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Biomedical subjects

J Ostman

Publications and source records attributed to J Ostman.

At least 163 records · Page 9Linked to original sources

Segmental pancreatic transplantation with duct ligation or drainage to a jejunal Roux-en-Y loop in nonuremic diabetic patients.

The results of seven segmental pancreas transplantations in diabetic patients, using a jejunal Roux-en-Y loop for drainage of digestive enzymes, are presented. An initial case with pancreatic duct ligation is also included. The patients ranged in age from 30 to 45 yr, with duration of diabetes from 8 to 24 yr, and were incapacitated but not uremic. Immunosuppression was attempted with azathioprine, prednisone, and antilymphocyte globulin, and, in one patient, thoracic duct drainage was added. The pancreas tolerated at least 16 min of warm ischemia and at least 4 h of cold storage; flushing with a balanced electrolyte solution was optimal. Six of the grafts provided control of blood glucose for 7--51 days, and, in one patient, an intravenous glucose tolerance test was normal at 7 and 21 days. Five of the grafts failed due to rejection 7--51 days after transplantation, and one was removed at 14 days, while still functioning, due to bleeding. In one case, early detection of rejection by a rise in post-prandial blood glucose was treated and reversed by corticosteroid administration. Two failed in the immediate postoperative period from vascular thrombosis. Drainage of pancreatic secretions from a fistula was a common problem.

Adult↗

Transplantation of fetal pancreatic microfragments via the portal vein to a diabetic patient.

Human fetal pancreas preserved in culture was used as a donor organ in a 45-yr-old man with diabetes of 14-yr duration complicated by severe retinopathy and nephropathy. Renal failure had been successfully treated by a cadaveric renal transplant 2 yr earlier. Six fetal pancreases, obtained within 30 min of delivery after prostaglandin-induced abortion at 14--20 wk of gestation, were minced and placed in tissue culture for 3 h at the earliest and 15 days at the longest duration. The cultures were harvested 2--3 h before transplantation. Approximately 3 ml of tissue was infused into a right portal vein branch. Azathioprine was continued at 2 mg/kg and prednisolone increased from 10 mg to 100 mg/day on the day of transplantation and gradually reduced to 25 mg/day. Only two doses of antilymphocytic globulin were given because of a severe reaction. During the 40 days since transplantation, insulin requirements have not changed, but C-peptide has appeared in the urine, suggesting function of the transplanted tissue.

C-Peptide↗

Influence of adipocyte isolation by collagenase on phosphodiesterase activity and lipolysis in man.

The maximum phosphodiesterase activity (Vmax) with low and high Km was, respectively, 10- and 3-times greater in tissue fragments than in collagenase-isolated adipocytes obtained from subcutaneous fat layers in man. The exposure of such tissue fragments to collagenase of various origins in order to isolate the fat cells resulted in a 60-70% inhibition of phosphodiesterase (PDE) activity. Noradrenaline- and isopropyl noradrenaline-induced rates of lipolysis were more rapid in the isolated fat cells than in the tissue fragments. The sensitivity to catecholamines, however, was the same for the two tissue preparations. Nor did they differ in respect to the effect of theophylline, a PDE inhibitor, on the rate of lipolysis. The time curve for cyclic AMP accumulation was significantly higher in the isolated adipocytes than in tissue fragments in the presence of isopropyl noradrenaline. It is concluded that the greater lipolytic response of collagenase-isolated adipocytes than of tissue fragments to catecholamines may be attributed, at least in some measure, to the higher concentration of cyclic AMP resulting from a decrease in PDE activity.

3',5'-Cyclic-AMP Phosphodiesterases↗

Relationship between lipolysis, cyclic AMP, and fat-cell size in human adipose tissue during fasting and in diabetes mellitus.

The in vitro relationship between fat-cell size, glycerol release, and peak concentration of cyclic AMP was investigated in human adipose tissue obtained from 25 obese nondiabetic patients before and after a 7-day fast and from 23 patients with untreated diabetes mellitus. In the obese nondiabetic patients there was a linear correlation between fat-cell size and cyclic AMP concentration, and fat-cell size and the rate of lipolysis. This was found both in nonfasting and fasting nondiabetic patients. However, in diabetes mellitus, there was only a relationship between cell size and cyclic AMP concentration. The alpha-adrenergic and beta-adrenergic activity in human adipose tissue was assessed by comparing the effect of isoprenaline and noradrenaline on the cyclic AMP concentration. The activity of both receptors was found to be increased in fasting obese patients and in diabetics. In both conditions the alpha-adrenergic response to catecholamines predominated in small fat cells, whereas in large ones the beta response predominated. The results suggest that during fasting and in diabetes mellitus there is a correlation between fat-cell size and the responsiveness of the adrenergic receptors. Thus, catecholamines may be involved in regulating the fat-cell volume. The view is expressed that the abnormal catecholamine-induced lipolysis is solely due to changes at the level of the adrenergic receptors during fasting, whereas in diabetes mellitus the sequentional activation of lipolysis is disturbed at deeper sites as well.

