36 results on '"Iwatsuki, S"'
Search Results
2. Positive crossmatch in primary human liver allografts under cyclosporine or FK 506 therapy.
- Author
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Takaya S, Duquesnoy R, Iwaki Y, Demetris J, Yagihashi A, Bronsther O, Iwatsuki S, and Starzl TE
- Subjects
- Adult, Follow-Up Studies, Graft Rejection, Humans, Liver Transplantation pathology, Tacrolimus, Transplantation, Homologous, Anti-Bacterial Agents therapeutic use, Cyclosporins therapeutic use, Graft Survival, Histocompatibility Testing, Immunosuppressive Agents therapeutic use, Liver Transplantation immunology
- Published
- 1991
Catalog
3. Experience in 1,000 liver transplants under cyclosporine-steroid therapy: a survival report.
- Author
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Iwatsuki S, Starzl TE, Todo S, Gordon RD, Esquivel CO, Tzakis AG, Makowka L, Marsh JW, Koneru B, and Stieber A
- Subjects
- Adolescent, Adrenal Cortex Hormones administration & dosage, Adult, Aged, Bile Duct Neoplasms surgery, Child, Child, Preschool, Colorado, Cyclosporins administration & dosage, Drug Therapy, Combination, Humans, Infant, Infant, Newborn, Liver Diseases surgery, Liver Neoplasms surgery, Middle Aged, Pennsylvania, Postoperative Complications mortality, Texas, Transplantation, Homologous mortality, Adrenal Cortex Hormones therapeutic use, Cyclosporins therapeutic use, Liver Transplantation
- Published
- 1988
4. Cadaveric renal transplantation under cyclosporine-steroid therapy.
- Author
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Rosenthal JT, Hakala TR, Iwatsuki S, Shaw BW Jr, and Starzl TE
- Subjects
- Azathioprine therapeutic use, Cadaver, Clinical Trials as Topic, Creatinine blood, Graft Rejection drug effects, Graft Survival drug effects, Humans, Postoperative Complications drug therapy, Prednisone therapeutic use, Reoperation, T-Lymphocytes immunology, Adrenal Cortex Hormones therapeutic use, Cyclosporins therapeutic use, Immunosuppressive Agents therapeutic use, Kidney Transplantation
- Abstract
Ninety-seven cadaveric renal transplants were performed upon 96 patients during 1981. The one year patient mortality was 2.1 per cent. Seventy of the recipients were undergoing transplantation for the first time. Of these patients, 38 were treated with cyclosporine and steroids with a one year graft survival rate of 89.5 per cent. The other 32 primary recipients were treated with azathioprine and steroids with a one year graft survival rate of 50 per cent. The difference between the cyclosporine-steroid versus conventional therapy groups was significant. Cyclosporine and steroids also were used to treat 26 patients who underwent retransplantation with 27 cadaveric grafts. The one year graft survival time was 77.8 per cent; most of the graft losses were in presensitized patients. The results with retransplantation were twice as good as in historical control groups. more...
- Published
- 1983
5. The influence of liver dysfunction on cyclosporine pharmacokinetics--a comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs.
- Author
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Takaya S, Iwatsuki S, Noguchi T, Koie H, Zaghloul I, Venkataramanan R, and Starzl TE
- Subjects
- Animals, Bile Ducts surgery, Biological Availability, Cholestasis metabolism, Cholestasis physiopathology, Dogs, Hepatectomy, Indocyanine Green pharmacokinetics, Liver metabolism, Bile Ducts physiopathology, Cyclosporins pharmacokinetics, Liver physiopathology
- Abstract
The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7 +/- 7.1 per cent (mean +/- SD) and the ICG-K decreased by 61.3 +/- 9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9 +/- 8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4 +/- 20.8 per cent and the bioavailability of CsA decreased by 26.4 +/- 14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1 +/- 12.8 per cent and the ICG-K decreased by 65.6 +/- 3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9 +/- 10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9 +/- 15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) more...
