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Biomedical subjects

P H Forsham

Publications and source records attributed to P H Forsham.

36 records · Page 2Linked to original sources
PubMed1977

Jejunoileal bypass as a treatment of morbid obesity.

Seventy-five morbidly obese patients underwent jejunoileal bypass between December 1968 and October 1975. The average weight of 45 patients who had had the bypasses for over two years stabilized at 62.4% of the maximum preoperative value. Postoperative complications included recurrent diarrhea in 11% (8/74) and serum electrolyte deficits in 64% (48/75), most of which were transient. Potassium and calcium deficiencies were usually correctable by oral supplementation, but hypomagnesemia persisted in 23% (16/71) despite supplementation. Nine percent (4/43) had biopsy-proved hepatic cirrhosis after one year. Other complications were polyarthralgia, bone demineralization, renal stones, and vasculitis. Three patients required reanastomosis to original bowel continuity; all rapidly regained weight. One died of vasculitis and hepatic failure attributable to the bypass. Jejunoileal bypass is suitable only in morbidly obese patients with particularly high motivation, whose risk factors outweigh those risks incurred through bypass.

Arteritis↗
PubMed1976

Role of glucagon in human diabetic ketoacidosis: studies using somatostatin.

The present studies demonstrate that endogenous glucagon is hyperglycaemic, lipolytic and ketogenic in man, and that insulin deficiency is necessary, but is in itself not sufficient, to cause fulminant diabetic ketoacidosis. Furthermore, continuous elevation of endogenous glucagon secretion appears to be necessary for the maintenance and continued development of the characteristic metabolic consequences of insulin lack.

Adult↗
PubMed1976

Effects of physiologic levels of glucagon and growth hormone on human carbohydrate and lipid metabolism. Studies involving administration of exogenous hormone during suppression of endogenous hormone secretion with somatostatin.

To study the individual effects of glucagon and growth hormone on human carbohydrate and lipid metabolism, endogenous secretion of both hormones was simultaneously suppressed with somatostatin and physiologic circulating levels of one or the other hormone were reproduced by exogenous infusion. The interaction of these hormones with insulin was evaluated by performing these studies in juvenile-onset, insulin-deficient diabetic subjects both during infusion of insulin and after its withdrawal. Infusion of glucagon (1 ng/kg-min) during suppression of its endogenous secretion with somatostatin produced circulating hormone levels of approximately 200 pg/ml. When glucagon was infused along with insulin, plasma glucose levels rose from 94 +/- 8 to 126 +/- 12 mg/100 ml over 1 h (P less than 0.01); growth hormone, beta-hydroxy-butyrate, alanine, FFA, and glycerol levels did not change. When insulin was withdrawn, plasma glucose, beta-hydroxybutyrate, FFA, and glycerol all rose to higher levels (P less than 0.01) than those observed under similar conditions when somatostatin alone had been infused to suppress glucagon secretion. Thus, under appropriate conditions, physiologic levels of glucagon can stimulate lipolysis and cause hyperketonemia and hyperglycemia in man; insulin antagonizes the lipolytic and ketogenic effects of glucagon more effectively than the hyperglycemic effect. Infusion of growth hormone (1 mug/kg-h) during suppression of its endogenous secretion with somastostatin produced circulating hormone levels of approximately 6 ng/ml. When growth hormone was administered along with insulin, no effects were observed. After insulin was withdrawn, plasma beta-hydroxybutyrate, glycerol, and FFA all rose to higher levels (P less than 0.01) than those observed during infusion of somatostatin alone when growth hormone secretion was suppressed; no difference in plasma glucose, alanine, and glucagon levels was evident. Thus, under appropriate conditions, physiologic levels of growth hormone can augment lipolysis and ketonemia in man, but these actions are ordinarily not apparent in the presence of physiologic levels of insulin.

Adult↗
PubMed1976

Islet transplantation into rat liver: in vitro secretion of insulin from the isolated perfused liver and in vivo glucagon suppression.

Islet isografts were injected into the portal veins of rats made diabetic with streptozotocin. The isografts normalized not only plasma glucose and insulin levels but also the elevated plasma immunoreactive glucagon level. The in vitro basal insulin secretion and prompt sensitivity to glucose were shown directly by perfusing isolated livers containing transplanted islets. In vitro glucagon secretion to an arginine stimulus could not be demonstrated, although it would have been expected demonstrated, although it would have been expected in normal islets. Thus, it appears that insulin derived from transplanted islets is capable of correcting endogenous hyperglucagonemia and of ameliorating the effects of experimental diabetes while transplanted islet glucagon secretion is relatively suppressed.

Animals↗
PubMed1976

Discordance of diabetic microangiopathy in identical twins.

