Depressed renal and vascular nitric oxide synthase expression in cyclosporine-induced hypertension.

BACKGROUND: Introduction of cyclosporine (CsA) for clinical use has greatly enhanced the outcome of organ transplantation. However, CsA can cause nephrotoxicity and hypertension (HTN). This study was designed to test the hypothesis that CsA-induced HTN is related to depressed nitric oxide (NO) production. METHODS: Urinary excretion of NO metabolites (NOx) and endothelial and inducible NO synthase (eNOS and iNOS) proteins were determined in thoracic aortas and kidneys of CsA-treated (given CsA 18 mg/kg/day for 3 weeks) and placebo-treated rats. In addition, renal tissue eNOS and iNOS mRNA and aorta iNOS activity were measured. RESULTS: CsA administration resulted ina significant rise in arterial blood pressure (BP) coupled with a steady decline in urinary NOx excretion, suggesting depressed NO production. This was accompanied by a significant reduction in iNOS protein abundance in the kidney and thoracic aorta but no change in eNOS protein abundance. The fall in renal iNOS protein in CsA-treated rats was accompanied by a parallel decline in iNOS mRNA abundance and enzymatic activity. CONCLUSION: Administration of CsA for three weeks resulted in a significant rise in BP together with marked reductions in urinary NOx excretion, and renal and vascular iNOS expression. These observations suggest that CsA-induced HTN may be, in part, related to impaired NO production. If true, strategies designed to restore NO availability may mitigate HTN and other vascular complications of CsA therapy.

Indefinite survival of human skin allografts in patients with long-term immunosuppression.

The transplantation of a sufficient quantity of good quality skin is of great clinical importance. Severe burn patients lack adequate skin donor sites to cover their wounds with autografts. Patients with severe injuries and burns of areas such as the entire face are presently reconstructed with multiple full- or split-thickness skin grafts. The final result is a patchwork appearance of skin with inferior qualities to normal full-thickness facial skin. Before structures such as hands should be transplanted, each individual tissue component should be evaluated to determine whether the tissue will survive and function with immunosuppression. Skin is obviously an important part of the hand. One hypothesis tested is the ability of transplanted human skin to survive indefinitely with long-term immunosuppression. The early detection of rejection of transplanted organs is paramount in reversing the rejection phenomena and hence saving the transplanted organ. Another hypothesis tested is the ability of a synchronously placed, same-donor, same-recipient skin graft to be used to detect rejection of a transplanted organ. As the skin and kidney from the same donor have similar antigens and the transplantation of both these tissues is to the same recipient and immunological system, it is hypothesized that there will be a correlation of rejection between the transplanted skin and the transplanted organ. To test the above hypotheses a small skin graft was placed on renal transplant patients synchronously with renal transplantation. The skin allografts were followed by direct observation and biopsy at regular intervals and at the time of suspected rejection. The patients were treated with the usual renal transplant immunosuppressant drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrioid adenosarcoma of the bladder arising from endometriosis.

Vesical endometriosis is an uncommon entity characterized by the deposition of benign, hyperplastic endometrial tissue in the bladder. To date, only about 160 cases have been reported in the world literature. More uncommon, however, are case reports of extrauterine malignancies arising from pre-existing endometriosis. We report a case of a large endometrial adenosarcoma in a patient who had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy 10 years previously for endometriosis. To our knowledge this malignancy has never been reported previously to involve the bladder. We review the pathological findings, possible mode of entry into the bladder and current concepts in its treatment.