- Published
- 1989
- Full Text
- View/download PDF
6. Cyclosporine absorption following orthotopic liver transplantation.
- Author
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Burckart GJ, Venkataramanan R, Ptachcinski RJ, Starzl TE, Gartner JC Jr, Zitelli BJ, Malatack JJ, Shaw BW, Iwatsuki S, and Van Thiel DH
- Subjects
- Adult, Biological Availability, Child, Preschool, Cyclosporins blood, Cyclosporins therapeutic use, Female, Half-Life, Humans, Infant, Intestinal Absorption, Kinetics, Male, Middle Aged, Cyclosporins metabolism, Liver Transplantation
- Abstract
Blood concentrations of cyclosporine were determined in adult and pediatric patients following orthotopic liver transplantation to quantitate cyclosporine blood clearance and oral absorption. Seventeen bioavailability studies were performed following transplantation surgery in nine children and seven adults. The intravenous cyclosporine study was performed following an average dose of 2.1 mg/kg. The patients were again studied when they received the same intravenous dose plus an oral dose of cyclosporine of 8.6 mg/kg or an oral dose alone. Blood samples were collected and analyzed for cyclosporine using high-performance liquid chromatography. Cyclosporine blood clearance ranged from 29 to 203 mL/min (1.9-21.5 mL/min/kg) in children and from 253 to 680 mL/min (3.2-7.6 mL/min/kg) in adults. The mean cyclosporine clearance value was 9.3 mL/min/kg in the pediatric patients and 5.5 mL/min/kg in the adults. Cyclosporine bioavailability was less than 5% in six studies on five pediatric patients in the immediate postoperative period. The bioavailability varied from 8% to 60% in adult liver transplant patients (mean, 27%). We conclude that: cyclosporine clearance is highly variable between patients, pediatric patients clear the drug more rapidly than adults and therefore need a higher cyclosporine dose on a body weight basis, cyclosporine is poorly and variably absorbed in liver transplant patients, and cyclosporine blood concentration monitoring is essential following orthotopic liver transplantation. more...
- Published
- 1986
- Full Text
- View/download PDF
7. Indications for liver transplantation in the cyclosporine era.
- Author
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Gordon RD, Shaw BW Jr, Iwatsuki S, Esquivel CO, and Starzl TE
- Subjects
- Adult, Biliary Tract Diseases therapy, Child, Cholangitis therapy, Follow-Up Studies, Humans, Liver Cirrhosis therapy, Liver Cirrhosis, Biliary therapy, Liver Neoplasms surgery, Metabolism, Inborn Errors therapy, Cyclosporins therapeutic use, Liver Transplantation
- Abstract
One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9 per cent and 20.0 per cent, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7 per cent and 62.8 per cent, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4 per cent at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20 per cent of patients require retransplantation for rejection, technical failure, or primary graft failure. Only four of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the twelve patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified. more...
- Published
- 1986
- Full Text
- View/download PDF
8. [Long-term results of orthotopic liver transplantation during the cyclosporin era. 393 orthotopic liver transplantations accomplished in 313 consecutive patients at the Pittsburgh Transplantation Center].
- Author
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Lerut J, Stieber AC, Makowka L, Esquivel CO, Iwatsuki S, Gordon RD, and Starzl TE
- Subjects
- Follow-Up Studies, Graft Rejection drug effects, Humans, Middle Aged, Pennsylvania, Survival Rate, Cyclosporins therapeutic use, Liver Diseases surgery, Liver Transplantation, Postoperative Complications mortality
- Abstract
During the cyclosporine era 1980-1984, 393 consecutive orthotopic liver transplantations (OLT) were performed in 313 patients at the University of Pittsburgh. This paper analyses the long-term results in this group of patients who have been followed-up for a minimum of three years. The results of OLT for different indications are discussed. The five-year survival rates after OLT for metabolic diseases, biliary atresia, primary biliary cirrhosis, posthepatic cirrhosis and primary hepatobiliary cancer are 75%, 68%, 60%, 58.9%, 53.2% and 23.8%, respectively. Recurrence of the primary disease after OLT is rare for benign diseases but rather frequent for malignant ones. The incidence of retransplantation for delayed rejection and for extrahepatic complications is discussed. The quality of life for most of the long-term survivors is good. Because of its good long-term results, OLT should become the therapy of choice in a lot of acute and chronic hepatopathies. more...
- Published
- 1989
9. Long-term use of cyclosporine in liver recipients. Reduction of dosages in the first year to avoid nephrotoxicity.
- Author
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Iwatsuki S, Starzl TE, Shaw BW Jr, Yang SL, Zitelli BJ, Gartner JC, and Malatack JJ
- Subjects
- Adolescent, Adult, Child, Cyclosporins toxicity, Humans, Time Factors, Cyclosporins administration & dosage, Kidney drug effects, Liver Transplantation
- Abstract
Cyclosporine is a potent immunosuppressive drug, which has dose-related nephrotoxicity. In renal transplantation, the differentiation between rejection and toxicity is difficult and even with the aid of blood levels of the drug, it may be difficult to establish a chronic maintenance dose. Long-term survivors after liver transplantation can provide modes with which to establish maintenance doses, as these are dictated by nephrotoxicity in these patients. Twenty-nine liver transplant patients who survived one year or more were followed for changes in their cyclosporine doses. Daily oral cyclosporine dose, BUN, serum creatinine and bilirubin were monitored. The reductions in cyclosporine were dictated almost entirely by the findings of nephrotoxicity. more...
