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PubMed1983

Long-term function of duct-ligated and free-duct whole pancreas transplants.

This report compares endocrine and exocrine responses of "free-duct" and "duct-ligated" whole pancreas isografts in Lewis diabetic rats during a 1-year period of observation. Fasting blood sugar, serum amylase, serum insulin, pancreozymin-secretin test, and L-arginine tolerance test assays were performed prior to and at periodic intervals after transplantation. Histological examinations of transplanted and native pancreas were performed monthly on animals in each group. Whole pancreas transplantations led to immediate and sustained normalization of FBS and insulin levels. In the "duct-ligated" group there was a gradual but insignificant decrease of serum insulin levels after 9 months. Depressed serum amylase levels in diabetic rats were reversed in both groups. Isolated islet iso- and allografts also reversed depressed amylase levels. The results of pancreozymin-secretin tests in islet isografted animals supported the postulated trophic effect of endocrine pancreas on exocrine pancreas. Although both whole-pancreas transplant groups showed a normal response to GTT for 12 months after transplantation, the "duct-ligated" group showed a significantly lower response to L-arginine tolerance test than the "free duct" model as early as 4 months after transplantation, suggesting a defect in B-cell function in long-term "duct-ligated" graft. Serial histological examinations of transplanted pancreases revealed more rapid atrophy and more intense fibrosis of acinar tissue in the "duct-ligated" group than in the "free duct" group. These results suggest that a "free duct" pancreatic isograft maintains a more stable endocrine function in a long-term study than does the "duct-ligated" pancreas, and that exocrine dysfunction in diabetic rats may be related to the endocrine disorder which can be reversed by both islet cell and whole-organ pancreatic transplantation.

Amylases↗
PubMed1987

gamma-Glutamyltransferase activity in atypical acinar cell nodules of rat pancreas.

The biochemical and histochemical measurement of the enzyme gamma-glutamyltransferase (GGT) was undertaken in normal rat pancreas and in rat pancreas containing azaserine-induced preneoplastic nodules. A steady decrease in pancreatic GGT activity was observed in the normal animals as they aged from 5 to 34 weeks. The azaserine-induced nodules contained a lower average GGT activity than the control pancreas although a 10-fold variation was noted in the GGT activity of individual nodules. A significant increase in concentrations of both reduced glutathione and oxidized glutathione was noted in pancreatic nodules from azaserine-treated rats compared to concentrations found in both control pancreas from untreated rats and internodular pancreas from azaserine-treated rats. A pancreatic acinar cell carcinoma contained low GGT activity--similar to that found in large nodules and about 10% of the level found in control pancreas. Pancreatic GGT levels were higher in 5- and 7-week-old rats fed chow than in rats fed a purified diet, but this effect of chow was not observed at 34 weeks of age. Feeding a purified diet supplemented with a retinoid, N-2-hydroxyethylretinamide (2-HER), for a period of 2 weeks did not influence the GGT activity level in either normal pancreas or in the azaserine-induced nodules. While decreased GGT activity does not serve as a marker for all atypical acinar cell nodules, deficient activity with concomitant increased glutathione levels appears to correlate generally with increased growth potential.

Animals↗
PubMed1986

Tracer diffusion has exaggerated CNS maps of direct preganglionic innervation of pancreas.

Small injections of True Blue (TB) into 4 different segments of the pancreas of the rat resulted in characteristic and different numbers and distributions of labeled cells within the dorsal motor nucleus of the vagus (DMN). Composites of these patterns of labeled cells in the DMN closely matched the distributions previously reported for more extensive injections of retrograde tracers into the pancreas. However, the application of a diffusion barrier (formed with a plastic wound spray) on the outer surface of the stomach and intestines adjacent to the pancreas segment which contained the TB injection depot prevented virtually all of the labeling of DMN cells. Similarly, applying a diffusion barrier directly to the injected pancreas segment itself prevented all or most (mean greater than 99%) of the DMN labeling. In contrast to this effect on DMN label, the barrier reduced more modestly the labeling of celiac ganglion somata after pancreas injections. Several additional control experiments also suggest that the absence of DMN label after the barrier application resulted from interference with tracer diffusion from the injected organ and not from neurotoxic effects. These include the following demonstrations in the presence of the barrier: (1) observation of unimpaired vagally stimulated insulin secretion, (2) uncompromised cell labeling of DMN from other organs treated with TB plus the barrier, and (3) normal hematoxylin and eosin stained pancreas tissue which had received TB injections and barrier application. It was concluded that both the number of parasympathetic preganglionic neurons that project monosynaptically to the pancreas and their distribution in the medulla may have been very significantly overestimated in previous tracer studies.

