BACKGROUND: Transplantation of pancreatic islets, rather than whole pancreas, has been introduced as a treatment for diabetes mellitus. We studied five patients ranging in age from 12 to 37 years who had severe chronic pancreatitis for which they underwent total pancreatectomy followed by isolation and hepatic transplantation of their own islets. METHODS: All patients had remained insulin-independent for 1 to 7 1/2 years after transplantation. The numbers of islets transplanted ranged from 110,000 to 412,000. Islet function was assessed by measuring the plasma insulin responses to intravenous glucose and arginine and the plasma glucagon responses to hypoglycemia and arginine. In one patient, islet function was studied during catheterization of the hepatic vein, portal vein, and splenic artery and by analysis of a liver-biopsy specimen. RESULTS: After transplantation, the mean (+/- SD) fasting plasma glucose concentration was 122 +/- 47 mg per deciliter (6.8 +/- 2.6 mmol per liter) and the hemoglobin A1c concentration was 6.0 +/- 0.8 percent in the five patients. The values were most abnormal--214 mg per deciliter (11.9 mmol per liter) and 7.3 percent, respectively--in the patient who received only 110,000 islets. The acute plasma insulin responses to glucose and to arginine in the five patients were 23 +/- 13 and 26 +/- 10 microU per milliliter (168 +/- 94 and 184 +/- 70 pmol per liter), respectively, as compared with 58 +/- 6 and 37 +/- 8 microU per milliliter (416 +/- 44 and 267 +/- 61 pmol per liter) in the normal subjects. The peak plasma glucagon responses to insulin and arginine were 21 +/- 4 and 65 +/- 36 pg per milliliter, respectively, as compared with 125 +/- 28 and 156 +/- 99 pg per milliliter in the normal subjects. All five patients had plasma epinephrine but not pancreatic polypeptide responses to hypoglycemia. The results of the hepatic-vein catheterization in one patient indicated that the transplanted islets released insulin and glucagon in response to arginine. Immunoperoxidase staining of this patient's liver-biopsy specimen showed that the islets contained insulin, glucagon, and somatostatin but not pancreatic polypeptide. CONCLUSIONS: Intrahepatic transplantation of as few as 265,000 islets can result in the release of insulin and glucagon at appropriate times and in prolonged periods of insulin independence.

Adolescent↗

PubMed1992

Analysis of infectious complications occurring after solid-organ transplantation.

To improve our understanding of posttransplant infections, we analyzed bacterial, viral, fungal, parasitic, and other infections in 604 consecutive recipients of kidney (n = 518), kidney-pancreas (n = 82), kidney-liver (n = 3), or kidney-islet (n = 1) allografts (355 cadaveric, 14 living-unrelated, 235 living-related donors) who also received cyclosporine, azathioprine, and prednisone immunosuppression. Recipients of cadaveric grafts received additional induction immunosuppression (antilymphocyte globulin or murine monoclonal antibody OKT3). Rejection episodes were treated with high-dose steroids, and either antilymphocyte globulin or OKT3 was administered when clinically indicated. Perioperative antibiotics and posttransplant prophylactic acyclovir sodium or ganciclovir sodium, trimethoprim-sulfamethoxazole, and clotrimazole or nystatin (Mycostatin) were administered to all recipients. Two hundred thirteen patients (35.3%) were found to have had no identifiable infections, while 391 (64.7%) had either isolated bacterial (97 [16.1%]), viral (53 [8.8%]), or fungal (34 [5.6%]) infections or combination (concurrent or sequential) infections with bacterial plus viral (46 [7.6%]), bacterial plus fungal (66 [10.9%]), viral plus fungal (20 [3.3%]), bacterial plus viral plus fungal (64 [10.6%]), or bacterial plus viral plus fungal plus parasitic (11 [1.8%]) pathogens in the posttransplantation period. Renal allograft survival (percentage, actuarial method) was diminished in patients with infections at both 1 year (91% vs 83%) and 3 years (81% vs 76%) after transplantation, as was actuarial patient survival (1 year, 97% vs 92%; 3 years, 93% vs 88%). We conclude that infection remains a major cause of both patient demise and allograft loss following successful solid-organ transplantation.