- Published
- 1983
- Full Text
- View/download PDF
10. Variable convalescence and therapy after cadaveric renal transplantation under cyclosporin A and steroids.
- Author
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Starzl TE, Hakala TR, Rosenthal JT, Iwatsuki S, and Shaw BW Jr
- Subjects
- Adolescent, Adult, Blood Grouping and Crossmatching, Cadaver, Chemical and Drug Induced Liver Injury etiology, Child, Cyclosporins adverse effects, Female, Follow-Up Studies, Humans, Hydrocortisone administration & dosage, Male, Middle Aged, Cyclosporins administration & dosage, Graft Survival drug effects, Kidney Transplantation, Prednisone administration & dosage
- Abstract
The postoperative convalescence period was analyzed for 42 consecutive patients who had cadaveric renal transplantation under therapy with cyclosporin A and steroids. Twenty-two of the patients underwent transplantation for the first time, and the other 20 had retransplantation. None of the recipients has died. With follow-up period of two to eight months, the survival rate of grafts is 96 per cent after first transplantation and 85 per cent after retransplantation. Immunosuppression with a standard regimen was used for all patients at the outset. Early convalescence was highly variable, often necessitating adjustments of cyclosporin A and steroid dosage to accommodate the possibilities of rejection or cyclosporin A nephrotoxicity, or both, simultaneously. Management problems were more frequent and complex in patients undergoing retransplantation. From the results, a classification of convalescence patterns was evolved, with recommendations about how standardized initial therapy should be adjusted if the renal graft does not function promptly or deteriorates later. more...
- Published
- 1982
11. Cyclosporin A hepatotoxicity in 66 renal allograft recipients.
- Author
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Klintmalm GB, Iwatsuki S, and Starzl TE
- Subjects
- Azathioprine therapeutic use, Dose-Response Relationship, Drug, Graft Rejection drug effects, Humans, Liver Function Tests, Prednisone therapeutic use, Time Factors, Chemical and Drug Induced Liver Injury physiopathology, Cyclosporins toxicity, Kidney Transplantation, Liver physiopathology
- Abstract
Liver functional abnormalities were seen in 13 (19.7%) of 66 recipients of cadaveric renal homografts treated with cyclosporin A and prednisone. However, such presumed hepatotoxicity was a minor problem in the use of cyclosporin A. The complication was less frequent than that of nephrotoxicity, was as easily manageable with reductions in the cyclosporin A dosage, and generally did not cause clinical illness. In an occasional case, late hepatotoxicity can force a therapeutic change from cyclosporin A to azathioprine, but careful consideration should be given to the dangers of subsequent rejection. more...
- Published
- 1981
- Full Text
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12. Monoclonal antibody therapy with ciclosporin and steroids in nonmatched cadaveric renal transplants.
- Author
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Gordon RD, Starzl TE, Fung JJ, Iwatsuki S, Esquivel CO, Tzakis A, and Todo S
- Subjects
- Adolescent, Adult, Antibodies, Monoclonal adverse effects, Child, Clinical Trials as Topic, Digestive System drug effects, Drug Therapy, Combination, Female, Graft Rejection, Humans, Male, Middle Aged, Antibodies, Monoclonal administration & dosage, Cyclosporins administration & dosage, Kidney Transplantation, Prednisone administration & dosage
- Abstract
Thirty-six ciclosporin-prednisone-treated recipients of nonmatched cadaver renal allografts were given a course of Orthoclone OKT3 monoclonal antibody for steroid-resistant cell-mediated rejection. Although side effects were common, only 2 patients had to be withdrawn from therapy and there were no deaths related to therapy. Twenty-three (63.9%) allografts were rescued with OKT3 therapy and 21 (58.3%) of the grafts have continued to function well. We conclude that OKT3 is an effective agent for the treatment of steroid-resistant cell-mediated rejection and that rebound rejection can be prevented in most patients if adequate therapy with ciclosporin-prednisone is maintained. more...
- Published
- 1987
- Full Text
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13. Reversibility of lymphomas and lymphoproliferative lesions developing under cyclosporin-steroid therapy.
