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Biomedical subjects

E J Rayfield

Publications and source records attributed to E J Rayfield.

At least 37 records · Page 2Linked to original sources

Studies of carbohydrate metabolism after hemodialysis and hemofiltration in uremic patients.

To assess the effects of dialysis or hemofiltration on carbohydrate metabolism in uremia, we performed intravenous (IV) glucose tolerance tests (IV GTTs) after an overnight fast 48 hours following the last treatment in ten patients with chronic renal failure. Samples were obtained for plasma glucose, insulin, glucagon, and growth hormone levels throughout the GTTs in addition to basal samples for levels of plasma potassium and bicarbonate. The IV GTTs were performed at the end of a four-month period of standard hemodialysis (period 1) and then at the end of a four-month period of hemofiltration (period 2). Patients had mild glucose intolerance that did not change after hemofiltration, although the exaggerated insulin responses to glucose administration did significantly decrease in period 2. The fasting hyperglucagonemia did not decrease after hemofiltration but exhibited normal suppression with IV glucose. Levels of basal plasma bicarbonate and basal plasma potassium did not change significantly in period 2. Further studies investigating the beneficial metabolic effect of hemofiltration would seem to be indicated based on the data reported herein.

Adult↗

Virus-induced alterations in insulin release in hamster islets of Langerhans.

After the inoculation of Golden Syrian hamsters with the TC-83 vaccine strain of Venezuelan encephalitis (VE) virus, a sustained diminution in glucose-stimulated insulin release and glucose intolerance of shorter duration develops. To understand better the mechanism of this defect in insulin release, we examined insulin secretion in response to several test agents in isolated perifused islets from control and 24-d post-VE virus-infected hamsters. 50 islets were used in all perifusion experiments, and data were expressed as total insulin released as well as peak response for each test agent during a 30-min perifusion period from control and VE-infected islets. After perifusion with 20 mM glucose, a 45% diminution of insulin release was noted in VE-infected islets in comparison with control islets, which in turn was similar to in vivo findings. However, following 1-mM tolbutamide stimulation, insulin release was similar in control and VE-infected islets. In separate studies, 1 mM tolbutamide, 10 mM theophilline, 1 mM dibutyryl cyclic (c)AMP, and 1 mM 8-bromo-cAMP resulted in statistically similar insulin-release curves in control and VE-infected islets. Additional experiments assessing [5-3H]glucose use in control and infected islets after 20 min of perifusion with 20 mM glucose revealed virtually identical values (239 +/- 30-control; and 222 +/- 27-VE-infected islets). Morphological and morphometric evaluation of VE-infected islets (21 d following virus inoculation) showed no changes in islet volume density, beta cell density, and beta cell granulation. Thus, VE virus induces a defect in glucose-stimulated insulin release from hamster beta cells that can be corrected by cAMP analogues and does not alter islet glucose use.

8-Bromo Cyclic Adenosine Monophosphate↗

Metabolic studies in a child with a pancreatic insulinoma.

An 8-year-old boy with a convulsive disorder for 3 1/2 years remined seizure free for 20 months while being treated with phenytoin (diphenylhydantoin) sodium, and then he had a relapse. He first demonstrated hypoglycemia when he fasted prior to being placed on a ketogenic diet. An oral glucose tolerance test indicated fasting and postglucose hypoglycemia and substantial hyperinsulinemia. Somatostatin infusion resulted in a modest increase in plasma glucose levels and a decrease in serum insulin concentrations. A discrete pancreatic mass was demonstrated preoperatively by celiac angiography that on surgical extirpation, proved to be a benign intrapancreatic insulinoma. Evaluation for islet cell tumors is of importance in children with seizure disorders unresponsive to anticonvulsant medication. Furthermore, somatostatin may be useful preoperatively in maintaining normal blood glucose concentrations in patients with islet cell adenomas.