Animals↗
PubMed1994

Effect of dietary lipids and endocrine changes on polyunsaturated fatty acids in phospholipids of pancreas and brown adipose tissue of obese and lean rats.

Obese (fa/fa) rats fed on control diet have lower proportions of linoleic acid (18:2n-6) and/or arachidonic acid (20:4n6) in IBAT and pancreas phospholipids compared with lean (Fa/-) rats. Lower stearic acid (18:0) to oleic acid (18:1n-9) mean ratios in fa/fa compared with Fa/- suggest enhanced delta 9-desaturase activity in the former. 18:2/20:4 mean ratios in pancreas, but not IBAT, are indicative of a reduced delta 6-desaturase activity in fa/fa rats. Absolute amounts of phospholipids (mg/unit tissue wt) were 2-fold greater in IBAT of fa/fa compared with Fa/- rats, irrespective of their diet. This was reflected in greater absolute amounts of 18:2n-6 and 20:4n-6 only in HSO and HTO fa/fa groups, but not in the control group. Adrenalectomy (Adx) or T3 treatment also modified phospholipid fatty acid composition of IBAT and pancreas phospholipids in animals fed on the control diet with fa/fa rats more sensitive to endocrine induced changes. In fa/fa rats T3 treatment increased docosahexaenoic acid (22:6n-3) in IBAT of both phenotypes compared with the control, but this effect was evident only in fa/fa and not Fa/- pancreas. T3 treatment also increased docosapentaenoic acid (22:5n-3) in IBAT from, both phenotypes, but no 22:5n-3 was evident in the pancreatic tissue of these animals. ADX also increased 22:6n-3 in the IBAT of fa/fa (Fa/- values were less than 1%) but not in the pancreas of fa/fa or Fa/-. ADX modified the relative proportions of 18:0 to 18:1 and 18:2 to 20:4 in IBAT and pancreas of fa/fa in a way that indicated decreased delta 9-desaturase and increased delta 6-desaturase activities; these effects tended toward normal again in pancreas of fa/fa rats on corticosterone replacement (CST).

Adipose Tissue, Brown↗
PubMed1979

Imaging of the pancreas with computed tomography.

In this paper we present our experience with computerized tomographic imaging of the pancreas, both in normal and abnormal conditions. Eighty patients were studied for evaluation of pancreatic disease. A further 50 patients, all with a normal pancreas, were studied for abnormalities of other abdominal organs and served as the control group. Helpful signs in establishing the diagnosis of carcinoma of the pancreas were mass effect within the pancreas, alteration of organ contour and obliteration of retroperitoneal fat planes. We found that differentiation from pancreatitis or retroperitoneal lymphadenopathy may at times be difficult. Our results showed that in 22 out of 23 patients with proven normal pancreas, the pancreas size on the CT display was within the adopted normal range. In 30 patients with proven carcinoma of the pancreas, a pancreatic mass was seen in 24 (83%). Computerized tomography is clearly a valuable method for viewing both normal pancreatic anatomy and anatomical variations and pathologies.

Adipose Tissue↗
PubMed2005

The anatomical study on the rat pancreas and its ducts with emphasis on the surgical approach.

