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Biomedical subjects

A Tzakis

Publications and source records attributed to A Tzakis.

At least 109 records · Page 6Linked to original sources
PubMed1994

Single-center experience with primary orthotopic liver transplantation with FK 506 immunosuppression.

OBJECTIVE: The efficacy for primary orthotopic liver transplantation of a new immunosuppressive agent, FK 506 (tacrolimus, Prograf, Fujisawa USA, Deerfield, IL), was determined. SUMMARY BACKGROUND DATA: After 3 years of preclinical research, a clinical trial of FK 506 for orthotopic liver transplantation was begun in February 1989, first as a rescue therapy for patients with intractable rejection with conventional immunosuppression, then as a primary drug. METHODS: Between August 1989 and December 1993, 1391 recipients (1188 adult and 203 pediatric) of primary liver allografts were treated with FK 506 from the outset. Results from these patients were analyzed and compared with those of 1212 historical control patients (971 adult and 241 pediatric) given cyclosporine-based immunosuppression. RESULTS: Actuarial survival at 4 years was 86.2% with FK 506 versus 65.5% with cyclosporine in the pediatric patients (p < 0.0000) and 71.4% versus 65.5% in the adults (p < 0.0005). The need for retransplantation was reduced significantly for FK 506 patients. Four-year graft survival was 77.0% with FK 506 versus 48.4% with cyclosporine in the pediatric patients (p < 0.0000), and 61.9% with FK 506 versus 51.4% with cyclosporine in the adult recipients (p < 0.0000). Regression analysis revealed that reduction in mortality or graft loss from uncontrollable rejection, sepsis, technical failure, and recurrent original liver disease were responsible for the improved results with FK 506 therapy. CONCLUSIONS: FK 506 is a potent and superior immunosuppressive agent for orthotopic liver transplantation.

Actuarial Analysis↗
PubMed1994

Portosystemic shunt for the treatment of portal vein thrombosis following orthotopic liver transplantation.

The efficacy of the portosystemic shunt operation for the treatment of portal vein thrombosis following orthotopic liver transplantation was demonstrated. From 1 July 1988 to 31 December 1991 42 portosystemic shunt operations were performed at our centre. In six of these cases portal vein thrombosis after orthotopic liver transplantation (OLT) was the indication for the procedure. All the patients retained adequate liver function but they demonstrated manifestations of significant portal hypertension, mainly variceal rebleeding. Two of the patients were children. Three patients underwent distal splenorenal shunt (DSRS), one mesocaval and one side-to-side splenorenal shunt and the last one side-to-side splenorenal shunt which was converted to DSRS 2 weeks later. All these patients were doing well after 30 months mean follow-up time without rebleeding or other signs of portal hypertension and none had so far required retransplantation.

Adolescent↗
PubMed1994

Intestinal transplantation at the University of Pittsburgh.

Our experience with clinical intestinal transplantation under FK 506 immunosuppression showed that 50% of the recipients were able to be independent from TPN after transplantation, but 10% require partial TPN with functioning grafts, 10% needed total TPN after graft removal, and 30% of the recipients died postoperatively, mostly from sepsis due to severe graft rejection. For further improvement in patient survival and in the quality of life for patients after intestinal transplantation, it is mandatory to establish a new strategy for treatment and prevention of graft rejection and systemic infection.

Adult↗
PubMed1994

Three years clinical experience with intestinal transplantation.

BACKGROUND: After the successful evolution of hepatic transplantation during the last decade, small bowel and multivisceral transplantation remains the sole elusive achievement for the next era of transplant surgeons. Until recently, and for the last thirty years, the results of the sporadic attempts of intestinal transplantation worldwide were discouraging because of unsatisfactory graft and patient survival. The experimental and clinical demonstration of the superior therapeutic efficacy of FK 506, a new immunosuppressive drug, ushered in the current era of small bowel and multivisceral transplantation with initial promising results. STUDY DESIGN: Forty-three consecutive patients with short bowel syndrome, intestinal insufficiency, or malignant tumors with or without associated liver disease, were given intestinal (n = 15), hepatic and intestinal (n = 21), or multivisceral allografts that contained four or more organs (n = 7). Treatment was with FK 506 based immunosuppression. The ascending and right transverse colon were included with the small intestine in 13 of the 43 grafts, almost evenly distributed between the three groups. RESULTS: After six to 39 months, 30 of the 43 patients are alive, 29 bearing grafts. The most rapid convalescence and resumption of diet, as well as the highest three month patient survival (100 percent) and graft survival (88 percent) were with the isolated intestinal procedure. However, this advantage was slowly eroded during the first two postoperative years, in part because the isolated intestine was more prone to rejection. By the end of this time, the best survival rate (86 percent) was with the multivisceral procedure. With all three operations, most of the patients were able to resume diet and discontinue parenteral alimentation, and in the best instances, the quality of life approached normal. However, the surveillance and intensity of care required for these patients for the first year, and in most instances thereafter, was very high, being far more than required for patients having transplants of the liver, kidney or heart. CONCLUSIONS: Although intestinal transplantation has gone through the feasibility phase, strategies will be required to increase its practicality. One possibility is to combine intestinal transplantation with contemporaneous autologous bone marrow transplantation.

