PubMed Health⌕ Search

Biomedical subjects

M A Pfeifer

Publications and source records attributed to M A Pfeifer.

At least 37 records · Page 2Linked to original sources
PubMed1989

Depression in obese men.

Using the Beck depression inventory (BDI), we studied depression in young, healthy, male subjects who represented a wide range of body weight. Body mass index (BMI), defined as the weight (in kilograms) divided by the square of height (in meters), was used to classify subjects as obese (BMI greater than 31.1, n = 27), overweight (BMI = 27.8-31.1, n = 10) or acceptable weight (BMI less than 27.8, n = 26). BDI scores of 0-9 indicated no depression; scores of 10-15 indicated mild depression. BDI scores from 16 to 63 indicated increasing depression. No group of subjects (obese, overweight or acceptable weight subjects), had mean BDI scores suggesting depression. The mean BDI score for the obese subjects was 5.6 +/- 0.8 (mean +/- s.e.m.), which was significantly higher than the mean BDI scores for both the overweight subjects (2.5 +/- 1.1; P less than 0.04) and the acceptable weight subjects (1.5 +/- 0.3; P less than 0.001). There was a weak positive correlation of BDI with BMI (n = 63, r = 0.404, P less than 0.001). In addition, the obese subjects did form a heterogeneous group with four obese subjects (14.8 percent) having BDI score of 10 or greater. The overweight subjects had one subject (10 percent) with a BDI score of 12. None of the acceptable weight subjects had a BDI score of greater than 5. There was no correlation between waist/hip ratios and BDI scores (n = 37, r = 0.262, P = 0.118). We conclude that mild depression is present in some obese persons even when medically healthy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Diabetic autonomic neuropathy--Part I. Autonomic nervous system data analysis by a computerized central unit in a multicenter trial.

To determine the feasibility of utilizing a central, computerized unit to analyze autonomic nervous system function tests for a 10-year, multicenter, clinical trial, the Autonomic Nervous System Reading Center was established. The Reading Center selected and standardized testing methods, designed the testing protocol, developed testing equipment, computerized data analysis, and instituted measures to monitor data quality. Three cardiovascular testing methods, RR-variation, Valsalva maneuver, and postural testing, were selected because each is a simple, non-invasive, quantitative, sensitive, and reproducible test. Furthermore, a hierarchy of sensitivity has been established with these cardiovascular autonomic nervous system measurements: RR-variation, Valsalva maneuver, and finally postural testing. Confounding variables were minimized by prescribing eligibility criteria. Testing equipment, designed to record time between RR intervals in a form easily read into a computer, has been in 21 clinics for three years and a total of 54 technicians have been trained. Over 85 percent of the autonomic nervous system tests performed have been usable at initial testing. A central reading center is an efficient and necessary means of collecting and analyzing data for a multicenter clinical trial.

Autonomic Nervous System Diseases↗
PubMed1988

Diabetic autonomic neuropathy--Part II. Coefficient of variation of RR-variation and Valsalva maneuver tests.

To confirm the reliability and validity of cardiovascular autonomic nervous system tests, RR-variation and Valsalva maneuver, coefficient of variation for triplicate tests was calculated. The testing data were collected from patients participating in the Statil Neuropathy Trial. Triplicate testing was done within a three-week period at three different time points: baseline, 12 months, and 18 months. BMDP Statistical Software was used in the analysis. There is no significant difference between the coefficients of variation between clinics for either RR-variation or Valsalva maneuver tests. The coefficient of variation of pooled data was not significantly different from the coefficient of variation of individual clinics. Furthermore, there was no evidence that there was a significant worsening of coefficient of variation with time. Thus, RR-variation and Valsalva maneuver provide reliable and reproducible results that do not vary in consistency over time.

Autonomic Nervous System Diseases↗
PubMed1988

Body fat and the activity of the autonomic nervous system.

