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Superior results with combined kidney-pancreas transplants.

From February of 1987 to February of 1991 the authors performed 23 pancreas transplants for Type I diabetes mellitus. Eight of the pancreas transplants were in patients who had a previous kidney transplant, 14 were simultaneous kidney and pancreas transplants, and 1 was in a pre-uremic diabetic. Two patients have been retransplanted after losing first grafts. All pancreata were retrieved from heart-beating cadaver donors. Pancreata were transplanted into the iliac fossa of the recipient using the iliac artery and vein as arterial inflow and venous outflow, respectively. Drainage of the pancreatic ductal system was accomplished by anastomosing either a patch or segment of duodenum surrounding the ampulla of Vater to the urinary bladder. All pancreata functioned initially with no patient requiring insulin 6 hours after surgery. Two grafts were lost early due to thrombosis of the venous drainage of the transplant; 4 grafts were lost to acute rejection; 3 were lost to chronic rejection; and 1 patient died with a functioning pancreas. One-year graft survival for all pancreatic grafts is 62 per cent. One-year patient survival is 96 per cent. One-year pancreatic graft and patient survival for the 14 combined kidney-pancreas transplants is 88 per cent and 100 per cent, respectively. Two kidneys transplanted with pancreata also were lost to acute rejection. Pancreas transplantation has proven to be a viable treatment alternative for selected patients with Type I diabetes mellitus. Long-term results are best when pancreas transplantation is done in combination with renal transplantation.

Adult↗

[The toxic effects of cadmium on pancreas.].

OBJECTIVE: In order to explore the toxic effects of cadmium on functions of endocrine and exocrine of pancreas. METHODS: 96 SD rats were administered with cadmium at different doses (0, 50, 100, 200 mg/L) by drinking water for 30 days, 60 days and 90 days. The contents of cadmium and zinc in the blood and pancreas, also the glucose level in blood and urine, the levels of insulin and the activity of amylase were determined. The gene expression of metallothionein (MT), insulin and pancreatic amylase were also measured. RESULTS: The results showed that the contents of cadmium in the serum and pancreas were higher than that of the control groups (P < 0.05). The contents of zinc in serum were decreased in the groups of 100 and 200 mg/L cadmium at the 90-day. As well as increased zinc in pancreas. The gene expression of insulin was not different compared with those of the control group except the middle-dose group at the 60-day. And the expression of amylase were higher in the groups of 100 and 200 mg/L cadmium at the 60-day and the 90-day. The expression of MT-1 and -2 were higher in the pancreas after cadmium administration. CONCLUSION: It is suggested that cadmium could be accumulated in the pancreas and caused the change of the zinc levels. Then it resulted in the change of the expression of gene and protein, and influence of the functions of both endocrine and exocrine in pancreas.

Amylases↗

[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↗

Expression of monocyte chemoattractant protein-1 in the pancreas of mice.

BACKGROUND: Type 1 diabetes has been recognized as an organ specific autoimmune disease owing to the immune destruction of pancreatic islet beta cells in genetically susceptible individuals. In both human and rodent models of type 1 diabetes, such as nonobese diabetic (NOD) mice, biobreeding rats, the disease has a distinct stage characterized by immune cells infiltrating in the pancreas (insulitis). The major populations of infiltrating cells are macrophages and T lymphocytes. Therefore, immune cell infiltration of pancreatic islets may be a crucial step in the pathogenesis of type 1 diabetes. Monocyte chemoattractant protein-1 can specifically attract monocytes in vivo. Interferon induced protein-10 has chemoattractant effects on the activated lymphocytes. In this study, we analysed the expression of monocyte chemoattractant protein-1 in the pancreas of mice and interferon inducible protein-10 mRNA in the pancreas of NOD mice, and discussed their possible role in the pathogenesis of type 1 diabetes. METHODS: The immunohistochemical method and immunoelectronmicroscopy were used to evaluate the expression of monocyte chemoattractant protein-1 in the pancreas of NOD mice and BALB/c mice. RT-PCR was used to evaluate the expression of monocyte chemoattractant protein-1 and interferon inducible protein mRNA in NOD mice. RESULTS: Monocyte chemoattractant protein-1 was positive in the pancreas of NOD mice, whereas negative in the pancreas of BALB/C mice. RT-PCR showed that monocyte chemoattractant protein-1 and interferon inducible protein-10 mRNA could be found in the pancreas of NOD mice. Immunoelectronmicroscopy demonstrated that monocyte chemoattractant protein-1 was produced by beta cells and stored in the cytoplasm of the cells. CONCLUSIONS: Pancreatic islet beta cells produce monocyte chemoattractantprotein-1 in NOD mice. Monocyte chemoattractant protein-1 may play an important part in the pathogenesis of type 1 diabetes by attracting monocytes/macrophages to infiltrate pancreatic islets.

