Carl B. Wallemark

Prevention of Acute Graft Rejection by the Prostaglandin E1 Analogue Misoprostol in Renal-Transplant Recipients Treated with Cyclosporine and Prednisone

Prostaglandins of the E series have been shown to have immunosuppressive properties. To study the effects of the prostaglandin E1 analogue misoprostol on renal function and graft rejection after transplantation, we conducted a randomized, double-blind, placebo-controlled trial in 77 renal-allograft recipients. The subjects received misoprostol (200 micrograms four times daily by mouth; n = 38) or placebo (n = 39) for the first 12 weeks after transplantation, in addition to standard immunosuppression with cyclosporine and prednisone. They were then observed for an additional four weeks after the drug or placebo was discontinued. Treatment with misoprostol was associated with a significant improvement in renal function as judged by the mean (+/- SEM) serum creatinine concentration (128 +/- 7 vs. 158 +/- 11 mumol per liter after 12 weeks; P = 0.03) and creatinine clearance (84 +/- 6 vs. 69 +/- 5 ml per minute per 1.73 m2 of body-surface area; P = 0.05). There was a significant reduction in the incidence of acute rejection in the group treated with misoprostol as compared with the placebo group (10 of 38 vs. 20 of 39; P = 0.02), and there was less need for rehospitalization after transplantation (4 +/- 1 days with misoprostol vs. 10 +/- 2 days for placebo; P = 0.03). Although blood levels of cyclosporine did not differ significantly between the groups, they tended to be higher in the misoprostol group, as did the incidence of acute nephrotoxicity due to cyclosporine (13 of 38 vs. 8 of 39). Infectious complications tended to be fewer in the misoprostol-treated group (14 of 38 vs. 21 of 39). We conclude that misoprostol improves renal function and safely reduces the incidence of acute rejection in renal-transplant recipients treated concurrently with cyclosporine and prednisone.

Cisplatin and 5-fluorouracil in the primary management of squamous esophageal cancer

A combined treatment program consisting of chemotherapy with cisplatin and infusion 5‐fluorouracil (5‐FU) for three cycles followed by esophagectomy or radiation, or both, has been conducted in 26 patients with squamous cancer of the esophagus localized to the primary site. Eleven patients had objective evidence of partial or complete response to the chemotherapy. Fourteen patients were operated on and ten underwent total esophagectomy. Drug toxicity was considerable with severe mucositis and myelosuppression occurring in 11 and seven patients, respectively. There were no drug‐related deaths. Median survival is 17.8 months. Ten patients have lived more than 2 years. Six of these patients have undergone total thoracic esophagectomy after the induction chemotherapy. Determination of the ultimate benefits of combined modality therapy may require prospective randomized trials isolating the major treatment components but our data suggest that chemotherapy contributes to improved results in this disease and that drug therapy is emerging as an integral component of combined therapy.

Emergency administration of radiocontrast media in high-risk patients

Patients with previous anaphylactoid reactions to radiographic contrast media (RCM) are at increased risk for subsequent reactions on repeat exposure. The most efficacious pretreatment regimens require administration of medications up to 13 hours before the anticipated procedure. Emergency administration of RCM in patients requiring essential procedures precludes prolonged pretreatment. We report results of pretreatment in nine patients requiring emergency administration of RCM. We recommend hydrocortisone, 200 mg intravenously, immediately, and every 4 hours until the procedure is completed, and diphenhydramine, 50 mg intravenously, 1 hour before the procedure. No reactions occurred in these patients, suggesting that this pretreatment regimen may be valuable in prophylaxis for patients requiring emergency administration of RCM who have experienced previous anaphylactoid reactions. Although used in only one additional patient, ephedrine, 25 mg orally, 1 hour before the procedure may also be valuable.

Prevalence of antibody to hepatitis B virus in foreign-born hospital employees

Hepatitis B surface and core antibodies were measured in 512 community hospital employees at increased risk for developing infection with hepatitis B virus. Antibody was detected in 140 (27 percent) participants. Multivariate logistic regression analysis indicated that seropositivity was strongly associated with the prevalence of hepatitis B in an employees country of birth and with age. These results suggest that reported differences among hospitals in hepatitis B seropositivity may in part be a reflection of the national origin of its employees. These data also indicate that each hospital should assess its own risk for hepatitis B infection and that prevaccination serologic testing is particularly worthwhile in hospitals having large numbers of foreign-born employees.

Antibody to human lymphotropic virus type iii: Immunologic status of homosexual contacts of patients with the acquired immunodeficiency syndrome and the acquired immunodeficiency-related complex

Twenty homosexual men who reported having sexual contact with homosexual men who had the acquired immunodeficiency syndrome (AIDS) or the AIDS-related complex were examined to determine their clinical status, immunologic profiles, and the presence of antibody to the human T-cell lymphotropic virus type III (HTLV-III). Of the 20, eight men had one or more signs or symptoms of the AIDS-related complex and 12 were asymptomatic. Antibodies to HTLV-III were present in 14 (70%) of 20 of the sexual contacts as compared with four (10%) of 40 healthy homosexuals without known contact with a patient who had AIDS (P less than .0001). Seropositive contacts had significantly higher mean counts of suppressor lymphocytes and lower helper: suppressor ratios (P less than .05 and .005, respectively) and higher serum levels of IgG than seronegative contacts (P less than .05). It was not possible to determine significant differences in sexual practices, drug use, length of relationship, or numbers of different sexual partners between symptomatic and asymptomatic contacts or between seropositive and seronegative contacts in this study.

Reanalysis of antisera specificities and binding characteristics of rat pituitary hormone assays

Rat pituitary hormone radioimmunoassays (RIAs) are widely used in reproductive research, yet data on specificity and binding characteristics of many of the antisera are not widely available. This report characterizes one set of rat antisera supplied by the National Institutes of Health (USA). Rat follicle-stimulating hormone (FSH) and thyrotropin-stimulating hormone (TSH) antisera appear specific, but TSH exhibited significant competition in the rat luteinizing hormone (LH) assay. In addition, statistically significant nonparallelism was demonstrable in all three assay systems. This creates further problems in characterizing antisera cross-reactivity and may make potency estimates for pituitary standards inaccurate.