The cause of most cases of human obesity is unknown. Specific alterations in the activity of the autonomic nervous system may mediate and perhaps cause obesity in animal models. We therefore looked for alterations in autonomic activity in human obesity. Fifty-six healthy men with various percentages of body fat underwent autonomic testing while at rest. Significant correlations were found between the percentage of body fat and the variation in the R-R interval after beta-adrenergic blockade (r = -0.30, P less than 0.03), the heart rate (r = 0.30, P less than 0.03), the plasma norepinephrine concentration (r = -0.30, P less than 0.05), the plasma epinephrine concentration (r = -0.49, P less than 0.001), and the pupillary latency period (r = 0.39, P less than 0.01). Each of these variables reflects the activity of the sympathetic nervous system or parasympathetic nervous system or both. Depressions in sympathetic and parasympathetic activity were significantly but weakly associated with increasing percentages of body fat. These associations indicate that in obese persons, autonomic changes, though not necessarily causal, involve several organ systems. We suggest that autonomic alterations are important in human obesity, as they are in animal obesity. A disordered homeostatic mechanism may promote excessive storage of energy by decreasing sympathetic activity, while defending against weight gain by decreasing parasympathetic activity. The use of autonomic profiles holds promise for classifying human obesity and identifying obese patients at increased risk for various disorders.

Adipose Tissue↗
PubMed1988

RR-variation: the autonomic test of choice in diabetes.

RR-variation is a sensitive, reproducible, and noninvasive autonomic test. It is simple to perform and easy for both the operator and the subject. Furthermore, RR-variation correlates to known physiologic function. It therefore fulfills many of the characteristics of a practical diagnostic test. Many of the confounding factors are known, and with proper standardization the test may not only have diagnostic capabilities but also predictive value. RR-variation should be included in clinical research trials of diabetic neuropathy and should be considered in routine clinical management of the diabetic patient.

Autonomic Nervous System↗
PubMed1988

Peripheral diabetic neuropathy.

Diabetic neuropathy is a common complication of diabetes mellitus with significant morbidity and mortality. Hyperglycemia with its secondary metabolic, vascular, and enzymatic consequences is most likely to be the predominant cause. The clinical manifestations includes a wide range of somatic and autonomic syndromes. Painful diabetic neuropathy may require symptomatic treatment. The precise role of therapies such as continuous subcutaneous insulin therapy and aldose reductase inhibitors remains to be clarified.

Autonomic Nervous System Diseases↗
PubMed1987

Development of a method to determine autonomic nervous system function in the rat.

A noninvasive method to evaluate autonomic nervous system (ANS) function in animals is needed for studies of diabetic autonomic neuropathy. These studies modified the RR-variation test, used to test diabetic ANS function in humans, and applied it to rats. Permanent wire electrodes were implanted in the chest wall of a rat. ECG complexes were obtained by connecting the electrodes to leads going to an impedence pneumograph and high gain coupler. This information was then converted into square waves by a trigger unit and recorded on magnetic tape for subsequent analysis by computer. Recordings were at least 60 seconds long, of which 30 seconds was used for analysis. In order to establish autonomic influence, RR-variation was measured before and after application of pharmacologic agents. Directly decreasing parasympathetic tone with atropine (20 mg/kg, n = 6) increased heart rate (P less than 0.001) and decreased RR-variation (P less than 0.05). Directly decreasing beta adrenergic tone with propranolol (10 mg/kg, n = 7) decreased heart rate (P less than 0.01) but had no effect on RR-variation (NS). Stimulation of the beta adrenergic receptors (isoproterenol, 0.1 mg/kg, n = 5) increased heart rate (P less than 0.01) but decreased RR-variation (P less than 0.01). Increasing parasympathetic tone reflexly with alpha-1 adrenergic receptor stimulation (phenylephrine, 1 mg/kg, n = 7) decreased heart rate (P less than 0.05) and increased RR-variation (P less than 0.025). The responses to phenylephrine could be blocked by parasympathetic blockade. Phentolamine (0.1 mg/kg, n = 7) caused an increase in heart rate (P less than 0.001) and a decrease in RR-variation (P less than 0.01). The responses to phentolamine could be blocked by beta adrenergic receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1987

The hemodynamic effects of sympathetic stimulation combined with parasympathetic blockade in man.