Animals↗

Size of the pancreas in non-insulin-dependent diabetic patients.

We investigated the relationship between the size of the pancreas in non-insulin-dependent diabetic patients (NIDDs) and normal subjects, and also the possible correlation between pancreatic size in diabetics and basal C-peptide concentrations. Eighty-four non-insulin-dependent diabetics and eighty control subjects matched for age, sex and body mass index (BMI) were studied, using a realtime sector system, with which we measured the head and body of the pancreas in cm2. Scans were performed twice in 50 subjects with no significant difference. Both the head and the body of the pancreas were significantly smaller in diabetics (4.60 +/- 1.10 cm2, 5.92 +/- 1.53 cm2, respectively) than in normal subjects (6.09 +/- 1.62 cm2, 7.43 +/- 2.14 cm2) (p less than 0.001). The mean total area of the pancreas for the diabetics was 10.53 +/- 2.45 cm2, and for the controls 13.53 +/- 3.60 cm2 (p less than 0.001). No correlation was found between the total area of the pancreas and the BMI in the two groups. In the diabetic group, there was a positive correlation between C-peptide and the total area of the pancreas (r = 0.30, p less than 0.01). We concluded that the size of the pancreas is smaller in NIDDs than in healthy controls, and there is a positive correlation with the basal C-peptide concentration.

C-Peptide↗

[Ultrasonography of the thyroid gland and the pancreas in healthy children and in patients with endocrinological disease].

The thyroid gland and pancreas were ultrasonographically examined in order to determine their normal sizes in children. In 418 healthy children the thickness and width of the right and left lobes of the thyroid gland were measured at the transverse section of the neck. In 145 healthy children the long axis and short axis diameters of the profile of the head and body of the pancreas were measured by the sagittal scanning at the epigastrium. The mean +/- standard deviations as a function of height was determined as the normal size in children. In 23 patients with congenital hypothyroidism and hyperthyropinanemia ultrasonographic findings of the thyroid gland were classified into 4 groups: large thyroid gland image, normal thyroid gland image, small thyroid gland image, and no image of the thyroid gland. The patients in the no image of the thyroid gland group revealed extremely high serum thyrotropin level at the initial diagnosis, and they needed a total replacement dose of l-T4. Thyroid scintigraphy was carried out in 7 of the 23 patients. The ultrasonographic findings coincided with the scintigrams in all 7 patients. We concluded that no image of the thyroid gland by ultrasonography was in accord with thyroid aplasia or ectopic thyroid gland, and large thyroid gland image by ultrasonography was goitorous congenital hypothyroidism. In 18 patients with insulin-dependent diabetes mellitus (IDDM) the size of the pancreas was smaller than in the healthy controls. However there was no correlation between the size of the pancreas and clinical parameters, such as duration of IDDM, mean HbA1 and the insulin dose. In 31 patients with growth hormone deficiency undergoing growth hormone therapy, pancreas size was not different from the healthy controls. Thus it was suggested that in IDDM patients the size of the pancreas was small at the time of onset, and that the growth hormone had morphologically no influence on the pancreas in patients with growth hormone deficiency.

