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Biomedical subjects

R R Wolfe

Publications and source records attributed to R R Wolfe.

At least 271 records · Page 15Linked to original sources
PubMed1986

Echocardiographic diagnosis and intravenous digoxin management of fetal tachyarrhythmias and congestive heart failure.

Fetal echocardiography now affords an accurate clinical diagnosis of nonimmune fetal hydrops secondary to fetal tachyarrhythmias and/or certain types of congenital heart disease. Individual case reports of the treatment of tachyarrhythmias have been reported that use various drugs, including digoxin, propranolol hydrochloride, procainamide hydrochloride, and digoxin plus verapamil hydrochloride. We found no report of intrauterine treatment of congestive heart failure due to congenital heart disease with sinus rhythm. The seven cases presented herein include five cases of isolated supraventricular tachycardia, one with supraventricular tachycardia and myocardial tumors, and one of congenital heart disease with congestive heart failure. Maternal treatment with digoxin converted tachyarrhythmia to sinus rhythm in all six fetuses, and resolved the hydrops in the fetus with congenital heart disease. Premature delivery was avoided in five of the seven cases with favorable outcome in six of the cases. In five mothers who were given oral digitalization, the fetuses had delayed (three to 35 days) response to therapy. Two mothers were treated intravenously and the fetus responded to therapy in less than 24 hours. Because of problems possibly related to poor absorption and/or rapid clearance of digoxin, the intravenous route of administration should be used as the best way to achieve adequate therapeutic levels in the fetus.

Atrioventricular Node↗
PubMed1986

Subclinical abnormalities of glucose metabolism in subjects with previous gestational diabetes.

To investigate whether there are subclinical abnormalities of glucose metabolism in women with previous gestational diabetes that are consistent with a high incidence of diabetes mellitus in later life, eight patients with previous gestational diabetes and normal oral glucose tolerance were evaluated by means of body composition studies, intravenous glucose tolerance tests, and the hyperinsulinemic-euglycemic clamp coupled with 6-6 dideuterated glucose infusion, indirect calorimetry, and measurement of islet cell antibodies. Eight control subjects were matched for percent body fat and diet and studied in a similar fashion. Abnormalities of insulin response and insulin resistance were present in four (50%) of patients with previous gestational diabetes. Insulin resistance was significantly greater in the patients than in the control subjects. When compared with lean patients, obese patients with previous gestational diabetes had significantly greater insulin response to the intravenous glucose tolerance test and insulin resistance. These changes are consistent with reported findings of an early and progressive development of overt diabetes in patients who had gestational diabetes.

Autoantibodies↗
PubMed1986

Effect of epinephrine infusion and adrenergic blockade on glucose oxidation in conscious dogs.

The effect of combined alpha- and beta-adrenergic blockade, and the effect of epinephrine infusion, on the rate of glucose oxidation has been tested in conscious dogs. The dogs were prepared seven to ten days before the experiment with chronic catheters and tracheostomy. Glucose oxidation was measured by means of the primed-constant infusion of U-14C-glucose and indirect calorimetry. Six experimental groups were tested. In all groups, insulin and glucagon concentrations were held constant throughout by the inhibition of their secretion with somatostatin and intraportal replacement at basal rates. All experiments consisted of two two-hour periods. In half of the experiments, combined alpha- and beta-adrenergic blockade was administered in the second period, and in the other experiments, epinephrine was infused in the second period. The adrenergic blockade or epinephrine infusion (E) was performed in three different groups. In one, free fatty acid (FFA) levels were allowed to change spontaneously in response to blockade or E; in a second group, liposyn and heparin were infused throughout periods 1 and 2 in order to maintain FFA levels at high, constant levels; and in a third group, FFA levels were maintained at a constant low level in periods 1 and 2 by means of an infusion of nicotinic acid. In all cases tested, epinephrine infusion caused an increase in the rate of glucose oxidation. Adrenergic blockade also caused an increase in glucose oxidation when FFA levels were allowed to spontaneously fall; but when FFA levels were held constant (either high or low), there was no effect on glucose oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Glucose, fatty acid, and urea kinetics in patients with severe pancreatitis. The response to substrate infusion and total parenteral nutrition.

