Renal transplantation for type II diabetic patients compared with type I diabetic patients and patients over 50 years old: a single-center experience.

INTRODUCTION: Transplantation of renal allografts for Type II diabetic patients has become increasingly common. Like Type I diabetics and patients over age 50, Type II diabetics are in a high-risk category for renal transplantation. Some investigators argue that the scarce resources of the valuable donor pool should not be allocated to these high-risk, older individuals with end-stage renal disease (ESRD) who often have significant comorbidity. We studied the outcome of renal transplantation for 90 Type II diabetics and compared it with the outcome for Type I diabetics and patients over age 50 with other primary diseases. METHODS: We conducted a retrospective review of data on all renal transplants performed at the University of Minnesota since September 1984 for Type II diabetics. We analyzed both patient and graft survival rates and compared them with the outcome for Type I diabetics and separately for all nondiabetics over age 50. We grouped recipients by donor source (living vs. cadaver) and age at transplant (< 50 vs. > 50). We studied reasons for graft loss, patient death, pre-operative morbidity, and post-operative complications. RESULTS: We found that recipient age and donor source did not affect outcome. Overall 5-yr patient survival for Type II diabetics was 61%; graft survival, 53%. Type II diabetics had significantly worse patient and graft survival than Type I diabetics and than nondiabetics over age 50. However, death-censored graft survival was not different between these groups, suggesting little difference in immunologic graft loss. CONCLUSIONS: Renal transplantation is a relatively safe, viable option for Type II diabetics with ESRD and significant comorbidity. Although their overall graft survival is less than for Type I diabetics and for nondiabetics over age 50, the immunologic graft failure rate is the same in all three groups.

The effect of hypercholesterolemia on the rabbit transarterial wall oxygen gradient.

The objective of this study was to determine the effect of hypercholesterolemia on the transarterial wall oxygen gradient. Female New Zealand white rabbits (3-4 kg) were fed a 0.5% cholesterol supplemented diet or a 0.25% cholesterol supplemented diet and their transarterial wall oxygen gradients measured prior to the formation of atherosclerotic lesions at 4 weeks (0.5% cholesterol group) or 8 weeks (0.25% cholesterol diet) after beginning the diet. Arterial blood oxygen content and arterial blood pressure were recorded during the experiments. Control rabbits had a serum cholesterol level of 52.8 +/- 6 mg/dl, rabbits fed the 0.25% cholesterol diet had serum cholesterol levels of 579.5 +/- 29.2 mg/dl, and those fed the 0.5% cholesterol diet had serum cholesterol levels of 1235.4 +/- 37.6 mg/dl. There was no difference in the transarterial wall oxygen gradients between any of the groups. These results were noted with no differences in arterial blood oxygen content, arterial blood pressure, or evidence of atherosclerotic lesions. Hypercholesterolemia does not alter the delivery of oxygen to the artery wall prior to the formation of atherosclerotic lesions.

Posttransplant nonfunction of canine islets in PVG rats deficient in complement component C6.

BACKGROUND: Discordant islet xenografts are immediately nonfunctional in nonimmunosuppressed recipients other than the mouse, a process called primary nonfunction. Although at present it is unknown whether complement is involved, complement might participate in the induction of primary nonfunction through a number of mechanisms. We investigated the potential role of the membrane attack complex of complement in primary nonfunction of transplanted xenoislets. METHODS: Canine islets were transplanted into both nonimmunosuppressed and immunosuppressed normocomplementemic and C6-deficient (C6D) PVG rats. Cyclosporine, rapamycin, deoxyspergualin, and mycophenolate mofetil were used for immunosuppression from day -3 to cessation of islet cell function. Serum glucose was measured at 6 hr after transplant and daily thereafter. Xenograft tissue sections were obtained at various times after transplant and stained for inflammatory cells and insulin. RESULTS: Canine islets grafted in nonimmunosuppressed C6D rats and normocomplementemic rats underwent primary nonfunction in all animals. The incidence of primary nonfunction in animals receiving a four-drug immunosuppressive regimen was 33% in the normocomplementemic rats but only 10% in the C6D rats. The mean functional islet survival time was 1.57+/-0.33 days in the normocomplementemic group and 2.70+/-0.67 days in the C6D group (P=0.38). The islet xenografts showed little difference in degree and composition of cell infiltration between normocomplementemic and C6D rats. CONCLUSION: The membrane attack complex does not appear to play a major role in primary nonfunction of canine islet xenografts in nonimmunosuppressed PVG rats. However, there was a lower incidence of primary nonfunction and a longer posttransplant survival time in immunosuppressed C6D rats, suggesting the membrane attack complex may play a minor role in recipients that are heavily immunosuppressed.

Cigarette smoking alters the rabbit transarterial wall oxygen gradient.

The objective of this study is to determine the effect of short-term (3 weeks) and long-term (10 weeks) cigarette smoking on the transarterial wall oxygen gradient. Female New Zealand White Rabbits (3-4 kg) were exposed to the smoke of seven nonfiltered cigarettes daily and their transarterial wall oxygen gradients measured at 3 weeks or 10 weeks before and during cigarette smoke exposure. Arterial blood oxygen content, percent of carboxyhemoglobin, and arterial blood pressure were recorded during the experiments. Short-term cigarette smoking resulted in a decrease in the artery wall oxygen content only during exposure to cigarette smoke that corresponded to arterial blood hypoxia. Long-term cigarette smoke exposure resulted in a sustained decrease in artery wall oxygen content noted 24 hours after last exposure to cigarette smoke with normal levels of arterial blood oxygen and an acute decrease during cigarette smoke exposure with corresponding arterial blood hypoxia. These results were noted despite no differences in blood pressure or evidence of atherosclerotic lesions. Short-term cigarette smoking results in artery wall hypoxia only during cigarette smoke exposure and arterial blood hypoxia while long-term cigarette smoking results in sustained artery wall hypoxia in the presence of normal arterial blood oxygen content.

