Outcome of live related and live unrelated renal transplants

Summary: This study compares the outcomes of 229 renal transplants, of which 156 were live related renal transplants done at our centre and 73 unrelated transplants done at other centres but followed up at our centre. All the patients were on triple immunosuppression for periods varying between 9 months and 1 year. Patient characteristics, rejections, infections and 1 and 5 years patient and graft survival were analyzed in the two groups. the outcome of patients who continued on cyclosporine beyond 1 year was compared to those who discontinued cyclosporine at 1 year. Males predominated (191 vs 38) in both groups, while younger patients (<50 years) predominated in live related group (152 vs four). There was no difference in the incidence of infection, rejection, graft dysfunction, graft loss or death between the two groups. the 1 and 5 year patient survival in the related and unrelated group, (93.7% and 71.4% vs and 85% and 66%) and graft survival (90.4% and 69.4% vs 83.3% and 65.4%) were similar. However, in the unrelated group, patients who discontinued cyclosporine had a higher incidence of rejections (38% vs 14%) and graft loss (43% vs 11.8%), while in the related group no such difference was found. It is concluded that 1 and 5 year patient and graft survival is comparable between live related and live unrelated transplantation. However, in the unrelated group it is necessary to continue cyclosporine beyond 1 year in order to achieve comparable results.     

Short term follow up of childhood focal segmental glomerulosclerosis in India

Summary: A retrospective analysis of 67 biopsy proven cases of focal segmental glomerulosclerosis (FSGS) in children was performed. After a mean duration of disease of 48.5 ± 44 months, 20 patients (30%) achieved sustained remission (SR), 23 (34%) had frequent relapses (FR) and 24 (36%) were steroid non-responders (NR). the NR group had a significantly higher mean age of onset 9.1 ± 1.01 years ( P = 0.003) and had higher number of females ( P = 0.0009). They also had a significantly higher prevalence of microhaematuria as compared to FR and SR groups ( P = 0.002). the initial steroid response category ( P <0.00001) and the percentage of glomeruli with segmental sclerosis on histopathology ( P = 0.001) correlated with the subsequent outcome. During this period six children developed progressive renal failure and all of them belonged to NR group (25%). There were four deaths and all of them were non-responders (16.6%). Features predictive of a poor therapeutic outcome in childhood FSGS are age of onset more than 9 years, female sex, microhaematuria, renal dysfunction at onset, initial non-response to steroids and percentage of glomeruli with segmental sclerosis on histopathology.     

Effect of RU-486 and Related Compounds on the Proliferation of Cultured Macrophages

PROBLEM : Macrophages are implicated in the pathophysiology of endometriosis and are influenced by anti-inflammatory steroids as well as anti-oxidants. METHODS : We tested the effect of RU-486, an antiprogesterone, antiglucocorticoid and an antioxidant, on the proliferation of RAW macrophages. RESULTS : The incorporation of ³H-thymidine was significantly inhibited by both progesterone and RU-486. Progesterone and RU-486, in combination, synergistically inhibited macrophage growth. In contrast, dexamethasone-stimulated growth was antagonized by RU-486 in a dose dependent manner. ZK 112,993 which is structurally related to RU-486 but lacks antioxidant properties, also inhibited thymidine incorporation. The synergistic effect of RU-486 and ZK 112,993 with progesterone implicate a mechanism of action separate from receptor bound antagonists. A cell permeable antioxidant, pyrrolidine dithiocarbamate was very effective in inhibiting the incorporation of ³H-thymidine into cells. CONCLUSIONS : These results suggest novel therapeutic modalities in the management of endometriosis via antiglucocorticoid as well as antioxidant mechanisms.     

Reproductive Effects of Theophylline in Mice and Rats

Reproductive Effects of Theophylline in Mice and Rats. MORRISSEY,R. E., COLLINS, J. J., LAMB, J. C, IV, MANUS, A. G., AND GULATI.D. K. (1988). Fundam Appl. Toxtcol. 10, 525–536. Theophyllinewas administered by gavage in 13-week studies to B6C3F, mice(0, 75, 150, 300 mg/kg/day) and F344 rats (0, 37.5, 75, 150mg/kg/day) with significant reductions in male mouse terminalbody and testicular weights. Male rats also displayed reducedtesticular weight, as well as nonsignificant but dose-relateddecreases in body weight. There was a significant but non-dose-relateddecrease in female mouse body weight. In parallel studies ofB6C3F, mice and F344 rats, theophylline administered in thediet (0, 0.1, 0.2, 0.4%) produced significantly decreased terminalbody weights in male and female mice, but not rats. In rats,cauda epididymis weight was reduced at the high dose comparedto the control group, and there was an increase in abnormalsperm. These studies were followed by continuous breeding reproductiveassays in CD-I mice in which theophylline was administered infeed (0.0, 0.075, 0.15, and 0.30% calculated doses of 0, 125,265, and 530 mg/kg/day, respectively) to breeding pairs for14 weeks. There was a dose-dependent decrease in the numberof live pups produced per litter, a significant decrease inthe number of litters produced per pair (0.30%) and in the adjustedlive pup weight (0.30%), a decrease in the percentage of pupsborn alive (0.15 and 0.30%), and an increase in the number ofdays needed to produce each litter (0.30%). After 19 weeks ofcontinuous treatment at 0.307%, a crossover mating trial indicatedthat females and males were adversely affected by theophylline,as judged by the decreased percentage of pups born alive, thedecreased live pup weight, and the decreased number of livepups per litter relative to matings within the control group,but the effects in females were more extensive. Based on otherstudies, there is a suggestion that the observed changes infertility may be partially attributed to embryotoxicity.     

Are Mouse Strains Differentially Susceptible to the Reproductive Toxicity of Ethylene Glycol Monomethyl Ether? A Study of Three Strains

Most rodent reproductive toxicology studies utilize strainsof high fecundity. These studies were conducted to examine thepossibility that mouse strains of differing fecundity wouldrespond differently to a known reproductive toxicant. Thirtypairs each of Swiss CD-1, C57B1, and C3H mice were cohabitedfor 14 weeks while consuming 0, 0.03, 0.10, or 0.30% EGME inthe drinking water. Litter data were collected during cohabitation.Body and organ weights, and various sperm data, were collectedat necropsy, and second-generation fertility was evaluated.The data show that the most fecund strain (Swiss) was affectedthe least by exposure to EGME, while the least fecund strain(C3H) suffered the greatest declines in fertility. These differencesmight alter interspecies extrapolation factors, or the permissibleexposure levels for humans.