Child↗

Pancreas transplantation: report from the International Registry and a preliminary analysis of United States results from the New United Network for Organ Sharing (UNOS) Registry.

This report contains information on analysis of 2,292 pancreas transplants worldwide reported to the International Pancreas Transplant Registry from 1966 through 1989, with 1-year recipient survival rates improving from 39% to 71% to 80% to 87% and 1-year graft survival rates from 5% to 26% to 40% to 56% for 1966 to 1977 (n = 64), 1977 to 1983 (n = 336), 1984 to 1985 (n = 364), and 1986 to 1989 (n = 1,220) cases, respectively. The last 2 eras were combined for analyses of multiple variables. In the analyses of all world cases for the 1984 to 1989 period (n = 1,604), the most important finding was the influence of HLA-DR matching or mismatching on pancreas graft survival rates; 1-year function rates for grafts in recipients matched for 2, 1, or 0 DR antigens with the donor were 73% (n = 52), 53%, (n = 468), and 48% (n = 67) (p less than 0.005 for all comparisons). Likewise, in an analysis of 1984 to 1989 cases according to DR mismatching, the 1-year graft survival rates with 0, 1, or 2 DR mismatches were 63% (n = 128), 50% (n = 583), and 49% (496) (p less than 0.02). An analysis of the 1986 to 1989 era cases worldwide confirms the trend in the period analysis for bladder drainage (BD) to be associated with significantly higher graft survival rates than intestinal drainage or duct injection, at 1-year being 59% (n = 656), 47% (n = 97), and 54% (n = 210). Likewise, for the 1986 to 1989 era, worldwide 1-year pancreas graft functional survival rates were significantly higher in recipients of simultaneous-pancreas/kidney transplants (SPK) than in recipients of pancreas-after-kidney (PAK) or a pancreas-transplant-alone (PTA); 63% (n = 865), 45% (n = 186), and 37% (n = 165). In a new analysis of the United States cases reported to the UNOS Registry from October 1, 1987 through June 30, 1989, 1-year patient and graft survival rates were 91% and 69%. Almost all United States cases reported to the UNOS Registry during 1987 to 1989 were with BD (n = 324).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Where are we with pancreas transplantation?

The question still remains: What is best for the patient? It appears that whole organ or segmental pancreas transplantation can be carried out, giving anywhere from a 46% to an 84% 1-year pancreas survival rate. At the moment there is no clear-cut evidence that patient survival--at least in the short term--is any better after a combined pancreas-kidney graft than after a kidney graft alone, and there are more complications from the combined procedure. It appears once again that patient survival is a function of control of ketoacidosis and its complications--whether by a pancreas graft or by better insulin delivery. Nevertheless, several things have been learned: (1) Patients who receive a pancreas-kidney graft simultaneously have the best pancreas 1-year survival. (2) A pancreatic graft without a simultaneous kidney graft does poorly. (3) A pancreas graft carried out after a kidney graft will not do as well. (4) A kidney transplanted to a diabetic patient may become nephropathic unless supported by a pancreatic graft. (5) Retinopathy is not improved by pancreatic transplantation. (6) Neuropathy is improved or stabilized by pancreatic transplantation. (7) Nephropathy is improved by pancreatic grafting. (8) There is no clear-cut difference in pancreatic graft survival, whether segmental or whole organ grafts are used. (9) Bladder-drained grafts appear to have slightly better survival at 1 year than enteric-drained or polymer-injected grafts. (10) Human islet cell homotransplantation is not yet an accomplished fact. As Barker has pointed out, the potential benefits of pancreatic grafting are for those who are prone to complications and who do not have irreversible diabetic complications. Predicting those in whom significant complications will develop is not easy, and a large percentage of the grafts done to date have been done for patients with end stage renal disease. It has been suggested that transplants are best used for those with early renal disease and for those with pre-proliferative retinopathy and for those that are metabolically difficult to handle with insulin and for those at high risk for complications with diabetes: namely, those with high levels of inactive renin that are associated with microvascular complications and high levels of insulin-like growth factor. These complications seem to be associated with accelerated progression of retinopathy. Diabetic children whose disease is associated with major neurovascular disease and children with impaired counter regulatory mechanisms may also be candidates for grafting.(ABSTRACT TRUNCATED AT 400 WORDS)

Diabetes Mellitus↗

Pancreas transplantation--registry report and a commentary.

