Relationship between load of virus in alveolar macrophages from human immunodeficiency virus type 1-infected persons, production of cytokines, and clinical status.

The level of human immunodeficiency virus type 1 (HIV-1) in lymphocytes and mononuclear phagocytes (MP) from the blood and pulmonary alveoli from 14 HIV-1-infected subjects during early (asymptomatic) and late (AIDS) stages of disease and the relationship between virus burden in MP and cytokine expression were assessed. Among asymptomatic subjects, HIV-1 was undetectable or low in both blood monocytes and alveolar macrophages (AM). Among subjects with AIDS, there was a significant increase of HIV-1 in AM but not monocytes. The level of HIV-1 in blood lymphocytes was higher than in either monocytes or AM. AM (but not monocytes) expressed increased levels of lipopolysaccharide-stimulated cytokine mRNA (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) during both early and late stages of HIV-1 infection regardless of virus load. AM thus may serve as a reservoir for virus in late stages of disease yet contribute to the immunopathogenesis of lung disease in both early and late stages through increased cytokine expression.

Beta 2-microglobulin, HIV-1 p24 antibody and acid-dissociated HIV-1 p24 antigen levels: predictive markers for vertical transmission of HIV-1 in pregnant Ugandan women.

OBJECTIVES: To evaluate the clinical utility of plasma beta 2-microglobulin (beta 2M) levels, acid-dissociated HIV-1 p24 antigen, and HIV-1 p24-antibody titers in predicting HIV-1 vertical transmission in 227 HIV-1-infected Ugandan pregnant women. DESIGN: Plasma beta 2M levels, acid-dissociated HIV-1 p24-antigen positivity, and HIV-1 p24-antibody titers were determined using commercial enzyme immunoassays (EIA) in a Ugandan cohort of 52 HIV-1-seropositive transmitting mothers, 175 HIV-1-seropositive non-transmitting mothers, and 52 seronegative mothers within 6 weeks prior to delivery. RESULTS: Transmitter mothers had significantly higher plasma concentrations of beta 2M (1.80 +/- 1.13 mg/l) than non-transmitter seropositive mothers (1.32 +/- 0.81 mg/l; P = 0.0013). Similarly, a significantly higher proportion of transmitter mothers had detectable p24 antigen than non-transmitter mothers [six out of 51 (11.8%) versus six out of 173 (3.5%); P = 0.03]. Compared with the vertical transmission rate of 23% in the seropositive group, the positive predictive values of a beta 2M level > 1.5 mg/l or detectable HIV-1 p24 antigen for vertical transmission were 34 and 50%, respectively. Five of six (83.3%) seropositive mothers with both a beta 2M level > 1.5 mg/l and detectable p24 antigenemia transmitted HIV-1 infection to their infants compared with 25 of 124 (20.2%) seropositive mothers with values below the cut-off values for both tests (P = 0.00249). However, beta 2M was not found to be a significant independent predictor of vertical transmission when analyzed in a multivariate model with p24 antigenemia. There was no significant difference in HIV-1 p24-antibody titers in transmitter mothers versus non-transmitter mothers (P = 0.299). CONCLUSION: beta 2M levels and acid-dissociated HIV-1 p24-antigen assays may be used to predict which HIV-1-infected pregnant women are at greatest risk for vertical transmission. However, only the p24-antigen test was independently predictive of vertical transmission and its clinical utility is limited.

Accessory function and properties of monocytes from healthy elderly humans for T lymphocyte responses to mitogen and antigen.

The waning of cell-mediated immunity during aging has been attributed primarily to defects in T lymphocyte properties and functions. We assessed the potential contribution of accessory dysfunction of monocytes from the elderly on responses of T cells to phytohemagglutinin (PHA) and to tetanus toxoid after in vivo boosting. Accessory function of monocytes from the elderly subjects for T lymphocyte responses to tetanus toxoid was comparable to the young. Expression of the cytokines interleukin-1, interleukin-6 and tumor necrosis factor, the cell adhesion molecules ICAM-1 and LFA-3 and the class II major histocompatibility molecule HLA-DR by monocytes from the elderly and young subjects was similar. T lymphocytes from the elderly responded poorly to PHA. Monocytes from the elderly had a decreased accessory function for PHA-stimulated T cells from young, third donors. Thus, although many accessory properties of monocytes from the elderly are normal, the monocyte and T lymphocyte defects in the elderly for mitogen may represent interactive factors in cell-mediated immunity during aging.