It was intended to present information about the anatomy of the pancreas and especially to emphasize the variation of pancreatic ducts in the rat, which may guide researchers in experimental studies. In 27 adult rats, latex dye was introduced into the biliopancreatic duct, portal vein and arteries. The pancreas with the neighboring structures was studied with the aid of the dissection microscope and measurements were by means of micrometric ocular. The pancreas was divided into three parts i.e. the biliary, duodenal and gastrosplenic portions. The biliopancreatic and pancreatic ducts as well as biliary and duodenal portions of the pancreas could be seen ventrally with a minor procedure such as pulling the duodenum caudally, and additionally the entire pancreas and its ducts could also be reached dorsally since the stomach was turned cranially with the duodenum. The biliopancreatic duct diameter and length of the ducts were 1.01+/-0.03 and 28.86+/-0.59 mm, respectively. The anterior pancreatic duct originated from the biliopancreatic duct on different sides, 17.96+/-0.75mm away from the duodenal papilla. The anterior pancreatic duct drained the gastrosplenic portion of the rat pancreas and this duct, via the duodenal duct, partially collected secretion of the duodenal portion at a ratio of 74.07%. The posterior pancreatic duct opened to the biliopancreatic duct and its distance from papilla duodeni was changed from 0 to 8 mm. When the biliopancreatic duct is ligated at the level of the duodenal opening, the posterior pancreatic duct or a small duct from duodenal portion should be taken into consideration because these ducts opened to biliopancreatic duct at the level of papilla duodeni at a ratio of 37.04%. In conclusion, the duct system of pancreas had a great variation and therefore the success rate of the surgery could be increased when surgeons have more knowledge on variations of the duct system in this region.

Animals↗
PubMed2004

Differential expression of electrogenic NBC1 (SLC4A4) variants in rat kidney and pancreas.

The purpose of this study was to determine expression and localization of NH(2)-terminal variants of the electrogenic Na(+)-HCO(3)(-) co-transporter NBC1 (SLC4A4) in the rat kidney and pancreas. We generated two anti-peptide antibodies: alpha333 against the "mste" start (kidney; kNBC1) and alpha332 against the "mede" start (pancreas; pNBC1). Transcripts for both NBC1 variants were detected in kidney and pancreas by RT-PCR, though kNBC1 was more prominent in the kidney and pNBC1 was more prominent in the pancreas. Similar protein expression levels were detected by immunoblotting of plasma membranes (PM) from kidney cortex and pancreas. Immunohistochemistry with alpha333 recognized the "mste"-epitope in the basolateral plasma membrane (BLM) of renal proximal tubule. The "mede"-protein (alpha332) was similarly localized although staining was much less and more diffuse. In the pancreas, alpha332 stained BLM of acinar and duct cells. Some isolated duct cells were also stained at the apical PM. The "mste"-protein (alpha333) was absent in acinar cells but was located at the apical PM of duct cells. The data indicate that the two NH(2)-terminal NBC1 variants are co-expressed in kidney and pancreas, where they may contribute to HCO(3)(-) transport and pH regulation.

Animals↗
PubMed2005

Transforming growth factor-beta pathway: role in pancreas development and pancreatic disease.

The pancreas is a complex exocrine and endocrine gland that controls many homeostatic functions. The exocrine pancreas produces and secretes digestive enzymes, whereas, the endocrine pancreas produces four distinct hormones, chief among them being the glucose regulating hormone-insulin. Diabetes, pancreatitis and pancreatic cancer are some of the main afflictions that result from pancreas dysfunction. Transforming growth factor-beta (TGF-beta) proteins are central regulators of pancreas cell function, and have key roles in pancreas development and pancreatic disease. Since expression levels and kinase activities of components of TGF-beta signaling are aberrantly altered in diseases of the pancreas, modulating the activity of TGF-beta provides a unique and rational opportunity for therapeutic intervention. Although TGF-beta still remains elusive in terms of our understanding of its multifunctional modes of action, research is moving closer to the design of approaches directed toward modulating its activities for therapeutic benefit.

Animals↗
PubMed2003

Influence of mild obesity on outcome of simultaneous pancreas and kidney transplantation.

