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Biomedical subjects

D E Sutherland

Publications and source records attributed to D E Sutherland.

At least 559 records · Page 31Linked to original sources
PubMed1986

Circadian stage-dependent prolongation by cyclosporine of segmental pancreatic allograft function in the rat.

While the toxicity of many drugs has been reduced by their administration at certain circadian rhythm stages (if not at certain times of day), as shown herein, direct therapeutic benefit from the improvement of the desired effect can be obtained by the circadian timing of intraperitoneal cyclosporine (Cs) for Lewis rats bearing an ACI segmental pancreas allograft. Under conditions of light (L) and darkness (D) alternating at 12-hour intervals, staggered by 8 h in 3 rooms kept at 24 degrees C, the effect of Cs in delaying graft rejection was improved by timing. When the mean time to rejection during the L span is equated to 100%, graft function is prolonged by 40% at the right time (injection daily during the D span) as compared to the wrong time (injection daily during the L span).

Animals↗
PubMed1986

Comparison of two methods of islet preparation and transplantation in dogs.

Seventy-nine mongrel dogs underwent total pancreatectomy. Fifteen dogs served as apancreatic controls and died 7.0 +/- 4.2 days later (mean +/- SD). The pancreases of 44 dogs (group 1) were intraductally distended by manual injection of Hanks' balanced salt solution (HBSS). Thereafter each organ was mechanically disrupted and subjected to collagenase digestion as described by Mirkovitch et al. The pancreases of 20 dogs (group 2) were intraductally distended and subsequently perfused with collagenase by a roller pump. The organs were then mechanically disrupted and filtered through screens as described by Horaguchi et al. The resulting tissue suspensions were injected into the spleens of the dogs as autotransplants in both groups, by direct punction of the splenic capsule in group 1 and by retrograde infusion via a splenic vein tributary in group 2. The functional outcome was better in group 2 than in group 1, as assessed by the number of animals that became normoglycemic after transplantation [15/20 (75%) vs. 13/44 (30%); P = .0025]. The degree of islet purification, as measured by an increase in the tissue insulin/amylase ratio, was higher in group 2, and in both groups it was higher in normoglycemic than in hyperglycemic animals. The percent engraftment [i.e., amount of insulin recovered from spleen as percent of tissue transplanted (mean, 15.4% in group 1 and 14.5% in group 2) or as percent of original pancreas (mean, 4.9% in group 1 and 4.4% in group 2)] was low in both groups but again was higher in normoglycemic than in hyperglycemic animals within each group. In conclusion, both the degree of engraftment and purification and the route of implantation influenced the functional outcome after dispersed pancreatic islet autotransplantation to the spleen of totally pancreatectomized dogs, with purified tissue injected retrogradely functioning better than unpurified tissue injected directly.

Amylases↗
PubMed1986

Relationship of muscle capillary basement membrane to renal structure and function in diabetes mellitus.

Muscle capillary basement membrane (MCBM) thickening has been considered to reflect microvascular changes in other tissues in diabetes mellitus. To explore the relationships between MCBM width and nephropathy, 27 patients aged 22-55 yr with type I diabetes for 14-33 yr were studied with creatinine clearances, urinary albumin excretion rates, multiple blood pressure measurements, glycosylated hemoglobin measurements, and renal and quadriceps muscle biopsies that were evaluated using standard stereologic techniques. MCBM width did not correlate with age, duration of diabetes, creatinine clearance, urinary albumin excretion, or fractional volume of the glomerular mesangium. MCBM width did correlate, although weakly, with glomerular basement membrane width (r = 0.47) and glycosylated hemoglobin (r = 0.44). There was no difference in MCBM width between patients with and without clinical nephropathy. Patients with normal fractional volume of mesangium exhibited a full range of MCBM width. Thus, while MCBM width may reflect glycemic control and glomerular basement membrane thickening, it does not relate to the functional or structural renal changes associated with progressive diabetic nephropathy.

Adult↗
PubMed1986

Current status of clinical pancreas transplantation.

Pancreas transplantation (PT) has become increasingly effective for the treatment of human diabetes. Islet transplants have been successful only in the laboratory; clinical human islet transplantation needs to be improved with a search to reduce islet cells immunogenicity. Up to now, the only effective method of endocrine replacement therapy in diabetic patients is vascularized pancreas transplantation. Analysis of the International Human Pancreas Registry shows that the best options in 1985 are enteric diversion of the exocrine function, simultaneous kidney graft from the same donor and cyclosporin combined with other immunosuppressive agents in the recipient.

Azathioprine↗
PubMed1986

[Status of clinical pancreas transplantation].