Adolescent↗

PubMed1992

Toxic effect of ethylene-oxide-sterilized freeze-dried bone allograft on human gingival fibroblasts.

Freeze-dried bone allograft (FDBA) which either had or had not been sterilized by exposure to ethylene oxide (EtO) prior to lyophilization was obtained from two commercial sources. EtO-sterilized FDBA was reexposed to EtO as a positive control. Gas chromatograph assays revealed that three out of four commercially obtained EtO sterilized FDBA had no detectable EtO, with one sample having 0.21 parts per million (PPM). Surprisingly, 0.24 PPM was detected in one sample which had not been sterilized with EtO gas. This was presumed due to contamination from a gas-sterilized rubber stopper. In the cell toxicity study, FDBA and human gingival fibroblasts (HGF) were added simultaneously, incubated for 72 h, and fixed and stained. Samples of FDBA sterilized with EtO which were free of EtO did not alter HGF growth. However, the positive control FDBA which contained 0.72 PPM EtO had a deleterious effect on HGF. FDBA with EtO residuals caused morphologic change in HGF.

Bone Transplantation↗

PubMed1992

Pancreas transplantation: indications and outcomes.

Explore the source record for details and available documents.

Diabetes Mellitus, Type 1↗

PubMed1992

Successful 96-Hr cold-storage preservation of canine pancreas with UW solution containing the thromboxane A2 synthesis inhibitor OKY046.

Prostanoids, such as prostacyclin (PGI) and thromboxane A2 (TxA), have been recently suggested to play an important role in preservation-induced injury of pancreas grafts. We have previously shown that the TxA synthesis inhibitor OKY046 prevents a decrease of both the PGI/TxA ratio and blood flow in pancreas grafts after 24-hr preservation with Euro-Collins solution. In our present study, we analyzed whether OKY046 added to University of Wisconsin (UW) solution could extend successful cold-storage preservation of segmental canine pancreas grafts, compared with UW alone. We divided 30 dogs into four preservation groups: Group 1, UW solution for 72 hr (n = 7); Group 2, UW solution for 96 hr (n = 8); Group 3, UW solution plus OKY046 (10(-4) M) for 72 hr (n = 7); and Group 4, UW solution plus OKY046 (10(-4) M) for 96 hr (n = 8). After the cold storage period, segmental pancreas auto-transplantation with immediate completion pancreatectomy was done. Preservation was deemed successful if serum glucose less than 150 mg/dl was maintained for at least 5 days. Intravenous glucose tolerance tests and biopsies were done in those dogs with functioning grafts 14 days post-transplant. Successful preservation rates were as follows: Group 1, 57.1%; Group 2, 12.5%; Group 3, 100%; and Group 4, 75%. The mean K values (+/- standard error) were: Group 1, 1.54 +/- 0.13; Group 2, 0.59; Group 3, 1.54 +/- 0.14; and Group 4, 1.59 +/- 0.24 (not statistically different).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Prolongation of canine islet allograft survival by 15-deoxyspergualin.

