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C Socci

Publications and source records attributed to C Socci.

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Selection of donors significantly improves pig islet isolation yield.

The purpose of the present study was to test the influence of donor age on islet isolation yield in swines. Large White pigs of 10 months (group 1, n = 10) and 2-3 years (group 2, n = 5) were used. A modification of the automated method for human islet isolation was used for pig islet separation. After ductal injection of a collagenase solution (Seromed, type C-1000) the islets were separated through a continuous digestion process. In group 1 it was possible to obtain an average of 636,100 islets (volume = 476.1 mm3, insulin content = 101.4 Units). In group 2 the average total islet number was 799,800 representing a volume of 1190.6 mm3 (Insulin content 210 Units). Total islet number was not significantly different in the two groups, however when islet volume and total insulin content were considered, older animals allowed a significantly higher yield (P less than 0.01 for volume and P less than 0.05 for insulin content). These findings indicate that it is possible to separate large number of pig islets from both young (10 months) and older (2-3 years) animals and that selection of donor pigs will improve islet isolation yield. These results may be of assistance in the definition of requirements for more effective islet isolation in swines.

Animals↗

Isolation of the elusive pig islet.

This study describes a procedure for large scale isolation of swine islets. The reported results are from 15 consecutive isolations. The glands were removed from live animals with no warm ischemia, and the pancreata were digested by a modification of the automated method for human islet isolation. It was possible to separate an average of 690,000 +/- 279,429 islets per pancreas corresponding to 10,360 +/- 4034 islets per gram of pancreas with a volume of 714 +/- 480 mm3. After purification the recovery was 255,000 +/- 32,407 islets corresponding to 4,000 +/- 567 islets per gram of pancreas. Purity of the final preparation was 80% to 95% islets. Insulin content resulted in an average of 146.8 +/- 78 U before purification and 71 +/- 53 U after purification. After a 10 mm3 aliquot of the final preparation was transplanted under the renal subcapsular space of seven nude mice with diabetes, normoglycemia occurred in six of the mice. Thirty days after transplantation, nephrectomy of the kidneys bearing the grafts produced a rapid return to the diabetic state in all cases. This method makes it possible to provide large numbers of intact swine islets for preliminary studies of prevention of the rejection of pig islet xenograft by immunoalteration and immunoisolation procedures.

Animals↗

Islet isolation assessment in man and large animals.

Recent progress in islet isolation from the pancreas of large mammals including man, accentuated the need for the development of precise and reproducible techniques to assess islet yield. In this report both quantitative and qualitative criteria for islet isolation assessment were discussed, the main topics being the determination of number, volume, purity, morphologic integrity and in vitro and in vivo function tests of the final islet preparations. It has been recommended that dithizone should be used as a specific stain for immediate detection of islet tissue making it possible to estimate both the total number of islets (dividing them into classes of 50 mu diameter range increments) and the purity of the final preparation. Appropriate morphological assessment should include confirmation of islet identification, assessment of the morphological integrity and of the purity of the islet preparation. The use of fluorometric inclusion and exclusion dyes together have been suggested as a viability assay to simultaneously quantitate the proportion of cells that are intact or damaged. Perifusion of islets with glucose provides a dynamic profile of glucose-mediated insulin release and of the ability of the cells to down regulate insulin secretion after the glycemic challenge is interrupted. Although perifusion data provides a useful guide to islet viability the quantity and kinetics of insulin release do not necessarily predict islet performance after implantation. Therefore, the ultimate test of islet viability is their function after transplantation into a diabetic recipient. For this reason, in vivo models of transplantation of an aliquot of the final islet preparation into diabetic nude (athymic) rodents have been suggested. We hope that these general guidelines will be of assistance to standardize the assessment of islet isolations, making it possible to better interpret and compare procedures from different centers.

Animals↗

Multivariate analysis of factors affecting patient and graft survival after renal transplant.

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.

Adult↗

Polarity of the first episode, clinical characteristics, and course of manic depressive illness: a systematic retrospective investigation of 320 bipolar I patients.

