Effects of acute exercise on insulin binding to monocytes in obesity

The effect of 3 hr of cycle erogmeter exercise on ¹²⁵I-insulin binding to monocytes was studied in 8 obese and 10 nonobese control subjects. In the basal state before exercise, total specific ¹²⁵I-insulin binding to monocytes in obese subjects (4.8% ± 0.3%) was 25% lower than in control subjects (6.6% ± 0 0.4%, p < 0.01). During exercise, insulin binding increased in both groups (p < 0.05), but the rise in obese subjects was minimal (13% ± 1%) and was 60%–70% lower than in controls (36% ± 3%, p < 0.01). The data indicate that the increment in insulin binding to monocytes induced by acute exercise is diminished in obesity.     

Influence of physical training on the fuel-hormone response to prolonged low intensity exercise

The effects of physical training on the fuel-hormone response to prolonged (3 hr), low intensity cycle ergometer exercise (40% maximal aerobic power) which in the untrained state fails to produce a rise in blood lactate, was examined in six healthy male subjects. The training program consisted of one hour cycle ergometer exercise performed 4 times weekly for 6 weeks and resulted in a 19% increase in maximal aerobic power. Prior to training, prolonged low intensity exercise resulted in a 20% decline in plasma glucose, a 2.5-fold rise in plasma free fatty acids (FFA), a 7-fold rise in plasma epinephrine, a 3-fold elevation in plasma norepinephrine, and a 2.5-fold rise in plasma glucagon. Following training, the exercise-induced decline in glucose was 60% less than before training, the elevations in plasma FFA and norepinephrine were respectively, 45% and 90% less than before training and no significant increment in plasma norepinephrine and glucagon was observed. Training also blunted the exercise-induced elevations in circulating ketones and growth hormone and resulted in a lower respiratory exchange ratio during exercise. The data indicate that training markedly diminishes the fuel-hormone perturbations associated with low intensity exercise and in the face of a lessened increment in plasma FFA results in a greater utilization of fat and less dependence on carbohydrate during the exercise.     

Modification of intraaortic balloon catheter to permit introduction by cardiac catheterization techniques

Intraaortic balloon counterpulsation has been widely applied for treatment of left ventricular pump failure and intractable angina. However, its use has been limited by the difficulty of balloon insertion in some patients and vascular complications in others. An AVCO intraaortic balloon was modified by the addition of a central lumen to allow pressure monitoring, injection of contrast medium and passage of a guide wire. The device was successfully used in 15 of 16 patients, including 4 of 5 in whom attempts to place a standard balloon catheter had failed. No significant vascular complications occurred in any patient. The modified balloon catheter appears to increase the efficacy and safety of insertion and allows immediate and continuous monitoring of arterial pressure.     

Four-valve polymicrobial endocarditis caused by pseudomonas aeruginosa and serratia marcescens

This report describes what is believed to be the first case of mixed Pseudomonas and Serratia endocarditis, of probable nosocomial etiology, with involvement of all four heart valves in a 56 year old nonaddicted patient. Although both organisms were recovered in culture, infection and tissue invasion were documented by light and electron microscopy. The clinical course in this patient differed from more typical patterns of Pseudomonas or Serratia endocarditis that have been observed as complications of narcotic addiction or compromised cardiac status. Our patient had the rare occurrence of endocarditis with two organisms and four-valve involvement. Clinically, however, this presented as a right-sided endocarditis and behaved as though only a single organism were present.     

Hemangioendothelioma of the thyroid and concurrent hyperthyroidism

A patient with an apparently nontoxic nodular goiter was found to have a hemangioendothelioma of the thyroid. Tissue obtained at surgery revealed vascular channels lined with endothelium. Isotope studies revealed increased vascular flow in the tumor, and thyroid angiography showed a large tumor with innumerable tortuous vessels and early venous drainage. Laboratory tests of thyroid function had long suggested hyperthyroidism, and during a preoperative evaluation, it was thought that clinical thyrotoxicosis had developed which subsequently responded to antithyroid therapy. Neither several attempts at suppressive therapy with thyroid hormone nor subsequent antithyroid therapy has had an effect on the slow progression of this obscure tumor, which has apparently been present for 15 years.     