The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney transplantation (SPK) has not been well described. We retrospectively reviewed 88 consecutive primary SPKs performed at our institution between March 15, 1995 and August 28, 2001. All patients received antibody induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemic-enteric implantation was performed in all patients. Primary end points were patient, pancreas, and kidney survival. Secondary end points were rates of anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat laparotomy, and length of hospital stay. Values are shown as mean+/-standard deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a BMI < or =24.9 (mean 21.7+/-2.2, range 15.4 to 24.9). Thirty-six patients were mild to moderately obese with a BMI > or =25 (mean 27.7+/-2.2, range 25 to 35.1). Distribution of recipient age, sex, and ethnicity was similar between groups. Kidney and pancreas preservation times were similar between nonobese and obese patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95% vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%, 91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%) survival were comparable between nonobese and obese (P=NS). The mean rates of pancreas thrombosis, major infection, pancreas rejection, kidney rejection, relaparotomy, and length of hospital stay were similar in the two groups. The overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17% incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese patients (P=0.012). Six of seven leaks occurred in obese patients. Mean BMI in the seven patients with a leak (27+/-1.9) was significantly higher than in patients who did not develop a leak (24+/-3.7; P=0.05). Although obesity had no effect on patient or graft survival, it was associated with a significantly higher leakage rate. There should therefore be a higher degree of suspicion for the presence of duodenojejunal anastomotic leaks in obese SPK recipients.

Adult↗
PubMed2005

Donors with a maximum body weight of 50 kg for simultaneous pancreas-kidney transplantation.

INTRODUCTION: Pediatric donors are rarely used for simultaneous pancreas-kidney transplantation (SPK). But the age of the donors may be less important than the body weight (BW). Therefore we retrospectively analyzed our data on SPK donors with a maximum BW of 50 kg. METHODS: Between June 1994 and December 2003, 22 patients received SPK transplants from cadaveric donors with a maximum BW of 50 kg (range, 25-50 kg; median, 42.4 kg). The median donor-recipient weight ratio was 0.61 (range, 0.47-0.91). RESULTS: Two kidney grafts (9.1%) displayed delayed graft function (2 and 9 dialyses). One patient needed insulin for 2 days (<20 IU/d), and the other patient for 1 month at a maximum of 7 IU/d. Four pancreas grafts (18.2%) were lost owing to graft thrombosis. One-year survival for patients was 95.5%; for kidneys, 86.4%; and for the pancreas, 72.7%. After a median observation period of 78 months, 6 acute rejection episodes were observed in 5 patients (22.7%). Five acute rejections were treated successfully, but 1 patient lost both organs. Two patients died of severe infections, at 3 months and 3 years, respectively, after SPK. Four kidney and 3 pancreas grafts developed chronic allograft dysfunction. CONCLUSIONS: Our results show that 1-year graft function in this series was less than the results reported to the International Pancreas Transplant Registry. The Main reason for early pancreas loss was graft thrombosis (18.2%). After a median observation period of 78 months, pancreas graft survival was 59.1%.

Adult↗
PubMed2005

Pancreas oxygenation is limited during preservation with the two-layer method.

BACKGROUND: The two-layer method (TLM) for pancreas preservation reportedly improves islet yield and transplantation outcome relative to previous methods. Increased ATP concentrations support the hypothesis that these improvements are related to better oxygenation from the perfluorocarbon solution. However, there are limited direct measurements of oxygen partial pressure, (pO(2)) in pancreata preserved with the TLM. Theory predicts that only a small fraction of a human pancreas can be oxygenated externally. In this report we examine pancreas oxygenation with the TLM using theory and direct pO(2) measurements. METHODS: pO(2) profiles in cylindrical pancreata were calculated at various temperatures with a diffusion-reaction model. The pO(2) was measured using fiber optic sensors in the core of porcine pancreatic tissue preserved with the TLM in media saturated with 100% oxygen. RESULTS: The model predicts that at 8 degrees C, even in the absence of an external pO(2) gradient, oxygen penetration depth is about 1 mm and insensitive to pancreas diameter, while the oxygenated volume fraction is about 15% for a 2.5-cm-diameter pancreas. Experimental measurements verified that pO(2) is virtually zero in the core of a 1-cm-thick pancreatic piece preserved with the TLM. Penetration of solution around the sensor may be responsible for the observed lag and for the previously reported nonzero pO(2) measurements. Reoxygenation of heat-treated tissue took several hours. CONCLUSIONS: The TLM can oxygenate only a small volume fraction of a human pancreas. Pancreas oxygenation through the native vasculature should be explored to further improve yield of viable islets.

