Ribavirin disposition in high-risk patients for acquired immunodeficiency syndrome.

Ribavirin is a broad-spectrum antiviral drug that has in vitro activity against human immunodeficiency virus. To determine the kinetics of ribavirin, 17 symptom-free homosexual men with lymphadenopathy were studied. Single doses of ribavirin, 600, 1200, or 2400 mg, were given orally or intravenously. The plasma ribavirin concentration-time profiles were well fitted by a three-compartment open model. Ribavirin followed linear kinetics over the dose range studied. The mean 1-hour postinfusion concentrations after intravenous ribavirin, 600, 1200, and 2400 mg, were 8.0, 19.7, and 37.1 mumol/L, respectively. The mean +/- SD plasma beta-phase half-life, terminal-phase (gamma) half-life, and volume of distribution at steady state were 2.0 +/- 1.1 hours, 35.5 +/- 14.0 hours, and 647 +/- 258 L, respectively. The mean ribavirin renal clearance and total body clearance were 99 +/- 30 and 283 +/- 37 ml/min, respectively. After an oral dose of 600, 1200, and 2400 mg, the mean peak plasma ribavirin concentrations (which occurred 1.5 hours after administration) were 5.1, 9.9, and 12.6 mumol/L, respectively. The mean absorption half-life and bioavailability of ribavirin were 0.5 hour and 45%. Ribavirin had no plasma protein binding and the drug accumulated within red blood cells. In conclusion, ribavirin is incompletely absorbed from the gastrointestinal tract, its renal excretion accounts for approximately one third of the drug's elimination, and drug accumulation (greater than threefold) will result with repetitive dosing at the 6- to 8-hour dosing interval currently used.

Expanded scoring criteria for the design fluency test: reliability and validity in neuropsychological and college samples.

In spite of sensitivity to right frontal lobe dysfunction, the Design Fluency Test (DFT) has been limited by one global score with little psychometric data. This study developed an expanded scoring system with standardized instructions for multiple dimensions of design performance and provided reliability and validity data in a college (n = 64) and diverse neuropsychological sample (n = 165). The scoring system allowed reliable scoring of number of novel designs, complexity of designs, variations in designs, and concrete, frankly perseverative, and scribbled responses. Performances for a college sample were relatively stable at 1-month retest, but showed practice effects for number of novel designs and complexity. Two principal components showed modest, expected relationships to other neuropsychological measures in the clinical sample. Clinical subjects with a history of closed-head injury or dementing disorder showed impaired DFT performances, with complexity the most sensitive indicator of impairment.

Cryptosporidiosis in homosexual men.

Between April 1982 and June 1983, cryptosporidiosis was diagnosed in six homosexual men. Four patients with the acquired immunodeficiency syndrome had lymphopenia, cutaneous anergy, and profoundly impaired cellular immunity; their cryptosporidiosis was severe, unremitting, and refractory to all therapy. Two patients without other opportunistic infections or Kaposi's sarcoma had moderately impaired cellular immunity but not lymphopenia or anergy; their enteric illness was self-limited. Cryptosporidium recently had been recognized as a human pathogen that is transmitted through fecal-oral contamination. The severity of human cryptosporidiosis appears to be determined primarily by immunocompetence of the patient. These six homosexual men, with different degrees of immunologic impairment, had two clinically divergent forms of cryptosporidiosis. Their cases raise questions about human transmission of Cryptosporidium and the prognostic significance of this disease in patients who are at high risk for developing the acquired immunodeficiency syndrome.