Effects of ethanol ingestion on glucose tolerance and insulin secretion in normal and diabetic subjects

To investigate the effect of ethanol on carbohydrate homeostasis in circumstances in which food and ethanol are usually ingested, ethanol was administered hourly in the afternoon prior to the ingestion of a glucose load at 5:00 p.m. in a group of normal subjects and in mild diabetics. In both groups the blood glucose levels following the glucose load were $\text{30–80 mg}\text{100 ml}$ lower and the early insulin secretory response (15–45 min) was 35%–40% higher after ethanol ingestion. In contrast, ethanol intake had no effect on the glucagon response to glucose ingestion. These data suggest that ethanol enhances glucose-stimulated insulin secretion. The dampened blood glucose rise observed with ethanol may be related to the augmented insulin response or to decreased gastrointestinal absorption of glucose. In mild diabetic patients, moderate intake of ethanol is without acute deleterious effects on carbohydrate homeostasis and may in some instances improve the blood glucose response to ingested carbohydrate.     

The role of fractional glucose extraction in the regulation of splanchnic glucose metabolism in normal and diabetic man

In order to express in equivalent terms seemingly divergent results obtained with isotopic tracer studies as compared to hepatic venous catheter studies on the role of the liver in the metabolism of oral glucose, our previously published studies using the hepatic venous catheter technique in normals and diabetics given intravenous and/or oral glucose were analyzed with respect to the splanchnic fractional extraction of glucose, total splanchnic glucose influx, and the proportion of total glucose metabolism accounted for by net splanchnic glucose uptake. In normal subjects during extreme hyperinsulinemia (plasma insulin, 500–1,200 μU/ml) induced by i.v. insulin while maintaining the blood glucose concentration at basal levels (insulin clamp), total glucose metabolism rose to 10.5 ± 0.9 mg/min · kg, while splanchnic fractional extraction of glucose was 4.2 ± 1.1%, and net splanchnic glucose uptake accounted for only 5 ± 2% of total glucose turnover. During hyperglycemic (blood glucose, 200 mg/dl) hyperinsulinemia induced by i.v. glucose, net splanchnic glucose uptake was twice that observed with euglycemic hyperinsulinemia, and the proportion of total glucose metabolism occurring in the splanchnic bed rose to 14 ± 4%. These increments were due entirely to a rise in splanchnic glucose influx since the fractional extraction (3.4 ± 0.5%) remained unchanged from that observed with euglycemic hyperinsulinemia. After oral glucose (100 g), splanchnic glucose influx was comparable to hyperglycemic hyperinsulinemia induced with i.v. glucose, but splanchnic fractional extraction rose to 13.1 ± 1.9% (p < 0.001 versus i.v. glucose), a value comparable to that observed with isotopic studies of oral glucose metabolism. Total glucose turnover was, however, 30% lower than after i.v. insulin (p < 0.01), so that net splanchnic glucose uptake accounted for 54 ± 5% of total glucose metabolism. In maturity-onset diabetics, after 100 g oral glucose splanchnic glucose influx was 69% greater than in controls (p < 0.001), but net splanchnic glucose uptake was 44% below controls (2.3 ± 0.5 versus 4.1 ± 0.5 mg/min · kg, p < 0.02). This reduction in glucose uptake could be accounted for by a splanchnic fractional extraction ratio (4.7 ± 1.4%) that was 64% lower than in controls given oral glucose (p < 0.001). It is concluded that: (1) in normal subjects, the ability of the splanchnic area to extract circulating glucose (as reflected by the splanchnic fractional extraction) is 2–3-fold greater after oral glucose than after intravenous glucose; (2) the rise in splanchnic fractional extraction to levels of 13% in association with only moderate increases in total glucose turnover fully accounts for the predominance of the splanchnic area in the metabolism of oral as compared to intravenous glucose; and (3) in maturity-onset diabetics, oral glucose fails to induce a rise in splanchnic fractional extraction of glucose comparable to that observed in normal subjects.     

Biphasic effect of somatostatin on oral glucose tolerance in maturity-onset diabetes

Oral glucose tolerance was examined in five maturity-onset diabetics during the infusion of somatostatin or saline. Somatostatin inhibited glucose-stimulated insulin release and reduced plasma glucagon by 50%--65%. The rise in plasma glucose after glucose ingestion was initially (at 30--120 min) reduced by somatostatin. However, beyond 3 hr, plasma glucose levels were 50--200 mg/100 ml higher, with somatostatin reaching concentrations at 6 hr that were twofold higher than those observed with saline ( p less than 0.005). The degree of late glucose intolerance was inversely related to postglucose plasma insulin concentrations (p less than 0.01). These findings demonstrate a biphasic effect of somatostatin on oral glucose tolerance in maturity-onset diabetes. The exaggerated later hyperglycemia is related to suppression of insulin secretion. The initial blunting of postprandial hyperglycemia may reflect decreased carbohydrate absorption and/or hypoglucagonemia-mediated enhancement of glucose disposal.     