To define the effects of circulating norepinephrine and epinephrine on cardiac function and to determine whether left ventricular function is influenced by parasympathetic mechanisms during catecholamine stimulation, hemodynamic changes were investigated in healthy young human subjects who were supine and awake during infusion of intravenous norepinephrine alone (125 ng/kg/min) (n = 6), norepinephrine (125 ng/kg/min) plus epinephrine (50 ng/kg/min) (n = 6), and norepinephrine plus epinephrine plus parasympathetic blockade induced by atropine (2 mg intravenously) (n = 5). Ejection fraction and changes in cardiac volumes were measured by radionuclide ventriculography. During the infusion of norepinephrine plus epinephrine, plasma norepinephrine increased from 358 +/- 35 to 1782 +/- 123 pg/ml (mean +/- SE) and plasma epinephrine increased from 31 +/- 5 to 355 +/- 90 pg/ml (both p less than .01 vs baseline). These increases in plasma catecholamines were associated with increases in the heart rate (58 +/- 3 to 67 +/- 2 beats/min, p = NS), systolic blood pressure (113 +/- 3 to 140 +/- 6 mm Hg, p less than .01), ejection fraction (0.64 +/- 0.02 to 0.72 +/- 0.02 ejection fraction units, p less than .01), stroke volume (+41 +/- 5%, p less than .01), and cardiac output (+54 +/- 8%, p less than .01), and a decrease in systemic vascular resistance (-31 +/- 3%, p less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Alpha-adrenergic blockade improves glucose-potentiated insulin secretion in non-insulin-dependent diabetes mellitus.

The impairment of glucose-potentiated insulin secretion present in non-insulin-dependent diabetes mellitus (NIDDM) can be approximated in normal subjects by an epinephrine infusion. Therefore, we sought to determine the role of the endogenous sympathetic nervous system in glucose-potentiated insulin secretion in both NIDDM (n = 6) and normal (n = 6) subjects. Glucose-potentiated insulin secretion was calculated as the slope of the curve relating increasing ambient glucose levels to the acute insulin response to an intravenous pulse of 5 g of L-arginine. Glucose-potentiated insulin secretion was determined on separate days during alpha-, beta-, and combined alpha- plus beta-adrenergic blockade and compared with a saline control. In normal subjects, there was no effect of alpha-, beta-, or alpha- plus beta-blockade on the slope of glucose potentiation. In NIDDM, the initially decreased slope of glucose potentiation (0.25 +/- 0.06 microU X ml-1 X mg-1 X dl, mean +/- SE; P less than .01) was not affected by beta-blockade but increased during alpha-blockade (0.91 +/- 0.22 microU X ml-1 X mg-1 X dl; P less than .05). However, this improvement was abolished by combined alpha- plus beta-blockade (0.32 +/- 0.07 microU X ml-1 X mg-1 X dl). Plasma norepinephrine was increased above basal levels in both normal (+260 +/- 89 pg/ml) and NIDDM (+438 +/- 162 pg/ml) subjects during alpha-blockade (P less than .05 for both). This increase in plasma norepinephrine strongly suggests that there is an increase in synaptic cleft norepinephrine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1986

Clinical trials of sorbinil on nerve function.

