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C Socci

Publications and source records attributed to C Socci.

At least 19 recordsLinked to original sources
PubMed2006

Triple arterial reconstruction improves vascularization of whole pancreas for transplantation.

We assessed the effect on duodenal stump vascular supply of reconstruction of the gastroduodenal artery performed before pancreas transplantation. The median pancreas graft and patient survival times were 144 and 72 months for cases with or without gastrointestinal bleeding. Transmural blood flow values were significantly different between the donor duodenal stump and the recipient anastomosed jejunum (P < .01). The rate of gastrointestinal bleeding was lower in patients who received a pancreatic graft with back-table reconstruction of the gastroduodenal artery (P = .005).

Adult↗
PubMed2005

Islet isolation for allotransplantation: variables associated with successful islet yield and graft function.

AIMS/HYPOTHESIS: Efficient islet isolation is an important prerequisite for successful clinical islet transplantation. Although progressively improved, islet yield and quality are, however, unpredictable and variable and require standardisation. METHODS: Since 1989 we have processed 437 pancreases using the automated method. The donor characteristics, pancreas procurement, and digestion and purification procedures including a wide enzyme characterisation of these pancreases were analysed and correlated with islet yield and transplant outcome. RESULTS: By univariate analysis, islet yield was significantly associated with donor age (r=0.16; p=0.0009), BMI (r=0.19; p=0.0004), good pancreas condition (p=0.0031) and weight (r=0.15; p=0.0056), total collagenase activity (r=0.22; p=0.0001), adjusted collagenase activity/mg (r=0.18; p=0.0002), collagenase activity/solution volume (r=0.18; p=0.0002) and neutral protease activity/solution volume (r=0.14; p=0.0029). A statistically significant contribution to the variability of islet yield in a multivariate analysis performed on donor variables was found for donor BMI (p=0.0008). In a multivariate analysis performed on pancreas variables a contribution was found for pancreas weight (p=0.0064), and for a multivariate analysis performed on digestion variables we found a contribution for digestion time (p=0.0048) and total collagenase activity (p=0.0001). Twenty-four patients with type 1 diabetes received single islet preparations from single donors. In these patients, multivariate analyses showed that the reduction in insulin requirement was significantly associated with morphological aspects of islets (p=0.0010) and that 1-month C-peptide values were associated with islet purity (p=0.0071). CONCLUSIONS/INTERPRETATION: These data provide baseline donor, digestion and purification selection criteria for islet isolation using the automated method and indicate that the morphological aspect may be a clinically relevant measure of islets on which the decision for transplant can be based.

Adolescent↗
PubMed2005

Cardiovascular benefits of simultaneous pancreas-kidney transplant versus kidney alone transplant in diabetic patients.

UNLABELLED: The aim of our study was to demonstrate the cardiovascular benefits of simultaneous pancreas-kidney transplantation when compared to kidney-alone transplants in diabetic recipients. PATIENTS AND METHODS: A total of 386 renal transplants were performed from 1985 to 2004, including 262 (68%) in diabetic recipients and 124 (32%) in nondiabetics. Among the former group, 200 kidneys were transplanted simultaneously to the pancreatic graft (KP group) and 62 were kidney-alone transplants (KA group). The mean time on dialysis was 31 +/- 20 months (range 0-126 months). The duration of diabetes was 24 +/- 7 years (range 5-51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% on hemodialysis and 20% on peritoneal dialysis). RESULTS: Among 262 patients, 28 (11%) died due to a cardiovascular event, which was higher among KA patients compared with the KP group (P = .004). Overall patient survival was significantly higher in the KP group when compared with the KA group (log-rank: P = .0004). Patient survivals were 80% and 70% versus 70% and 40% at 5 and 10 years in the KP and KA groups, respectively. Kidney graft survivals were 81% and 60% versus 63% and 26% at 5 and 10 years in the KP and KA groups, respectively. Pancreas graft survival was 70% and 50% at 5 and 10 years, respectively. CONCLUSIONS: This clinical evaluation, even if retrospective, confirmed that simultaneous pancreas-kidney transplantation has a protective effect against cardiovascular mortality in diabetic recipients affected by end-stage renal disease.

Cardiovascular Physiological Phenomena↗
PubMed2004

Simultaneous pancreas-kidney transplantation: short- and long-term results.

