Acitretin therapy is effective for psoriasis associated with human immunodeficiency virus infection.

OBJECTIVE: To determine the safety, tolerability, and effectiveness of a newer retinoid, acitretin, as monotherapy for psoriasis associated with human immunodeficiency virus infection (PS-HIV). DESIGN: Pilot investigation. SETTING: An academic medical center. PATIENTS: Eleven patients selected from volunteers with PS-HIV were enrolled in a 20-week treatment protocol. Two patients discontinued participation in the study because of worsening psoriasis; a third patient was unable to continue treatment after having a myocardial infarction, presumably unrelated to acitretin therapy. INTERVENTION: Each patient received an optimized dose of acitretin during the period of observation. Clinical and laboratory assessments were performed every 2 weeks during the trial. MAIN OUTCOME MEASURES: The Psoriasis Area and Severity Index was used to assess the clinical response to treatment. To monitor for toxic drug effects, a panel of laboratory parameters, including complete blood cell count, biochemistry profile, urinalysis, HLA typing, skin biopsy for histological examination, and T-cell counts, was performed. RESULTS: Six (54%) of 11 patients with PS-HIV achieved good to excellent responses using acitretin monotherapy. Four patients (36%) achieved complete clearing. There was no evidence of a correlation between the pretreatment measures of immunosuppression and the therapeutic response. Parameters of immunosuppression were not exacerbated by acitretin therapy. CONCLUSIONS: Acitretin is a safe and effective treatment for PS-HIV. Both skin and joint manifestations of PS-HIV responded to acitretin therapy in most patients. Optimal results were achieved with a dose of 75 mg/d. The adverse effects were moderate and well tolerated. Acitretin does not appear to have immunosuppressive properties. A formal randomized clinical trial is warranted.

Immunochemical analysis of human kidney reticulin.

This study characterized the nature of reticulin fibrils from human kidney cortex by immunochemical analysis. Controls consisted of type I collagen fibrils derived from the kidney parietal capsule. Most of the fibrils in the capsule ranged in diameter from 60 to 80 nm whereas reticulin fibrils from the cortex ranged from 30-45 nm. Immunochemistry by light and electron microscopic examinations was carried out with antibodies directed against type I and type III collagens, their corresponding aminopropeptides, and decorin (PG-II). The ratio of type I to type III collagen was determined by cyanogen bromide peptide digests. This study showed that reticulin fibrils are hybrids of type I and type III collagens. Double immunoelectron microscopic examination showed that fibrils 20-25 nm consisted mainly of type I collagen some of which retained their aminopropeptide. Larger fibrils 30-35 nm labeled simultaneously for type I and type III collagens. However, most fibrils with diameters between 40-55 nm labeled for type III collagen and its corresponding aminopropeptide. No decorin was detected at the surface of reticulin fibrils. Purified reticulin consisted of 82% type III and 18% type I collagen whereas collagen derived from the capsule revealed 76% type I and 24% type III. The presence of the aminopropeptide of type III procollagen in reticulin fibrils is a striking feature and may play a role in regulating their diameter.

Percutaneous penetration and metabolism of topical (14C)flutamide in men.

This study was designed to determine the fate of the nonsteroid antiandrogen flutamide in men following a single 6-hr topical application of 5 mg 14C-labeled drug dissolved in 50% ethanol/50% propylene glycol. Analysis of 0-120 hr urine shows at least 16% of the applied flutamide is absorbed. Fifty-six percent of the dose is recovered from the site of application with cotton swabs moistened with 50% ethanol/50% propylene glycol. Flutamide plasma levels peak in 4 to 6 hr at about 1.3 ng/ml and then decline rapidly to about 0.08 ng/ml 24 hr after application. Only 13% of plasma 14C is associated with flutamide 6 hr after drug application. There are at least 10 plasma metabolites, of which 6 have been tentatively identified. These are alpha, alpha, alpha-trifluoro-4'-amino-m-acetotoluidide (A); alpha, alpha, alpha-trifluoro-4'-amino-2-methyl-m-lactotoluidide (B); alpha, alpha, alpha-trifluoro-4'-nitro-m-acetotoluidide (C); alpha, alpha, alpha-trifluoro-2-methyl-4'-nitro-m-lactotoluidide (D); alpha, alpha, alpha-trifluoro-4'-amino-2-methyl-m-propionotoluidide (E); and alpha, alpha, alpha-trifluoro-6-nitro-m-toluidine (F). (D) is the major plasma metabolite, and its concentration exceeds flutamide's between 8 and 24 hr after drug. All the plasma metabolites are found in 0-24 hr urine in minor amounts. An additional metabolite, alpha, alpha, alpha-trifluoro-amino-5-nitro-p-cresol (G), accounts for 27% of urine 14C.

Disposition of a new, nonsteroid, antiandrogen, alpha,alpha,alpha-trifluoro-2-methyl-4'-nitro-m-propionotoluidide (Flutamide), in men following a single oral 200 mg dose.

A single oral 200 mg dose of tritium-labeled alpha,alpha,alpha-trifluoro-2-methyl-4'-nitro-m-propionotoluidide (flutamide) was given to 3 men. Analysis of plasma, urine and feces shows flutamide is rapidly and completely absorbed and excreted mainly through the kidneys. Analysis of plasma radioactivity shows flutamide is rapidly and extensively metabolized--only 2.5% of plasma radioactivity 1 h after dosing is associated with flutamide. At least 10 other metabolites are present, of which 6 have been tentatively identified. These are alpha,alpha,alpha-trifluoro-4'-amino-m-acetotoluidide (A); alpha,alpha,alpha-trifluoro-4'-amino-2-methyl-m-lactotoluidede (B); alpha,alpha,alpha-trifluoro-4'-nitro-m-acetotoluidede (C); alpha,alpha,alpha-trifluoro-2-methyl-4'-nitro-m-lactotoluidide (D); alpha,alpha,alpha-trifluoro-4'-amino-2-methyl-m-propionotoluidide (E); and alpha,alpha,alpha-trifluoro-6-nitro-m-toluidine (F). (D) represents 23% of plasma tritium 1 h after drug and is a major metabolite at all other measured times. Each of the other metabolites accounts for less than 10% of plasma radioactivity. Minor amounts of flutamide and (A) through (F) are found in 0-24-h urine. An additional metabolite, alpha,alpha,alpha-trifluoro-2-amino-5-nitro-p-cresol, constitutes 25% of urine tritium. The rapid conversion of flutamide to (D) and the high plasma levels of (D) suggest (D) might be the active form of flutamide.

Maternal and fetal hemodynamic effects of diazoxide.

Effects of diazoxide on systemic and uterine hemodynamics as well as on fetal circulation and blood respiratory gases were investigated in chronically instrumented pregnant sheep. Diazoxide was administered intravenously either to the ewe or directly to the fetus in doses calculated on the basis of body weight. Transfer of drug across placenta was also investigated. Results showed that: a) when injected into the mother, there was consistent hypotensive effect with increased cardiac output and decreased systemic vascular resistance; uterine blood flow might not change or might decrease slightly with moderate hypotension; when maternal systemic arterial pressure fell to critical closing pressure level, uterine flow decreased significantly; but despite these maternal changes, the fetal circulatory functions were not significantly altered; b) when injected into the fetus in doses up to 15 mg/kg, diazoxide failed to alter fetal circulation appreciably; c) diazoxide crossed the placenta when injected intoeither mother or fetus according to a definite gradient; fetal levels were always lower than maternal levels because of rapid loss of the drug by the fetus; d) moderate maternal and fetal hyperglycemia occurred after drug administration.