Rates of glucose turnover and oxidation in normal volunteers (N = 16) and in severely ill patients with pancreatitis (N = 9) were isotopically determined. Glucose turnover was determined using primed constant infusions of either 6-3H-glucose or 6-d2-glucose, and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Urea kinetics were determined using primed constant infusions of either (15N2)-urea or U-14C-urea, whereas free fatty acid (FFA) kinetics were determined by the constant infusion of 1,2-13C palmitate. Basal rates of glucose production and plasma glucose clearance were significantly higher in the patients than in the volunteers. During glucose infusion (4 mg/kg/min) endogenous glucose production was virtually totally suppressed in the volunteers (94 +/- 4%). There was significantly less suppression in the patients, however (44 +/- 1%). In addition, the percentage of available glucose oxidized (i.e., percentage of uptake oxidized) was significantly less in the patients than in the volunteers. The basal rate of urea production was significantly higher in the patients; however, in both patients and volunteers, glucose infusion resulted in a significant decrease. The rate of FFA turnover was similar in the patients and volunteers, and the patients and volunteers were equally sensitive to the suppressive effects of glucose infusion. When the patients were studied during total parenteral nutrition (TPN), there was no further suppression of endogenous glucose turnover than that seen during 2 hours of glucose infusion, and the mean rate of urea turnover measured during TPN (7.0 +/- 1.9 mumol/kg/min) was also not significantly different than the value determined during glucose infusion (8.9 +/- 1.8 mumol/kg/min). It was concluded from these studies that patients with pancreatitis are metabolically similar to septic patients, have an impairment in their ability to oxidize infused glucose when compared with normal volunteers, have an elevated rate of net protein catabolism, and have FFA kinetics similar to those seen in normal humans.

Acute Disease↗
PubMed1986

Determinations of glucose turnover and oxidation in normal volunteers and septic patients using stable and radio-isotopes: the response to glucose infusion and total parenteral feeding.

Rates of glucose turnover and oxidation were isotopically determined in normal volunteers (n = 16) and in severely septic patients (n = 10). Glucose turnover was determined using primed constant infusions of either 6-3H- or 6,6-d-glucose and glucose oxidation with either U-14C-glucose or U-13C-glucose after appropriate priming of the bicarbonate pool. Basal rates of glucose turnover, oxidation, and plasma clearance were significantly higher in the septic patients than in the volunteers. During glucose infusion (4 mg/kg.min) endogenous glucose production was virtually abolished in the volunteers (94 +/- 4% suppression). There was significantly less suppression in the septic patients (39 +/- 7%); (P less than 0.01). In addition, the percentage of available glucose oxidized (i.e. the percentage of glucose uptake oxidized) was significantly less in the septic patients. When the patients were studied during total parenteral nutrition (at a similar rate of glucose infusion) there was no further suppression of endogenous glucose production compared with that seen during 2 h of glucose infusion. However, the percentage of available glucose oxidized increased significantly. From these studies it is concluded that septic patients continue to have ongoing consumption of host tissue despite receiving either glucose infusion or total parenteral nutrition, and septic patients are less able to oxidize glucose than normal volunteers when infused for only 2 h. However, adaptation occurs with the longer infusion time used in total parenteral nutrition (TPN).

Adult↗
PubMed1986

Response to glucose infusion in humans: role of changes in insulin concentration.