- Author
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Starzl TE, Nalesnik MA, Porter KA, Ho M, Iwatsuki S, Griffith BP, Rosenthal JT, Hakala TR, Shaw BW Jr, and Hardesty RL
- Subjects
- Adolescent, Adult, Cadaver, Female, Heart Transplantation, Herpesviridae Infections etiology, Humans, Kidney Transplantation, Liver Transplantation, Lung Transplantation, Male, Middle Aged, Postoperative Complications etiology, Transplantation, Homologous, Cyclosporins adverse effects, Immunosuppression Therapy adverse effects, Lymphoma etiology, Lymphoproliferative Disorders etiology, Prednisone adverse effects
- Abstract
Post-transplant lymphomas or other lymphoproliferative lesions, which were usually associated with Epstein-Barr virus infections, developed in 8, 4, 3, and 2 recipients, respectively, of cadaveric kidney, liver, heart, and heart-lung homografts. Reduction or discontinuance of immunosuppression caused regression of the lesions, often without subsequent rejection of the grafts. Chemotherapy and irradiation were not valuable. The findings may influence policies about treating other kinds of post-transplantation neoplasms. more...
- Published
- 1984
- Full Text
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14. 99mTc-DTPA and 131I-hippuran findings in liver transplant recipients treated with cyclosporin A.
- Author
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Klintmalm GB, Klingensmith WC 3rd, Iwatsuki S, Schröter GP, and Starzl TE
- Subjects
- Bilirubin blood, Creatinine blood, Humans, Kidney drug effects, Postoperative Period, Radionuclide Imaging, Technetium Tc 99m Pentetate, Cyclosporins adverse effects, Iodohippuric Acid, Kidney diagnostic imaging, Liver Transplantation, Pentetic Acid, Technetium
- Abstract
The effects of cyclosporin A (CyA), an immunosuppressive agent that is potentially nephrotoxic, on the kidneys of 9 liver transplant recipients were studied with serial 99mTc-DTPA and 131I-hippuran scans. In addition, renal function was determined by measuring serum creatinine levels during the second postoperative week in the 9 unselected CyA-treated patients and, retrospectively, in a control group of 29 liver transplant recipients who had not been treated with CyA and who were selected because they had survived for at least 3 months postoperatively. The early postoperative creatinine level was significantly greater in the CyA group. Eight of the 9 CyA patients showed imaging abnormalities in all preoperative and postoperative studies. Five of the 8 patients showed a pattern similar to that of acute tubular necrosis (relatively preserved perfusion) in at least one study. Lowering the dosage of CyA permitted the continuation of therapy, and all 9 patients are alive after 8 to 14 months. more...
- Published
- 1982
- Full Text
- View/download PDF
15. Cyclosporine-steroid combination therapy in 84 cadaveric renal transplants.
- Author
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Gordon RD, Iwatsuki S, Shaw BW Jr, and Starzl TE
- Subjects
- Administration, Oral, Adolescent, Adult, Aged, Blood Transfusion, Cadaver, Child, Cyclosporins adverse effects, Diabetes Complications, Drug Evaluation, Drug Therapy, Combination, Female, Humans, Immunosuppression Therapy, Male, Middle Aged, Postoperative Complications, Postoperative Period, Preoperative Care, Cyclosporins therapeutic use, Graft Survival drug effects, Kidney Transplantation, Prednisone therapeutic use
- Abstract
Sixty-three primary and 21 retransplant cadaver kidney allografts were placed in 77 patients over a one-year period with three- to six-month follow-up. Eight primary grafts (12.7%) and six retransplants (28.6%) were lost to rejection. Patient mortality was 3.9%. There were no grafts lost and no deaths due to opportunistic infections. Renal function at 6 months after transplantation was similar in all primary transplant recipients regardless of risk factors, including advanced age, diabetes, or the need for postoperative dialysis. more...
- Published
- 1985
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16. Results with cyclosporine in renal transplantation in patients who have lost two previous allografts.
- Author
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Ladowski JS, Rosenthal JT, Taylor RJ, Starzl TE, Carpenter B, Gordon R, Iwatsuki S, and Hakala TR
- Subjects
- Cadaver, Follow-Up Studies, Graft Survival, Histocompatibility Testing, Humans, Immunosuppression Therapy, Prednisone therapeutic use, Time Factors, Cyclosporins therapeutic use, Graft Rejection drug effects, Kidney Transplantation
- Abstract
We investigated the fate of the cadaver renal transplant done with cyclosporine and prednisone immunosuppression into a recipient who had suffered the loss of at least two prior allografts. Nineteen cadaver renal allografts were transplanted into 18 recipients. All 18 recipients had previously rejected at least two prior allografts. One of these rejected an allograft done at our institution with cyclosporine and prednisone and was included a second time in this series when a fourth allograft was received. Nine of 19 allografts were successfully transplanted. Average follow-up time was 39 months. Eight allografts were rejected. One graft was lost to technical complications. In one instance, the recipient died with a functioning graft. Duration of function of previous allografts was not found to be a critical determinant of third or fourth graft survival. Human leukocyte antigen matching was not a statistically significant determinant. Panel reactive antibody was higher in those who rejected the third or fourth allograft, but not with statistical significance. Recipients with the blood type A were less likely to enjoy successful third or fourth cadaver renal transplantation. We concluded that the "two time loser" renal allograft recipient should not be systematically denied subsequent transplantation. more...
