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Biomedical subjects

R Weil

Publications and source records attributed to R Weil.

At least 109 records · Page 6Linked to original sources

Cyclosporin A and steroid therapy in sixty-six cadaver kidney recipients.

From nine to 18 months ago, 66 patients were given 67 randomly matched cadaveric kidneys with cyclosporin A and steroid therapy. Nine of the recipients were undergoing retransplantation. The over-all kidney survival rate to date has been 77.6 per cent, and 78.8 per cent of the recipients are dialysis-free. The patient mortality in this learning phase was 13.3 per cent. Nephrotoxicity, hepatotoxicity and other side-effects of cyclosporin A could usually be dealt with by dosage adjustments, making feasible the chronic use of this agent. One B-cell immunoblastic sarcoma was encountered which was monoclonal. It was not responsible for death. Another patient had a perforation of the intestine from a lympho-proliferative reaction in which the B cells were polyclonal. After jejunal resection a year ago, there were no further complications. This lesion was not classified as a lymphoma. Both lympho-proliferative lesions were associated with a rise in antibody to viral capsid antigen of Epstein-Barr virus. Results of this study have verified the effectiveness and relative safety of cyclosporin A with steroids for immunosuppression in human recipients of cadaveric kidneys.

Adolescent↗

Late follow-up after thoracic duct drainage in cadaveric renal transplantation.

Thoracic duct drainage was added to conventional immunosuppression with azathioprine, prednisone and, sometimes, antilymphocyte globulin in 83 patients given cadaveric kidneys, including 65 primary graft recipients. The most effective use of thoracic duct drainage was for pretreatment. Optimal conditioning was at least four weeks duration, and when lymph drainage was this long, the incidence of rejection during the first three postoperative months was reduced to 4.5 per cent. Shorter pretreatment or institution of thoracic duct drainage contemporaneous with transplantation were less effective, but the one year results were still better than those with conventional immunosuppression alone. However, the advantage gained with thoracic duct drainage during the first year was diminished in all the treatment groups by graft losses in the second postoperative year. It was concluded that, without better maintenance therapy, the full value of temporary early lymphoid depletion procedures cannot be fully exploited.

Cadaver↗

Amino acid sequence analysis of fragments generated by partial proteolysis from large simian virus 40 tumor antigen.

Large simian virus 40 tumor antigen was bound as immune complex to protein A-Sepharose and then subjected to limited proteolysis which yielded several discrete fragments. Primary structures near the cleavage sites were determined by radiosequencing techniques. Experimental data for five fragments matched an amino acid sequence predicted from a nucleotide sequence at 0.51 map unit of the viral genome. We have thus identified the reading frame of translation beyond the intervening sequence at 0.60 to 0.53 map units. A cleavage map of tumor antigen was established on the basis of the sequence data and of the apparent molecular weights of the fragments. The bond most susceptible to cleavage by trypsin was between arginine-130 and lysine-131 in a cluster of five basis amino acids. Other cleavage sites were located in the COOH-terminal half of tumor antigen. Each fragment was analyzed by complete tryptic proteolysis and peptide mapping on an ion exchange column. Peaks occurring in the peptide map of large tumor antigen could thus be assigned to different segments of the protein. Two specific regions of tumor antigen were shown to be phosphorylated.

Amino Acid Sequence↗

Decline in survival after liver transplantation.

Twenty-three recent cases of orthotopic liver transplantation were individually reviewed in an effort to determine why survival had declined from the 50% one-year survival rate of an immediately precedent series. In the series of 23, only six (26%) achieved one-year survival. Faulty case selection, technical complications, the use of damaged organs, and complications of immunosuppression were the main causes of death. Attention was directed to the possible use of preoperative lymphoid depletion to improve the effectiveness and safety of immunosuppression.

Adolescent↗

Impotence after kidney transplantation.

Sexual performance was evaluated in 28 men, thirty to sixty years of age, with functioning renal allografts: 13 were potent (controls), 10 had moderate sexual dysfunction, 5 had marked sexual dysfunction. Penile blood pressures, serum hormone levels, plasma zinc levels, and penile venous angiography were evaluated in search of causes of impotence. Thirteen of 15 impotent transplant patients (87 per cent) had marked abnormalities in at least one of the four areas studied. Systematic search for etiologic factors may permit specific therapy for impotence, which occurred in 54 per cent of the 28 kidney transplant patients analyzed.

Adult↗

Simian virus 40 and polyoma virus stimulate overall cellular RNA and protein synthesis.

In lytic infection with simian virus 40 and polyoma virus of monkey and mouse cells in tissue culture, synthesis of the viral tumor (T) antigens (T antigens) is rapidly followed by a mitogenic response of the host cell. The latter begins with virus-induced stimulation of overall cellular RNA and protein synthesis, leading to a substantial increase in cytoplasmic and nuclear RNA and protein. Stimulation begins within 1 hr after onset of T-antigen synthesis and also occurs if virus-induced DNA synthesis is blocked by metabolic inhibitors. The broad spectrum of biological and molecular effects induced by simian virus 40 and polyoma virus is, at least phenotypically, reminescent of the pleiotropic impact exerted on target cells by nonviral mitogens and by certain growth-promoting steroid and polypeptide hormones.