Adipose Tissue↗

Regional differences in the control of lipolysis in human adipose tissue.

Omental fat cells were 30% smaller than those in subcutaneous regions. In omental fat cells with a mean diameter of 95 mu, the basal cAMP concentration was 50% lower, but the basal rate of glycerol release was three times as rapid as in subcutaneous (epigastric) fat cells of identical size. Added at maximal effective concentration, noradrenaline increased the level of cAMP and the rate of glycerol release more markedly in the omental than in the subcutaneous adipocytes, whereas the response to isopropyl noradrenaline was similar. Before starvation the lipolytic effects of noradrenaline and isopropyl noradrenaline, respectively, were identical in the two regions of subcutaneous adipose tissue investigated (femoral and hypogastric). The findings were well related to the tissue levels of cAMP induced by the two agents. During starvation noradrenaline and isopropyl noradrenaline increased the cAMP level and the rate of lipolysis in fat cells obtained from the hypogastric region, whereas noradrenaline decreased these parameters in femoral adipocytes. Starvation was associated with a more prominent inhibitory effect of phenylephrine on basal and isopropyl-noradrenaline-induced lipolysis in femoral than in hypogastric adipose tissue. In conclusion, differences exist between different regions of adipose tissue in their lipolytic responsiveness to noradrenaline, which seems related to the balance between alpha- and beta-adrenergic receptor response.

Adipose Tissue↗

Regulation of lipolysis by human adipose tissue in hyperthyroidism.

The effects of noradrenaline (NA) and isopropyl-noradrenaline (ISNA) on glycerol release and cAMP levels in sc adipose tissue were studied in vitro in 27 patients with hyperthyroidism. In 11 patients, the studies were repeated after 6--12 months of treatment for hyperthyroidism. A third group comprised 21 euthyroid patients otherwise healthy except for morbid obesity. The lipolytic response to ISNA, observed in untreated thyrotoxic patients, was found to be reduced by 30% when the patients were reexamined after treatment for thyrotoxicosis. This reduction was attributable to a decrease in the cAMP level. This was observed whether adipose tissue was incubated in the presence or absence of a phosphodiesterase inhibitor, theophylline. Both NA and ISNA induced 50% more rapid glycerol release and 4 times higher cAMP levels in adipose tissue of the thyrotoxic subjects than in the obese euthyroid patients. A positive correlation between tissue cAMP and glycerol release, on one hand, and mean fat cell size, on the other hand, was observed in treated thyrotoxic patients and obese euthyroid patients but was not recorded in the untreated hyperthyroid patients. The basal rate of lipolysis was not altered in thyrotoxicosis. The results suggest that the enhanced lipolytic response to catecholamines in adipose tissue of hyperthyroid patients is due to increased beta-adrenergic responsiveness. In addition, a disruption in subsequent stages of the regulatory pathway at the level of protein kinase or hormone-sensitive lipase also seems possible.

Adipose Tissue↗

Influence of phenformin and metformin on exercise induced lactataemia in patients with diabetes mellitus.

The effect of long-term treatment with phenformin and metformin respectively on blood lactate concentrations in relation to submaximal muscular exercise has been examined in 21 maturity-onset diabetics, using a cross-over method. At similar degrees of diabetic control the mean blood lactate concentration during exercise and shortly thereafter was significantly higher when the patients had received phenformin. The mean fasting lactate concentration was 1.07 mmol/l with phenformin and 1.03 mmol/l with metformin and the peak concentration was 2.56 mmol/l and 2.19 mmol/l respectively. The mean fasting blood glucose concentration before the exercise was 11.2 mmol/l with phenformin and 11.3 mmol/l with metformin; the glucose output in the urine during the preceding 24 hours was 93 mmol and 105 mmol respectively. The mean work load during exercise was 60 watts.

Adult↗