- Published
- 1987
17. Liver and kidney transplantation in children receiving cyclosporin A and steroids.
- Author
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Starzl TE, Iwatsuki S, Malatack JJ, Zitelli BJ, Gartner JC Jr, Hakala TR, Rosenthal JT, and Shaw BW Jr
- Subjects
- Adolescent, Biliary Tract Surgical Procedures, Child, Child, Preschool, Female, Humans, Length of Stay, Liver Function Tests, Male, Postoperative Complications, Reoperation, Cyclosporins therapeutic use, Hydrocortisone administration & dosage, Kidney Transplantation, Liver Transplantation, Prednisone administration & dosage
- Abstract
The new immunosuppressive agent, cyclosporin A, was used with low doses of steroids to treat eight patients undergoing hepatic transplantation and three patients undergoing cadaveric renal transplantation. Seven of the eight liver recipients are well, including one who was given two livers. The three kidney recipients who had developed cytotoxic antibodies after previously rejecting grafts with conventional immunosuppressive therapy, have had good results despite conditions which usually preclude attempts at transplantation. The ability to control rejection effectively and safely without chronic high-dose steroid therapy may make the described therapeutic regimen valuable for pediatric recipients of whole organs. more...
- Published
- 1982
- Full Text
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18. Successful small bowel allotransplantation in dogs with cyclosporine and prednisone.
- Author
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Diliz-Perez HS, McClure J, Bedetti C, Hong HQ, de Santibanes E, Shaw BW Jr, van Thiel D, Iwatsuki S, and Starzl TE
- Subjects
- Animals, Body Weight, Dogs, Female, Graft Rejection drug effects, Intestinal Absorption, Intestinal Mucosa pathology, Intestine, Small pathology, Male, Short Bowel Syndrome etiology, Short Bowel Syndrome physiopathology, Transplantation, Homologous adverse effects, Transplantation, Homologous mortality, Cyclosporins administration & dosage, Intestine, Small transplantation, Prednisone administration & dosage, Transplantation, Homologous methods
- Abstract
Twelve dogs had transplantation of almost the entire small intestine in the orthotopic location; immunosuppression was with cyclosporine and prednisone. Half the dogs had survival of at least one month, and a third lived for at least four months. Two of the animals are still living after 550 and 555 days. Maintenance of nutrition, and absorption of D-xylose and fat were better than in control animals with an iatrogenic short gut syndrome, but distinctly worse than that of normal dogs. more...
- Published
- 1984
- Full Text
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19. Cyclosporine pharmacokinetic profiles in liver, heart, and kidney transplant patients as determined by high-performance liquid chromatography.
- Author
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Burckart GJ, Venkataramanan R, Ptachcinski RJ, Starzl TE, Griffith BP, Hakala TR, Rosenthal JT, Hardesty RL, Iwatsuki S, and Brady J
- Subjects
- Adult, Animals, Biological Availability, Child, Cyclosporins blood, Female, Humans, Male, Chromatography, High Pressure Liquid, Cyclosporins metabolism, Heart Transplantation, Kidney Transplantation, Liver Transplantation
- Abstract
Cs pharmacokinetic profiles using HPLC have aided in predicting necessary dosage alterations for specific groups of transplant patients. Additional information has been gained by HPLC profiles in nontransplant subjects who are healthy or have a stable disease state. The clinician now knows that liver disease not only impairs Cs elimination but may also have a pronounced effect upon drug absorption. While the cardiac failure patient may have reversible inhibition of Cs clearance, other factors may affect the distribution of the drug to lower dosage requirements. Impaired renal function is not an impediment to Cs elimination, but malabsorption similar to that observed in liver and bone marrow transplant patients may still occasionally complicate therapy. Pharmacokinetic information on Cs must be integrated into the complex care plan of a transplant patient to optimally utilize and monitor this pharmacologic agent. more...
- Published
- 1986
20. Total pancreaticoduodenal homotransplantation in dogs immunosuppressed with cyclosporine and steroids.
- Author
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Diliz-Perez HS, Hong HQ, de Santibanes E, Bedetti C, Iwatsuki S, Shaw BW Jr, and Starzl TE
- Subjects
- Animals, Dogs, Gallbladder surgery, Graft Rejection, Jejunum surgery, Pancreatectomy, Stomach surgery, Time Factors, Transplantation, Homologous, Cyclosporins pharmacology, Duodenum transplantation, Immunosuppression Therapy methods, Pancreas Transplantation, Prednisone pharmacology
- Abstract
Pancreaticoduodenal transplantation was performed with cyclosporine and steroid immunosuppressive therapy in 10 mongrel dogs that had pancreaticoduodenectomy. There was an average animal survival of 50.6 days and an average duration of normoglycemia of 41.8 days. We suggest that pancreaticoduodenal transplantation, which was abandoned as a clinical procedure 10 years ago, be reconsidered for clinical application. more...
