Ethical requirements for occupational health research--compliance arrangements for a single company in relation to a recent major nuclear industry study.

The media coverage given to occupational health studies in the field of ionizing radiation has, on occasion, been the cause of very real distress to radiation workers and their families. In response to this situation the Chief Medical Officers of the major UK nuclear companies developed an ethical policy for future involvement in research, based on the duty of care which researchers owe to a key customer of such studies: the worker. The policy consists of four principal elements: medical confidentiality; worker information; worker consent and the guarantee of the availability to the workers of pre-publication knowledge of the results. The policy issued in 1991/92 has achieved growing acceptance among researchers and medical journals, though the medical officers involved have been aware of some scepticism, particularly in relation to the practicalities of the dissemination of pre-publication information. The Record Linkage Study published in November 1997 marked a major piece of research work involving data from 120,000 radiation workers that had been carried out since the development of the policy. This paper reports on the successful compliance arrangements to meet the ethical requirements of that study within a single UK nuclear company, and is published to demonstrate that with commitment from researchers, the journal and occupational health staff such ethical requirements, and particularly the need for pre-publication information can be met in full.

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.

Antiviral therapy with ganciclovir for cytomegalovirus retinitis and bilateral exudative retinal detachments in an immunocompromised child.

A child with bilateral cytomegalovirus (CMV) retinitis, vitritis, and exudative retinal detachments, who was in remission from stage IV neuroblastoma and status post-chemotherapy and autologous bone marrow transplantation, was treated with ganciclovir. The drug is a new acyclic nucleoside antiviral drug with potent antiCMV activity. There was bilateral retinal reattachment, clearing of vitritis and regression of retinal exudates and hemorrhages, with concomitant resolution of viral shedding in urine and blood, on ganciclovir 7.5 mg/kg per day. There was recurrence of exudative detachments, vitritis and retinitis when the dose was reduced to 2.5 mg/kg per day, and regression of these findings when the dose was again increased to 7.5 mg/kg per day. Despite continued therapy at this dose, a relapse occurred. When the dose of drug was doubled to 15 mg/kg per day, there initially was a partial therapeutic response, followed by a subsequent relapse. No further response was seen when the dose was increased to 19.5 mg/kg per day. This patient was treated with ganciclovir for a total of 192 days. No adverse reactions to ganciclovir were seen. On the last day of drug administration, there were persistent bilateral exudative retinal detachments and progressive optic nerve head involvement with optic disc pallor, despite quiescence of the retinitis.

Herpes zoster and zosteriform herpes simplex virus infections in immunocompetent adults.

Among 111 immunocompetent patients referred to a general hospital setting with the clinical diagnosis of herpes zoster, viral cultures were obtained from 47 patients. Six of these patients (13 percent) had herpes simplex virus isolated, with four of the six infections involving the facial distribution, and the other two involving the T4 (breast) distribution. Excluding those in whom herpes simplex virus was isolated, the mean age (+/- SD) of the remaining 105 patients was 50 +/- 19 years. Thirty-two percent of the patients were at least 65 years old; however, 39 percent were younger than 40 years of age. Thus, herpes zoster frequently occurs in young, immunocompetent adults. Also, since zosteriform rashes may be caused by herpes simplex virus, viral cultures of lesions are useful to differentiate infections caused by herpes simplex virus from those due to varicella-zoster virus. The need to distinguish between these two viruses may be important with the advent of antiviral drugs and for use of the proper epidemiologic isolation procedures.

Antiviral therapy for cytomegalovirus retinitis in AIDS with dihydroxy propoxymethyl guanine.

Six patients (all male, five homosexual and one bisexual, 23 to 48 years old) with the acquired immune deficiency syndrome (AIDS) who had cytomegalovirus retinitis were treated with a new antiviral drug as a part of a prospective open-labeled trial for serious cytomegalovirus infections. The drug, 9-[2-hydroxy-1-(hydroxymethyl)ethoxymethyl] guanine (referred to as dihydroxy propoxymethyl guanine), a new acyclic nucleoside antiviral agent similar in structure to acyclovir, produced positive results. These patients treated with dihydroxy propoxymethyl guanine (2.5 mg/kg of body weight every eight hours) showed regression and often disappearance of the lesions of cytomegalovirus retinitis during and for several weeks after therapy, usually with concomitant resolution of viral shedding. The cytomegalovirus retinitis recurred in four patients (the other two were lost to follow-up), but retreatment usually led to remission. Adverse drug toxicity (reversible granulocytopenia) occurred in two patients.

Pentamidine-induced hypoglycemia in patients with the acquired immune deficiency syndrome.

We conducted an analysis of 37 patients with the acquired immune deficiency syndrome (AIDS) who received pentamidine for the treatment of Pneumocystis carinii pneumonia to quantitate the incidence and severity of pentamidine-induced hypoglycemia. Ten of these patients (27%), nine of whom were symptomatic, developed hypoglycemia during or shortly after pentamidine therapy. The mean nadir blood glucose concentration in those who developed hypoglycemia during or shortly after pentamidine therapy was 38 mg/dl (range 20 to 55 mg/dl). The hypoglycemia frequently persisted after the end of pentamidine therapy. The incidence of nephrotoxicity in patients who developed hypoglycemia was 100%, as compared with 38% in the group who remained euglycemic (P less than 0.01). The overall incidence of pentamidine-induced hypoglycemia with AIDS is several-fold higher than previously reported for patients with other immunocompromising diseases who receive pentamidine. We conclude that pentamidine-induced hypoglycemia is a frequent adverse reaction in patients with AIDS and is potentially life-threatening if not recognized.

Homophobia among physicians and nurses: an empirical study.

In a large urban teaching hospital treating many patients with AIDS, 37 medical house officers and 91 registered nurses completed a questionnaire designed to measure attitudes about homosexuality. Mean scores for both physicians and nurses fell in the low-grade homophobic range. No significant differences were found between scores for doctors and nurses, but women respondents were significantly more homophobic than men. Respondents who had a friend or relative who was homosexual were less homophobic than those who did not. Nearly 10 percent of respondents agreed with the statement that homosexuals who contract AIDS are getting what they deserve. The authors consider this to be an alarming statistic and conclude from the findings that homophobia is higher than desirable in this group of health professionals.