Previously we have shown that nonsteroidal, multimodal immunosuppression consisting of cyclosporine (CsA), azathioprine (AZA), and RBC-absorbed goat anti-dog lymphoblast globulin (ALG), at doses considered tolerable in humans, results in limited canine islet allograft survival. Regimens including the diabetogenic agent prednisone are even less successful. In our search for an immunosuppressive regimen that could be applied to human islet transplantation, we tested the effect of 15-deoxyspergualin (DSG) in a canine model. Animals received either CsA, 20 mg/kg/day; AZA, 2.5 mg/kg/day; and ALG, 20 mg/kg/day x 14 days (Group I) or CsA, AZA, ALG at the same doses with the addition of low dose DSG, 0.5 mg/kg/day (Group II). Trough CsA levels by high pressure liquid chromatography ranged in both groups between 100 and 200 micrograms/liter. Rejection of the islets was diagnosed when serum glucose remained greater than 200 mg/dl for 3 consecutive days. There was no significant difference in the number of islets per kilogram of body weight of recipient transplanted in Group I and Group II (5754 +/- 2544 islets/kg versus 7953 +/- 3440 islets/kg, respectively). Animals receiving ALG, CsA, and AZA alone achieved a median islet allograft survival of 4 days, with a mean of 10.8 days. However, with the addition of low-dose DSG, median islet allograft survival was improved to 22 days, with a mean of 32.4 days (P = 0.012, Mann-Whitney test). We conclude that the addition of low-dose DSG to an ALG induction, cyclosporine-based immunosuppressive regimen enhances canine islet allograft survival and has potential for application in clinical islet allotransplantation.

Animals↗

PubMed1992

Relationship of systemic blood pressure to nephropathology in insulin-dependent diabetes mellitus.

Although hypertension is an important complication of diabetes it is unclear whether its association with other diabetic complications represents cause or consequence. Our study is a cross sectional evaluation of the relationship of blood pressure to renal structural and functional parameters. In 139 patients with insulin dependent diabetes for 18.9 +/- 7.4 years (mean +/- SD), we divided the patients into those with markedly increased mesangial volume fraction [Vv(mes/glom) greater than or equal to 0.37] and those with less [Vv(mes/glom) less than 0.37]. Hypertension (systolic BP greater than or equal to 160 and/or diastolic BP greater than 90 mm Hg or receiving BP medications) occurred in 29/40 with Vv(mes/glom) greater than or equal to 0.37. All 40 had clinical nephropathy with urinary albumin excretion (UAE) greater than 200 mg/24 hr. By two-way ANOVA creatinine clearance was lower and albuminuria was increased with both hypertension and the expanded mesangium. Also other measures of renal structure including filtration surface, index of interstitial fibrosis and index of arteriolar hyalinosis were increased by hypertension and mesangial expansion. Most patients with hypertension had other criteria for clinical nephropathy. Since, in these studies, we could not determine if hypertension contributed to or resulted from the renal lesions, we developed an estimate of the rate of mesangial expansion. We found that patients with normal BP (119 +/- 11/78 +/- 7 mm Hg) can be rapidly developing mesangial expansion. These studies support the view that the development of serious renal lesions can be independent of hypertension in IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Simultaneous pancreas-kidney transplant versus kidney transplant alone in diabetic patients.

The decision for simultaneous pancreas-kidney (SPK) versus kidney transplant alone (KTA) in diabetic patients with renal failure depends on the potential risks and benefits for each procedure. The purpose of this study was to compare the morbidity, mortality, and renal allograft survival in diabetic patients who underwent SPK versus KTA, and to discern the added risks associated with pancreas transplantation. Between 7/1/86 and 9/30/90, 69 primary cadaver SPK and 59 primary cadaver KTA were performed in type I diabetic patients with chronic renal failure. Antilymphocyte globulin or OKT3 was used for induction therapy, followed by standard triple therapy (prednisone, azathioprine, and cyclosporine). Patient and graft survivals were retrospectively analyzed. In addition, a detailed comparison of morbidity in those patients treated after 7/1/87 was performed (53 SPK, 49 KTA). For those less than 45 years of age (65 SPK, 42 KTA), there were no significant differences (P greater than 0.6) in the actuarial patient survival at one year (SPK 92%, KTA 95%), or two years (SPK 89%, KTA 92%), or actuarial renal allograft survival at one year (SPK 82%, KTA 83%) or two years (SPK 77%, KTA 83%). However, for those greater than 45 years old, actuarial renal allograft survival was significantly higher (P less than 0.03) in the KTA group. The mean serum creatinine levels were similar at one year (SPK 1.8, KTA 1.9 mg/d).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