From December 1966 through December 1984, there were 561 pancreas transplants reported to the American College of Surgeons/National Institutes of Health Organ Transplant Registry, including 60 from 1966 through June 1977, 206 from July 1977 through December 1982 and 295 from January 1983 through December 1984. One-year graft function-survival rates (insulin-independent) in each of the three periods were 3%, 20% and 40%, and the corresponding patient survival rates were 40%, 72% and 77%. Currently 140 patients have functioning grafts, 76 for more than one year. Of the transplants since July 1977, one-year graft survival rates according to technique are 41% for enteric drainage (N = 155), 30% for polymer injection (N = 260) and 29% for urinary drainage (N = 47). Pancreas graft survival rates at one year according to whether or not the recipients have had a kidney transplant were 35% for recipients of simultaneous grafts (N = 281), 28% in recipients of a pancreas after a kidney (N = 112) and 26% in recipients of a pancreas only who did not have uremia (N = 106); corresponding patient survival rates were 69%, 83% and 83%. Overall, one-year pancreas graft survival rates according to whether the patients did or did not have end-stage diabetic nephropathy were 33% versus 25% and the corresponding patient survival rates were 73% versus 84% (P < .01). Patient survival rates were significantly higher in those without than in those with end-stage diabetic nephropathy. An analysis of technically successful grafts according to principal immunosuppressant showed one-year function rates of 46% in 258 cyclosporine-treated recipients and 26% in 143 azathioprine-treated recipients. Pancreas graft survival rates have progressively improved and the procedure has become safer with advances in surgical technique and immunosuppression. Pancreas transplantation is currently applicable to patients with diabetes mellitus whose complications are, or predictably will be, more serious than the possible side effects of long-term immunosuppression.

Diabetes Mellitus↗

Staple closure of the pancreas.

Since modern surgical stapling instruments have found a wide range of usefulness in gastrointestinal surgery, we have attempted to establish the feasibility of staple rather than suture closure of the transected pancreas. Distal pancreatic resection has been performed in eight dogs utilizing the Auto Suture Model TA-55 surgical staple instrument for primary closure of the transected margin of the remaining pancreas. Serial serum amylase determinations for each of the animals remained within normal range. Each animal was sacrificed one week after the initial surgery with examination of the remaining pancreas. None of the animals demonstrated any evidence of pancreatic fistula or abscess. Similar technique for distal pancreatic resection has been utilized in 12 patients. Five of the resections were performed for malignancies, four for trauma, and three for benign pancreatic disease. In each case, the residual pancreas was closed with the TA-55 surgical staple instrument. Although two patients died during the postoperative period of causes unrelated to the pancreas, none developed either fistula or other evidence of difficulty in healing of the pancreas. It is our conclusion that staple closure of the transected margin of the pancreas is a reasonable and safe alternative to standard suture closure technique.

Adult↗

[Advantages and disadvantages of combination kidney and pancreas transplantation].

Simultaneous kidney-pancreas transplantation represents an established method for the treatment of the diabetic patient with advanced renal failure. Continuous improvements of the surgical technique and of the immunosuppressive protocols resulted in 1-year graft survivals of the pancreas and the kidney of 75% and 85%, respectively. Currently the preferred surgical procedure is represented by the bladder drainage technique with a side-to-side duodenocystostomy. An intensive immunosuppressive regimen consisting of antilymphocytic antibodies, cyclosporine, azathioprine and steroids is mandatory to prevent and to treat rejection episodes. Graft rejection usually affects both kidney and pancreas concurrently; however, rejection generally manifests itself more distinct in the kidney, where it can be recognized and diagnosed much easier than in the pancreas. Simultaneous kidney-pancreas transplantation ensures normoglycaemia without the addition of exogenous insulin. Thereby, a substantial improvement in the quality of life can be attained. Furthermore, the transplantation of the pancreas leads to a stabilization of the neuropathy with a tendency towards improvement and effectively prevents the development of diabetic nephropathy in the simultaneously transplanted kidney. But no clear advantage has been shown for other diabetic complications like proliferative retinopathy and nephropathy. Compared to the transplantation of a kidney alone, one has to take into consideration a modest increase in patient morbidity due to the additional transplantation of the pancreas and to the more pronounced immunosuppressive therapy.

