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M Kalayoglu

Publications and source records attributed to M Kalayoglu.

At least 109 records · Page 6Linked to original sources

Liver transplantation in infants and children.

Orthotopic liver transplantation has become an accepted form of therapy for advanced liver disease. Over a 44-month period, we performed 27 liver transplants in 25 pediatric recipients, including 14 infants (mean age, 7.2 months; mean weight, 5.9 kg) and 11 children (mean age, 9.0 years; mean weight, 34.8 kg). Indications for transplantation were biliary atresia (16), tyrosinemia (3), chronic hepatitis with cirrhosis (2), fulminant hepatic failure (2), and one patient each with Wilson's disease and primary hepatoma. Eighteen patients (72%) had undergone a previous laparotomy, including 19 Kasai procedures in 13 patients with biliary atresia. The average time on the waiting list was 26.8 days (range, 1 to 60), and no patients died while awaiting transplantation. Mean preservation time was 6.9 hours (range, 2 to 13.5), employing cold storage with Collin's solution (16), or more recently, UW solution (11). Urgent liver transplantation was performed in seven cases (25.9%), although at present, we perform liver transplantation as a scheduled semielective procedure with extended preservation times in stable patients. The recipient hepatectomy and orthotopic liver transplantation were performed by standard techniques, with venous bypass used in three cases. Biliary reconstruction was performed with a Roux limb in 16 and via choledochocholedochostomy in ten cases, while arterial reconstruction was end-to-end hepatic artery in 21, and aorto-aortic anastomosis in the remaining six. Two hepatic artery thromboses (7.4%) and two biliary complications (7.4%) occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Combined cold storage-perfusion preservation with a new synthetic perfusate.

Based upon encouraging experimental results, we began employing a synthetic perfusate for cadaver kidney preservation. The new perfusate contains hydroxyethyl starch (HES) as the sole colloid for oncotic support; 107 cadaver kidneys were preserved and transplanted (93 primary, 14 nonprimary) using the HES solution and were compared with our previous experience of 180 cadaver kidneys (161 primary, 19 nonprimary) preserved and transplanted utilizing an albumin-based perfusate. All cadaver kidneys were locally harvested and preserved by machine perfusion. Donor and preservation characteristics in the HES (n = 61) and the albumin (n = 101) groups were comparable, with a mean preservation time of 30.9 hr. Cold storage in combination with hypothermic pulsatile perfusion (HPP) preservation was performed more often in the HES group (68.2% vs. 31.1%, P less than 0.001). Recipient characteristics were also comparable, and all received quadruple immunosuppressive therapy with sequential/Minnesota antilymphoblast globulin/(MALG)/cyclosporine. After primary transplantation, the incidence of immediate function (82.6% vs. 89.2%), preservation-related dialysis (14.9% vs. 8.6%), and primary nonfunction (2.5% vs. 0) were similar between the 2 groups, with trends favoring the latter HES data. One-month serum creatinine (1.8 vs. 1.7 mg/dl) and graft survival (95% vs. 97.8%) also were comparable. Similar trends were present in the retransplant group, including a significantly lower 1-month serum creatinine in the HES group (2.2 vs. 1.5 mg/dl; P less than 0.05). The preservation-related dialysis rate did not differ between primary and nonprimary transplants. Primary nonfunction has not occurred with our new perfusate. Combined cold-storage-HPP preservation with HES perfusate offers advantages over standard retrieval technology and provides excellent immediate allograft function.

Albumins↗

Sequential antilymphocyte globulin/cyclosporine immunosuppression in cadaveric renal transplantation. Effect of duration of ALG therapy.