Adolescent↗
PubMed1994

Improving results of pediatric renal transplantation.

BACKGROUND: Outcome after renal transplantation in children has been variable. We undertook a retrospective study of our experience over the past five years. STUDY DESIGN: From January 1, 1988, to October 15, 1992, 60 renal transplantations were performed upon 59 children at the Children's Hospital of Pittsburgh. Twenty-eight (47 percent) of the kidneys were from cadaveric donors, and 32 (53 percent) were from living donors. The recipients ranged in age from 0.8 to 17.4 years, with a mean of 9.8 +/- 4.8 years. Forty-six (77 percent) recipients were undergoing a first transplant, while 14 (23 percent) received a second or third transplant. Eight (13 percent) of the patients were sensitized, with a panel reactive antibody of more than 40 percent. Eleven of the 14 patients undergoing retransplantation and seven of the eight patients who were sensitized received kidneys from cadaveric donors. Thirty-three (55 percent) patients received cyclosporine-based immunosuppression, and 27 (45 percent) received FK506 as the primary immunosuppressive agent. RESULTS: The median follow-up period was 36 months, with a range of six to 63 months. The one- and four-year actuarial patient survival rate was 100 and 98 percent. The one- and four-year actuarial graft survival rate was 98 and 83 percent. For living donor recipients, the one- and four-year actuarial patient survival rate was 100 and 100 percent; for cadaveric recipients, it was 100 and 96 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 95 percent for the living donor recipients and 96 and 69 percent for the cadaveric recipients. Patients on cyclosporine had a one- and four-year patient survival rate of 100 and 97 percent, and patients on FK506 had a one- and three-year patient survival rate of 100 and 100 percent. Corresponding one- and four-year actuarial graft survival rates were 100 and 85 percent in the cyclosporine group, while one- and three-year actuarial graft survival rates were 96 and 84 percent in the FK506 group. The mean serum creatinine level was 1.24 +/- 0.64 mg per dL; the blood urea nitrogen level was 26 +/- 13 mg per dL. The incidence of rejection was 47 percent; 75 percent of the rejections were steroid-responsive. The incidence of cytomegalovirus was 10 percent. The incidence of post-transplant lymphoproliferative disorder was 8 percent. None of the patients on cyclosporine were able to be taken off prednisone; 56 percent of the patients receiving FK506 were taken off prednisone successfully. Early growth and development data suggest that the patients receiving FK506 off prednisone had significant gains in growth. CONCLUSIONS: These results support the idea that renal transplantation is a successful therapy for end-stage renal disease in children. They also illustrate the potential benefits of a new immunosuppressive agent, FK506.

Adolescent↗
PubMed1994

A prospective, randomized trial of FK-506 in renal transplantation--a comparison between double- and triple-drug therapy.

Previous clinical evaluation of FK506 in renal transplantation has demonstrated equivalent patient and graft survival when compared with cyclosporine-based regimens. However, lower steroid and anti-hypertensive mediation requirements and lower serum cholesterol levels have been seen in patients receiving FK506. In August, 1991, a prospective, randomized trial was begun, comparing FK506/prednisone with FK506/azathioprine/prednisone. Two-hundred-and-four adults were entered into this trial between August 1, 1991, and October 11, 1992. The mean recipient age was 43.8 +/- 13.7 years, with a range of 17.6-78.0 years. Sixty-one (30%) recipients received a 2nd, 3rd or 4th transplant, while 35 (17%) had a PRA greater than 40% at the time of transplant. Thirty-three (16%) of the transplants were in recipients over 60 years of age, Thirteen percent of the kidneys were from living donors; 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hours, and the mean donor age was 34 +/- 2.10 years, with a range from 4 months to 75 years. With a mean follow-up of 9 +/- 4 months, the 1-year actuarial patient survival is 93%; for the two-drug group it is 95%, and for the three-drug group it is 91% (p = NS). One-year actuarial graft survival is 86%; in the two-drug group it is 90%, while in the three-drug group it is 82% (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1994

Rejection of human intestinal allografts: alone or in combination with the liver.

The current results of the present series demonstrate that intestinal allografts are more vulnerable to rejection and continue to be at a significantly higher risk long after transplantation compared with isolated liver allograft recipients. Unexpectedly, a combined liver allograft does not protect small bowel from rejection. The necessarily continuous heavy immunosuppression for these unique recipients is potentially self-defeating. This is clearly demonstrated by their high susceptibility to early and late infectious complications after transplantation as reported in this issue. With the minimal graft-versus-host disease threat in this clinical trial, our revised protocol for future intestinal transplantation is to maximize the passenger leukocyte traffic with supplementary bone marrow from the same intestinal donor in an attempt to augment the development of systemic chimerism and the gradual induction of donor-specific nonreactivity.

Acute Disease↗