Humans↗
PubMed2006

Pancreas versus islet transplantation in diabetes mellitus: How to allocate deceased donor pancreata?

Transplant options for the diabetic recipient include pancreas and islet transplantation. Pancreas transplantation has been increasingly performed in the last 3 decades with increasing success rates. Nevertheless, islet transplantation offers the advantage of being less invasive with fewer complications. However, current experience shows that multiple transplants are required to achieve and maintain insulin-independence in the intermediate term, and long-term function remains a problem even with multiple transplants. Early successes with single-donor islet transplants are encouraging and if maintained will largely substitute pancreas transplants. Currently, single-donor islet transplants have been shown to work in recipients with low insulin requirements who receive a pancreas from a donor with high body mass index. However, pancreas transplants from obese donors are associated with increased surgical risk. Therefore, it is logical to preferentially allocate obese donor pancreata to islet recipients. In addition, older donor (50 to 65 years) pancreata could be preferentially allocated to islets since their islet yield is still good, whereas they are associated with decreased survival in whole-organ pancreas transplants. With increasing efficiency and success of islet transplants the criteria for pancreas allocation for islets will need to be periodically reviewed.

Diabetes Mellitus↗
PubMed2005

In vivo gene transfer to healthy and diabetic canine pancreas.

Gene therapy may provide new treatments for severe pancreatic disorders. However, gene transfer to the pancreas is difficult because of its anatomic location and structure, and pancreatitis is a serious concern. Like the human pancreas, the canine pancreas is compact, with similar vascularization and lobular structure. It is therefore a suitable model in which to assess gene transfer strategies. Here we examined the ability of adenoviral vectors to transfer genes into the pancreas of dogs in which pancreatic circulation had been clamped. Adenoviruses carrying the beta-galactosidase (beta-gal) gene were injected into the pancreatic-duodenal vein and the clamp was released 10 min later. These dogs showed beta-gal-positive cells throughout the pancreas, with no evidence of pancreatic damage. beta-Gal was expressed mainly in acinar cells, but also in ducts and islets. Moreover, transduction was prominent in connective tissue of the lobe septa. beta-Gal expression in the exocrine pancreas of a diabetic dog was also found to be similar to that observed in healthy dogs. Thus, efficient gene transfer to canine pancreas in vivo may be achieved by adenovirus injection after clamping pancreatic circulation. This technique may be used to assay new gene therapy approaches for diabetes mellitus and other pancreatic disorders.

Adenoviridae↗
PubMed1996

Cholecystokinin receptors in human pancreas and gallbladder muscle: a comparative study.

BACKGROUND & AIMS: Cholecystokinin (CCK) receptors mediate pancreatic secretion and gallbladder contraction. Hitherto, little information on characteristics of CCK receptors in the human pancreas was available. This study identifies CCK receptors in the human pancreas and compares their characteristics with the CCK receptors in the human gallbladder. METHODS: Visualization and quantification of 125I-Bolton-Hunter sulfated CCK octapeptide (125I-BH-CCK-8) binding to tissue sections of the human pancreas and gallbladder were performed by storage phosphor autoradiography. RESULTS: Specific bindings for CCK were visualized in pancreatic tissue and the smooth muscle layer of the gallbladder. Binding of 125I-BH-CCK-8 to the pancreas was inhibited by agonists with the affinities (dissociation constant) of CCK (0.11 nmol/L) approximately gastrin (0.15 nmol/L) and by antagonists with the affinities of CCK-B receptor antagonist (L365,260, 0.18 nmol/L) > CCK-A receptor antagonist (lorglumide, 8.1 nmol/L). In contrast to the pancreas, binding of 125I-BH-CCK-8 to the gallbladder muscle was inhibited with high affinity by CCK-8 and lorglumide but was replaced to a small degree by gastrin and L365,260. CONCLUSIONS: The sub-types of receptors for CCK in the human pancreas and gallbladder are different. The human pancreas predominantly expresses CCK-B receptors, whereas only CCK-A receptors were localized in the human gallbladder muscle.