Adenoma, Islet Cell↗

Studies of glucose metabolism in rhesus monkeys after Venezuelan equine encephalitis virus infection.

Previous studies have demonstrated a diabetogenic effect of Venezuelan equine encephalitis (VEE) virus in hamsters. A preliminary study was conducted in which five 2- to 3-year-old rhesus monkeys were infected with the virulent Trinidad donkey strain of VEE virus and their carbohydrate metabolism was studied over 10 months. All animals developed mild clinical illness (rhinorrhea, cough, fever), were viremic, and developed antibodies. As compared with the results of preinoculation intravenous glucose tolerance tests (IVGTT), the monkeys had abnormally high glucose values by 2 months postinoculation (PI), progressively diminished insulin responses between 8 days and 5 months PI, and significantly lower glucagon curves 2, 5, and 10 months PI. Pancreatic histology and insulin content were normal. A second, controlled study was conducted of glucose and insulin metabolism in somewhat older (3- to 8-year-old) rhesus monkey after they were infected with both the Trinidad donkey strain of VEE virus and the attenuated VEE vaccine (TC-83). Groups of six monkeys received the virulent virus and the TC-83 vaccine, and five animals were sham-inoculated with saline. Monkeys inoculated with virulent virus became viremic, and 50% became febrile without overt signs of illness, whereas those given TC-83 virus remained afebrile and did not become viremic, but five of six developed antibodies. Intravenous glucose tolerance tests were performed and serum immunoreactive insulin responses to glucose administration measured before infection and 2 and 5 months later. No significant and consistent alterations of glucose or insulin responses were detected in the infected or control groups. Although several animals had preinoculation anti-islet cell antibodies, none developed new antibodies during the study.

Animals↗

C-Peptide reserve in insulin-dependent diabetes. Comparative responses to glucose, glucagon and tolbutamide.

Residual beta cell secretory capacity was assessed in short term (2 months to 2 years) and long term (5 to 8 years) insulin-dependent diabetics by measurement of serum C-peptide immunoreactivity during three provocative tests: glucose, tolbutamide, and glucagon. Minimal C-peptide secretion could be detected in only one out of seven long term diabetics by the stimulatory tests. All seven short-term diabetics responded to at least one provocative test of beta cell reserve, although these responses were blunted. The greatest C-peptide responses occurred after glucagon administration (mean increase 0.62 pmol/ml) in short-term responders. Patients who responded to one test did not necessarily respond to another stimulus. There was no correlation between basal C-peptide levels and the ability to provoke further C-peptide secretion by any of the three tests. C-peptide responses did not correlate with % Haemoglobin A1c, mean fasting blood glucose levels, or mean blood glucose concentrations during an oral glucose tolerance test. The data indicate that stimulation tests are only useful in assessing endogenous beta cell reserve in patients with diabetes of less than 5 years duration. In diabetics of longer duration there is little insulin reserve above basal levels.

Adolescent↗

Disopyramide (Norpace)-induced hypoglycemia.

Disopyramide (Norpace) is a recently released antiarrhythmic agent with quinidine-like actions, but structurally unique. We describe a patient in whom impressive hypoglycemia developed following treatment with this agent. Blood glucose levels returned to normal after cessation of therapy, but dropped again following rechallenge with the drug. The pathogenesis of the hypoglycemia was investigated by assessment of serum insulin, plasma glucagon and serum alanine levels during disopyramide rechallenge. Clinicians should be aware of fasting hypoglycemia as an unusual but potentially serious complication of disopyramide therapy.

Aged↗

Effects of acute endotoxemia and glucose administration on circulating leukocyte populations in normal and diabetic subjects.