We have used the primed-constant infusion of stable isotopes of glucose ([6,6-d2]glucose), alanine([3-13C] alanine), and urea ([15N2]urea) to investigate their kinetic interrelationships in normal volunteers in the postabsorptive state and during the infusion of unlabeled glucose at two rates. Each glucose infusion was tested with and without the simultaneous infusion of somatostatin (S), insulin (I), and glucagon (G) to clamp those hormonal levels. When glucose was infused at 1 mg X kg-1 X min-1, endogenous glucose production was suppressed almost exactly 1 mg X kg-1 X min-1, regardless of whether S plus I plus G were infused. The 4 mg X kg-1 X min-1 glucose infusion suppressed endogenous glucose production, both with and without hormonal control. The plasma concentration of glucose also increased to the same extent during the 4 mg X kg-1 X min-1 infusion in both protocols, which indicated that the spontaneous insulin response to the glucose infusion (an increase from 11 +/- 2 to 24 +/- 3 microU/ml) did not stimulate the peripheral clearance of glucose. The high rate of glucose infusion, both with or without hormonal control, stimulated alanine flux and inhibited urea production. These results indicate that glucose, per se, is an important direct controller of normal metabolic interactions of endogenous alanine, glucose, and urea kinetics.

Adult↗
PubMed1986

Role of changes in insulin and glucagon in glucose homeostasis in exercise.

This experiment was performed to determine if plasma glucose homeostasis is maintained in normal human volunteers during light exercise (40% maximal oxygen consumption [VO2 max]) when changes in insulin and glucagon are prevented. Hormonal control was achieved by the infusion of somatostatin, insulin, and glucagon. Glucose kinetics and oxidation rates were determined with stable isotopic tracers of glucose, and by indirect calorimetry. Two different rates of replacement of insulin and glucagon were used; in one group, insulin was clamped at 19.8 +/- 2.6 microU/ml (high-insulin group), and in the other group insulin was clamped at 9.2 +/- 1.3 microU/ml (low-insulin group). Glucagon was maintained at 261 +/- 16.2 and 124 +/- 6.4 pg/ml, respectively, in the high-insulin and low-insulin groups. Without hormonal control, plasma glucose homeostasis was maintained during exercise because the increase in glucose uptake was balanced by a corresponding increase in glucose production. When changes in insulin and glucagon were prevented, plasma glucose concentration fell, particularly in the high-insulin group. Glucose uptake increased to a greater extent than when hormones were not controlled, and glucose production did not increase sufficiently to compensate. The increase in glucose uptake in the hormonal control groups was associated with an increased rate of glucose oxidation. When euglycemia was maintained by glucose infusion in the hormonal control subjects, the modest increase in glucose production that otherwise occurred was prevented. It is concluded that during light exercise there must be a reduction in insulin concentration and/or an increase in glucagon concentration if plasma glucose homeostasis is to be maintained. If such changes do not occur, hypoglycemia, and hence exhaustion, may occur.

Blood Glucose↗
PubMed1986

Role of insulin and glucagon in the response of glucose and alanine kinetics in burn-injured patients.

We investigated the roles of insulin and glucagon as mediators of changes in glucose and alanine kinetics during the hypermetabolic response to injury in 10 burn patients by infusing somatostatin with and without insulin replacement. Glucose and alanine kinetics were measured by primed-constant infusions of 6,6-d2-glucose and [3-13C]alanine. The basal rate of glucose production and alanine flux were significantly elevated in all patients. Lowering both hormones simultaneously caused an insignificant reduction in glucose production, but plasma glucose rose significantly (P less than 0.01), because of reduced clearance. Alanine flux and total plasma amino nitrogen increased significantly (P less than 0.05) above basal. Selectively lowering glucagon concentration decreased glucose production (P less than 0.05), and exogenous glucose was infused to maintain euglycemia. Alanine flux and total plasma amino nitrogen remained unchanged. In severely burned patients hyperglucagonemia stimulates increased glucose production, basal insulin suppression glucose production, stimulates basal glucose clearance, and is important for regulation of plasma amino acid concentrations, and the selective lowering of glucagon while maintaining basal insulin constant normalized glucose kinetics.

Adult↗
PubMed1986

Palmitate and glycerol kinetics during brief starvation in normal weight young adult and elderly subjects.