Adult↗
PubMed2001

Recording of electroneurograms from the nerves innervating the pancreas of a dog.

Electroneurograms (ENGs) from the vagus, splanchnic and pancreatic nerves innervating the pancreas of a dog, were recorded with chronically implanted silicone multi-electrode circular cuffs in an intact pancreas and in a pancreas partly disabled with alloxan. The cuffs contained 33 platinum electrodes (0.6x1.5 mm) arranged in three parallel circular groups integrated into the inner surface of the cuff. Each circular group contained 11 electrodes at a distance of 0.5 mm apart, with 6 mm between the circular groups. The cuffs had an inner diameter of 2.5 mm and the length of 18 mm. In a 2-year study, the cuffs were implanted into two adult Beagle dogs (one female and one male). In the vagus nerve, the cuff was installed on the nerve at the neck, whilst in the splanchnic nerve, the cuff was installed on the nerve before the celiac ganglion, and in the pancreatic nerve, the cuff was installed on the nerve just before it enters the pancreas. In each of the three implanted cuffs, the electrodes of the central circular group were connected to each other and this signal provided one input to a multi-channel ENG amplifying system. The electrodes of each of the two outer spiral groups were connected to each other and then both these groups were short-circuited. This signal then provided another input to the multi-channel ENG amplifying system. The ENG amplifying system was designed to amplify the ENGs 100000 times and to pass frequencies of between 500 and 10 kHz. In our study, three recordings in each animal were conducted. Recordings in the intact pancreas were conducted 2 and 6 months after the implantation, while the recording in the partly disabled pancreas, was conducted 10 months after the implantation and 10 days after the disablement. Due to the fact that the results obtained in both animals were actually quite similar, we present the results of the recordings obtained in one animal. In both animals the cuffs were left implanted for more than 1 year and were used for pancreatic stimulation, although this is not in this paper. The results show that cuffs implanted chronically on the nerves innervating the pancreas of a dog could reliably record the ENGs. This information could be used effectively in further study of pancreatic innervation and its function. Moreover, the results suggest that cuffs could also be useful in recording the ENGs from other nerves of the autonomic nervous system that innervate various glands and internal organs.

Action Potentials↗
PubMed2001

Distribution of vasoactive intestinal polypeptide, neuropeptide-Y and substance P and their effects on insulin secretion from the in vitro pancreas of normal and diabetic rats.

This study examined the pattern of distribution of vasoactive intestinal polypeptide (VIP), neuropeptide-Y (NPY) and substance P (SP) in the pancreas of diabetic rat to determine whether there are changes in the number and pattern of distribution of these neuropeptides after the onset of diabetes. Moreover, the effect of VIP, NPY and SP on insulin secretion from the pancreas of normal and diabetic rats was also examined. Diabetes mellitus (DM) was induced by a single dose of streptozotocin (STZ) given intraperitoneally (i.p.) (60 mg kg body weight(-1)). Four weeks after the induction of DM, diabetic (n = 6) and normal (n = 6) rats were anesthetized with chloral hydrate and their pancreases removed and processed for immunohistochemistry and insulin secretion. The number of insulin-positive cells in the islets of Langerhans was reduced while that of VIP and NPY increased significantly after the onset of diabetes. The pattern of distribution of VIP, NPY and SP in the nerves innervating the pancreas was similar in both normal and diabetic rats. VIP-evoked large and significant (P < 0.02) increases in insulin secretion from the pancreas of normal and diabetic rats. NPY also induced a marked (P < 0.005) increase in insulin release from pancreatic tissue fragments of normal rat. Stimulation of pancreatic tissue fragments of diabetic rat with NPY resulted in a slight but not significant increase in insulin release. SP induced a large and significant (P < 0.005) increase in insulin secretion from the pancreas of normal rat but inhibited insulin secretion significantly (P < 0.03) from isolated pancreas of diabetic rat. In summary, VIP and NPY can stimulate insulin secretion from the pancreas after the onset of diabetes. The stimulatory effect of SP on insulin secretion is reversed to inhibitory in diabetic rats.