Simultaneous kidney and pancreas transplantation (SKPT) is the treatment of choice for a majority of type I diabetic patients with end-stage renal disease. With continual refinements in surgical technique and an evolving immunosuppressive arsenal, graft and patient survival have continually improved. The purpose of this study was to evaluate the short- and long-term results of SKPTs performed in 174 recipients from June 1985 to March 2003 including 37 segmental grafts with duct occlusion, 73 whole pancreas transplants with bladder diversion, and 64 whole pancreas grafts with enteric diversion. The series includes 160 cases with systemic drainage and 14 with portal drainage. In the segmental pancreas group, patient survival was 85%, 76%, and 53% with pancreas survival of 67%, 36%, and 15%, and kidney survival of 82%, 63%, and 15%, respectively, at 1, 5, and 10 years. Among the bladder diversion group, patient survival was 94%, 83%, and 73% pancreas survival 72%, 67%, and 65%, and kidney survival 89%, 78%, and 58%, respectively, 1, 5, and 10 years. Among the enter diversion group patient survival was 90% and 90% at 12 and 108 months, pancreas survival 80% and 65%, and kidney survival 85% and 85%, respectively. There were significant differences between curves of survival distribution according to the surgical technique applied for patients (P =.04), pancreas (P =.007), and kidney (P =.005). Based on the results from our study, the short- and long-term prognosis after SKPT is satisfactory, especially compared to the outcomes of long-term dialysis among patients with end-stage renal disease caused by type I diabetes.

Adult↗
PubMed2004

Long-term survival after kidney and kidney-pancreas transplantation in diabetic patients.

PURPOSE: To investigate the influence of diabetes mellitus on patient and graft survival among renal versus renal-pancreatic recipients. METHODS: Among 270 renal transplants performed from 1985 to 2002, a total of 204 (75%) were in diabetic patients and 66 (25%) in nondiabetic patients. Among the 204 diabetic patients 161 (60%) kidneys were transplanted simultaneously with a pancreatic graft (SKPT group). The overall group of patient included 164 (61%) men and 106 (39%) women with mean time on dialysis of 31 +/- 21 months (range 0 to 126 months). The mean duration of diabetes was 24 +/- 7 years (range 5 to 51 years). Ninety-nine percent of the patients were on renal replacement therapy (79% hemodialysis and 20% peritoneal dialysis). RESULTS: The overall rejection rate was similar (NS). Both patient and kidney graft survival rates were worse in diabetics. Patient survival was 82% at 5 years among patients undergoing SKPT, 60% in diabetics receiving only a kidney, and 88% in nondiabetic transplanted patients. Kidney graft survival at 5 years was 77% in diabetics receiving SKPT, 68% in diabetics receiving a kidney alone, and 82% in nondiabetic patients. Overall patient survival was significantly greater among nondiabetics (P =.002) or in diabetics who received SKPT compared with diabetics who only had a kidney transplant (P =.001). CONCLUSIONS: This retrospective clinical evaluation confirms that combined pancreas and kidney transplantation should be the first choice to insulin-dependent diabetes mellitus (IDDM) patients with end-stage diabetic nephropathy.

Diabetes Mellitus, Type 1↗
PubMed2004

Outcome of simultaneous kidney pancreas transplantation: a single center analysis.

The aim of this study was to evaluate the outcome of simultaneous kidney pancreas transplantation (SKPT) by various surgical techniques. The 161 patients submitted to SKPT underwent the following: 36 pancreas with duct occlusion (from 1985 to 1989), 75 with whole pancreas with bladder diversion (from 1990 to 1998), and 50 whole pancreas with enteric diversion (40 with systemic and 10 with portal drainage) (from 1999 to September 2002). A positive effect on patient survival was evident using enteric diversion versus the duct occlusion group (P = .005), and versus the bladder diversion group (.035), and on pancreas graft survival in the enteric diversion versus the duct occlusion group (P < .028). These improvements may be due to refined donor and patient selection criteria, surgical technique, and immunosuppression.

Adult↗
PubMed2001

Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients.

Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by only partial function. Moreover, the duration of full function is variable and cannot be sufficiently predicted with available methods. In contrast, most grafts retain partial function for a long time. We hypothesized that partial function can restore normal protein and lipid metabolism in diabetic individuals. We studied 45 diabetic patients after islet transplantation. Labeled glucose and leucine were infused to assess whole-body glucose and protein turnover in 1) 6 type 1 diabetic patients with full function after intraportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insulin dosage 0.03 +/- 0.02 U x kg(-1) body wt x day(-1); fasting plasma glucose < 7.7 mmol/l; HbA1c < or = 6.5%), 2) 17 patients with partial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U x kg(-1) body wt x day(-1)), 3) 9 patients with no function (NF group; C-peptide < 0.16 nmol/l; insulin dosage > 0.4 U x kg(-1) body wt x day(-1)), and 4) 6 patients with chronic uveitis as control subjects (CU group). Hepatic albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-2H3]leucine. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levels for the PF group. In the basal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 micromol/l) and branched-chain amino acids (337.6 +/- 16.6 micromol/l) were similar in the PF, FF, and CU groups, and significantly lower than in the NF group (P < 0.01). During insulin infusion, the metabolic clearance rate of glucose was defective in the NF group versus in the other groups (P < 0.01). Both the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in the NF group (P = 0.05). In addition, the PF group had a normal hepatic albumin synthesis. Plasma free fatty acid concentrations in the PF and FF groups were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the restoration of approximately 60% of endogenous insulin secretion is capable of normalizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The results of the present study indicate that "success" of islet transplantation may be best defined by a number of metabolic criteria, not just glucose concentration/metabolism alone.

Adult↗
PubMed2000

Insights from a successful case of intrahepatic islet transplantation into a type 1 diabetic patient.

We report a case of long-term (>4 yr) successful intrahepatic islet transplantation into a type 1 diabetic patient chronically immunosuppressed for a prior kidney graft. The exogenous insulin requirement decreased progressively after transplantation, and insulin treatment was withdrawn at 6 months. Glycosylated hemoglobin levels were in the normal range at 1 and 2 yr (5.3%) and increased slightly above the upper normal limit at 3 and 4 yr (6.3% and 6.4%). Fasting C peptide levels remained stable during the entire follow-up, but the proinsulin to insulin ratios increased dramatically at yr 3. Glycemic levels after an oral glucose tolerance test showed a diabetic profile at 1 yr, a normal profile at 2 yr, and an impaired glucose tolerance profile at 3 yr. Intravenous glucose tolerance test-induced first phase insulin release, present at 1 and 2 yr, disappeared at 3 yr. Diabetes-related autoantibodies (islet cell antibodies, glutamic acid decarboxylase antibodies, and tyrosine phosphatase-like protein antibodies) were undetectable before transplantation and remained so during the entire follow-up. The patient died of myocardial infarction 50 months after transplantation while she was still in good metabolic control (glycosylated hemoglobin, <6.8%) in the absence of exogenous insulin administration. The autoptic liver showed well granulated islets, richly vascularized and without evidence of lympho-mononuclear cell infiltration. The morphometrically extrapolated intrahepatic beta-cell mass was 99.9 mg. In conclusion, this successful islet graft showed a bell-shaped clinical effect, maximal at 2 yr after transplantation, followed by a slow progressive decline. The absence of allo- and autoreactivities against the transplanted islets points to a nonimmune-mediated beta-cell loss as the cause of graft functional deterioration.

Adult↗
PubMed1999

Effects of cryopreservation on in vitro and in vivo long-term function of human islets.

BACKGROUND: The possibility of performing transplantation several days after explant seems to be a peculiarity of islet grafts, and the opportunity to cryopreserve human islets may permit an indefinite period for modulating the recipient immune system. The aim of the present study was the evaluation of in vitro and in vivo functional properties of cryopreserved human islets. METHODS: We used six consecutive human islet preparations not suitable for an immediate transplantation in diabetic patients because the limited islet mass separated. The in vitro function of cryo and fresh islets was studied by determination of insulin and glucagon secretion in response to such classical stimuli as glucose (16.7 mM), glucose (16.7 mM) + 3-isobutyl-1-methylxanthine (0.1 mM), arginine (10 mM), and tolbutamide (100 microM). In vivo islet function was assessed through intravenous glucose tolerance tests performed at 15, 30, 60, and 90 days after transplantation of 1000 hand-picked fresh or cryopreserved islets in nude mice. RESULTS: Basal secretion of true insulin was significantly higher in cryopreserved islets than in fresh ones. The response of cryopreserved islets to arginine and glucose + isobutyl-1-methylxanthine seemed partially impaired. Proinsulin-like molecule secretion seemed higher in cryopreserved than in fresh islets in response to all secretagogues used, and the difference was statistically significant for arginine. The capacity of human cryopreserved islets to maintain a correct metabolic control in diabetic nude mice was progressively lost in 3 months. CONCLUSIONS: These findings showed that cryopreservation affects the function of isolated human islets, maintaining in vivo function for a limited period of time.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Glucocorticoids affect human dendritic cell differentiation and maturation.

