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Biomedical subjects

C Berne

Publications and source records attributed to C Berne.

185 records · Page 11Linked to original sources

Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation.

BACKGROUND: Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. METHODS: Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. FINDINGS: Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor VIIa, a candidate drug for inhibition of TF activity in vivo. INTERPRETATION: Blockade of TF represents a new therapeutic approach that might increase the success of islet transplantation in patients with type 1 diabetes, in terms of both the risk of intraportal thrombosis and the need for islets from more than one donor.

Adult↗

Decreasing insulin requirements in CAPD patients given intraperitoneal insulin.

In a retrospective study, insulin requirements were examined in two groups of dialyzed diabetic patients: one treated with subcutaneous insulin and the other with intraperitoneal insulin. In the first group, insulin requirements did not change with time on dialysis irrespective of whether the patients were treated with hemodialysis or continuous ambulatory peritoneal dialysis (CAPD); however, in CAPD patients using the intraperitoneal route of administration, a significant decrease in insulin requirements occurred simultaneously with improved metabolic control. This observation may indicate that intraperitoneal administration of insulin is advantageous as compared to the subcutaneous route.

Adult↗

Pregnancy outcome and infant mortality in diabetic patients in Sweden.

Between 1983 and 1986, 914 single births to women with diabetes mellitus before pregnancy and a randomly selected control sample of 4000 births were identified by using the Swedish Medical Birth Registry. Twenty-four percent of diabetic women were delivered preterm, as compared with 6% in the control group. The rates of late fetal death were a 1.3% among infants born to women with diabetes and 0.4% in the control group. Infant mortality was 0.9% and 0.5% among infants to mothers with and without diabetes mellitus, respectively. The increased rates of late fetal and infant deaths in the diabetes group were largely explained by higher mortality in the more prevalent preterm deliveries. Fourteen of 20 late fetal and infant deaths occurred among preterm infants in diabetic pregnancies, while in the control group, 17 of 33 late fetal and infant deaths occurred among preterm infants. Elimination of the increased rates of late fetal death and congenital malformation in diabetic pregnancy is required to meet the goals of the St Vincent Declaration. A nation-wide registry of diabetic pregnancy outcomes is feasible and necessary for further quality assurance of diabetic pregnancies.

Adolescent↗

Insulin wastage in ambulant practice.

The total insulin consumption in 162 insulin-requiring diabetic patients was calculated from the prescriptions of purchased insulin for 1979-80. The mean daily consumption was 58.6 U, whereas the actual dose injected was 41.7 U. A mean of 1.9 doses was injected daily, which yields a loss per dose of 8.9 U (SD +/- 7.9). The dose loss was independent of age and sex and only marginally dependent on insulin dose. Visual impairment increased the loss. From a direct study of 101 patients while drawing their usual morning dose of insulin into the syringe, the following major factors underlying insulin wastage emerged: (1) expulsion of surplus insulin into the air instead of into the vial, when adjustment of the insulin dose is made; (2) use of syringes with a separate needle instead of new low-dead-space syringes; and (3) unnecessary use of 2-ml syringes for doses of insulin less than or equal to 40 U (less than or equal to 1 ml).

Adolescent↗

How accurate are insulin mixtures prepared by the patient?

The accuracy of mixing two types of insulin in one syringe was studied in 41 insulin-dependent diabetic patients who prepared a mixture of two fluids (saline and sterile water) with either a disposable, 1-ml plastic syringe with a fixed needle, i.e., with a small dead space, or one equipped with a separate needle. Syringes with fixed needles delivered the two components very accurately and were associated with only slight wastage of insulin of 0.011 ml per injection. The syringe with a separate needle delivered 0.033-0.065 ml more than the intended dose of the "first insulin" and correspondingly less of the intended dose of the "second insulin," since the total dose delivered was approximately correct. The magnitude of the insulin wastage of two daily injections was calculated to be 64 ml per patient annually, which could be reduced to 8 ml per patient if fixed needles were used. It is therefore recommended that patients preparing mixtures of two insulins in the same syringe abandon syringes with separate needles.

Adult↗