Animals↗
PubMed1988

Experience with OKT3 in vascularized pancreas transplantation.

With refinements in technical aspects of whole organ pancreas transplantation, allograft rejection is currently the major cause of graft failure. The monoclonal antibody OKT3 has emerged as a highly effective antirejection therapy in renal and hepatic allograft recipients, but its efficacy in pancreas transplantation remains to be determined. During a 12-month period, 28 vascularized whole organ pancreas transplants were performed with pancreatico-cystostomy. Sixteen episodes of allograft rejection were treated with monoclonal antibody OKT3. Indications for OKT3 use included steroid- or antilymphocyte globulin (ALG)-resistant allograft rejection in isolated pancreas (n = 8) or simultaneous kidney-pancreas (n = 8) transplants. A total of 34 rejection episodes occurred in the 16 patients (mean, 2.1; range, one to five). The diagnosis of rejection was based on clinical criteria, a reduction in urinary amylase clearance, radionuclide scanning, hyperglycemia, or associated renal allograft dysfunction in combined engraftments. Postoperative immunosuppression consisted of cyclosporine, prednisone, azathioprine, and prophylactic ALG. OKT3 was administered for a full 14-day course concomitant with low-dose steroids, azathioprine, and cyclosporine. The mean age of the patient population was 32.1 years (range 24 to 39) with a mean duration of insulin-dependent diabetes mellitus (IDDM) of 20.9 years. Monoclonal antibody therapy was instituted in two clinical settings: early rejection (within 3 months of transplant, n = 10); and late rejection (after 3 months, n = 6). OKT3 successfully reversed allograft rejection in ten (62.5%) cases, including six early (60%) and four late (66.7%) episodes. In isolated pancreas transplants, OKT3 therapy reversed pancreas allograft rejection in only two patients (25%).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMedDate not supplied

Renal transplantation in diabetic patients is confirmed therapy while pancreas transplantation should be performed only in an investigational setting.

Kidney transplantation is now firmly established as the standard treatment for all diabetic patients with end-stage renal failure. In an analysis of all renal transplants at the University of Minnesota between June 1, 1980 and May 31, 1987, there were no differences in renal allograft functional survival rates for diabetic and nondiabetic recipients. At one year the survival rates were 84% (n = 151) and 86% (n = 260) for those treated with azathioprine, prednisone and ALG; 86% (n = 101) and 87% (n = 104) for those treated with cyclosporine-prednisone, and 92% (n = 165) and 89% (n = 191) for those treated with triple therapy (cyclosporine, azathioprine, and prednisone). Pancreas transplantation remains an investigational procedure for nonuremic diabetic patients but may be considered therapeutic in diabetic renal allograft recipients because such patients are obligated to immunosuppression and only the surgical risks of pancreas transplantation need to be considered, which are now acceptably low. Recipients of pancreas transplants performed simultaneous with the kidney have patient and pancreas graft survival rates of greater than 90% and +/- 60% at several institutions, including our own. The potential for benefit of pancreas transplantation, however, is greater in the nonuremic nonkidney transplant patient, and pancreas transplantations are being performed in such patients at a few institutions. An early beneficial effect of pancreas transplantation preexisting proliferative retinopathy has not been discerned, although long-term retinopathy has been stable in patients with functioning grafts. Preliminary studies have shown a beneficial effect on neuropathy and on microscopic lesions of diabetic nephropathy, but at the expense of cyclosporine toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus, Type 1↗