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Biomedical subjects

M Melandri

Publications and source records attributed to M Melandri.

At least 19 recordsLinked to original sources

Erythrocyte calcium influx is related to severity of ventricular arrhythmias in uraemic patients.

BACKGROUND: Myocardial disorders are a remarkable cause of morbidity and mortality in chronic haemodialysed patients (HD). They could be favoured by alteration of cell Ca(2+) handling. In previous studies we characterized an erythrocyte Ca(2+) influx, sensitive to membrane potential and inhibited by Ca(2+) antagonists. Since its maximal influx rate was decreased in HD patients, this study investigates if Ca(2+) influx alterations are related to myocardial disorders in HD patients. METHODS: Voltage-sensitive erythrocyte Ca(2+) influx was measured in 30 healthy controls and in 53 patients (47 HD patients and six patients with left ventricular hypertrophy and normal kidney function), using fura 2. In 29 HD patients and in six healthy subjects Ca(2+) influx was also determined in the presence of parathyroid hormone (PTH) in vitro. Patients were classified according to Lown's ventricular arrhythmias classification after 24-h Holter electrocardiograph (ECG) monitoring. Forty-six patients underwent echocardiography. RESULTS: Voltage-sensitive erythrocyte Ca(2+) influx was significantly reduced in HD patients. Maximal influx rate was significantly higher in HD patients of Lown's classes 3 and 4 (0.789 +/- 0.156 nmol/s, n = 8; P < 0.01) than in patients of classes 1 and 2 (0.499 +/- 0.055 nmol/s, n=15), or without ventricular arrhythmias (0.400 +/- 0.041 nmol/s, n = 24). Maximal influx rate was directly correlated to left ventricular mass index (LVM) (r = 0.353, P < 0.05). Subjects with left ventricular hypertrophy and normal kidney function displayed erythrocyte Ca(2+) influx similar to that of normal subjects. Multiple regression indicates that LVM and Ca(2+) influx were independently related to severity of arrhythmias. When added to the influx assay, PTH increased the maximal influx rate only in patients with ventricular arrhythmias. CONCLUSION: Myocardial dysfunction and altered ventricular excitability could be related in uraemic HD patients to alterations of calcium transport, as found in the erythrocyte model. Reduced resistance to PTH could contribute to this phenomenon.

Arrhythmias, Cardiac↗

Deranged platelet calcium homeostasis in diabetic patients with end-stage renal failure. A possible link to increased cardiovascular mortality?

OBJECTIVE: Platelet hyperfunction is a typical feature of the prothrombotic state that frequently complicates the natural history of diabetes. In uremia, a bleeding diathesis is present, which principally involves the primary phase of hemostasis. Thus, in patients with uremia of diabetic origin, the infrequent coexistence of two opposite alterations of hemostasis takes place. In patients with uremia, an increased incidence of cardiovascular events and related mortality is observed. This phenomenon is greatly amplified in uremia of diabetic origin. Calcium homeostasis is a critical aspect of platelet function, which has recently become available in human diseases. The aim of this study was to evaluate calcium homeostasis in platelets from patients with uremia of diabetic and nondiabetic origin. RESEARCH DESIGN AND METHODS: We evaluated, by means of Fura 2, the intracellular concentration of ionized calcium ([Ca2+]i) in platelets from 18 patients with uremia of diabetic origin, 12 patients with uremia of nondiabetic origin and 16 healthy control subjects [Ca2+]i was evaluated in resting conditions and after stimulation with 0.05, 0.1, 0.5 U/ml thrombin. RESULTS: Platelets from uremic patients with diabetes had higher resting [Ca2+]i than both control subjects (P = 0.01) and uremic patients without diabetes (P = 0.001). Similarly, after stimulation with thrombin, the absolute increase of [Ca2+]i was higher (P < 0.05) in platelets from uremic patients with diabetes compared with both control subjects and uremic patients without diabetes. The relative increase of [Ca2+]i was higher (P < 0.05) than normal in platelets from uremic patients after weak or intermediate strength thrombin. No correlation were present between [Ca2+]i values and other clinical and laboratory variables potentially associated with platelet hyperfunction. CONCLUSIONS: Diabetes and uremia in combination further deteriorate the abnormal platelet calcium homeostasis observed in uremia.

Biomarkers↗

Bioelectrical impedance in the evaluation of the nutritional status of hemodialyzed diabetic patients.

