Advances in human neoprene-injected pancreas transplantation: experience with 47 cases.
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Biomedical subjects
Publications and source records attributed to A Secchi.
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The aim of the present study was to evaluate the insulin and glucagon responses to various stimuli in patients following pancreatic transplantation. Four Type 1 (insulin-dependent) diabetic patients with end-stage renal failure who had received a cadaveric segmental, neoprene-injected, pancreas transplant, in association with kidney transplantation, were investigated. Free-insulin, pancreatic glucagon, and growth hormone concentrations were measured after both oral and intravenous glucose tolerance tests, and following tolbutamide, arginine and arginine plus somatostatin infusions. Tests were performed 1 month (three cases) and 30 months (one case) after surgery, when no insulin administration was required. Four non-diabetic kidney grafted patients, matched for duration of graft survival and immunosuppressive treatment (steroids, azathioprine and anti-lymphocyte-globulins), served as control subjects. Impaired glucose tolerance was present in all diabetic and control patients. This was possibly related to immunosuppressive treatment. In comparison with control subjects, insulin release was normal in response to arginine and tolbutamide but was reduced in response to oral and intravenous glucose, while glucagon and growth hormone release were similar in both groups. Somatostatin was less effective in diabetic patients than in control subjects in suppressing insulin and glucagon release.
Pancreatic transplantation is intended to normalize carbohydrate metabolism in insulin-dependent diabetics by restoring endogenous insulin release, and it is usually performed together with kidney transplantation in patients with end-stage renal failure. A major problem in these patients is the daily control of the grafted pancreas because traditional measurements do not appear to be adequate to evaluate pancreatic function. Aiming at early detection of graft failure, we have analyzed in 8 such patients and in 20 nondiabetic kidney-grafted patients (a control group) the following variables: 24-hr glycosuria (absolute values, or values after natural logarithmic transformation) and 24-hr urinary C-peptide excretion (corrected for 24-hr urinary creatinine). These measurements, considered alone, did not detect pancreatic graft failure; for instance, glycosuria can depend on immunosuppressive steroid treatment, and it was often found even in the control group. On the contrary, the ratio Ln 24-hr glycosuria: 24-hr urinary C-peptide varied from 0.00 to 0.18 in the control group and in normally working pancreatic grafts; when the pancreatic grafts failed, however, as confirmed by arteriographic evidence, histologic findings, or dynamic endocrine tests, this ratio rose far higher than 0.18, reaching values as high as 12.2. Use of this ratio provides a simple technique for daily evaluation of pancreatic graft function and for early detection of graft failure.
Using the artificial pancreas, blood glucose levels were maintained at 80 mg/dl in nine hypoglycemic patients (four with histologically proven insulinomas and five with nontumoral hypoglycemia) and in four normal subjects during a 24-h fast. The amount of glucose used, serum insulin levels, and glucose clearance were higher in patients with nontumoral hypoglycemia than in normal subjects and highest in the patients with an insulinoma. Surgical or pharmacological treatment resulted in normalization of all parameters. In contrast to the 72-h fast, the 24-h glucose clamp technique allowed the study of hypoglycemic patients without inducing hazardous hypoglycemia.
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We performed 39 neoprene-injected pancreatic transplants (38 segmental and 1 total) in 37 insulin-dependent diabetic recipients from October 1976 to May 1983. The best results were obtained when the pancreas was transplanted simultaneously with the kidney (25 cases). The use of Cyclosporin A (CyA) for immunosuppression did not reduce the early pancreatic failures, but it seems to have slightly improved the long-term survival. The glycaemic control was better in patients treated by CyA alone than in those receiving steroids. The main side effects of CyA were nephrotoxicity and some immunoglobulin abnormalities with or without lymphoproliferative disorders occurring after treatment with CyA and ALG.
Regular or crystalline insulin with sodium glycocholate as surfactant administered intranasally to normal volunteers induced hypoglycaemia and an increase in serum immunoreactive insulin concentrations. Serum C-peptide concentrations decreased or remained unchanged. Insulin administered intravenously to three of these subjects yielded a potency ratio of 1:8 for intranasal and intravenous insulin. In four insulin-dependent diabetics a cross-over study was performed on different days, insulin being administered once intranasally and once subcutaneously in a ratio of 1:9. In these patients the intranasal insulin was more effective than the subcutaneous insulin in preventing hyperglycaemia after breakfast. In four other insulin-dependent diabetics 11-hours monitoring was performed twice on two different days, insulin being administered in divided dosage sufficient to achieve a reasonable glycaemic profile. The administration during the morning, whereas subcutaneous insulin was more effective than intranasal during the afternoon.