Recent studies have documented the efficacy of quadruple immunotherapy with sequential ALG/cyclosporine in cadaveric renal transplantation. However, the exact role of ALG in this regimen is controversial. Over a four-year period, we performed 429 cadaveric renal transplants (367 primary, 62 retransplants) with prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and CsA. ALG therapy was divided into three protocols: true sequential (n = 259, mean no. days of ALG = 8.2); extended (defined as sequential MALG/CsA continued for 14 days irrespective of renal function or CsA level, n = 103, mean no. days of ALG = 14.1); and therapeutic (continued MALG therapy for early breakthrough rejection, n = 67 [15.6%], mean no. days of ALG = 17.2). The study groups were comparable and retrospectively analyzed in multivariate fashion for 15 variables. Requirement for postoperative dialysis was equivalent (14%) in both sequential and extended ALG groups. Extended ALG therapy failed to reduce the incidence of acute rejection (46.5% vs. 40.4% with true sequential therapy). Prolonging the duration of ALG treatment (greater than 10 days) was associated with a higher risk of infection. Logistic regression analysis revealed that the use of OKT3 after ALG accounted for the higher infection rate. Duration of ALG therapy had no impact on patient or graft survival after a mean follow-up interval of 20 months. We recommended a quadruple immunosuppressive strategy in cadaveric renal transplantation with sequential MALG/CsA to minimize early allograft dysfunction and to achieve excellent patient and graft survival. MALG therapy should be stopped after renal function is documented and CsA levels are therapeutic. Further ALG therapy offers no immunologic advantage and may place the patient at high risk for infection if OKT3 rescue therapy is required.

Antilymphocyte Serum↗

Comparison between duodenal button and duodenal segment in pancreas transplantation.

Two technical modifications have been suggested for whole-pancreas transplantation with bladder drainage. The duodenal button technique (DB [Madison]) and the duodenal segment technique (DS [Iowa]) are the most commonly performed procedures (1,2). From December 1985 until May 1988 we performed 32 combined pancreas-kidney transplants using DB and DS techniques in 17 and 15 patients, respectively. Bladder leaks, pancreatitis, bleeding episodes, and surgically related infections were all decreased with the duodenal segment technique. Metabolic acidosis was more common with DS but was easily managed with oral sodium bicarbonate. The one-year actuarial graft survival with DB is less when compared with DS (76.1% vs. 87.5%). Three technical graft losses occurred with DB vs. none with DS. One graft was lost in each group to rejection. Our results indicate that the duodenal segment technique of bladder implantation adds safety to whole-pancreas transplantation and must now be considered the procedure of choice.

Diabetes Mellitus, Type 2↗

Cadaveric renal transplantation with cyclosporine in patients more than 60 years of age.

Advanced age has been a relative contraindication to kidney transplantation because of the likelihood of increased morbidity and mortality in the geriatric population. However, the introduction of cyclosporine has improved renal allograft survival rates dramatically, and higher-risk patients are now being successfully transplanted. With the introduction of cyclosporine in 1983, we have performed 36 cadaveric renal transplants in 34 recipients 60 years of age or older, including 34 primary and 2 retransplants. Most of the patients (88%) were on dialysis prior to transplantation and 29% had ASCVD. Three-year actuarial patient and allograft survival are 91% and 74%, respectively. Surgical complications were infrequent, and postoperative rejection episodes were less frequent than in younger patients but were more likely to lead to graft loss. Medical complications, especially infection, were common after transplantation but easily managed. Cadaveric renal transplantation with cyclosporine immunosuppression is a safe and effective therapeutic modality that is no longer contraindicated in elderly patients.

Adolescent↗

Cadaveric renal transplantation with quadruple immunosuppression in patients with a positive antiglobulin crossmatch.

