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The pharmacokinetics of ganciclovir after oral valganciclovir versus intravenous ganciclovir were compared in allogeneic stem cell transplant recipients with stable graft-versus-host disease of the gastrointestinal tract. Twenty-two evaluable adult patients were randomized to receive a single dose of open-label study drug (900 mg of oral valganciclovir or 5 mg/kg of intravenous ganciclovir). After a washout period of 2 to 7 days, patients were crossed over to receive the alternate study drug. Ganciclovir and valganciclovir concentrations in plasma were measured over 24 hours after dosing. Noninferiority of 900 mg of valganciclovir relative to intravenous ganciclovir was concluded if the lower limit of the 1-sided 95% confidence interval of the ratio of least-square means of the ganciclovir area under the curve (AUC) for the 2 study drugs was >80%. Valganciclovir was found to be rapidly absorbed and converted into ganciclovir. The ganciclovir exposure after 900 mg of valganciclovir noninferior to that of intravenous ganciclovir (AUC0-infinity, 52.1 and 53.8 microg.h/mL, respectively; 95% confidence interval of the ratio of least square means of AUC0-infinity, 82.48%-118.02%). Oral valganciclovir could be a useful alternative to intravenous ganciclovir in certain stable stem cell transplant patients who require prophylaxis or preemptive therapy for cytomegalovirus infection. more...

The diagnosis and management of infectious complications associated with injection drug use (IDU) are among some of the more challenging aspects of working with substance abusing populations. As the population of injection drug users age, we expect the number and severity of these complications to increase. Commonly seen infections, such as bacterial endocarditis and bacterial infections of bones, joints, and soft tissue, are now frequently complicated by concurrent immunodeficiency. Parenterally and sexually transmitted viral hepatitis is responsible for significant IDU morbidity and mortality. The human leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU with uncertain long-term clinical effects. Immune dysfunction has been described in the IDU for decades, but the impact of host immune compromise on the transmission and the course of HIV-1 has yet to be fully appreciated. The integration of the treatment of substance abuse and its concurrent psychiatric disorders with the management of infectious complications, including immunodeficiency, promises to improve patient compliance with possible savings of overall medical costs. more...

The seroprevalence and incidence of hepatitis A, B, C, and E virus infection were determined among North American missionaries (n = 328) serving in various geographic locations between 1967 and 1984. The mean age of subjects at entry into the study was 39.7 years (range 5-73 years); 65% were female; 89% had lived outside the United States before the study began. Seventy-eight percent of subjects served in sub-Saharan Africa during the study. At initial evaluation, 50.9% of the subjects had antibodies to hepatitis A virus (total anti-HAV), 8.5% to hepatitis B virus core antigen (total anti-HBc), 0.6% to hepatitis C virus (total anti-HCV by second-generation immunoblot assay), and 0% to hepatitis E virus (IgG anti-HEV). After an average period of service of 7.3 years (2,396 person-years total), 5.8% of the missionaries seroconverted to anti-HAV, 5.5% to anti-HBc, 0.6% to anti-HCV, and 0% to anti-HEV. This study indicates a relatively low risk of hepatitis C and E virus infection among missionaries while confirming the previously reported high risk of hepatitis A and B virus infection. Hepatitis A and B vaccination is recommended for long-term travelers to developing countries. more...

This study examined current and proposed drug testing policies from a stratified random sample of colleges and universities in the United States. Two-hundred forty-five of the 288 athletic directors surveyed responded, and 29% reported drug testing of their student athletes. Testing was most commonly conducted on a random basis, with cocaine and amphetamines the most frequently screened drugs, 85% and 83%, respectively. Only 56% tested for other specific performance-enhancing drugs such as steroids. Referral for treatment was the most common consequence of testing positive. Among schools conducting testing, the majority of students supported the program, whereas in schools without a testing program, it was anticipated that the majority of students would be opposed. It is suspected that more schools will initiate testing over the short term. more...

A retrospective Medical Examiner case review of all deaths in Maryland where either fluoxetine or tricyclic antidepressant (TCA) use was forensically detected was conducted for the time period January 1987-July 1991. Case records and toxicology reports from the Office of the Chief Medical Examiner were reviewed to determine cause and manner of death, circumstances of death, demographic information on the decedent, prior medical history of the decedent, and presence and level of either fluoxetine or TCA in various body fluids/tissues. Suicide was the manner of death most frequently associated with TCA and fluoxetine detection. Violent methods were more often associated with fluoxetine suicides than with TCA suicides (65% v. 23%, P < 0.001). Demographic characteristics of antidepressant-related deaths in Maryland were similar to those of the entire USA. Possible explanations for the results obtained include the inherent lower lethality of fluoxetine compared to the TCAs, necessitating the use of additional means to complete the act of suicide; that physicians may have switched more impulsive, high risk patients to this new agent as it became available, thus creating a selection bias for more violence-prone individuals in the fluoxetine group; or that fluoxetine may be associated with induction of violence and/or suicidal ideation. Further research examining the possible association of these agents with violent acts is warranted. more...

The U.S. Public Health Service Commissioned Corps performs health promotion and disease prevention activities and provides clinical care. The authors examined the epidemiology of deaths among active duty personnel and the hypothesis that, based on the mission, mortality would be less than in the general population, and that deaths would reflect nonpreventable causes. A retrospective record review for the period 1965-89 showed 118 active duty deaths, 26 percent of the number anticipated in a general population group adjusted for age, sex, and race or ethnicity. The five major causes of death were coronary heart disease, suicide, motor vehicle crash, malignant neoplasm, and drowning. Beginning with the mid-1980s, infectious disease became a principal cause of death, the only cause for which the rate trended upward. Among professionals, death rates were highest among sanitarians and veterinarians, and lowest among pharmacists. The only causes for which deaths exceeded the expected number involved suicides and possibly deaths related to acquired immunodeficiency syndrome. Active duty status in the Commissioned Corps was associated with a death rate less than that of comparable groups in the general population. Many of the premature deaths were attributable to preventable causes. more...

Serum specimens obtained from a nationwide sample of parenteral drug abusers (PDAs) during the period 1971-72 had previously been screened for human immunodeficiency virus (HIV) antibodies. Some specimens were considered to be positive to both ELISA and Western blot (WB) analysis. These findings have been a topic of controversy, since HIV was not thought to have penetrated at-risk populations at such an early date. This study was a followup of those PDAs with apparent seropositivity to WB analysis. Of 10 persons followed, only one death (in 1985) was documented, and postmortem findings were inconsistent with HIV infection. Eight of the remaining PDAs were traced and found to be alive and well in 1989. Fresh specimens were obtained from the two persons with the strongest 1971-72 WB staining and were found to be both ELISA and WB negative on retesting. Their T-cell parameters were within normal limits. We concluded that the earlier WB results were most likely false positives and that definitive evidence of HIV infection in the U.S. addict population as early as 1971-72 is still lacking. more...