No statistically significant correlations were detected between plasma CEA levels, DNCB skin test responses, peripheral lymphocytes and plasma immunoglobulins in 90 patients with G.I. advanced adenocarcinomas, treated with BCG aspecific immunotherapy and chemoterapy.
Ninety-seven pancreatic grafts in 92 insulin-dependent diabetic patients were performed during the last 11 years. Eighty-three of these grafts were carried out after neoprene duct injection, the other patients underwent pancreato-duodenal transplantation. In 80 cases, a double pancreas and kidney graft was performed. Five different immunosuppressive protocols were subsequently applied. Actuarial survival of patients and pancreata was 75.1% and 47%, after one year and 54.6% and 22.1%, respectively, 4 years after transplantation. Slightly better results were observed in double pancreas and kidney transplantation. The survival of both patients and pancreas improved when the most recent immunosuppressive protocols including cyclosporin A and only small doses of steroids were applied. The main causes of loss of the pancreatic graft were rejection, vascular thrombosis and death of the patient with functioning organ. Metabolic studies showed good insulin secretion with normal or impaired glucose tolerance as well as good short and half-term glycemic control. Whole pancreas grafts with enteric diversion yielded prompter and higher insulin secretion but the incidence of surgical complications was increased. In comparison to the data recorded at 6 months after pancreas transplantation, 5 patients of our series with still functioning organ showed an equally satisfactory and unchanged glycemic control after more than 4 years from surgery. In these patients, the previously high insulinemic values decreased to normal levels. However, 3 of these patients showed a decrease in post-prandial peaks as confirmed also by OGTT. However, mean blood glucose level was not altered. In our series the suppression of exocrine pancreatic secretion by neoprene duct injection did not appear to represent a relevant cause of decrease in endocrine function. The results obtained do not yet allow us to draw definite conclusions as to the efficacy of pancreas transplantation in the treatment of degenerative complications in diabetic patients.
In a previous study, we observed an impairment of the theophylline-induced suppressive system in recent onset IDDM patients, and demonstrated also a correlation with metabolic derangement. The aim of this study was to better investigate the relationship between theophylline sensitivity (ThS) and blood glucose/plasma insulin levels in recent onset IDDM patients subjected to preprogrammed variations by an insulin/glucose clamp with artificial pancreas. Eight patients were studied within 8 weeks from the onset of IDDM. ThS was evaluated as the ability of theophylline to inhibit blastogenic response of peripheral blood lymphocytes (PBL) to Concanavalin A (ConA), after 120 min preincubation of the cells. All patients were connected to an artificial pancreas. Through i.v. continuous insulin infusion (0.02 U/kg/h) and/or i.v. continuous glucose and saline infusion, the following experimental conditions, lasting at least 1h, were obtained: T1: relative euglycemia and normal insulinemia; T2: relative euglycemia and hyperinsulinemia; T3: hyperglycemia and normal insulinemia; T4: hyperglycemia and hyperinsulinemia. ThS was maintained in 6/8 patients at T1 and in 8/8 patients at T4. ThS was lost in 4/8 patients at T2 and T3. These data suggest that the loss of ThS induced by hyperglycemia can be corrected by hyperinsulinemia, and that it is maintained when euglycemia is accompanied by hypoinsulinemia. It is lost when these two parameters lose their interrelationship.
UNLABELLED: Simultaneous pancreas-kidney (SPK) transplantation has become a standard therapy for patients with type 1 diabetes and end-stage renal disease. We analyzed metabolic data in this clinical setting under tacrolimus- versus cyclosporine microemulsion (ME)-based immunosuppressive therapy. PATIENTS AND METHODS: We analyzed 205 patients enrolled in the Euro-SPK001 study for fasting blood glucose, fasting C peptide, glycated hemoglobin (HbA(1c)), blood lipids (total cholesterol and triglycerides), and pancreatic enzymes at regular intervals during the study. We compared blood pressure values with target levels for diabetic patients published by the European Society for Hypertension. RESULTS: Throughout the study, HbA(1c) and fasting C peptide levels were within the normal range in the two groups. Fasting blood glucose was higher during the first 2 months posttransplant in the tacrolimus group than in the cyclosporine-ME group, but no differences were seen thereafter. From month 2 posttransplant, mean levels of total cholesterol were significantly lower among patients receiving tacrolimus than those in the cyclosporine-ME group. In addition, patients receiving cyclosporine-ME showed serologic features of mild pancreatitis with elevated blood amylase and lipase levels during the first 6 months posttransplant. The two regimens were comparable with respect to hypertension, but target levels were reached in only 50% of the patients. CONCLUSION: Except for lipid profiles, no major differences in metabolic effects or blood pressure control were observed among SPK transplant patients receiving immunosuppression based on tacrolimus versus cyclosporine-ME. In view of the potential risk of hypertension, antihypertensive strategies should be implemented for all patients.