The significance of the antiglobulin crossmatch in the cyclosporine era remains controversial. Over an 11-month period, 124 recipients of cadaveric renal allografts (109 primary, 15 nonprimary) were retrospectively crossmatched via the antiglobulin technique. Criteria for recipient selection for transplantation included a negative T lymphocytotoxic (CDC) crossmatch for current and historical sera. Fourteen patients (11.3%) underwent transplantation in the setting of a negative T and positive antiglobulin crossmatch. The patient group included 10 female and 4 male patients with a mean age of 43.8 years. All but one patient received a primary transplant, and current sera were positive in the antiglobulin crossmatch in all cases. The mean HLA-ABDR match was 1.4 (range 0-4). Preoperative PRA titers ranged from 0 to 80% (mean 18.3%). All patients underwent successful renal transplantation with quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of MALG/cyclosporine. There were no episodes of hyperacute rejection. However, 10 patients (71.4%) experienced acute rejection, including 7 episodes within 4 days of transplant. Early rejection was significantly more common in patients with a positive antiglobulin test (50% vs. 20.9%, P less than 0.05). The mean one-month serum creatinine was 1.7 mg/dl. Actual patient and allograft survival are 92.9% and 85.7%, respectively. Risk factors for a positive antiglobulin crossmatch included female sex and prior sensitization as measured by PRA. Although these patients represent a high-risk group for early rejection, no adverse effect on patient or graft survival was noted with quadruple immunotherapy. In conclusion, a positive antiglobulin crossmatch is no longer a contraindication to renal transplantation with current immunosuppressive strategies.

Adolescent↗

OKT3 salvage therapy in a quadruple immunosuppressive protocol in cadaveric renal transplantation.

Since the introduction of OKT3 at our center in January 1986, we have performed 246 cadaveric renal transplants (220 primary, 26 nonprimary). All patients received quadruple immunosuppression consisting of prednisone, azathioprine, and the sequential use of Minnesota antilymphoblast globulin (MALG) and cyclosporine. OKT3 (Orthoclone OKT3) therapy was reserved for corticosteroid- and/or ALG-resistant rejection. Of the 246 patients, 138 developed one or more rejection episodes (56.1%). Ninety-seven (70.3%) were successfully reversed with prednisone and/or ALG, whereas 41 (29.7%) required additional treatment with OKT3. Initial graft salvage occurred in 34 (82.9%) patients treated with OKT3, but rejection recurred in 18 (52.9%) and was successfully reversed in only 6 patients. However, the rate of recurrent rejection was much lower in patients given OKT3 early (14%), shortly after it was apparent that high-dose corticosteroid therapy was proving ineffective, than in patients who received OKT3 after a prolonged or second course of corticosteroids (64%) or ALG (60%). Graft survival after a mean follow-up interval of 11 months in all OKT3-treated patients was 54%. One or more infections occurred in 19 (46%) patients treated with OKT3. Patients developing infections following OKT3 therapy received significantly larger total doses of prednisone during graft rejection (46.3 mg/kg vs. 27.9 mg/kg, P less than .05) than OKT3-treated patients who did not develop infectious complications. Our experience shows that use of OKT3 for treatment of corticosteroid- and/or ALG-resistant rejection is associated with a high rate of recurrent rejection, except when given early, as soon as it is clear that high-dose corticosteroid therapy is not reversing the rejection episode. It further suggests that prolonged administration of high-dose corticosteroids and possibly ALG for the treatment of rejection prior to beginning OKT3 greatly increases the rate of infection following OKT3 therapy.

Adult↗

Early detection of rejection in pancreas transplantation.

A major dilemma in pancreas transplantation is the lack of reliable methods for the early detection of allograft rejection. Over a 26-mo period, 70 rejection episodes occurred in 36 patients (13 isolated-pancreas, 23 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 300 radionuclide pancreas examinations were performed (mean 8.3/patient) utilizing 99mTc-labeled DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft (technetium index, TI). Rejection episodes were defined as isolated pancreas, isolated kidney, or combined pancreas-kidney. Mean urinary amylase (UA) levels and TI during normal allograft function were 30,256 U/L and 0.57%, respectively, whereas levels heralding rejection were 6873 U/L and 0.39% (P less than .05). The treatment of rejection based on kidney dysfunction or combined pancreas-kidney dysfunction resulted in significantly higher graft salvage and a lower incidence of hyperglycemia compared with isolated-pancreas-allograft rejection. After therapy, a TI greater than 0.3% was associated with 95.9% graft survival, whereas levels less than 0.3% resulted in a 72.7% rate of graft loss (P less than .001). Similarly, pancreas allografts with a UA greater than 10,000 U/L had 92.2% functional survival, whereas levels less than 10,000 U/L resulted in a 53.3% rate of graft loss (P less than 0.001). Overall, reversal of rejection occurred in 80% of cases, with 10 pancreas and 2 kidney allografts lost due to rejection. Monitoring pancreas-allograft function by UA, TI, and renal function in simultaneous transplants allows for the timely diagnosis and successful treatment of pancreas-allograft rejection.