Data obtained in vitro suggest that the ability to mobilize fat decreases with age. We determined lipolytic rates in vivo in normal weight young adult (22-33 yr) and elderly (65-77 yr) subjects using a simultaneous infusion of [1,2-13C2]palmitate and [2H5]glycerol. The subjects were studied after a 12-h fast and again after 60-82 h of fasting. When lipolysis was expressed per unit of adipose tissue the values for the young adults were more than double those for the elderly (P less than 0.05). However, the amount of body fat in the elderly was twice that of the young adults, so that lipolysis per unit of body weight was similar in both groups. These results demonstrate that lipolysis per unit of adipose tissue is lower in elderly subjects. This may be due to their increase in body fat, however, since the total amount of potential energy mobilized from adipose tissue was similar to that of the young adults.

Adipose Tissue↗
PubMed1986

Aortoventriculoplasty in children.

Aortoventriculoplasty was performed in 16 children between July, 1980, and July, 1984. Indications for the procedure were 1) aortic stenosis or insufficiency, or both, necessitating replacement of an aortic valve whose anulus would not accept a 19 mm diameter valve, (2) replacement of a small valve prosthesis, or (3) recurrent tunnel subaortic stenosis. Patients were 5 months to 17 years old at operation, 14 had previous repairs, and four had prior aortic valve replacement. There were 13 long-term survivors followed up for 14 to 38 months; 12 are asymptomatic with normal exercise tolerance. Three had residual ventricular septal defects, two requiring repair. All patients were given warfarin with or without antiplatelet agents. There have been no thromboembolic episodes and no hemorrhagic complications. Aortoventriculoplasty is well tolerated in children and appears to be a viable surgical option in the management of young patients with a hypoplastic left ventricular outflow tract.

Adolescent↗
PubMed1985

Response to glucose and lipid infusions in sepsis: a kinetic analysis.

The kinetics and oxidation of glucose and free fatty acid (FFA) metabolism were assessed in control and Escherichia coli septicemic dogs by using primed, constant infusions of U-14C-glucose and 1,2, 13C-palmitic acid. In the controls, the infusion of glucose suppressed endogenous glucose production completely, whereas, in the septic dogs, only a 30% suppression of glucose production occurred. The ability of the septic dogs to oxidize endogenous or exogenous glucose was decreased significantly. The basal rate of appearance of FFA was significantly higher in the septic dogs, but their ability to oxidize FFA was comparable to that of the control dogs; therefore, the basal rate of FFA oxidation was higher in the septic dogs. These studies indicate that septic dogs have a decreased capacity to oxidize glucose, but that they retain their ability to oxidize long-chain fatty acids. Because the rate of lipolysis was increased in sepsis, lipid was the predominate energy substrate in this septic model.

Animals↗
PubMed1985

Interrelationships of glucose and protein metabolism in obese adolescents during short-term hypocaloric dietary therapy.

We studied the interrelationship of nitrogen balance (N-bal) and rates of glucose appearance (Ra), determined isotopically using U-13C-glucose, in 14 obese adolescents consuming either (1.5 g protein and 1.0 g glucose)/kg ideal body weight/day or an isonitrogenous diet made isocaloric with fat. Nitrogen balance was significantly (p less than .01) more positive with added glucose. Changes in plasma insulin, free fatty acids, or beta-hydroxybutyrate did not reliably predict N-bal. The Ra of glucose decreased significantly on both diets, but was significantly lower (p less than .001) after the addition of fat. A significant correlation of N-bal with Ra (r = 0.70, p less than .01) was observed only in the absence of dietary glucose. Insulin levels correlated with N-bal only in the presence of dietary glucose (r = 0.72, p less than .01). Nitrogen balance in the absence of dietary carbohydrate may be a consequence of net peripheral protein catabolism that is not directly mediated by the need for gluconeogenic precursors.

Adolescent↗
PubMed1985

Glucose and FFA kinetics in sepsis: role of glucagon and sympathetic nervous system activity.