Because dendritic cells (DC) play a major role in the initiation of T cell-mediated immunity, we studied the effects of glucocorticoids, well-known inhibitors of the immune and inflammatory response, on the differentiation and maturation of human DC. DC were differentiated from human monocytes by culture with GM-CSF and IL-4 for 7 days with and without dexamethasone (Dex). Cells treated with Dex (10-8 M) (Dex-DC) developed a characteristic dendritic morphology; however, membrane phenotype analysis demonstrated that they were not fully differentiated. Dex-DC expressed low levels of CD1a and, unlike untreated cells, high levels of CD14 and CD16. Molecules involved in Ag presentation (CD40, CD86, CD54) were also impaired. In contrast, molecules involved in Ag uptake (mannose receptor, CD32) and cell adhesion (CD11/CD18, CD54) were up-regulated. After exposure to TNF-alpha or CD40 ligand, Dex-DC expressed lower levels of CD83 and CD86 than untreated cells. Dex-DC showed a higher endocytic activity, a lower APC function, and a lower capacity to secrete cytokines than untreated cells. Overall, these results indicate that DC differentiated in the presence of Dex are at a more immature stage. Moreover, Dex also partially blocked terminal maturation of already differentiated DC. In conclusion, our data suggest that glucocorticoids may act at the very first step of the immune response by modulating DC differentiation, maturation, and function.

Antigen Presentation↗
PubMed1999

Insulin and intracellular calcium responsiveness to glucagon-like peptide-1 and pituitary adenylate cyclase-activating peptide by dispersed adult porcine islet cells.

BACKGROUND: There is a great need to learn more about porcine islet physiology because porcine islets represent a promising source of xenogeneic tissue for beta-cell replacement therapy in humans. METHODS: We evaluated the effects of two important physiological regulators of insulin secretion, glucagon-like peptide-1 (GLP-1) and pituitary adenylate cyclase-activating peptide (PACAP), on insulin release and intracellular calcium ([Ca++]i) by adult porcine islet cells. RESULTS: Exposure to GLP-1 and PACAP significantly potentiated glucose-induced insulin release and improved the sensitivity to glucose as a secretagogue. About 70% of cells stimulated with 20 mmol/L glucose alone showed an increase in [Ca++]i, whereas the addition of GLP-1 and PACAP induced [Ca++]i increases in 86% and 93% of cells, respectively. CONCLUSIONS: The good insulin and [Ca++]i responsiveness of porcine islet cells to both GLP-1 and PACAP provides an additional proof of their suitability for transplantation.

Animals↗
PubMed1999

Insulin secretory patterns and blood glucose homeostasis after islet allotransplantation in IDDM patients: comparison with segmental- or whole-pancreas transplanted patients through a long term longitudinal study.

IDDM patients undergoing islet, segmental pancreas or whole pancreas allotransplantation were studied at regular intervals after surgery (3-6 months, 1, 2, 3 and 4 years) to evaluate glycometabolic control (24 h metabolic profile, OGTT) and serum free insulin response to insulinogenic stimuli (arginine, IVGTT). Patients received the same immunosuppressive therapy, based on cyclosporin, steroids and azathioprine. Islet transplanted patients showed: 1) an early peak of insulin secretion after arginine, that was maintained up to 4 years; 2) an early, but low peak of insulin secretion after IVGTT, which was lost at 3 years, despite evidence that islets were still functioning (insulin independence with normal HbAlc levels); 3) a diabetic-like response to OGTT at 3 months, which improved at 2 years (IGT response); 4) fasting euglycemia with mild and reversible post-prandial hyperglycemia during the 24 h metabolic profile, which was maintained for up to 2 years. Insulin secretory patterns of islet transplanted patients were similar to segmental pancreas transplanted patients, and lower than whole pancreas transplanted patients. The reduced beta cell mass transplanted and the functional denervation of the transplanted islets seem to be the major determinants of this behaviour.