Clinical spectrum of postpartum renal failure

Four patients in whom renal functional abnormalities developed in the postpartum period are discussed. Two patients had a fulminant, fatal course, typical of most of the previously reported cases of postpartum renal failure. The other two patients, however, had only mild, transient renal abnormalities. Pathologically, all four patients showed changes suggestive of fibrin deposition in the renal vasculature. It is suggested that postpartum renal failure includes a spectrum of disease from fulminant renal failure with extensive fibrin deposition to minor renal dysfunction with minimal fibrin deposition.     

Effect of somatostatin on the plasma amino acid response to ingested protein in man.

To evaluate the effect of somatostatin on the plasma amino acid response to ingested protein and amino acids, normal subjects received a 6-hr intravenous infusion of somatostatin or saline initiated 2 hr before consuming a lean beef meal (3 g/kg) or oral leucine (5 g). The effect of somatostatin on intravenous leucine disposal was also examined. In the saline control study, the branched-chain amino acids exhibited the largest elevations in plasma concentration after protein ingestion. Somatostatin markedly reduced the protein-induced increments in plasma branched-chain amino acids by 50%–75% (p < 0.001) throughout the study period. This effect was not attributable to augmented systemic disposal of these amino acids since somatostatin exaggerated by 70%–75% the rise in plasma leucine produced by intravenous leucine (p < 0.05). Somato-statin also blunted by 40%–80% the elevations in most other amino acids after protein feeding. When leucine alone was ingested, somatostatin delayed the peak rise in plasma leucine by 1 hr, but did not alter the total area under the plasma leucine response curve. We conclude that somatostatin causes a sustained reduction in the systemic availability of amino acids contained in ingested protein, while availability of free leucine is only transiently delayed. These findings raise the possibility that somatostatin reduces systemic availability of protein-derived amino acids primarily by interfering with the digestive process.     

Influence of physiologic hyperglucagonemia on urinary glucose,nitrogen, and electrolyte excretion in diabetes

To evaluate the effect of physiologic hyperglucagonemia on nitrogen and glucose metabolism and on urinary electrolyte excretion, pancreatic glucagon was administered as a continuous 3-day infusion to three adult-onset non-insulin-dependent diabetics and two insulin-treated juvenile diabetics while on a constant dietary intake. The glucagon infusion resulted in increases in plasma glucagon which were 4–6-fold greater than control values. Despite prolonged hyperglucagonemia, urinary glucose excretion was unchanged. Similarly, urinary urea nitrogen and total nitrogen excretion were not altered by glucagon administration. Urinary sodium tended to rise, albeit not significantly (P < 0.1), on the first infusion day, but later declined to control values despite increasing plasma glucagon concentrations. Urinary chloride, potassium, calcium, and phophorus excretion remained unchanged. We conclude that continuous physiologic increments in plasma glucagon do not enhance glycosuria or increase protein catabolism and ureagenesis in diabetes when insulin is available. The augmented protein catabolism and gluconeogenesis that accompany diabetic ketoacidosis can not be explained primarily on the basis of hyperglucagonemia.     

Insulin binding to monocytes and insulin sensitivity in anorexia nervosa

In six female patients with anorexia nervosa, we examined specific binding of ¹²⁵I-insuIin to monocytes and in vivo sensitivity to insulin before and after treatment. Insulin sensitivity was determined by the rate of glucose disappearance during an intravenous insulin tolerance test (K_ITT).In the untreated state, the patients with anorexia nervosa were 26 to 41 per cent below ideal weight and amenorrheic. Fasting plasma glucose and insulin levels were, respectively, 20 per cent and 55 per cent below those observed in healthy controls. Insulin binding to monocytes was 70 per cent greater than that in controls. Scatchard analysis of the insulin binding data revealed an increase in binding capacity with no change in binding affinity. During the insulin tolerance test, K_ITT (9.7 ± 0.7 per cent · min^?1) was 50 per cent greater in untreated patients than in healthy controls.Following treatment with behavior modification, there was a gain in body weight to within 2 to 11 per cent of ideal body weight, and menstrual function returned. Plasma glucose and insulin levels rose to values similar to those in healthy controls. Insulin binding declined by 40 per cent to values comparable to those in the controls. The decrease in insulin binding was due to a reduction in binding capacity. The plasma glucose response to the insulin tolerance test (K_ITT) fell 50 per cent below pretreatment values to levels comparable to those in healthy controls.Both before and after treatment, an inverse correlation was observed between plasma insulin concentration and insulin binding to monocytes whereas a direct correlation was demonstrable between insulin binding to monocytes and k_ITT.The data indicate that in anorexia nervosa insulin binding to monocytes and in vivo sensitivity to insulin are increased. The increase in insulin binding may be a consequence of a decrease in plasma insulin and may, in turn, be responsible for the increase in insulin sensitivity. The increases in insulin binding and insulin sensitivity return to normal following regain of body weight.     

