Phase I study of epirubicin given on a weekly schedule

Epirubicin was studied in a phase I setting to find the maximum tolerated dose when given weekly for 3 of 4 weeks. Forty-one evaluable patients were treated in groups at doses increasing from 20 to 45 mg/m2. The highest dose level produced the maximum degree of myelosuppression (lowest neutrophil count, 1.9 X 10(9)/L; range, 0-3.7) recorded on Day 22. This was well-tolerated in this group of mainly pretreated patients. Nonhematologic side effects were minimal. This dose schedule allows a greater dose per unit time to be administered than other recommended schedules for epirubicin.     

Surgical treatment of colostomy complications

One hundred and twenty-three patients (M:F, 0.9:1; mean age 62 years) underwent 156 operations between 1954 and 1984 for correction of late colostomy complications (stenosis 65 patients, prolapse 16 patients, paracolostomy hernia 42 patients). Sixty-three per cent of patients eventually had a good result but in some up to 5 operations were necessary. Local excision of scar tissue at the mucocutaneous junction was associated with a 61 per cent (43/71) success rate for relief of colostomy stenosis. Where local fixation failed to prevent recurrent colostomy prolapse (13/20, 65 per cent of local fixation operations), colectomy and ileostomy was the most effective second procedure (2/3, 67 per cent success rate). Where local repair of a paracolostomy hernia failed (15/32, 47 per cent of local operations), resiting of the stoma to the umbilicus or right side of the abdomen produced better results (3/7, 43 per cent success rate) than resiting to another trephine on the left side of the abdomen (2/14, 14 per cent success rate).     

A REPRODUCIBLE MODEL OF CHRONIC REJECTION IN RAT RENAL ALLOGRAFTS

A reproducible animal model is essential for the study of the pathogenesis of chronic rejection. This study investigates: (i) the optimal pre-transplant blood transfusion conditions to induce tolerance in a strongly rejecting rat kidney allograft model (Dark Agouti to Albino-Surgery) and avoiding post-transplant immunosuppression; (ii) the functional and histological changes that occur in long-term surviving kidneys and their similarity to chronic rejection; and (iii) the maintenance of tolerance. Prolonged survival occurred after administration of at least two donor blood transfusions with concomitant cyclosporin A (5 mg/kg per day). The time-span between transfusions appeared to be critical: 4 days was more effective than 2 or 7 days. Ineffective treatment led to death within the first 2 weeks post-transplant with histological evidence of acute graft rejection. Seventy-five per cent of long-term survivors experienced impaired renal function in the first week which improved spontaneously and remained stable in 93% of the surviving animals after 100 days and in 668 after 200 days. The morphology of long-term allografts was extremely variable from minor to extensive tubular atrophy, interstitial fibrosis, glomerular hypertrophy, focal and segmental glomerulosclerosis and vascular changes. Glomerular hypertrophy occurred in uninephrectomized controls and probably denoted a response to uninephrectomy. Glomerulosclerosis increased with time and was absent in controls. Although chronic damage was evident, the rats remained tolerant to fresh donor skin. Replacement of the original kidney allograft with a fresh donor kidney resulted in 70% survival. These second grafts showed less severe renal dysfunction and morphological damage than the original allografts in the long-term follow up.     

Urinary and fecal excretions and absorption of a large supplement of selenium: superiority of selenate over selenite

A correction needs to be made to the form of selenium used in earlier studies; what was believed to be selenite-Se in solution is now known to have been selenate-Se. In the present study, excretion of Se was followed in 13 women after ingestion of 1 mg Se as selenite or selenate in solution. Fecal excretion of selenate-Se was less than for selenite-Se reflecting a higher apparent absorption [94 +/- 4% (SD), 62 +/- 14%, respectively]. Peak excretion of Se occurred 3 h earlier for selenate-Se than for selenite-Se and was 6 times higher. Total urinary excretion of selenate-Se was 3 times that of selenite-Se and still 2 times as high when expressed as % absorbed dose. Total recovery of Se in urine and feces was similar for both forms. There was remarkable agreement between these results and those reported earlier for selenate-Se (Selovet-1) and selenite-Se.     

Immunological changes in normal pregnancy.

During pregnancy the mother must tolerate intra-uterine allogenic fetal tissue. Failure of this tolerance may cause spontaneous abortion. The immunological changes occurring in normal pregnancy are poorly understood. The aim of this study was to investigate the immunological changes occurring in pregnancy. Thirty women in the first trimester; 10 in the second and 10 in the third trimester of pregnancy were studied and compared to age matched non-pregnant controls. In normal pregnancy there was an increase in the total white cell count with no change in the lymphocyte count. There was a fall in total T cell numbers and activated T cell numbers, with no change in helper/inducer or suppressor/cytotoxic T cell numbers. [3H]Thymidine uptake in response to three different mitogens was increased. This implies an increase in potential for the cells to respond to mitogens. There was no change in interleukin-2 receptor levels, suggesting that despite this increased potential there was no general activation of the immune system. A rise in IgM and IgG was found after mitogen stimulation of peripheral blood lymphocytes, suggesting an increase in potential antibody production. These results demonstrate that lymphocytes from pregnant women have an increased potential rather than an increased activity.