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Biomedical subjects

R J Tesi

Publications and source records attributed to R J Tesi.

At least 19 recordsLinked to original sources

Minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in type 1 (insulin-dependent) diabetic pancreas allograft recipients.

Decreased insulin sensitivity and glucose-dependent glucose disposal (glucose effectiveness) have been demonstrated in poorly-controlled Type 1 (insulin-dependent) diabetic patients. We have therefore examined the effects of successful pancreas transplantation that results in long-term physiologic normoglycaemia as measured by insulin sensitivity index and glucose effectiveness in 14 Type 1 diabetic recipients (Group 1) using the Bergman minimal model method. Their results were compared with those of five non-diabetic patients with kidney transplant alone (Group 2) and 10 healthy control subjects (Group 3). Mean plasma glucose levels were indistinguishable in Group 1 when compared to Groups 2 and 3. However, mean basal plasma insulin levels were two- and eight-fold greater in Group 1 (36 +/- 6 microU/ml) than in Group 2 (17 +/- 7 microU/ml) and Group 3 (4.5 +/- 0.6 microU/ml), respectively. Following intravenous glucose (t = 0 min) and tolbutamide (t = 20), peak incremental insulin levels were significantly (p less than 0.001) greater in Group 1 vs Groups 2 and 3. Mean insulin sensitivity index was 65% and 50% lower in Group 1 (2.89 +/- 0.45) and Group 2 (4.11 +/- 1.30), respectively, when compared to Group 3 (8.40 +/- 1.24 x 10(-1) min-1 (microU/ml)-1. In contrast, glucose effectiveness was similar in the three groups (Group 1, 2.48 +/- 0.26; Group 2, 2.05 +/- 0.21; and Group 3, 2.10 +/- 0.17 x 10(-2).min-1). We conclude that, despite prednisone-induced insulin resistance, normal glucose tolerance is achieved by hyperinsulinaemia and normalisation of glucose-dependent glucose disposal following pancreas-kidney transplantation in Type 1 diabetic patients.

Adult

Renal autotransplantation in the loin pain-hematuria syndrome: a cautionary note.

The current literature suggests that renal autotransplantation is nearly uniformly effective in controlling the severe and debilitating pain of the loin pain-hematuria syndrome (LPHS). However, we report two patients thought to have this syndrome in whom renal autotransplantation did not result in long-term control of pain. In case 1, autotransplantation resulted in immediate cessation of pain; however, the flank pain recurred 7 1/2 months later. The recurrent pain was also severe and debilitating, requiring narcotic medications for control. In case 2, autotransplantation of the left kidney resulted in chronic pain in the left pelvic area, the site of the autotransplanted kidney. In addition, the patient continued to experience chronic discomfort in the left flank and along the flank incision. One year after autotransplantation, the patient still requires multiple daily doses of narcotic medications for pain control. Our two patients represent the 13th and 14th reported patients subjected to renal autotransplantation for management of LPHS. They represent only the third and fourth reported patients with recurrence of pain after renal autotransplantation. Because studies with negative results are less likely to be reported in the literature than studies with positive results, it is possible that the literature overestimates the effectiveness of renal autotransplantation in the LPHS. To assess the true effectiveness of renal autotransplantation in LPHS, a survey of patients with LPHS who have undergone renal autotransplantation needs to be performed.

Adult

Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients.

We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C-peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Combined kidney/pancreas transplantation at the Ohio State University Hospitals.

We conclude that combined kidney and pancreas transplantation is a safe and effective procedure to treat complicated Type I diabetic patients. It does carry significant potential for morbidity; therefore, it is essential that potential recipients understand these details prior to considering the procedure. Adequate preoperative screening for coronary artery disease is essential. The most difficult problem is dealing with early posttransplant dehydration and acidosis. More sensitive tools are needed to diagnose acute rejection in both combined kidney/pancreas recipients, as well as pancreas-alone grafts. Infectious complications are frequent, but most pose little morbidity. Currently, the incidence of early thrombosis is negligible. Even with these complications, overall excellent patient outcome demonstrates that kidney and pancreas transplantation should be the procedure of choice in well-selected Type 1 diabetics with end-stage renal disease.

Adult

Orthotopic liver transplantation with abdominal situs inversus and dextrocardia.

Anatomic anomalies may present technical difficulties during orthotopic liver transplantation. Abdominal situs inversus was considered a contraindication to liver transplantation. A successful liver transplant in a patient with both situs inversus and dextrocardia is described, along with a technical review.

Abnormalities, Multiple

Safety of simultaneous aortic reconstruction and renal transplantation.