Effects of intravenous endotoxin and glucose administration on circulating leukocyte populations were compared in seven normal subjects and seven patients with juvenile-onset diabetes by means of automated cytochemical differential counting to quantitate each cell type. Both groups had comparable control cell counts that were unaffected by glucose tolerance testing but altered significantly by endotoxin. Different patterns of response to endotoxin were observed for different circulating cell types. The response of diabetics was parallel to that of normals but showed lower neutrophil and monocyte rebound, longer lasting depression of lymphocytes and eosinophils, and greater rebound of basophils on the day following endotoxin exposure. Characterization of distinctive normal response patterns of circulating leukocyte populations to endotoxin and comparison with responses in diabetes revealed abnormalities under conditions of stress that may impair the diabetic's ability to cope with acute infection.

Adult↗

Effect of glucose infusion on the concentration of individual serum free amino acids during sandfly fever in man.

After an intravenous glucose load in man, total serum amino acid concentrations are rapidly depressed and remain below baseline values for at least 2 to 3 hr after serum glucose and insulin have returned to preload concentrations. Despite the presence of basal hypoaminoacidemia, a decreased glucose disappearance rate, and hyperinsulinemia in volunteers who were ill with sandfly fever, an intravenous glucose load resulted in a further depression of serum amino acids which was equal to or slightly greater than that observed in the same individuals before exposure to the virus. Although the infectious process may have some effect on insulin-stimulated hepatic disposal of a glucose load, it does not appear to influence the ability on insulin to decrease the rate of release of certain amino acids from skeletal muscle.

Adult↗

Altered hepatic glycogen metabolism and glucoregulatory hormones during sepsis.

Levels of glucose, insulin, and glucagon in portal vein plasma and of liver glycogen and cyclic AMP and activities of glycogen synthase and phosphorylase in liver were assayed in control (CONT) rats and rats infected (INF) with Diplococcus pneumoniae. In INF rats compared with CONT rats, insulin and glucagon levels were higher (8,12,24 h). Activity of synthase I was lower (8, 12, 24 h) and of phosphorylase higher (12 and 24 h) in INF rats. Cyclic AMP levels were higher in INF rats at 12 and 24 h. Total synthase activity was lower in INF rats at 24 h. Glucose given intravenously increased glycogen less in INF than in CONT rats and activated synthase and inactivated phosphorylase in all animals except at 24 h in INF rats. However, in situ perfusion of the livers at 24 h with glucose in buffer decreased phosphorylase activities in all animals and increased synthase I activities in CONT but not INF rats.

Animals↗

Nonautonomous function of a pancreatic insulinoma.

A 56-year-old woman with symptoms of weakness, visual blurring, and sweating underwent diagnostic studies to evaluate the etiology of her hypoglycemia. Fasting hypoglycemia was never documented; in diagnostic studies performed during her two hospitalizations and several outpatient glucose tolerance tests, the lowest fasting plasma glucose recorded was 56 mg/dl. The patient displayed exaggerated plasma insulin responses following oral glucose (peak response: 447 muU/ml at 30 min) and following 1 gm of iv tolbutamide (peak response: 719 muU/ml at 5 min) with symptomatic profound hypoglyceria during both tests. Basal per cent proinsulin was elevated at 49% (normal range 5-22%). Throughout a 72 h fast, values for plasma glucose, insulin, and glucose/insulin ratios were all within the normal range. During the infusion of exogenous insulin (0.1 U/kg for 60 min) serum C-peptide reactivity suppressed to less than 1.3 ng/ml when the plasma glucose fell below 40 mg/dl representing normal suppression. At surgery, a pancreatic beta cell adenoma was found and removed. This patient represents the uncommon circumstances in which stimulation tests with tolbutamide and glucose were more helpful in establishing a preoperative diagnosis than were the suppression tests.

Adenoma, Islet Cell↗

Virus-induced pancreatic disease by Venezuelan encephalitis virus. Alterations in glucose tolerance and insulin release.