Excellence of the two-layer method (University of Wisconsin solution/perfluorochemical) in pancreas preservation before islet isolation.

BACKGROUND: In islet transplantation pancreatic preservation before islet isolation is an obstacle compromising islet yield and viability. We tested the feasibility of a two-layer method (University of Wisconsin solution [UW]/perfluorochemical) for pancreatic preservation before islet isolation. METHODS: Dog pancreases were processed into pure islets by the method of Ricordi preceded by five different preservations (groups 1-a and 1-b, the two-layer method for 3 and 24 hours; groups 2-a and 2-b, simple cold storage in UW for 3 and 24 hours; group 3, without preservation). Islet yields and functional success after autotransplantation into the liver were compared among the groups. RESULTS: Postpurification islet equivalents (IE)/gm pancreas and functional success rate were 5600 (mean), 83% in group 1-a; 4000, 56% in group 1-b; 4700, 33% in group 2-a; 1300, 0% in group 2-b; and 5000, 89% in group 3 (p < 0.05; 2b versus 1-a, 1-b, and 3), respectively. There was no statistical difference among groups 1-a, 1-b, and 3 in terms of islet yield and function (p > 0.2). CONCLUSIONS: The two-layer method is more effective than conventional simple cold storage in UW for pancreatic preservation before islet isolation. Clinical trials with the two-layer method are warranted.

Effect of pancreatic warm ischemia on islet yield and viability in dogs.

BACKGROUND: Defining tolerable warm ischemia (WI) is mandatory before nonheartbeating cadavers can be used to enlarge the donor pool. No studies to date have precisely evaluated the effect of pancreatic WI on islet yield and viability in a large animal model. METHODS: We used mongrel dogs in our study at the University of Minnesota. Excised pancreases were left in situ for a designated period (0, 30, 45, and 60 min in groups 1 to 4, respectively) of WI. Then, they were digested by the automated collagenase digestion method of Ricordi, purified on Euro-Ficoll discontinuous gradients with the COBE cell processor, and autotransplanted into the liver via a mesenteric vein. We compared the four groups in terms of islet yield, expressed as islet equivalents (IE; diameter standardizing to 150 microm) per pancreas weight (IE/g pancreas), and viability, assessed by functional success (maintenance of normoglycemia for 2 weeks) after transplant. RESULTS: Mean islet yield (+/- SD) and the functional success rate after transplant were as follows: 6200+/-1800 IE/g pancreas and 4 of 4 (100%) in group 1; 6300+/-4400 and 4 of 4 (100%) in group 2; 3800+/-2600 and 2 of 4 (50%) in group 3; and 1400+/-1300 and 0 of 4 (0%) in group 4 (P=0.01 vs. group 1). CONCLUSIONS: With 30 min or less of WI, there are no deleterious effects on islet yield and viability. However, with periods of WI longer than 30 min, the loss in islet yield is severe, resulting in functional failure after autotransplantation. The limit of WI that is tolerable for islets is shorter than for a whole pancreas.

Arterial anatomic considerations in colon interposition for esophageal replacement.

BACKGROUND: Little has been written regarding the arterial anatomy predictive of success following esophagectomy and colon interposition. DESIGN: Retrospective review. SETTING: University teaching hospital. PATIENTS: Twenty-five patients undergoing planned left colon interposition. INTERVENTION: Colon interposition was performed via an isoperistaltic left colon graft based on the ascending branch of the left colic artery. MAIN OUTCOME MEASURES: Five angiographic features were considered important to successful use of the left colon: (1) a patient inferior mesenteric artery, (2) a visible ascending branch of the left colic artery, (3) a well-defined anastomosis between the middle colic and left colic systems, (4) a single middle colic trunk prior to its division into right and left branches, and (5) a separate origin of the right colic artery. Venous drainage via a patent marginal vein, inferior mesenteric vein, and superior hemorrhoidal veins was preserved in all patients. RESULTS: Left colon interposition could be performed in 21 (84%) of 25 patients. Eighty percent of the patients (20/25) had at least four of the five criteria thought necessary for optimal graft perfusion. Three or fewer criteria were present in five patients, three of whom underwent gastric interposition. The inferior mesenteric artery was patent in all patients except one who required a right colon interposition. Ninety-two percent (23/25) demonstrated an adequate ascending left colic artery. The superior-inferior mesenteric artery anastomosis was seen in 52% (13/25). A single-trunked middle colic artery was present 80% (20/25) of the time. A single incidence of graft necrosis occurred secondary to venous insufficiency. Ninety-six percent of patients (24/25) were able to swallow without difficulty at the time of discharge from the hospital. CONCLUSIONS: Replacement of the esophagus with colon can be successful in over 80% of patients screened by angiographic criteria. Patients with an occluded or stenotic inferior mesenteric artery or variant middle colic arterial anatomy should undergo an alternate reconstruction.