In a pair of 19-year-old monozygotic twin girls, one developed insulin-dependent, ketosis-prone diabetes at the age of three and has required insulin for the past 16 years. Her identical twin has maintained normal oral and intravenous glucose tolerance with normal insulin release and glucagon suppression. An unequivocal hypertrophy of the muscle capillary basement membrane (1,800 +/- 148 A) was dound in the diabetic twin, while a normal thickness of 1,149 +/- 62 A was present in her nondiabetic sister. Follow-up of the present subjects and data from other discordant identical twins who have reached adulthood could determine whether muscle capillary basement membrane hypertrophy is an independent marker of genetic diabetes in adults. Discordance of diabetic microangiopathy in a pair of monozygotic twins has important implications regarding the influence of heredity and environment on diabetic microangiopathy.

Adult↗
PubMed1976

Effects of acute insulin withdrawal and administration on plasma glucagon responses to intravenous arginine in insulin-dependent diabetic subjects.

To assess further the role of insulin in the abnormal alpha-cell dysfunction found in human diabetes mellitus, the effects of acute insulin withdrawal and administration on plasma glucagon responses to intravenous arginine were studied in eight insulin-dependent diabetic subjects. Arginine infusions (30 gm. over 30 minutes) were performed during and at one and four hours after discontinuation of a 14-hour insulin infusion (1.5 U. per hour), which had rendered the subjects euglycemic, and on another occasion before and one and four hours into a five-hour infusion of insulin (1.5 U. per hour). During the last hour of the 14-hour infusion, glucagon responses to arginine (area under the curve, nanograms per milliliter per minute) were similar to those found in normal subjects (10.3 +/- 0.8 vs. 9.0 +/- 0.8, respectively). After discontinuation of the insulin infusions, glucagon responses increased progressively (p less than 0.01) to values (16.8 +/- 1.2) that exceeded those of normal subjects by four hours (p less than 0.01). These were similar to results found in the same subjects studied when their diabetes was in less than optimal control (14.9 +/- 1.3). Infusion of insulin under these conditions progressively decreased glucagon responses to arginine to values (9.6 +/- 0.8; p less than 0.01) that, at four hours, were similar to those of normal subjects and to values found at the end of the 14-hour infusion of insulin in the same diabetic individuals. These results demonstrate a rapid effect of insulin on glucagon responses to arginine and suggest that the abnormal responses seen in diabetes mellitus are the immediate result of insulin deficiency. Since abnormal glucagon responses to glucose in diabetes are not as readily corrected by insulin, the mechanisms underlying the abnormal responses to these two stimuli may differ.

Adolescent↗
PubMed1975

The effect of somatostatin on coagulation and platelet function in man.

Preliminary evidence has suggested that somatostatin might interfere with platelet function in the baboon. Because this agent is currently being administered experimentally to human beings, we studied its effect on coagulation and platelet function in man. In five subjects, a four-hour infusion of somatostatin (500 micrograms per hour) had no definite effect on platelet count, leukocyte count, hematocrit, platelet adhesiveness and aggregation, bleeding time, partial thromboplastin time, prothrombin time, and fibrinogen levels. A similar infusion for 18 hours in three subjects was likewise without effect. These studies indicate that somatostatin does not affect coagulation and platelet function in man and that its prolonged administration lacks ostensible toxicity.

Adenosine Diphosphate↗
PubMed1975

Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon.

To evaluate the role of glucagon in the pathogenesis of diabetic ketoacidosis in man, we studied the effect of suppression of glucagon secretion by somatostatin on changes in plasma beta-hydroxybutyrate and glucose concentrations (as well as changes in their precursors) after acute withdrawal of insulin from seven patients with juvenile-type diabetes. Suppression of glucagon secretion prevented the development of ketoacidosis for 18 hours after acute insulin withdrawal, whereas in control studies mild ketoacidosis occurred 10 hours after insulin was stopped. Plasma beta-hydroxybutyrate, glucose, free fatty acid, and glycerol levels were all markedly lower during suppression of glucagon secretion (p smaller than 0.001), whereas plasma alanine levels were higher (p smaller than 0.001). These studies indicate that insulin lack per se does not lead to fulminant diabetic ketoacidosis in man and that glucagon, by means of its gluconeogenic, ketogenic, and lipolytic actions, is a prerequisite to the development of this condition.

Adult↗
PubMed1975

Evidence for a physiologic role of pancreatic glucagon in human glucose homeostasis: studies with somatostatin.