Adult↗

Use of UW solution in pancreas transplantation.

We have recently reported successful 72-h preservation of the canine pancreas with a new cold-storage solution developed at the University of Wisconsin (UW solution). Over 10 mo, we performed 11 combined pancreas-kidney and 4 isolated-pancreas transplants with this solution. In situ cooling of the donor pancreas was performed with 1000 ml of UW solution followed by ex vivo perfusion with an additional 250-500 ml. Graft preservation times ranged from 3 to 19 h (mean 10.2 h). Pancreas transplants were vascularized whole-organ grafts with pancreaticoduodenocystostomy. Early graft function was excellent as assessed by immediate insulin independence, high urinary amylase and low serum amylase levels, and a technetium perfusion index indicating good pancreatic blood flow. There were no episodes of primary nonfunction, graft pancreatitis, or vascular thrombosis. Actuarial patient and graft survival at 1 mo was 92.9%. We conclude that UW solution provides excellent early graft function for up to 19 h of cold storage. Based on previously reported data on its efficacy in liver and kidney preservation, UW solution seems ideally suited as a universal intra-aortic flush and cold-storage solution.

Amylases↗

OKT3 rescue therapy in pancreas-allograft rejection.

OKT3 has emerged as a highly effective antirejection therapy, but its efficacy in pancreas transplantation remains to be determined. During a 26-mo period, 46 vascularized pancreas transplants were performed with pancreaticoduodenocystostomy. Twenty-one patients (45.7%) were treated with OKT3. Indications for OKT3 use included steroid- and/or antilymphoblast globulin-resistant rejection in isolated-pancreas transplant (n = 8) or simultaneous pancreas-kidney-transplant (n = 13) recipients. A total of 46 rejection episodes occurred (mean 2.2). OKT3 was administered for a 14-day course concomitant with pulsed corticosteroids, azathioprine, and cyclosporin. OKT3 rescue therapy was successful in 13 cases (61.9%). The mean time to rejection reversal was 8.8 days (range 5-14 days). In isolated-pancreas transplants, OKT3 reversed only 1 episode of rejection (12.5%). In contrast, 12 episodes (92.3%) of allograft rejection were responsive to OKT3 in simultaneous pancreas-kidney recipients (P less than .05). Graft loss from rejection occurred at a mean 5.5 mo posttransplantation. OKT3 therapy was more successful in the setting of early rejection, rejection in combined pancreas-kidney transplants, and rejection not associated with hyperglycemia. No graft loss due to infection or patient death has occurred after OKT3 therapy. After a mean follow-up of 17.3 mo, patient survival was 89.1%, and allograft survival was 26.3% in isolated-pancreas and 85.2% in simultaneous pancreas-kidney transplants (P less than .05). Salvage therapy with OKT3 is a safe and effective means of reversing rejection in pancreas-allograft recipients. OKT3 is more effective in simultaneous pancreas-kidney recipients due to the earlier diagnosis of rejection.

Adult↗

The current status of the University of Wisconsin experience in pancreas transplantation.

The data presented demonstrate that combined kidney-pancreas grafting can be performed with excellent patient and graft survival. Current long-term studies at our center investigating the effect of pancreas transplantation on diabetic retinopathy and comprehensive quality of life assessment will address the question of whether pancreas transplantation can be considered an effective and therapeutic procedure.