Since 1977 and especially within the latest 5 years there was a volatile development in the pancreas transplantation. If we had only 60 transplants between 1966-1977, prevalent duodeno-pancreas-transplants, the cases rose to 215 up to 1982 and to 447 transplantations between 1983 to 1985. Altogether there were 722 pancreas transplants, up to November, 15, 1985 registered. Before 1977 only 2 patients had a 1 year function rate of the transplant and of the 447 transplantations within the latest 3 years 201 transplants functioned more than 12 months. That was a 1-year function rate of 45% in contrast to 3% before 1977. The clear improvement of the results in pancreas transplantation can be attributed to operative aspects and to the employment of Cyclosporine A. The segmental pancreas transplantation with duct occlusion and intestinal or external drainage of the duct system were the most sure operative procedures. The combination of Azathioprine and Cyclosporin A brought with a 1-year function rate of 54% better results in comparison to the singular application of Azathioprine (22%) and Cyclosporin A (41%). The simultaneous pancreas-kidney transplantation had a 1-year function rate of 39%, the pancreas transplantation after kidney of 31% and the pancreas transplantation alone of 20%.

Azathioprine↗
PubMed1985

Studies of kidney and muscle biopsy specimens from identical twins discordant for type I diabetes mellitus.

To distinguish metabolic from genetic factors in the development of microangiopathy in diabetes, we evaluated biopsy specimens of kidney and quadriceps muscle from seven pairs of identical twins who were discordant for Type I (insulin-dependent) diabetes mellitus. Two of the diabetic patients had clinical diabetic nephropathy, including hypertension, marked albuminuria, and a substantially reduced creatinine clearance; the other five had normal renal function and only minor clinical indications of complications. All the twins of the diabetic patients had normal glomerular basement membrane widths and normal fractional volumes of the glomerular mesangium. Values for glomerular basement membrane width, tubular basement membrane width, and mesangial volume in each diabetic twin exceeded the values in the respective sibling (P less than or equal to 0.0035), even if the value in the diabetic twin lay within established normal ranges. Values for muscle capillary basement membrane width in the diabetic twins did not differ from those in their siblings (P = 0.5). Our observations suggest that the metabolic abnormalities of diabetes are necessary, if not sufficient, for the development of glomerular abnormalities. We also conclude that in diabetic patients, alterations in muscle capillary basement membrane width do not necessarily accompany pathologic lesions in the kidney.

Adult↗
PubMed1985

Relationship of renal size to nephropathy in type 1 (insulin-dependent) diabetes.

Thirty-five patients with Type 1 (insulin-dependent) diabetes mellitus and 90 normal subjects had renal size (renal area index) determined by X-ray and also had examination of renal biopsies by light and electron microscopy. Renal area index of 206 +/- 32 cm2/1.73 m2 (mean +/- SD) in the Type 1 diabetic patients exceeded that in the normal subjects (180 +/- 25 cm2/1.73 m2, p less than 0.001). In the diabetic patients, the renal area index correlated with creatinine clearance (r = +0.43, p less than 0.05), but did not correlate with urinary albumin excretion, or the electron microscopic measurements of percentage total mesangium and glomerular basement membrane width. In diabetic patients with clinical nephropathy or severe glomerulopathy on biopsy, the kidneys may remain large. Thus, renal size does not indicate the severity of diabetic renal lesions on biopsy.

Adolescent↗
PubMed1985

Effect of a cyclic hexapeptide analog (L363,586) of somatostatin on the function of pancreas grafts in dogs.

Complications related to the exocrine secretions cause some pancreas grafts to fail in the early postoperative period. Somatostatin inhibits exocrine secretion, as well as insulin and glucagon release. L363,586 is a cyclic hexapeptide analog of somatostatin that is 50 to 100 times more potent than the native hormone in inhibiting islet hormone release. In a preliminary experiment in which permanent fistulas were created in two dogs, we demonstrated that L363,586 (0.3 micrograms/kg/60 min) results in a fourfold decrease in pancreatic exocrine secretion when measured for 210 min following a beef meal. In a separate experiment, five totally pancreatectomized dogs who received segmental pancreas autografts with pancreaticoductocystostomy 10 months previously had L363,586 (0.3 micrograms/kg/hr) administered by the Alzet osmotic pump subcutaneously for 7 days. Mean (+/-SE) daily serum amylase activity (IU/dl) during the week before the implant was 78 +/- 3, during the week of infusion was 65 +/- 2 (P less than 0.001), and during the week afterward was 76 +/- 2. In a prospective experiment, 12 totally pancreatectomized dogs received segmental pancreas autografts with anastomosis of the graft vessels to the iliac vessels and of the pancreatic duct to the bladder. L363,586 was administered by osmotic pump for 7 days to seven dogs at a dose of 0.3 micrograms/kg/hr. Mean (+/-SE) daily serum amylase levels at 1, 2, and 3 weeks posttransplant were 223 +/- 17, 81 +/- 3, and 82 +/- 5 in the L363,586-treated dogs and 229 +/- 18, 108 +/- 5, and 90 +/- 5 in the five untreated dogs (P less than 0.001 at 2 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)

Amylases↗