Viral infections have been implicated in the induction of diabetes mellitus in man and laboratory animals. Since virus-specific immunofluorescence (FA) is detectable in hamster pancreas during the acute phase of Venezuelan encephalitis (VE), experiments were designed to correlate pathologic and virologic events with metabolic studies in VE-infected hamsters. Golden Syrian hamsters were inoculated s.c. in groups of four to 12 with 100,000 plaque-forming units (PFU) of the vaccine strain (TC-83) of VE or 1,000 PFU of the virulent Trinidad strain of VE. Ultrastructurally, during Trinidad infection, mature virions were associated with the cell surfaces and within pancreatic beta cells in contrast to absence of virus-related changes in TC-83-infected hamsters. Virus-specific-FA was noted in islet cells and acinar cells of Trinidad-infected hamsters. VE growth curves demonstrated viral replication in pancreas with both strains. Although ultrastructural and FA changes were much more prominent in Trinidad-infected hamsters in contrast to TC-83-infected hamsters during the first few days of illness, the rapid lethality of the Trinidad-infected group necessitated performing all metabolic studies in TC-83-strain-infected hamsters. Accordingly, for the metabolic studies, glucose tolerance tests (GTT) using 2 mg. or 5 gm./kg. glucose i.p. were performed in groups of hamsters acutely infected two days earlier with the TC-83 vaccine strain and in 24-day and 90-day convalescent hamsters after TC-83 vaccine strain. Samples were obtained for glucose and immunoreactive insulin (IRI) determinations. Glucose intolerance occurred in hamsters in each of the infected groups given 5 gm./kg. glucose except for the 90-day convalescent TC-83 group. Severely decreased IRI responses occurred in the 24-day and 90-day convalescent TC-83 hamsters following both 2- and 5-gm./kg. glucose. Pancreatic IRI content in 24-day convalescent TC-83 hamsters was within normal limits, suggesting a defect in IRI release from the beta cells at this stage of convalescence.

Animals↗

Technique for portal catheterization in rhesus monkeys (Macaca mulatta).

A technique was developed for catheterization of the portal vein in rhesus monkeys (Macaca mulatta). Silicone rubber catheters (0.040 ID by 0.085 inch OD, or 0.030 ID by 0.065 inch OD) were surgically placed into the portal vein via the umbilical, inferior mesenteric, right colic, or ileocolic veins. The right colic and ileocolic veins proved to be the preferred route for catheterization. Both single end-hole and multiple end-hole catheters with 2 side holes were used. Catheter function was dependent upon proper placement within the portal vein and on maintaining patency. Single-hole catheters were successfully maintained by periodic flushing (2-3 times daily) with heparinized saline solution (1.5-4.0 units/ml), and multiple-hole catheters were best maintained by a continuous flow (1-2 ml/hour) of heparinized saline solution (1.5 units/ml). No adverse clinical effects due to the portal catheter were observed in any of the monkeys catheterized. The technique allowed placing the monkey in a restraint chair, thus enabling one to utilize the monkey in a conscious state.

Animals↗

Portal and peripheral vein insulin responses to intravenous glucose in the rhesus monkey.

Catheterization of the portal vein and bilateral femoral veins were performed under general anesthesia in 6 healthy male rhesus monkeys. Four days later, sequential, simultaneous peripheral and portal plasma samples were obtained for glucose and immunoreactive insulin determinations before and after administration of 0.5 Gm. of glucose per kilogram (over a 1-minute period) via the opposite peripheral catheter. Two phases of insulin secretion were noted in both portal and peripheral plasma samples. An immediate early-phase insulin response was noted with a peak response at 1 minute followed by a rapid decline to a nadir at 5 minutes. A second phase of insulin secretion was evident with a peak response at 10 minutes and a subsequent decline to basal levels by 60 minutes. Simultaneous portal vein and peripheral vein glucose concentrations were not significantly different from each other by paired analysis. Thus, in the rhesus monkey peripheral insulin concentrations following intravenous glucose exhibit a biphasic response closely paralleling pancreatic insulin secretion.

Animals↗