Humans↗

Cadaveric renal transplantation in the cyclosporine and OKT3 eras: an update of the University of Wisconsin-Madison experience.

1. Quadruple immunosuppression yields excellent early renal allograft survival in primary renal transplant recipients when compared with non-primary renal transplant recipients. Although significant, the difference between primary and nonprimary recipients at 5 years has narrowed considerably (8%). 2. No beneficial effect of HLA or DR matching was noted in this study in primary transplant recipients. However, a trend toward improved graft survival was noted when patients with greater than or equal to 3 antigens matched or less than 3 antigens mismatched were compared to their counterparts. Further analysis of variables related to graft loss is required before statements regarding this trend can be made. 3. Significantly better results in nonprimary renal transplantation continues to be seen in DR matched recipients. Additionally, the use of OKT3 rather than ALG in DR matched recipients has resulted in a 92.3% 3-year allograft survival despite over half of these patients being highly sensitized. 4. Further follow-up of 2 high-risk groups of patients (diabetics and elderly patients) revealed significant decreases in patient survival at 5 years. This difference was not apparent in our earlier results (3-year follow-up) published in Clinical Transplants 1987. Despite this difference, we believe renal transplantation should continue to be offered to diabetic and elderly patients without other contraindications to transplantation. 5. The availability of the monoclonal antibody OKT3 during the CsA era has resulted in a trend toward improved patient and graft survival when compared with patients in the CsA pre-OKT3 era. This trend toward improved survival is also seen in the high-risk diabetic recipients.

Antibodies, Monoclonal↗

Tertiary hyperparathyroidism after renal transplantation: operative indications.

A retrospective analysis of our renal transplant population between 1981 and 1987 was undertaken to study the natural history of posttransplant hypercalcemia and to review indications and recommendations regarding the timing of parathyroidectomy. During this period, 1158 renal transplant procedures were performed in 1025 patients, with 819 allografts (71%) functioning currently. Posttransplant hypercalcemia greater than 10.5 mg/dl was associated with a longer duration of dialysis and developed in 227 patients, with onset of hypercalcemia occurring in 90% of these patients by 1 year. In 69% of these patients, spontaneous resolution of the hypercalcemia occurred between 6 months and 7 years after transplantation. A total of 42 patients with asymptomatic hypercalcemia are currently being followed up, with a mean serum calcium level of 11.0 +/- 0.41 mg/dl and a mean follow-up interval of 3.3 +/- 1.6 years since transplantation. Nine symptom-free patients with moderate hypercalcemia (12.0 to 12.4 mg/dl) more than 1 year after transplantation were identified. Five of these patients had spontaneous resolution of the hypercalcemia between 2 and 7 years. Fifteen patients with posttransplant hyperparathyroidism (6.6%) required parathyroidectomy--11 for symptomatic and four for asymptomatic hyperparathyroidism. One patient had symptomatic hyperparathyroidism despite the presence of normocalcemia. One symptom-free patient with significant hypercalcemia (serum calcium level, 14.7 mg/dl) underwent parathyroidectomy 3 months after transplantation. The remaining three symptom-free patients had serum calcium determinations of greater than or equal to 12.5 mg/dl more than 1 year after renal transplantation. Patients with pretransplant and posttransplant hypercalcemia required parathyroidectomy more frequently than did patients with only posttransplant hypercalcemia (18% versus 3.0%; p less than 0.001). An unusual finding was the occurrence of a single adenoma in two patients, which represents sporadic primary hyperparathyroidism in the patient undergoing renal transplantation rather than tertiary hyperparathyroidism. We recommend a conservative approach to posttransplant hypercalcemia, with surgery reserved for patients with symptomatic disease and patients with asymptomatic persistent hypercalcemia greater than or equal to 12.5 mg/dl more than 1 year after transplantation.

Follow-Up Studies↗