- Published
- 1984
- Full Text
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21. Second cadaver kidney transplants: improved graft survival in secondary kidney transplants using cyclosporin A.
- Author
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Rosenthal JT, Hakala TR, Starzl T, Iwatsuki S, and Shaw BW
- Subjects
- Adolescent, Adult, Azathioprine therapeutic use, Cadaver, Child, Follow-Up Studies, Humans, Middle Aged, Prednisone administration & dosage, Reoperation, Cyclosporins therapeutic use, Graft Survival drug effects, Kidney Transplantation
- Abstract
A total of 42 patients who had failed prior renal transplantation underwent repeat cadaveric transplantation using cyclosporin A and low dose steroid immunosuppression. Patient survival at 1 year was 100 per cent. Over-all graft survival was 83 per cent at 1 year, which was significantly better than had been obtainable previously in this high risk group. Repeat cadaver transplantation with cyclosporin A is safe and offers those who have failed previous transplantation an opportunity for existence free of dialysis. more...
- Published
- 1984
- Full Text
- View/download PDF
22. Effect of liver dysfunction on cyclosporine pharmacokinetics.
- Author
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Takaya S, Zaghloul I, Iwatsuki S, Starzl TE, Noguchi T, Ohmori Y, Burckart GJ, Ptachcinski RJ, and Venkataramanan R
- Subjects
- Animals, Bilirubin blood, Dogs, Liver Function Tests, Reference Values, Bile Ducts physiology, Cyclosporins pharmacokinetics, Hepatectomy
- Published
- 1987
23. Nephrotoxicity of cyclosporine in liver transplantation.
- Author
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Iwatsuki S, Esquivel CO, Klintmalm GB, Gordon RD, Shaw BW Jr, and Starzl TE
- Subjects
- Administration, Oral, Adolescent, Adrenal Cortex Hormones administration & dosage, Adult, Child, Cyclosporins administration & dosage, Drug Administration Schedule, Drug Therapy, Combination, Humans, Kidney Diseases physiopathology, Kidney Failure, Chronic chemically induced, Kidney Failure, Chronic physiopathology, Kidney Function Tests, Cyclosporins adverse effects, Kidney Diseases chemically induced, Liver Transplantation
- Published
- 1985
24. Effect of bile on cyclosporin absorption in liver transplant patients.
- Author
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Mehta MU, Venkataramanan R, Burckart GJ, Ptachcinski RJ, Delamos B, Stachak S, Van Thiel DH, Iwatsuki S, and Starzl TE
- Subjects
- Adult, Cyclosporins blood, Female, Humans, Intestinal Absorption, Male, Bile physiology, Cyclosporins pharmacokinetics, Liver Transplantation
- Abstract
1. We quantitated the effect of biliary diversion on cyclosporin (CyA) absorption in liver transplant patients. Multiple blood samples were obtained over one dosing interval following oral CyA administration in eight liver transplant patients before and after T-tube clamping. 2. Cyclosporin concentrations were measured by a high pressure liquid chromatographic method. 3. The mean (+/- s.d.) dose-normalized area under the blood concentration vs time curve (AUC) over a dosing interval was 5.23 (+/- 3.22) ng ml-1 h during the pre clamping period and 15.79 +/- 7.92 ng ml-1 h during the post clamping period. A significant (P less than 0.05) increase (276%) in the dose normalized AUC was observed following the T-tube clamping. 4. Analysis of bile revealed less than 1 mg (less than 1% of dose) of unchanged CyA to be eliminated in bile over 12 h. Therefore the increased CyA AUC/dose following T-tube ligation cannot be explained by enterohepatic recirculation. 5. Increased bile flow secondary to clamping of the T-tube most likely increased the absorption of CyA. Increase in CyA absorption may be due to a bile mediated increase in CyA solubility or gastrointestinal membrane permeability, or increased residence time at the site of absorption. 6. Independent of the mechanism involved, our results indicate that adjustments in CyA dosage must be made whenever external bile diversion is instituted or discontinued. more...
- Published
- 1988
- Full Text
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25. Past and future prospects of orthoptic liver transplantation.