We have assessed the role of glucagon and sympathetic nervous system (SNS) activity on glucose and palmitate kinetics and oxidation in the conscious dog infused with live Escherichia coli bacteria by means of the simultaneous primed constant infusion of [1,2-13C]palmitate and [U-14C]-glucose. The basal rate of glucose production in septic dogs and controls was similar. However, when the glucagon concentration was selectively decreased in the septic animals by the appropriate infusion of somatostatin (S), insulin (I), and glucagon (G), the rate of glucose production decreased significantly, whereas in control animals S + I + G infusion had no effect on glucose kinetics. When alpha- and beta-adrenergic blockade was added to the infusion, the rate of glucose production decreased further and hypoglycemia developed in the septic dogs, whereas in the controls both glucose production and concentration increased. The basal rate of appearance of palmitate was increased in the septic dogs (P less than 0.01). S + I + G had no effect on palmitate appearance in either group, and sympathetic blockade caused a significant decrease in palmitate appearance in both groups of dogs. The rates of oxidation of both glucose and palmitate was related directly to their availability in plasma. Thus, in sepsis, glucagon and SNS activity play important roles in the mobilization of glucose and palmitate into the plasma and therefore in the overall state of energy metabolism.

Animals↗
PubMed1985

Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion.

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.

Animals↗
PubMed1985

Increased lung vasoreactivity in children from Leadville, Colorado, after recovery from high-altitude pulmonary edema.

Cardiac catheterization was performed on seven children after recovery from high-altitude pulmonary edema. All were life-long residents at elevations above 10,000 feet. Three of the seven had developed pulmonary edema without antecedent travel to low altitude but had an upper respiratory infection. Response of pulmonary arterial pressure to 16% inspired oxygen in all seven was compared with that in six well children who resided at a similar altitude and had no history of high-altitude pulmonary edema. With hypoxia the susceptible patients had a greater mean pulmonary arterial pressure (56.3 +/- 23.8) than the nonsusceptible children (18.8 +/- 3.9, p less than .05). Comparison with historical hemodynamic responses in children at high altitudes showed a similar greater mean pulmonary arterial pressure in the susceptible children. Thus, in children from high altitudes, increased pulmonary vasoreactivity to hypoxia may play a role in the pathogenesis of high-altitude pulmonary edema. The development of pulmonary edema in high-altitude residents with upper respiratory infections and no antecedent low-altitude journey is consistent with the presence of other factors such as inflammation, which may play a role in the pathogenesis of the edema. The finding of right ventricular hypertrophy on an electrocardiogram in children from high altitudes may be predictive of their susceptibility to high-altitude pulmonary edema.

Altitude↗
PubMed1985

Substrate cycling between gluconeogenesis and glycolysis in euthyroid, hypothyroid, and hyperthyroid man.