Clinical management of keratoconus. A multicenter analysis.

The clinical management of 746 eyes in 417 patients referred for keratoconus from January 1984 through January 1988 was retrospectively analyzed. In 357 patients, 554 eyes (74%) did not require surgery and were managed with contact lenses or spectacles, 156 eyes (21%) in 137 patients either underwent penetrating keratoplasty (PK) (140 eyes) or surgery was recommended (16 eyes), and 36 eyes (4%) in 34 patients underwent epikeratoplasty. Comparing baseline and final examination findings, the nonsurgical group showed a significant improvement in average best-corrected visual acuity from 20/30 to 20/25, the PK group from 20/70 to 20/25, and the epikeratoplasty group from 20/40 to 20/30. Average keratometry was unchanged in the nonsurgical group, but decreased by 10.7 diopters (D) for the PK group and 6.5 D for the epikeratoplasty group. Corneal cylinder was unchanged in the nonsurgical group, whereas there was a reduction of the percentage of eyes with indeterminant cylinder from 55 to 2% in the PK group and from 36 to 0% in the epikeratoplasty group. Previous contact lens history, best-corrected visual acuity of 20/50 or worse, and average keratometry of 55 D or greater at baseline were associated with a significant risk for PK. No baseline variables were associated with significant risk for epikeratoplasty, suggesting that this group was similar to the nonsurgical group, except for contact lens intolerance. The nonsurgical management of keratoconus continues to play a predominant role in the management of this disorder in a referral population.

Lipoprotein cholesterol, vitamin A, and vitamin E in an alcoholic population.

Elevated alcohol consumption is associated with an increased risk of cancer. Reasons for this association are not well established but may relate to alterations in cholesterol, vitamin A (carotene and retinol), and vitamin E metabolism, since low levels of these factors have been linked to risk of cancer. Blood levels of cholesterol, carotene, retinol, and vitamin E were determined in 192 male alcoholics entering into an alcohol detoxification program. Compared to nonalcoholic populations, their cholesterol (187 mg/dl) and carotene (94 micrograms/dl) concentrations were markedly reduced at entrance; however, abstinence of 33 days returned both to normal levels. In contrast, the retinol and vitamin E levels were within the normal range at baseline and remained relatively stable throughout rehabilitation. Of particular interest was that the low density lipoprotein cholesterol was highly correlated with carotene (r = +0.40, whites, r = +0.54, blacks). The results suggest that alterations in the metabolism of cholesterol and carotene, due to alcohol intake, may partially account for the relationship of alcohol to increased cancer risk.

Alcohol consumption and high density lipoprotein cholesterol concentration among alcoholics.

Alcohol consumption is one of the major determinants of serum high density lipoprotein (HDL) cholesterol. Very few studies have examined the correlation between alcohol consumption and high density lipoprotein subclasses. It has been suggested that HDL2 is probably the fraction that is associated with reduced coronary heart disease. The current research investigated the relationship between alcohol consumption and HDL2 and HDL3 cholesterol among 234 alcoholics who were admitted for abstinence. The results indicated that the elevated serum HDL cholesterol concentrations among alcoholics were a combination of an increase in both HDL2 and HDL3 cholesterol. HDL cholesterol and HDL2 cholesterol increased with more alcohol consumption until about 450 ml of ethanol consumption per day when serum HDL cholesterol and HDL2 cholesterol decreased. HDL3 cholesterol showed a similar trend but was not statistically significant. In addition, the serum concentrations of HDL cholesterol and subclasses were positively correlated with liver enzymes. Those with alcohol-related liver disease had significantly higher HDL and HDL2 cholesterol levels than those without. Both HDL cholesterol and subclasses decreased concomitantly with the decline in liver enzymes within one month of abstinence. The possible biologic mechanisms linking alcohol drinking with HDL cholesterol through liver induction and sex hormone changes are discussed.