- Author
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Starzl TE, Klintmalm GB, Iwatsuki S, and Fernandez-Bueno C
- Subjects
- Animals, Azathioprine therapeutic use, Cyclosporins pharmacology, Female, Humans, Kidney Transplantation, Prednisone therapeutic use, Cyclosporins therapeutic use, Graft Survival drug effects, Liver Transplantation
- Abstract
The hopes for liver transplantation have been increased by experience with the new immunosuppressive drug cyclosporin A. Optimal therapy with cyclosporin A has required steroid therapy, but the amounts of prednisone used have been a small fraction of those used in the past. more...
- Published
- 1981
- Full Text
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26. Use of OKT3 with cyclosporin and steroids for reversal of acute kidney and liver allograft rejection.
- Author
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Fung JJ, Demetris AJ, Porter KA, Iwatsuki S, Gordon RD, Esquivel CO, Jaffe R, Tzakis A, Shaw BW Jr, and Starzl TE
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Clinical Trials as Topic, Drug Therapy, Combination, Humans, Infant, Kidney Transplantation, Liver pathology, Liver Transplantation, Middle Aged, Antibodies, Monoclonal administration & dosage, Cyclosporins administration & dosage, Graft Rejection, Steroids administration & dosage
- Abstract
OKT3 monoclonal antibody therapy was added to preexisting baseline immunosuppressive treatment with ciclosporin and steroids to treat rejection in 52 recipients of cadaveric livers and 10 recipients of cadaveric kidneys. Rejection was controlled in 75% of patients treated, often after high-dose steroid therapy had failed. Rejection recurred during the 17-month follow-up period, after completion of OKT3, in only 25% of the patients who had responded. The safety and effectiveness of this monoclonal therapy, added to ciclosporin and steroids, has been established in this study. more...
- Published
- 1987
- Full Text
- View/download PDF
27. Cyclosporine monitoring in liver transplant patients.
- Author
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Andrews W, Iwatsuki S, Shaw BW Jr, and Starzl TE
- Subjects
- Adult, Female, Humans, Kinetics, Male, Middle Aged, Cyclosporins blood, Liver Transplantation
- Published
- 1985
28. Cyclosporine trough concentration monitoring in liver transplant patients.
- Author
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Burckart GJ, Ptachcinski RJ, Venkataramanan R, Iwatsuki S, Esquivel C, Van Thiel DH, and Starzl TE
- Subjects
- Chromatography, High Pressure Liquid, Cyclosporins metabolism, Drug Interactions, Humans, Radioimmunoassay, Cyclosporins blood, Liver Transplantation
- Abstract
Trough blood or plasma concentration measurements of CsA must be carefully interpreted in OLT patients in relation to hepatic function, sample timing, assay specificity, and concurrent drug therapy. The RIA:HPLC ratio of blood or plasma measurements will vary with the patient's liver function, the time of blood sampling in reference to the time of drug administration, the absolute CsA concentration, and concurrent use of drugs that may alter the metabolism of CsA. The RIA assay should be used in conjunction with HPLC for trough blood or plasma measurement during the first postoperative weeks, during periods of changing hepatic function, and during changing drug regimens. In the future, the specific measurement of active or toxic metabolites of CsA should improve trough CsA concentration monitoring in OLT patients. more...
- Published
- 1986
29. Cyclosporin A and steroid therapy in sixty-six cadaver kidney recipients.
- Author
-
Starzl TE, Klintmalm GB, Weil R 3rd, Porter KA, Iwatsuki S, Schroter GP, Fernandez-Bueno C, and MacHugh N
- Subjects
- Adolescent, Adult, Antibodies, Viral analysis, Cadaver, Cyclosporins adverse effects, Female, Follow-Up Studies, Graft Rejection drug effects, Graft Survival, Hepatitis B Surface Antigens analysis, Herpesvirus 4, Human immunology, Humans, Male, Middle Aged, Cyclosporins therapeutic use, Immunosuppression Therapy, Kidney Transplantation, Prednisone therapeutic use
- Abstract
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. more...
- Published
- 1981
30. Liver transplantation in the ciclosporin era.
- Author
-
Starzl TE, Iwatsuki S, Shaw BW Jr, Gordon RD, and Esquivel C
- Subjects
- Age Factors, Biliary Tract Surgical Procedures, Histocompatibility Testing, Humans, Immunosuppression Therapy, Kidney Transplantation, Lymphoma complications, Organ Preservation, Prognosis, Cyclosporins therapeutic use, Liver Transplantation
- Published
- 1986
- Full Text
- View/download PDF
31. Clinical presentation of hepatic artery thrombosis after liver transplantation in the cyclosporine era.
- Author
-
Tzakis AG, Gordon RD, Shaw BW Jr, Iwatsuki S, and Starzl TE
- Subjects
- Adult, Aspartate Aminotransferases blood, Child, Female, Humans, Liver pathology, Liver Function Tests, Necrosis, Cyclosporins therapeutic use, Hepatic Artery, Liver Transplantation, Thrombosis etiology
- Abstract
Hepatic artery thrombosis is a dreadful complication of orthotopic liver transplantation. It should be suspected in cases of fulminant liver failure, delayed bile leak, or intermittent sepsis of unknown cause after liver transplantation. Accurate diagnosis is assisted by ultrasound and computerized tomography scans, but usually requires arteriography. Prompt retransplantation is required in most of the cases. more...
