Immunosuppression in renal transplantation: Long-term clinical trial of a double versus triple therapy regimen

Summary: Sixty-nine renal allograft recipients were randomized to two immunosuppressive regimens: 35 patients received cyclosporine A and prednisolone (PC) while 34 patients received low dose cyclosporine A, prednisolone and short term azathioprine (PCA). the data of 66 patients (34 in PC and 32 in PCA groups) were analysed. the median follow-up periods were 62 months for the PC group and 60 months for the PCA group. There was no difference in graft survival between the two groups but five patients died in the PC group compared to none in the PCA group (graft survival: 88 vs 90% at 1 year and 82 vs 82% at 5 years, P = not significant at any time point; patient survival: 90 vs 100% at 1 year and 88 vs 100% at 5 years, P = 0.05 at 5 years). There was a trend for patients in the PCA group to develop earlier and more frequent rejections (not significant; P = 0.106 and P = 0.062, respectively). There were also more episodes of acute cyclosporine A nephrotoxicity and cytomegalovirus (CMV) infection in the PC group. the mean serum creatinine at 5 years was significantly higher in the PCA group when compared to the PC group (179.8 ± 76.5 μmol/L vs 154.7 ± 41.0 μmol/L; P =0.05). We found that both therapeutic regimens were effective in preventing renal allograft rejections. However, double therapy was associated with higher patient mortality secondary to infection. Patients on triple therapy, on the other hand, were more prone to develop rejections in the early post-transplant period and were associated with less favourable renal function in the long run.     

Frostbite: experimental assessment of tissue damage using Tc-99m pyrophosphate. Work in progress

We designed an experimental model using a new method of freezing to study the pathogenesis and treatment of frostbite. Frostbite was simulated in a manner that closely resembles that which occurs in a natural environment. We used a radionuclide imaging technique to monitor the evolution and extent of tissue damage relative to temperature, rate of freezing, and controlled rewarming. Characteristic sequential changes were demonstrated on sequential nuclear scans. Nonperfusion, followed by perfusion, and finally again by nonperfusion occurred in all areas in which necrosis developed. The reappearance of nonperfusion corresponded to vascular injury and thrombosis evidenced at pathologic examination. We determined that lack of tissue perfusion corresponded to tissue injury. We believe that our experimental model provides an effective means of evaluating potential therapeutic regimens.     

CDRI-85/287, a novel antiestrogen and antiimplantation agent: biological profile and interaction with the estrogen receptors in immature rat uterus.

Postcoital antifertility efficacy, estrogenic and antiestrogenic activities of compound 85/287 were determined by the subcutaneous route in rats. It was 100% effective in preventing implantation at 0.5 mg/kg dose when administered within 24 h of mating and at 0.05 mg/kg in the days 1-5 post-coitum regimen. In the immature rat bioassay, it exhibited mild uterotrophic effect at the contraceptive dose but when administered along with estradiol (E2), it caused almost complete inhibition of uterine weight gain and vaginal cornification at the 2 mg/kg dose. E2 administration to immature rats (0.1 microgram, s.c., 3 days) caused 3-5 fold increase in the nuclear as well as cytoplasmic estradiol receptor (ER) content as compared to controls. In contrast, 85/287 (0.5 mg/kg and 2 mg/kg; s.c.), only translocated the ER to the nuclear compartment resulting in a depletion of cytoplasmic ER levels. Concurrent administration of 85/287 and E2 inhibited E2-induced increase in cytoplasmic ER. It is suggested that compound 85/287 exerts its antiestrogenic and antiimplantation action by interfering with the formation of E2-receptor complexes in the uterus.     

Studies in antifertility agents. 8. Seco steroids. 2. 5,6-Secoestradiol and some related compounds.

Three ring beta-secoestradiols, 2alpha,3beta- and 2beta,3beta-2-ethyl-3-(p-hydroxyphenyl)-6beta-methyl-trans-bicyclo[4.3.0]nonan-7beta-ols, have been synthesized and some of them shown to possess significant antiimplantation activity in rats.     

Radioactive materials in biosolids: dose modeling

The Interagency Steering Committee on Radiation Standards (ISCORS) has recently completed a study of the occurrence within the United States of radioactive materials in sewage sludge and sewage incineration ash. One component of that effort was an examination of the possible transport of radioactivity from sludge into the local environment and the subsequent exposure of humans. A stochastic environmental pathway model was applied separately to seven hypothetical, generic sludge-release scenarios, leading to the creation of seven tables of Dose-to-Source Ratios (DSR), which can be used in translating from specific activity in sludge into dose to an individual. These DSR values were then combined with the results of an ISCORS survey of sludge and ash at more than 300 publicly owned treatment works, to explore the potential for radiation exposure of sludge workers and members of the public. This paper provides a brief overview of the pathway modeling methodology employed in the exposure and dose assessments and discusses technical aspects of the results obtained.