To study the role of glucagon in human glucose homeostasis, experimental glucagon deficiency was produced by infusing somatostatin (i. v. 250 mug bolus, followed by infusion of 500 mug/hr) in six normal subjects and in two hypophysectomized patients-an insulin-dependent diabetic and a nondiabetic. In normal subjects, somatostatin lowered plasma glucagon from a mean (plus or minus SE) basal level of 85 plus or minus 15 to 33 plus or minus 10 pg/ml, p smaller than 0.001. Concurrently, plasma glucose fell from 90 plus or minus 2 to 73 plus or minus 3 mg/100 ml, p smaller than 0.001. Serum insulin and growth hormone fell slightly during somatostatin infusion, while plasma free fatty acids rose. In both hypophysectomized patients, somatostatin lowered plasma glucagon and glucose levels. In all subjects, after stopping somatostatin infusions, plasma glucagon and glucose returned promptly to control values, while serum growth hormone did not change. In additional in vitro studies, somatostatin (1 mug/ml) had no effect on muscle glucose uptake. Since it is known that somatostatin has no direct effect on hepatic glucose production, these results suggest that the fall in plasma glucose during somatostatin infusion resulted from inhibition of glucagon secretion, thus providing evidence that this hormone plays a physiologic role in the maintenance of fasting euglycemia in man.

Adult↗
PubMed1975

Growth hormone responses following double pulse oral glucose administration in various clinical states.

The 8-h double pulse oral glucose test is proposed as an alternative screening procedure for determining the adequacy of growth hormone (GH) release. The second pulse of glucose is timely in suppressing GH release and delaying it for a more predictable controlled elevation. Peak GH (mean plus or minus SD) values following the double pulse glucose test were 17 plus or minus 10.2, 16.5 plus or minus 2.2, and 1.3 plus or minus 0.5 ng/ml in normal controls, short stature patients and GH deficient patients, respectively. Peak GH values following insulin hypoglycemia were 36.9 plus or minus 13.8, 21.9 plus or minus 23.0 and 1.8 plus or minus 1.1 ng/ml in normal controls, short stature patients and GH-deficient patients. Peak GH values during a 5-h oral glucose tolerance test were 16.4 plus or minus 6.0 and 10.2 plus or minus 3.3 ng/ml in normal controls and short patients, respectively. These differences in peak GH values between the various clinical and control groups were not significantly different except for the greater GH peak values reached in short patients in the double pulse glucose test compared to the 5-h oral glucose tolerance test. The rise in GH following double pulse oral glucose is more timely predictab-e than after the 5-h oral glucose test and involves less professional time than the insulin tolerance test as it does not require close medical supervision.

Adolescent↗
PubMed1975

Failure of somatostatin to inhibit tolbutamide-induced insulin secretion in patients with insulinomas: a possible diagnostic tool.

The effects of somatostatin on tolbutamide-stimulated insulin release were studied in 4 patients with insulin-producing tumors of the pancreas and in 6 normal subjects. In contrast to its effective inhibition of insulin release in normal subjects, somatostatin, without exception, failed to inhibit tolbutamide-induced insulin release in the patients with pancreatic beta-cell tumors. This differential effect of somatostatin may prove useful in the diagnosis of insulin-producing tumors of the pancreas.

Adenoma, Islet Cell↗
PubMed1975

Inhibition by somatostatin of ACTH secretion in Nelson's syndrome.

Somatostatin (GHIF), when administered as a 1-hr infusion (500 mug/hr) to 5 patients with Nelson's Syndrome;resulted in a sustained, progressive fall in plasma ACTH in each patient to 40% to 71% of basal values with a return toward initail levels after cessation of the infusion. The meanreduction in plasma ADTH was 48% (p less than 0.005). These finding suggest that GHIF receptors not fuctional or present in normal pituitary tissue are present in ACTH-producing pituitary tumors.

Adenoma↗
PubMed1975

Altered hypothalamic-pituitary-adrenal responsiveness to dexamethasone-insulin tolerance test in active acromegaly.

Eight acromegalic patients showed a plasma cortisol (11-OHCS) rise after insulin hypoglycemia which was similar to that seen in control patients, with mean peak values (+/-SEM) of 23.2 +/- 3.5 mug/100 ml and 27.2 +/- 3.3 mug/100 ml, respectively. One mg of dexamethasone was given the evening prior to repeat insulin hypoglycemia (DEX-ITT). After dexamethasone, the control subjects showed a mean post hypoglycemic plasma 11-OHCS rise to 18.3 +/- 2.3 mug/100 ml. In contrast, acromegalic patients had a negligible rise is plasma 11-OHCS, despite a comparable degree of hypoglycemia. These data indicate that, in active acromegaly, abnormal hypothalamic-pituitary-adrenal suppressibility can be induced to insulin hypoglycemia after dexamethasone.

11-Hydroxycorticosteroids↗