Bioelectrical impedance is a technique allowing a quick, repeatable and reliable assessment of body composition. This method was applied to detect total body water (TBW), fat (FAT) and fat-free mass (FFM) in 80 normal subjects, 65 diabetic (45 insulin-dependent [IDD], 20 non insulin-dependent [NIDD]) and 34 uremic diabetic patients (20 IDD, 14 NIDD) submitted to hemodialysis three times a week. Uremic patients were tested at the end of the dialytic session. Multivariated analysis adjusted for age, sex and disease showed the following results: body mass index (BMI) increased with age (p < 0.005) and in the presence of NIDD (p < .001); TBW was lower in nephropathic patients (p < 0.05) and in the female sex (p < 0.0001); FFM decreased with age (p < 0.005), female sex (p < 0.0001) and in nonuremic NIDD (p < 0.001). Correspondingly FAT increased with age (p < 0.005), female sex (p < 0.0001) and in nonuremic NIDD (p < 0.001). Sixteen uremic subjects, randomly selected from both IDD and NIDD groups, tested at the beginning and at the end of the same hemodialytic session, showed a significant decrease of TBW which corresponded to the correction of their overhydratation. In our patients uremia does not seem to influence the nutritional status and the bioelectrical analysis could be applied to determine the real dry weight in hemodialyzed diabetic patients.

Body Composition↗

[Vascular access for chronic hemodialysis in diabetic patients].

The aim of this study carried out on 33 uremic diabetic patients submitted to chronic hemodialytic treatment was to assess the kind of complications related to the vascular approach used as well as their short- and long-term incidences. Out of the 46 anastomoses prepared, 39 were arteriovenous fistulae according to Brescia-Cimino and 7 were PTFE grafts. The actuarial survival rate was 88%, 79%, and 63% after one, two and four years, respectively. The most frequent compliance was thrombosis. Our experience demonstrates that the distal arteriovenous fistula may be considered a valid vascular access for hemodialysis also in diabetic patients.

Adult↗

Endocrinometabolic effects of whole versus segmental pancreas allotransplantation in diabetic patients--a two-year follow-up.

We have investigated the metabolic effects of segmental (neoprene-injected) pancreas transplantation versus whole (enteric-diverted) pancreas transplantation. Seventeen uremic insulin-dependent diabetes mellitus (IDDM) patients received a simultaneous pancreaticorenal transplant: in a prospective, randomized study, 9 patients received a segmental neoprene-injected graft (group A) while 8 patients received a total pancreaticoduodenal graft, with enteric diversion (group B). The immunosuppressive therapy was based on ALG, CsA, azathioprine, and steroids. Three months after surgery, patients were submitted to the following metabolic investigation: i.v. and oral glucose tolerance tests, Hba1, i.v. arginine test, and a 24-hr metabolic profile. The OGTT, HbA1, and metabolic profile were repeated 12 and 24 months after transplantation. At 3 months after transplantation, the OGTT showed delayed insulin secretion and higher blood glucose levels in group A. Serum insulin levels after IVGTT or arginine were higher in group B than in group A. OGTT at 12 and 24 months were unchanged in group B, while in group A a higher incidence of impaired glucose tolerance (IGT) and diabetes mellitus response were observed. HbA1 and blood glucose levels during the 24-hr profile showed good metabolic control in both groups at 3, 12, and 24 months. We can conclude that both the segmental and total pancreas transplantation restore a good metabolic control in IDDM patients, though a higher incidence of IGT and DM responses were observed after OGTT in the patients receiving a segmental graft. These abnormalities do not seem to interfere with metabolic control in everyday life. These results seem to be the consequence of the different B cell masses transplanted with these two techniques.

Adult↗

Segmental duct-obstructed pancreas grafts versus pancreaticoduodenal grafts with enteric diversion.

Between January 1985 and September 1987, we performed a prospective comparative study between segmental-pancreas transplantation with duct obstruction by neoprene (n = 17) and pancreaticoduodenal transplantation with enteric diversion to a Roux-en-Y intestinal loop (n = 14). All recipients had insulin-dependent diabetes. The immunosuppressive protocol consisted of low doses of the steroids cyclosporin A and azathioprine. Mean follow-up was 16.5 mo for the enteric-diversion group and 13.5 mo for duct-obstructed groups. Two-year patient and pancreas- and kidney-graft actuarial survival rates were 92.9, 75.5, and 74.2%, respectively, in the former group and 92.3, 58.4, and 63.7%, respectively, in the latter group (NS). Five whole-organ grafts were lost (3 vascular thromboses, 1 pancreatitis, 1 rejection), and four segmental grafts were lost (2 vascular thromboses, 1 bleeding, 1 patient's death with functional graft). More surgical complications occurred in the recipients of whole-organ grafts and were often related to the intestinal anastomosis. A satisfactory blood glucose control was observed at 3 mo and 1 yr in both groups. Provocative tests showed higher and prompter insulin secretion in patients with whole-organ grafts. In patients with segmental grafts, the response was lower and delayed with a general tendency to impaired glucose tolerance. A marked hyperinsulinemia after meals was observed in whole-organ graft recipients. Slight nocturnal hyperinsulinemia was observed in both groups. At 1 yr, glycosylated hemoglobin was normal in both groups. The absence of a significant difference between the two groups, in terms of survival and graft function, and the lower surgical complication rate seen with segmental grafts have made us return to neoprene-injected segmental grafts.

