Dehydroepiandrosterone as predictor for progression to AIDS in asymptomatic human immunodeficiency virus-infected men.

The steroid hormone dehydroepiandrosterone (DHEA) has been reported to protect against certain viral infections in animal models and to be a modest inhibitor of human immunodeficiency virus type 1 (HIV-1) infection in vitro. Serum DHEA levels were determined in 41 asymptomatic HIV-1-seropositive subjects, who progressed to AIDS within 5 years after entering a cohort study, in 41 HIV-1-seropositive controls, who remained asymptomatic, and in 41 HIV-1-seronegative controls. At entry, DHEA levels were higher in the seronegative group (median, 13.3 nmol/l) than in either the seropositive nonprogressors (median, 9.2 nmol/l; P = .01) or the progressors (median, 7.2 nmol/l; P less than .001). DHEA levels in the progressors approximately 5 months before the diagnosis of AIDS were lower than the levels in the nonprogressors after the same follow-up (median, 5.6 vs. 8.8 nmol/l; P = .007). DHEA levels less than 7 nmol/l and CD4+ cell counts less than 0.5 x 10(9)/l both proved to be independent predictors for disease progression in HIV-1-infected men.

Sensitivity and tolerance to nicotine in smokers and nonsmokers.

We studied the responses of smokers and lifelong non-smokers to transdermal nicotine patches over 24 h in three groups of subjects: non-smokers on a 15 mg patch (n = 8), non-smokers on a 30 mg patch (n = 8) and smokers on a 30 mg patch (n = 8). Unexpectedly, the non-smokers appeared to absorb nicotine more rapidly. The increase in blood nicotine concentrations of non-smokers over the first 2 h of patch use was double that of the smokers, with mean increases of 4.5 (SD = 3.7), 10.9 (SD = 4.2) and 4.1 (SD = 2.7) ng/ml in the three groups, respectively (P less than 0.005). The smokers had no pleasant or unpleasant effects from the 30 mg patch (X Cmax 13.9 ng/ml, SD = 4.9; Tmax 8.75 h) but all eight non-smokers experienced mild nausea and lightheadedness (P less than 0.01) within the first hour, and seven dropped out (P less than 0.01) at 3-8 h due mainly to severe nausea, vomiting or headache (X Cmax 18.4 ng/ml, SD = 4.9; Tmax 5.25 h). Only one non-smoker dropped out on the 15 mg patch, but five had transient nausea in the first hour (X Cmax 7.9 ng/ml, SD = 3.0; Tmax 8.0). Our study provides evidence of chronic pharmacodynamic nicotine tolerance in smokers, but does not address whether this is acquired or innate. The higher rate of transdermal nicotine absorption in non-smokers is unexplained and requires replication.

Clinical and pharmacokinetic properties of a transdermal nicotine patch.

We examined the pharmacokinetics of a transdermal nicotine patch and evaluated the usefulness of such a patch in a pilot smoking-cessation program. Use of the patch was associated with plasma nicotine concentrations that were comparable to smoking or to the use of other smoking-cessation devices. However, these plasma concentrations were maintained for 24 hours, and the patch appeared to be suitable for use once a day. Its use in a 6-week placebo-controlled double-blind study resulted in a significant degree of smoking cessation or in reduction of smoking activity. The findings suggest that it may be valuable to extend investigations to a larger population and that transdermal nicotine may have a useful role in smoking-cessation therapy.

Lipoid proteinosis; a clinical, pathological and genetic study.

The clinical, pathological, and genetic findings in two closely related families in which a number of cases of lipoid proteinosis occurred are described. The necropsy findings, particularly the neuropathological aspects, in a patient who died from a coincidental pancreatic carcinoma are detailed. The genetic aspects are reviewed.

Familial partial trisomy 15.

A family, including two sibs with partial trisomy 15 is described. Maternal chromosome analysis revealed 46,XX/47,XX,+15q-, mosaicism. These findings are discussed in relation to seventeen previously published cases, some of which were sporadic and others due to maternal balanced translocation.