmed at autopsy in small numbers of such patients, although a pathogenic opportunistic infectious agent can rarely be identified. METHODS: All patients had moderate to severe global left ventricular hypokinesia on two-dimensional echocardiography. Endomyocardial biopsy samples were evaluated by standard histologic studies, immunoperoxidase staining and in situ hybridization for cytomegalovirus and HIV-1 gene sequences. RESULTS: Twenty-eight patients presented with New York Heart Association functional class III or IV congestive heart failure. Four patients had myocarditis secondary to known etiologies (opportunistic infection n = 2; drug-induced hypersensitivity myocarditis n = 2). Of the remaining 33 samples, 17 (51%) showed histologic evidence of idiopathic active or borderline myocarditis. Immunohistologic findings revealed induced expression of major histocompatibility class I antigen on myocytes and increased numbers of infiltrating CD8+ T lymphocytes. Specific hybridization within myocytes was observed in 5 of 33 samples with the HIV-1 antisense riboprobe and in 16 of 33 samples with the cytomegalovirus immediate early (IE-2) antisense riboprobe. All but one patient with specific myocyte hybridization presented with congestive heart failure; all patients had myocarditis and CD4+ cell counts < 100/mm3. CONCLUSIONS: This study demonstrates that cardiotropic virus infection and myocarditis may be important in the pathogenesis of symptomatic HIV-associated cardiomyopathy.

Photoperiod and temperature affect reproductive and nonreproductive functions in male prairie voles (Microtus ochrogaster).

Adult male prairie voles (Microtus ochrogaster) were housed for 10 wk and exposed to long (16L:8D) or short (8L:16D) photoperiods at 21 degrees or 5 degrees C. Maintenance in short day lengths reduced testicular, epididymal, and seminal vesicle mass and also significantly depressed spermatogenic activity. Cold ambient temperature further suppressed gonadal size in voles exposed to short days. Several pelage characteristics were affected by photoperiod, but not by temperature. Increased fur density, fur depth, and length of guard hair and underhair were observed in voles exposed to short days. Intrascapular brown fat and gonadal fat pad mass as well as body mass were significantly less in voles housed in cold temperatures than in voles exposed to warm ambient temperatures; photoperiod did not affect these parameters. Approximately 30% of the male voles exposed to short days maintained their reproductive systems, yet they clearly processed photoperiodic information; all short-day males, regardless of reproductive condition, had comparable winter pelage development. Our results suggest that in prairie voles, photoperiod may be a predictive cue for reproductive function in nature; however, it appears that pelage development is a more obligatory response to photoperiod than is reproduction.