Circadian Rhythm↗

Impact of immunosuppression on improvement of results in clinical pancreas transplantation.

Since November 1975, 103 pancreas transplantations have been performed in 97 insulin-dependent diabetic patients. Pancreas and kidney were grafted simultaneously in 84 patients (plus 1 double retransplantation). Eighty-nine pancreas grafts were prepared by duct obstruction with neoprene, and 14 were pancreaticoduodenal grafts with enteric diversion in a Roux-en-Y loop. Five immunosuppressive protocols were subsequently used. With the latest protocols, patient and pancreas survival improved to 93 and 72% at 1 yr, respectively. The improvement in graft survival appeared to be particularly related to the reduction of the number of pancreas grafts lost in rejection. The patients treated with the last protocols, including cyclosporin A (CsA) and only low doses of steroids, showed a better glucose tolerance after provocative tests. Pancreas-graft function did not appear to be influenced by CsA treatment.

Antilymphocyte Serum↗

Kidney-graft survival in simultaneous kidney-pancreas transplantation.

Patient and kidney survival rates were compared between 69 diabetic patients undergoing simultaneous kidney-pancreas transplantation (group 1) and 723 nondiabetic patients undergoing kidney transplantation (group 2). The patients were treated with different immunosuppressive regimens over the years: steroids plus antilymphocyte globulin (ALG) plus azathioprine (Aza); cyclosporin A (CsA) plus ALG; steroids plus ALG plus Aza, replacing Aza 1 mo posttransplantation; or low doses of steroids plus CsA plus Aza. One-year kidney survival rates with the different regimens were 50, 42, 54, and 76%, respectively, in group 1 and 71, 74, 78, and 84%, respectively, in group 2. Patient survival was 60, 57, 71, and 86%, respectively, in group 1 and 93, 95, 94, and 96%, respectively, in group 2. Differences between the two groups were statistically significant for the first three protocols but not for the one used in this study. In group 1, 38 patients (55%) had a functioning kidney graft, whereas 15 (21%) lost their kidney to rejection. Between these two patient categories, there was no significant difference in age, sex, duration of diabetes, time on dialysis, blood transfusion number, HLA immunization, or HLA matching. Thus, since 1984, kidney-graft survival has not been inferior in diabetic patients. This improvement is mainly due to a decreased mortality related to better patient preparation and improvement in immunosuppression.

Graft Survival↗

Intermediary metabolism and glycemic control in insulin-dependent diabetic uremic patients treated by continuous peritoneal dialysis.

The effect on metabolic control and on intermediate metabolism of continuous ambulatory peritoneal dialysis (CAPD) was evaluated in 6 insulin-dependent diabetic uremic patients treated by CAPD, in 6 nondiabetic uremic patients in CAPD and in 6 normal subjects. During the study, 4 dialysis exchanges with 1.36 g/dl dextrose concentration were performed daily; regular insulin was added to the bags in diabetic patients. Our data show a well-controlled mean blood glucose in CAPD diabetic patients by intraperitoneal insulin administration as well as higher insulinemic levels in comparison with those of normal subjects. Plasma lactate and serum glycerol levels were higher and butyrate levels were lower reflecting a continuous ketogenesis inhibition.

Adult↗

Long-term continuous intraperitoneal insulin treatment in brittle diabetes.

Attempts to achieve a fair metabolic equilibrium in a young woman with brittle diabetes by continuous subcutaneous, intramuscular, and continuous intravenous administration of insulin were unsuccessful. Continuous intraperitoneal administration of insulin through a permanently inserted polyethylene catheter connected to an open-loop peristaltic pump led to an appreciable improvement in mean blood glucose concentration, mean amplitude of glycaemic excursions, and M value and to normalisation of intermediate metabolic products. The peritoneal catheter was well tolerated for over 120 days without appreciable adverse effects. This case suggests that long-term intraperitoneal administration of insulin is a feasible therapeutic approach in the management of brittle diabetes.

Adult↗