Diabetic Nephropathies↗

Simultaneous kidney and pancreas transplantation at the San Raffaele Scientific Institute: clinical experience and results.

Pancreas and kidney transplantation is performed in uremic IDDM patients to cure end-stage renal failure and diabetes. Seventy-two simultaneous kidney-pancreas transplantations were performed at our Institution between July 1985 and November 1994. All transplants were performed using heart-beating cadaver donors. The first 25 patients received 26 segmental pancreas according to Dubernard (KPS), whereas the last 46 patients received a whole, bladder-drained pancrea according to Sollinger (KPW). Mean pancreas cold and warm ischemia times were 294 +/- 14 and 44 +/- 2 minutes, respectively, in the KPS group and 660 +/- 37 and 40 +/- 8 minutes, respectively, in the KPW group. Twelve (48%) KPS patients and 19 (41%) KPW patients had postoperative pancreas surgical complications: vascular thrombosis led to graft failure in 5 KPS patients (20%) and 2 KPW patients (4%) (p = 0.01). Pancreatic fistula, hemorrhagic complications, and duodenum-bladder leakage were the surgical complications observed more frequently. Six KPS patients (24%) and 8 KPW patients (17%) underwent reintervention as a consequence of surgical complications. Fifteen KPS patients (60%) and 30 KPW patients (65%) experienced an acute kidney rejection episode, which was steroid-resistant in 14 KPW and 2 KPS patients. The actuarial survival rates for simultaneous kidney-pancreas recipients at one and 4 years were 92% and 84%, respectively, for KPS recipients, and 95% and 88%, respectively, for KPW patients. Kidney actuarial survival rates at one and 4 years were 96% and 76% respectively, for group KPS, and 93% and 89%, respectively, for KPW patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Pancreas transplant results in the United Network for Organ Sharing (UNOS) United States of America (USA) Registry compared with non-USA data in the International Registry.

As of 1994, more than 6,300 pancreas transplants were reported to the IPTR. More than 4,300 were performed in the USA, including more than 3,000 since the inception of the UNOS Registry in October 1987. The BD technique was used for 96% of USA cases but only for 64% of non-USA cases. In the overall analysis of USA BD cadaveric pancreas transplants reported to the registry by August 1994 (n = 3,000), patient survival and pancreas graft function survival rates were 91% and 72% at one year, 87% and 67% at 2 years, and 84% and 62% at 3 years, respectively. When the USA data for BD cases were analyzed according to the 3 major recipient categories: SPK, (n = 2584); PAK (n = 241); and PTA (n = 175)], patient survival rates were no different (91%, 91%, and 90% at one year, respectively), but pancreas graft survival rates were significantly higher in the SPK than in the PAK and PTA categories (76%, 47%, and 48%, at one year, respectively). In the SPK group, kidney graft survival rate at one year was 85%. Although the overall results were not as good for non-USA as for USA pancreas transplants, this was probably because the results with non-BD techniques were not as good as when BD was used, and in Europe, more than one-third of the cases were by techniques other than BD. The patient, pancreas, and kidney graft survival rates at one year for BD SPK transplants in Europe (n = 579) and other non-USA locations (n = 66) were similar to those in the USA; in Europe they were 92%, 78% and 84%, respectively. The graft survival rates for solitary pancreas transplants, however, were higher in the USA. Outcomes were also compared according to whether induction immunotherapy in USA recipients included ALG/ATG, OKT3, or neither. In the SPK category, there was no difference among the protocols, with one-year graft survival rates being 76% in the ALG/ATG (n = 1,130), 78% in the OKT3, (n = 927) but 69% in the Neither (n = 294) group (which had a significantly lower graft survival). In the PAK category, the use of OKT3 (n = 49) was associated with lower graft survival rates than when ALG/ATG (n = 154) or neither (n = 37) were given (33%, 51%, and 48% at one year, respectively). In the PTA category, the use of ALG/ATG (n = 109) was associated with significantly higher one-year graft survival rates than when OKT3 (n = 55) or neither (n = 8) were used (52%, 46%, and none, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗

[Localization of NADPH-diaphorase activity and NOS immunoreactivity in the pancreas of rat and dog].

To clarify the role of nitric oxide (NO) in the pancreas, we investigate the localization of NADPH-diaphorase activity and neuronal nitric oxide synthase (nNOS) immunoreactivity in the pancreas of the rat and dog. NADPH-diaphorase activity and nNOS immunoreactivity were identical in the neuronal element of both species. NADPH-diaphorase activity and nNOS immunoreactivity were localized in neurons and endothelial cells of vascular system. Numerous NADPH-diaphorase positive and nNOS immunoreactive fibers were observed around pancreatic ducts and arteries. A moderate number of NADPH-diaphorase positive and nNOS immunoreactive fibers were observed surrounding the acini of dog pancreas, but there were few of these structures in rat pancreas. The islets of the rat pancreas contained a moderate number of NADPH-diaphorase positive and nNOS immunoreactive fibers. However in the dog, these positive fibers were not detected inside the islets. In the rat pancreas, 85% of the ganglion cells showed NADPH-diaphorase staining. In the dog, however, 30-50% of the ganglion cells demonstrated NADPH-diaphorase activity. Although NADPH-diaphorase histochemistry did not show any positive staining in the islet cells of pancreas in either species, NOS immunocytochemical method demonstrated weak positive staining in the rat islet cells. These results indicate that NO may play an important role for the neuronal regulation of pancreatic exocrine and endocrine activities in both species, but in the species-specific manner.

Animals↗

Glomerular ultrastructure in kidneys transplanted simultaneously with a segmental pancreas to patients with type 1 diabetes.

BACKGROUND: Pancreas transplantation has been reported to prevent development and progression of diabetic glomerulopathy. STUDY DESIGN: Kidneys transplanted to type 1 diabetic patients were investigated for signs of diabetic glomerulopathy. Biopsies were obtained from 11 patients 2-4 years after simultaneous pancreas and kidney transplantation and from six patients 2-6 years after kidney transplantation alone. During follow-up, glycaemic control was monitored as glycated haemoglobin and, in the pancreas transplant patients, as i.v. glucose tolerance. RESULTS: Measures of glycaemic control were consistently normal in only two pancreas transplant patients. Four had mean k values <1.0. In kidney biopsies from the pancreas transplant patients, thickness of the glomerular basement membrane was 395 (0.13) nm (mean, coefficient of variation), which is higher than normal (324 (0.13) nm, P=0.01) and not different from diabetic patients with kidney transplants alone, 418 (0.15) nm. The mean calculated annual increase in thickness did not differ between patients with and without a pancreas transplant, 26 (0.77) versus 29 (0.54) nm/year. Estimates of the mesangium and mesangial matrix were in the normal range in both groups while the interstitial volume fraction was increased and to a similar extent. CONCLUSION: The increase in thickness of the glomerular basement membrane in kidneys transplanted simultaneously with a segmental pancreas is probably an expression of diabetic glomerulopathy caused by the modest impairment in glucose metabolism present in most patients.

Adult↗

The case for pancreas transplantation.