Adult↗
PubMed1999

Avoidant personality in social phobia and panic-agoraphobic disorder: a comparison.

BACKGROUND: Avoidant personality disorder (APD) is generally believed to be related to social phobia (SP), especially to generalized subtype. However, it has also been reported to be prevalent in panic disorder-agoraphobia (PDA). In the present investigation, we wished to explore whether APD in each of these disorders has discriminatory features. METHOD: We studied 71 SP and 119 PDA patients with state-of-the-art clinical instruments based on DSM-III-R. RESULTS: The pattern of social avoidance in SP was more pervasive: it was characterized by a higher level of interpersonal sensitivity and greater severity, associated with psychopathology as well as a higher rate of Axis I comorbidity. By contrast, avoidance of non-routine situations characterized APD occurring in the setting of PDA. LIMITATIONS: Differences in inclusion criteria and comorbidity rates, as well as overlap between different operational disorders, may have influenced our findings. CONCLUSION: ADP is operationally broad, and 'avoidant' as a specifier of a personality type is insufficiently precise. ADP captures avoidant traits --which appear secondary to a core dimension such as interpersonal sensitivity--but is basically a heterogeneous condition influenced by the nature of comorbid Axis I disorders.

Adult↗
PubMed1999

Mechanisms of coordination of Ca2+ signals in pancreatic islet cells.

Within pancreatic islet cells, rhythmic changes in the cytosolic Ca2+ concentration have been reported to occur in response to stimulatory glucose concentrations and to be synchronous with pulsatile release of insulin. We explored the possible mechanisms responsible for Ca2+ signal propagation within islet cells, with particular regard to gap junction communication, the pathway widely credited with being responsible for coordination of the secretory activity. Using fura-2 imaging, we found that multiple mechanisms control Ca2+ signaling in pancreatic islet cells. Gap junction blockade by 18 alpha-glycyrrhetinic acid greatly restricted the propagation of Ca2+ waves induced by mechanical stimulation of cells but affected neither Ca2+ signals nor insulin secretion elicited by glucose elevation. The source of Ca2+ elevation was also different under the two experimental conditions, the first being sustained by release from inner stores and the second by nifedipine-sensitive Ca2+ influx. Furthermore, glucose-induced Ca2+ waves were able to propagate across cell-free clefts, indicating that diffusible factors can control Ca2+ signal coordination. Our results provide evidence that multiple mechanisms of Ca2+ signaling operate in beta-cells and that gap junctions are not required for intercellular Ca2+ wave propagation or insulin secretion in response to glucose.

Animals↗
PubMed1999

Impaired beta-cell functions induced by chronic exposure of cultured human pancreatic islets to high glucose.

In type 2 diabetes, chronic hyperglycemia has been suggested to be detrimental to beta-cell function, causing reduced glucose-stimulated insulin secretion and disproportionately elevated proinsulin. In the present study, we investigated the effect on several beta-cell functions of prolonged in vitro exposure of human pancreatic islet cultures to high glucose concentrations. Islets exposed to high glucose levels (33 mmol/l) for 4 and 9 days showed dramatic decreases in glucose-induced insulin release and in islet insulin content, with increased proportion of proinsulin-like peptides relative to insulin. The depletion in insulin stores correlated with the reduction in insulin mRNA levels and human insulin promoter transcriptional activity. We also demonstrated that high glucose dramatically lowered the binding activity of pancreatic duodenal homeobox 1 (the glucose-sensitive transcription factor), whereas the transcription factor rat insulin promoter element 3b1 activator was less influenced and insulin enhancer factor 1 remained unaffected. Most of these beta-cell impairments were partially reversible when islets first incubated for 6 days in high glucose were transferred to normal glucose (5.5 mmol/l) concentrations for 3 days. We conclude that cultured human islets are sensitive to the deleterious effect of high glucose concentrations at multiple functional levels, and that such mechanisms may play an important role in the decreased insulin production and secretion of type 2 diabetic patients.

Adult↗