Substrate, or futile cycles, have been hypothesized to be under hormonal control, and important in metabolic regulation and thermogenesis. To define the role of thyroid hormones in the regulation of substrate cycling in glycolysis and gluconeogenesis, we measured rates of cycling in normal (n = 4), hypothyroid (n = 5), and hyperthyroid (n = 5) subjects employing a stable isotope turnover technique. Glucose labeled with deuterium at different positions (2-D1-, 3-D1-, and 6,6-D2-glucose) was given as a primed-constant infusion in tracer doses, and arterialized plasma samples were obtained and analyzed by gas-chromatography mass-spectrometry for the steady state enrichment of glucose that was labeled at the various positions. The rate of appearance (Ra) was then calculated for each isotopic tracer. The difference between the Ra determined by 2-D1-glucose (Ra2) and the Ra determined by 3-D1-glucose (Ra3) represents the substrate cycling rate (SCR) between glucose and glucose-6-phosphate. The difference between the Ra determined by 3-D1-glucose (Ra3) and the Ra determined by 6,6-D2-glucose (Ra6) represents the SCR between fructose-6-phosphate and fructose-1,6-diphosphate. The difference between Ra2 and Ra6 represents the combined SCR of both cycles. In normal subjects (serum thyroxine [T4] = 8.4 +/- 1.2 microgram/dl (all expressions, mean +/- SD), n = 4), the rates of appearance for Ra2, Ra3, and Ra6 were 3.23 +/- 0.56, 2.64 +/- 0.50, and 2.00 +/- 0.27 mg/kg X min, respectively, whereas those in the hypothyroid subjects (T4 = 1.0 +/- 0.8 microgram/dl; n = 5) were 1.77 +/- 0.56 (P less than 0.01), 1.52, 1.57 +/- 0.31 (P less than 0.05) mg/kg X min, respectively. Conversely, the rates of appearance for Ra2 and Ra6 in the hyperthyroid subjects (T4 = 23.9 +/- 3.6 micrograms/dl) were 3.94 +/- 0.43 (P less than 0.05) and 2.54 +/- 0.22 (P less than 0.02), respectively, compared with the normal subjects. On the basis of these data, we noted that the normal subjects had a combined SCR of 1.23 +/- 0.35 mg/kg X min. In contrast, the hypothyroid patients had a significantly decreased combined SCR, 0.20 +/- 0.54 mg/kg X min (P less than 0.02). The hyperthyroid patients had a combined SCR of 1.39 +/- 0.23 mg/kg X min (P less than NS). To determine whether these cycles responded to thyroid hormone treatment, these same hypothyroid subjects were acutely treated for 1 wk with parenteral 50 micrograms/d sodium L-triiodothyronine and chronically with 100-150 micrograms/d L-thyroxine. After 7 d, their mean oxygen consumption rate and carbon dioxide production rate increased significantly from 102+/-13 micromol/kg.min, to 147+/-34 micromol/kg.min (P<0.05), and from 76+/-13 micromol/kg.min to 111+/-19 micromol/kg.min (P<0.05), respectively. The combined SCR (Ra(2)--Ra(6) remained unchanged at 0.07+/-0.37 mg/kg.min. However, after 6 mo of oral L-thyroxine therapy (T(4)=9.5+/-1.4 microgram/kl) the treated hypothyroid patients had increased their combined SCR (Ra(2)--Ra(6)) to 0.86 +/-0.23 mg/kg.min (P<0.02), a value not significantly different from the combined SCR of normal subjects. We conclude that substrate cycling between glucose and glucose-6-phosphate and between fructose-6-phosphate and fructose-1,6-diphosphate occurs in man and is affected by thyroid hormone. Substrate cycles may represent a mechanism by which thyroid hormone alters the sensitivity of certain reactions to metabolic signals.

Adult↗
PubMed1985

Pulmonary vascular response to oxygen in infants with severe bronchopulmonary dysplasia.

The cardiac catheterization data of six infants with bronchopulmonary dysplasia (BPD) were reviewed to examine the responsiveness of their pulmonary vascular beds to changes in oxygen tension. The infants were studied because of slow recovery from their oxygen requirements and clinical evidence of persistent pulmonary hypertension. All were receiving home oxygen therapy and had abnormal chest radiographs and right ventricular hypertrophy by ECG at the time of catheterization (mean age, 25 months). All infants had mean pulmonary artery pressure greater than 25 mm Hg in room air, with a mean of 48 mm Hg. All decreased mean pulmonary artery pressure by at least 10 mm Hg when placed in high levels of inspired oxygen (FiO2 greater than 80), with a mean pulmonary artery pressure of 25 mm Hg. This represented a significant decrease in mean pulmonary artery pressure from room air pressures (P less than .005). Mean pulmonary artery pressure was also measured in three infants who were breathing supplemental oxygen by nasal cannula at flow rates similar to levels used for outpatient therapy. Most of the reduction in mean pulmonary artery pressure that occurred at high FiO2 occurred at these lower flow rates of supplemental oxygen. It is concluded that infants with bronchopulmonary dysplasia who have pulmonary hypertension generally have reactive pulmonary vascular beds, responsive to supplemental oxygen. Continuous oxygen therapy by nasal cannula may be useful in the treatment of pulmonary hypertension associated with bronchopulmonary dysplasia.

Bronchopulmonary Dysplasia↗