More than 6,000 pancreas transplants had been performed by the end of 1994. Insulin-independence currently persists for more than one year in over 75% of diabetic recipients of simultaneous pancreas-kidney transplants, and in approximately 50% of recipients of a pancreas transplant alone. As kidney recipients are obligated to undergo immunosuppression in conjunction with this operation, the addition of a pancreas transplant entails only extra surgery. For non-uremic recipients of a pancreas transplant alone, immunosuppression itself is the trade-off for correction of diabetes. The problems of diabetes must be of a magnitude to justify the use of anti-rejection drugs. Thus, the main pancreas transplant applications have been in patients who are extremely labile or experience hypoglycaemic unawareness syndrome. Application to non-uremic patients without current problems would require randomisation to determine whether the probability of freedom from problems or the occurrence of complications differs over years of follow-up between a non-diabetic condition on immunosuppression and a diabetic status off immunosuppression. In the meantime, pancreas transplantation should be applied routinely to diabetic recipients of a kidney transplant or those whose quality of life is poor because of lability.

Diabetes Mellitus, Type 1↗

The effect of prostacyclin analogue--iloprost on the pancreas regeneration after caerulein-induced acute pancreatitis in rats.

UNLABELLED: Prostacyclin (PGI2) and its stable analogue iloprost (I) exert beneficial effect in acute pancreatitis (AP). The aim of the study was to evaluate the role of iloprost in pancreas regeneration after AP in rats. METHODS: AP was induced in male Wistar rats by s.c. injections of caerulein 12 micrograms/kg t.i.d. for 2 days. Rats were divided into four groups: control + saline (C); control + iloprost (C/I); AP + saline (AP); AP + I (AP/I). Rats were treated for 7 or 14 days. I (Schering AG) was given at the dose I microgram/kg b.w., i.p., t.i.d. After the rats were killed, the pancreata were weighed and their protein, DNA, RNA, chymotrypsin, alpha-amylase contents were evaluated. Light microscopic examination of representative pieces of pancreas was performed. RESULTS: Acute pancreatitis resulted in pancreas destruction observed even 7 days after the onset of the disease. The significant decrease of pancreatic weight, RNA and chymotrypsin contents were observed in AP rats when compared to C. The improvement of pancreatic histology and significant increase of DNA content were found in I treated (during 7 days) AP rats in comparison to untreated AP group. Two weeks after pancreatitis induction the pancreas regeneration occurred in both pancreatitis groups and it was connected with pancreas hypertrophy. Treatment with I resulted in slight not significant increase of some of cellular hypertrophy indices when compared to AP untreated animals. Healthy rats injected with I during 7 days showed significant elevation of DNA content in comparison to C. When treatment with I was prolonged up to 14 days such hyperplastic effect was not observed. Our results suggest, that treatment with iloprost exerts temporary hyperplastic influence on the pancreas of healthy rats and pancreas regenerating after caerulein-induced pancreatitis.

Acute Disease↗

Pancreas transplantation: results and indications.

Pancreatic transplantation is the best method of replacing the endocrine function of the gland in Type 1 insulin-dependent diabetic patients. At the end of 1996, 9,000 pancreas transplants had been reported to the international Pancreas Transplant Registry. For 1994-1996, one-year pancreas survival rates were 81% for simultaneous pancreas and kidney transplantation (n = 1,516), 71% for pancreas after kidney (n = 141) and 64% for pancreas alone (n = 64). In patients with a functional graft, glycosylated haemoglobin, fasting blood sugar, and 24-h metabolic profiles are normal. The effect of pancreatic transplantation on secondary complications often appears after several years of normal pancreatic function. Successful transplantation is associated with an improvement in different aspects of the quality of life. The decision to perform pancreatic transplantation depends on the balance between the risks of transplantation, mainly surgical or related to immunosuppression, and those of diabetes development. The advantages and drawbacks of pancreatic transplantation and insulin therapy need to be honestly and carefully analysed for specific populations of diabetic patients as well as for each individual. At present, simultaneous pancreaticorenal transplantation is the best treatment for diabetic patients with chronic renal failure. Transplantation of the pancreas alone in non-uraemic patients may also be considered in carefully selected subjects.

Diabetes Mellitus, Type 1↗