In 320 patients with established bipolar I disorder, we examined the past course on the basis of polarity at onset (depressive, mixed, and manic). Despite the obvious limitations of retrospective methodology, information on course parameters in a large sample of affective disorders is most practically obtained by such methodology. We believe that our systematic interview of patients and their relatives--as well as the systematic study of their records--minimized potential biases. Depressive onsets were the most common, accounting for 50%, followed by mixed and manic onsets in about equal proportion. In general, the polarity of episodes over time reflected polarity at onset. Those with depressive onset had significantly higher levels of rapid cycling, as well as suicide attempts, but were significantly less likely to develop psychotic symptoms. Mixed onsets, too, had high rates of suicide attempts, but differed from depressive onsets in having significantly more chronicity yet negligible rates of rapid cycling at follow-up evaluation. Because cases with depressive onset had received significantly higher rates of psychopharmacologic treatment, our data are compatible with the hypothesis that antidepressants may play a role in the induction of rapid cycling. Overall, our data support the existence of distinct longitudinal patterns within bipolar I disorder, which in turn appear correlated with the polarity at onset. In particular, rapid cycling and mixed states emerge as distinct psychopathologic processes.

Adolescent↗

Immunocytochemical detection and characterization of intrahepatic human pancreatic islets after combined liver-islet allotransplantation.

The unique availability of an explanted liver-islet allograft, removed for primary nonfunction of the liver, led us to evaluate distribution and phenotype of exocrine and endocrine components of the pancreatic graft. Immunocytochemistry was used to map patterns of gene products for islet hormones, proprotein processing enzymes, panneuroendocrine markers, and pancreatic exocrine markers. When compared with age-matched control pancreases, insulin-, glucagon-, somatostatin-, and pancreatic polypeptide-producing cells were similarly represented and distributed within the grafted islet. We also demonstrate that the intrahepatic transplanted islets retained the enzyme machinery able to process the hormone precursors into bioactive fragments. In the clinical setting, this resulted in an immediate functioning of the graft and insulin-independence of the patient one month after transplantation. The purity in islets, as assessed by immunocytochemistry with antibodies to tissue constituents of endocrine and exocrine lineages, was around 40%. Despite the massive intraportal presence of pancreatic acinar tissue, no signs or symptoms attributable to ectopic hypersecretion of exocrine enzymes occurred. In fact, when tested with antibodies to such enzymes, low levels of immunoreactivity were observed in the grafted acinar cells.

Biomarkers↗

[Simultaneous pancreas-kidney transplantation: a single center experience on 148 cases].

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.

Adult↗

Thymopentin increases the survival of mice after allogeneic blood transfusion, bacterial gavage, and burn injury.

OBJECTIVE: To investigate the effect of blood transfusion on mortality and the incidence of bacterial translocation in mice subjected to thermal burn or bacterial gavage, or both, and to assess the influence of thymopentin on mortality. DESIGN: Randomly controlled experiments. SETTING: University departments of surgery, immunology and nuclear medicine. MATERIAL: 235 Balb/c (H-2d) and C3H/HeJ (H-2k) mice. INTERVENTIONS: 8 groups of 20 mice each received: saline infusion (controls), blood transfusion (BT) alone, 20% burn alone, gavage with 1 x 10(10) Escherichia coli alone, BT and gavage, BT and burn, burn and gavage, or BT, burn, and gavage. A further 3 groups of 10 mice were all gavaged with 111In-biotin labelled E coli and randomised to additional BT and burn, BT alone, or burn alone. 98 mice that had had BT, burn, and gavage, were then randomised to receive thymopentin 0, 0.1, 1, or 5 mg/kg/day for 15 days. The impact of the pretreatment with thymopentin on PGE2 concentration was also evaluated in a separate group of 45 mice that received BT, burn, and gavage; or burn and gavage. MAIN OUTCOME MEASURES: Survival, degree of translocation. RESULTS: The highest mortality (75%) was in the BT, burn, and gavage group. BT alone significantly reduced survival in burned mice, whereas BT alone or associated with gavage had no effect. Thermal injury had the most influence on bacterial translocation, whereas BT did not increase it. Thymopentin significantly improved survival, particularly in the higher doses. The pretreatment with thymopentin significantly reduced PGE2 concentration after BT, burn and gavage. CONCLUSION: Burn injury significantly increased mortality in the presence of immune deficiency caused by BT. Thymopentin reduced mortality, possibly by immunomodulation.

Animals↗