- Published
- 1985
- Full Text
- View/download PDF
32. Effect of danazol on cyclosporine pharmacokinetics.
- Author
-
Koneru B, Hartner C, Iwatsuki S, and Starzl TE
- Subjects
- Female, Humans, Liver physiology, Liver Transplantation, Middle Aged, Cyclosporins pharmacokinetics, Danazol pharmacology, Pregnadienes pharmacology
- Published
- 1988
- Full Text
- View/download PDF
33. Cyclosporine Trough Concentration Monitoring in Liver Transplant Patients
- Author
-
Burckart, G. J., Ptachcinski, R. J., Venkataramanan, R., Iwatsuki, S., Esquivel, C., Van Thiel, D. H., and Starzl, T. E.
- Subjects
Radioimmunoassay ,Humans ,Cyclosporins ,Drug Interactions ,Article ,Chromatography, High Pressure Liquid ,Liver Transplantation - Abstract
Trough blood or plasma concentration measurements of CsA must be carefully interpreted in OLT patients in relation to hepatic function, sample timing, assay specificity, and concurrent drug therapy. The RIA:HPLC ratio of blood or plasma measurements will vary with the patient's liver function, the time of blood sampling in reference to the time of drug administration, the absolute CsA concentration, and concurrent use of drugs that may alter the metabolism of CsA. The RIA assay should be used in conjunction with HPLC for trough blood or plasma measurement during the first postoperative weeks, during periods of changing hepatic function, and during changing drug regimens. In the future, the specific measurement of active or toxic metabolites of CsA should improve trough CsA concentration monitoring in OLT patients. more...
- Published
- 1986
34. Nephrotoxicity of Cyclosporine in Liver Transplantation
- Author
-
Iwatsuki, S., Esquivel, C.O., Klintmalm, G.B.G., Gordon, R.D., Shaw, B.W., and Starzl, T.E.
- Subjects
Adult ,Adolescent ,Administration, Oral ,Cyclosporins ,Kidney Function Tests ,Article ,Drug Administration Schedule ,Liver Transplantation ,Adrenal Cortex Hormones ,Humans ,Kidney Failure, Chronic ,Drug Therapy, Combination ,Kidney Diseases ,Child - Published
- 1985
35. Effect of Liver Dysfunction on Cyclosporine Pharmacokinetics
- Author
-
Takaya, S., Zaghloul, I., Iwatsuki, S., Starzl, T.E., Noguchi, T., Ohmori, Y., Burckart, G.J., Ptachcinski, R.J., and Venkataramanan, R.
- Subjects
Dogs ,Liver Function Tests ,Reference Values ,Animals ,Hepatectomy ,Bilirubin ,Cyclosporins ,Bile Ducts ,Article - Published
- 1987
36. Excretion of Cyclosporine and its Metabolites in Human Bile
- Author
-
Burckart, G.J., Starzl, T.E., Venkataramanan, R., Hashim, H., Wong, L., Wang, P., Makowka, L., Zeevi, A., Ptachcinski, R.J., Knapp, J.E., Iwatsuki, S., Esquivel, C., Sanghvi, A., and Van Thiel, D.H.
- Subjects
Liver Diseases ,Bile ,Cyclosporins ,Article ,Chromatography, High Pressure Liquid ,Liver Transplantation - Abstract
Quantitative and qualitative studies of cyclosporine and its metabolites were performed on human bile from liver transplant and liver disease patients. The concentration of CsA in bile is higher in patients with normal liver function than in those with poor liver function but in neither case could account for more than 2% of an absorbed dose of CsA. Although concentrations of CsA plus metabolites in bile measured by RIA were 18 to 36 times higher than HPLC concentrations, they accounted for less than 50% of an absorbed CsA dose. By means of mass spectrometry and HPLC retention times of known metabolites, peaks equivalent to the previously isolated CsA M8, M13, M17, M1, M18, and M21 of Maurer et al were found in the ether extracts of bile. Future studies should not only concentrate on the pharmacologic and toxicologic effects of the metabolites but should also accurately quantitate these compounds in blood, plasma, urine, and bile. more...
- Published
- 1986
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