Patients with aortic disease and end-stage renal failure who require both aortic reconstruction and renal transplantation (simultaneously or staged) pose a formidable clinical challenge. Traditionally, the performance of either one of these procedures has been viewed as a relative contraindication to the performance of the other. From 1978 to 1989, eight patients were referred to us with the combination of aortic disease and end-stage renal failure. Seven had aneurysmal disease and one had aorto-iliac occlusive disease. Five patients presented with their diseases sequentially and had two sequential operations, with a mean interval of 4 years between procedures. Three patients presented with their diseases simultaneously and underwent simultaneous aortic reconstruction and living related renal transplantation. All patients were followed up for a mean interval of 4.5 years. By life-table analysis, the 5-year renal graft survival was 100%, the primary aortic graft patency was 82%, and the secondary aortic graft patency was 100%. The only death in this series occurred 11 years after aortic reconstruction and 4 months after a renal transplantation and was due to overwhelming cytomegalovirus sepsis. There were no significant differences between the simultaneous and staged groups in terms of operative mortality, postoperative complications, transplant function, or aortic graft patency. From this experience, we conclude that: (1) patients who present simultaneously with aortic disease and end-stage renal failure can safely undergo simultaneous aortic reconstruction and renal transplantation; (2) patients who present with these two diseases sequentially can undergo a second reconstructive procedure with very low operative morbidity and mortality rates; (3) when these two procedures have been performed sequentially, the second procedure has not significantly altered the 30-day or 5-year results of the first procedure; and (4) the 30-day and 5-year results of each procedure have been excellent regardless of the temporal sequence in which they were performed.

Adult

Physiological and pharmacological stimulation of pancreatic islet hormone secretion in type I diabetic pancreas allograft recipients.

Successful heterotopic and denervated pancreas allograft transplantation (PAT) often results in normoglycemia and peripheral hyperinsulinemia in insulin-dependent (type I) diabetic recipients. The contribution of altered hepatic insulin extraction (HIE) to the resulting hyperinsulinemia in such patients remains uncertain. Furthermore, whether the denervated pancreas allografts exhibit beta-cell hyperresponsiveness to physiological and pharmacological stimulation is controversial. We evaluated beta-cell function and HIE after successful whole cadaveric PAT with systemic venous drainage in 13 type I diabetic patients before and after mixed-meal and intravenous glucose and glucagon administration. The results were compared with those of 5 nondiabetic patients with kidney transplantation only, who had native innervated pancreases with portal insulin delivery and were receiving an equivalent triple immunosuppressive therapy (cyclosporin, azathioprine, and prednisone), and 7 healthy control subjects with no family history of diabetes. After PAT, fasting and poststimulation serum glucose concentrations were normalized. PAT was associated with marked basal hyperinsulinemia (3- to 8-fold) as assessed by immunoreactive insulin (IRI) levels in type I diabetic patients (mean +/- SE 345 +/- 43 pM) compared with control subjects (43 +/- 14 pM) and nondiabetic kidney-transplantation patients (129 +/- 38 pM). After mixed-meal ingestion, the mean incremental integrated insulin area was similar in PAT patients (18 +/- 3 nM.min) compared with kidney-transplantation patients (20 +/- 4 nM.min) and healthy control subjects (21 +/- 3 nM.min). Basal serum C-peptide levels were significantly greater in PAT (1.72 +/- 0.13 nM) and kidney-transplantation (2.15 +/- 0.33 nM) patients than in healthy control subjects (0.50 +/- 0.10 nM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

The role of transplantation in diabetics with end-stage renal disease.

At our center, KPT is the treatment of choice for diabetics with ESRD who are not irreversibly disabled by their secondary complications of diabetes. Mortality, as a result of cardiovascular complications, has a significant impact on the outcome of patients in both the KPT and KTA groups. Metabolic complications are problematic in the early posttransplant period. Infectious complications are frequent but not life threatening in the combined recipients. Excellent graft outcome (pancreas and kidney) can be achieved in those patients selected to undergo the KPT procedure.

Adult

The effect of verapamil on cellular uptake, organ distribution, and pharmacology of cyclosporine.

Verapamil has been shown to potentiate cyclosporine's effect in inhibiting lectin-stimulated proliferation of murine and human lymphocytes, and in prolonging graft survival in experimental heterotopic cardiac transplantation in rats. A series of experiments were designed to determine whether verapamil's effect occurred by increasing cyclosporine uptake or decreasing cyclosporine's clearance by lymphocytes utilizing human peripheral blood lymphocytes and radiolabeled cyclosporine. Verapamil had no effect. The distribution of radiolabeled cyclosporine was also studied in mice that had been given verapamil (10 mg/kg) 1 hr prior to cyclosporine injection. No significant changes in organ distribution occurred. Lectin-stimulated release of intracellular ionized calcium was studied using a flurometric technique (Quin-2 and Fura-2). Neither cyclosporine nor verapamil had any effect on either lectin-stimulated or phorbol ester-stimulated release of intracellular ionized calcium. Phorbol ester and subproliferative doses of lectin were used to determine the effect of cyclosporine and verapamil on protein kinase C-mediated lymphocyte activation. Cyclosporine inhibited phorbol ester stimulated proliferation and verapamil potentiated this inhibition. Verapamil does not change cell or organ uptake of cyclosporine, and it does not affect the initial increase in intracellular ionized calcium that occurs with lymphocyte activation. Verapamil potentiates cyclosporine in inhibiting protein kinase C-mediated events in lymphocyte activation.

Animals