Pharmacokinetics of digoxin and digitoxin in patients undergoing hemodialysis

The pharmacokinetics of digoxin and digitoxin in patients undergoing long-term hemodialysis were examined to determine which is the preferred cardiac glycoside in this patient population.Absorption curves from 0 to 24 hours after an oral dose of digitoxin were similar in dlalyzed patients and in control patients. Serum glycoside concentrations after an oral dose of digoxin were higher in dialyzed patients than in control patients, significantly so from 2 to 24 hours, reflecting the absence of the predominantly renal route of excretion of digoxin.When nine dialyzed patients were placed on a maintenance dose of digoxin, 0.125 mg 5 days a week, serum levels plateaued at 30 days at a mean concentration (± SE) of 0.84 ± 0.05 ng/ml. Maintenance therapy with 0.1 mg digitoxin 5 days a week resulted in stabilization of serum levels within 30 days at a mean concentration of 19 ± 1 ng/ml. Variability in the serum glycoside concentrations was determined after stabilization of levels during 2 to 19 week follow-up periods with each drug. Variability in serum levels was somewhat increased during maintenance therapy with digitoxin. On the basis of the pharmacokinetic data obtained in this study, no clear cut preference for one glycoside over the other could be established.     

Cellular immune findings in Lyme disease. Correlation with serum IgM and disease activity

Cellular immune findings were studied in 48 patients with various stages of Lyme disease. At each stage, some patients, particularly those with neuritis or carditis, had elevated serum IgM levels and lymphopenia. During early disease, mononuclear cells tended to respond normally to phytohemagglutinin, and spontaneous suppressor cell activity was greater than normal. Later, during active neuritis, carditis, or arthritis, the trend was toward heightened phytohemagglutinin responsiveness and less suppression than normal. By multiple regression analysis, serum IgM levels correlated directly with disease activity (p = 0.025) and inversely with the number of T cells (p = 0.02); during acute disease only, elevated IgM levels correlated with increased phytohemagglutinin responsiveness (p = 0.004) and decreased suppressor cell activity (p = 0.03). Decreased suppression, observed later in the disease, may permit damage to host tissues because of either autoimmune phenomena or a heightened response to the Lyme spirochete.     

Immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura

The results of 17 courses of immunosuppressive therapy in 12 adult patients with chronic idiopathic thrombocytopenic purpura were compared to those reported in 94 patients in the literature. About 50 per cent of the reported patients with chronic idiopathic thrombocytopenic purpura treated with immunosuppressive drugs have had a successful response. In most of these, however, the idiopathic thrombocytopenic purpura was of short duration which suggests that many of the responses were spontaneous. The probability of response to immunosuppressive agents is much greater in the splenectomized patient than in the nonsplenectomized patient.Azathioprine and cyclophosphamide are the drugs of choice for the immunosuppressive therapy of chronic idiopathic thrombocytopenic purpura. The immunosuppressive effects of cyclophosphamide probably are better, but the potential complications of this drug in patients with chronic idiopathic thrombocytopenic purpura are more serious. Nonsteroidal immunosuppressive therapy should be used as the primary form of treatment only in patients with serious disease who fail to respond to corticosteroid therapy and who are poor risks for splenectomy. One or more courses of nonsteroidal immunosuppressive therapy may be indicated in patients with chronic refractory idiopathic thrombocytopenic purpura with life-threatening disease. It is expected that from 15 to 35 per cent of adults and probably more children with chronic refractory idiopathic thrombocytopenic purpura will have a successful response.The use of nonsteroidal immunosuppressive drugs in patients with chronic idiopathic thrombocytopenic purpura remains experimental and involves uncertain risks to the patient.