AIM: To evaluate factors affecting patient and kidney survival after renal transplant. PATIENT AND METHODS: Among 361 patients undergoing renal transplant: 52% (n = 189) were simultaneous with pancreas transplant (SPKT group) and 48% (n = 172), a kidney transplant alone (KT group). Out of 361 patients, 75% (n = 270) were diabetics. The patients were 220 (61%) men and 141 (39%) women of mean age 41 +/- 9 years. The mean time of dialysis was 42 +/- 21 months (range 0 to 126), and the mean duration of diabetes 24 +/- 7 years (range 5 to 51). A Cox regression analysis was done. RESULTS: The multivariate analysis revealed that in the final model diabetes and donor age were significant predictors of kidney graft survival; moreover, diabetes and recipient age were predictors of patient survival. Overall patient survival was significantly greater among nondiabetic patients (P = .002) or in diabetic patients who received SPKT, when compared with diabetics in whom only the kidney was transplanted (P = .001). CONCLUSIONS: Diabetes and donor age were independent prognostic factors affecting kidney graft survival after renal transplant, and recipient age and diabetes were prognostic factors affecting patient survival. Combined pancreas and kidney transplantation should be offered to patients with end-stage diabetic nephropathy.
In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.
The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of diabetes in kidney transplant recipients is between 4 and 20% in patients previously not affected by this pathology. This difference is partially due to the immunosuppressive therapy administered. The incidence of diabetes is very high during the first quarter after the transplant, and it becomes stable during the following quarters. The presence of diabetes - evaluated by postprandial glycemia and glycated hemoglobin - should be checked quarterly during the first year after the transplant, every six months during the second year, and yearly starting from the third year. The immunosuppressive therapy (calcineurin inhibitors and steroids), familial history, age, race, and weight (BMI) are among the risk factors of diabetes post-transplant. An increased risk of rejection seems to be among the principal consequences of diabetes in transplant recipients. Moreover, these patients are more prone to infections, cardiovascular disease, and the degenerative complications of diabetes. These facts increase the risk of organ insufficiency, morbidity, and mortality. To manage diabetes in transplant recipients it is necessary to identify at-risk patients before the transplantation, thus avoiding complicated and hazardous examinations after the transplant. After the transplantation, the modifiable risk factors, such as the immunosuppressant drugs used and the control of body weight, must be checked. The control of hypertension is important as well.
AIM: To evaluate the outcome of simultaneous pancreas transplantation (SKPT) focusing on the surgical technique applied. PATIENTS AND METHODS: One hundred forty-eight patients were submitted to SKPT 33 with segmental pancreas with duct occlusion (from 1985 to 1990), 77 with whole pancreas with bladder diversion (from 1990 to 1998) and 38 whole pancreas with enteric diversion (29 with systemic and 9 with portal drainage) (from 1998 to December 2001). RESULTS: Patient survival was 92%, 82%, 63% at 1, 5, and 10 years respectively. Kidney survival was 87%, 75%, and 48% at 1, 5, 10 years. Pancreas graft survival was 71%, 58%, and 46% at 1, 5, 10 years. In the enteric diversion group patient, kidney, pancreas survival at one year was 93%, 92%, and 75%. A positive effect on patient survival was evident in enteric diversion versus duct occlusion group (p = 0.03), but not versus bladder diversion group and on pancreas graft survival in enteric diversion versus duct occlusion group (p < 0.01). CONCLUSIONS: These data suggest that SKPT has become a successful intervention for patients with type I diabetes and end stage renal disease. Reasons for these improvements include improved donor and patient selection criteria, refinements in surgical technique and better immunosuppression.