Antigens, Neoplasm↗

Excisional treatment of cavernous hemangioma of the liver.

Fifteen patients had hepatic hemangiomas removed with liver resections that ranged in extent from local excision to right trisegmentectomy. There was no mortality and little morbidity. The propriety and feasibility of extirpative treatment of such liver tumors has been emphasized by this experience.

Adult↗

Renal isotransplantation without immunosuppression.

Four renal isografts have been performed and all have had satisfactory function for 7 1/2 to 17 2/3 years without prophylactic or therapeutic immunosuppression. Three of these patients originally had glomerulonephritis, and in one there was histologic evidence of recurrent disease, 7 1/2 years after transplantation, without proteinura and without change in renal function. Although this experience is small, it suggests that prophylactic immunosuppression is not appropriate for recipients of renal isografts.

Diseases in Twins↗

Preliminary evidence of dual-marked lymphocytes in thoracic duct lymph fluid.

Thoracic duct lymphocytes from patients receiving thoracic duct drainage as a pretransplant therapy were examined for cell surface markers. Patients followed over the drainage time period showed a variable but decreasing percentage of E-rosette-positive cells in the lymph fluid. A substantial percentage of these E-rosette-positive cells also had C3 receptors on their cell surface. Reactions of the whole lymphocytes with a heteroantisera to human B-lymphocyte antigens reflected the increasing proportion of B cells in the samples, but also indicated that a fraction of the T cells have Ia-like antigens on their surface marker characteristics. Significance of these cells with respect to graft survival is discussed.

Animals↗

New approaches for immunosuppression.

New approaches for experimental immunosuppression have been reviewed. These include the following: 1) cyclosporin A, a metabolite from fungus that suppresses multiplying but not resting T and B lymphocytes and can be used in pulsed manner with interspersed drug-free periods; 2) total lymphoid irradiation (transplantation tolerance in rats has been achieved by pretransplant radiation); 3) thoracic duct drainage, which is being revived following its demonstrated effectiveness in the treatment of some autoimmune disease; 4) hyperbaric oxygen (HBOX). We have found that HBOX 2 1/2 ATA for five hours daily depresses cell-mediated immunity in mice and that this can be reversed by intravenous administration of autologous macrophages.

Animals↗

The use of cyclosporin A and prednisone in cadaver kidney transplantation.

Eighteen patients were treated with primary cadaveric renal transplantation using cyclosporin A therapy, and four more patients undersent cadaveric retransplantation. Eleven of the 22 recipients were conditioned with lymphoid depletion before transplantation, using thoracic duct drainage or lymphapheresis for two to eight and one-half weeks. Cyclosporin A was begun a few hours before grafting. The other 11 patients were pretreated with cyclosporin A for from one day to 18 days. After transplantation, the majority of patients in both subgroups of 11 had rejection develop, but in most, the immunologic process was readily controlled with relatively small dosages of prednisone. After follow-up periods of two to four and one-half months, one patient has died of the complications of a coronary artery reconstruction that was not related to the transplantation. Another graft was lost from rejection, and a third organ was removed because of ureteral necrosis. Nineteen of the original 22 cadaveric kidneys are functioning, including 17 of the 18 kidneys given to patients who were undergoing transplantation for the first time. The only loss in the latter group of 18 patients was in the patient who died after an open heart operation. Results of these studies have shown that cyclosporin A is a superior and safe immunosuppressive drug but that, for optimal use in cadaveric transplantation, it usually should not be given alone. Steroid therapy greatly amplified the value of cyclosporin A. Unless major delayed morbidity develops which is not obvious so far, this drug combination should permit revolutionary advances in the transplantation of all organs. Other adjuncts to the cyclosporin A-steroid combination, including lymphoid depletion techniques, will require further investigation.

Adult↗

Right trisegmentectomy for hepatic neoplasms.

Thirty patients had right trisegmentectomy for 19 primary hepatic malignant tumors, seven localized liver metastases and four benign lesions. A technical refinement that aided resection of bulky posterior and superior tumors was intrahepatic identification and control of the right hepatic vein. The operative mortality was 3.3 per cent. Late hepatic insufficiency was not observed. More than one-half of the patients operated upon a year or more ago for primary hepatic malignant growths had a tumor-free state at the 12 month follow-up period. Beyond this time, there was only one recurrence. The results in children were twice as good as in adults. The results in treating localized liver metastases from distant primary sites were inferior to those in treating primary hepatic tumors. A hypothetical case was made for combining hepatic resection with adjuvant chemotherapy, even though our experience could not be construed as direct support for this practice.

Adolescent↗