Three clinical trials to evaluate the efficacy of the aldose reductase inhibitor sorbinil in improving or preventing diabetic neural function have either been completed or are currently in progress. In the first study from Seattle and Chicago, motor and sensory nerve conduction velocities (NCV) were evaluated in 39 insulin- and noninsulin-dependent, glycemic-stable diabetic patients in a randomized, double-blind, crossover trial. During the 9 weeks of treatment with 250 mg/d of sorbinil, there was a faster nerve conduction velocity of all 3 nerves tested when compared with the placebo period: peroneal motor NCV (+0.70 +/- 0.24 m/s; means +/- SEM; P less than 0.008), median motor NCV (+0.66 +/- 0.27 m/s; P less than 0.005), and median sensory NCV (+1.16 +/- 0.50 m/s; P less than 0.035). Conduction velocity for all 3 nerves declined significantly within 3 weeks following cessation of the drug. These effects of sorbinil were unrelated to glycemic control, which was constant during the study. Although the effects of sorbinil in improving nerve conduction velocity were small, the findings suggest that the polyol-pathway activity contributes to slowed nerve conduction velocity in diabetics. The second study is a seven-center, double-blind, randomized, 12-month trial of 210 to 280 diabetic patients with clinical signs, symptoms, and objective measurements of neuropathy. The trial has a common-core protocol with end-point evaluations of scored neural signs, symptoms, and neural measurements. Two unique neural tests were designed and validated for use in this trial: thermal and tactile perception thresholds of the fingers and toes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1986

Development of a predictive model for symptomatic neuropathy in diabetes.

In evaluating therapeutic interventions aimed at preventing diabetic neuropathy, choosing a suitable measure of neural function is difficult, partly because the relation between most available objective measures and the development of symptomatic neuropathy (SN) is unclear. Using data from 67 diabetic patients, we developed a linear logistic regression model to assess the relationship between SN and a set of neural measures, including dark-adapted pupil size; pupillary latency; heart rate; a measure of respiratory sinus arrhythmia (R); the Valsalva ratio; and conduction velocities for the peroneal, median motor, and median sensory nerves. Models allowed for possible effects related to age, sex, duration and type of diabetes, glycosylated hemoglobin, and adiposity. Thirty-two of the patients reported SN (autonomic and/or sensorimotor). The best-fitting model for predicting the presence of any SN included only heart rate, duration of disease, and R. Exclusion of duration (P less than .01), or heart rate (P less than .05), or R (P less than .001) significantly impaired the fit of the model. To evaluate the temporally predictive power of the model, nine of the asymptomatic patients were reinterviewed 2 yr later by the same interviewer, who was unaware of the results of the modeling. Four of five to whom the model had assigned high probability of symptoms had indeed developed SN during the follow-up period, whereas none of the four assigned low probability had developed SN (P less than .05). Thus it seems that a measure of respiratory sinus arrhythmia provides an index of neural function strongly related to SN, and our follow-up data suggest that diminished R can be used to predict the development of SN in diabetes.

Adult↗
PubMed1985

Effects of glycemic control and aldose reductase inhibition on nerve conduction velocity.

In two studies of patients with diabetes who did not have neurologic symptoms, nerve conduction velocity was increased either by an improvement in glucose control or by the administration of the aldose reductase inhibitor sorbinil. In a 1981 study by Graf et al, glycemic control and motor and sensory nerve conduction velocities were evaluated in 18 patients with non-insulin-dependent diabetes before and after one, three, six, and 12 months of antihyperglycemic therapy. There was an improvement in motor nerve conduction velocity (median motor, p less than 0.01; peroneal motor, p less than 0.05; and tibial motor, p less than 0.05), which was associated with the improvement in fasting plasma glucose levels after three months for some motor nerves (median motor: r = -0.62, p less than 0.01; peroneal motor: r = -0.50, p less than 0.05). A direct linear relationship between the change in fasting glucose and glycosylated hemoglobin levels and the change in median motor nerve conduction velocity after 12 months of antihyperglycemic therapy was also found. Thus, there was a tendency for those patients who had the greatest improvement in glycemic control to have the greatest improvement in motor nerve conduction velocity. The findings in the first study are consistent with the hypothesis that hyperglycemia contributes to slowed nerve conduction velocity. In a 1983 randomized, double-blind, crossover study by Judzewitsch et al, motor and sensory nerve conduction velocities were evaluated in 39 patients with insulin-dependent or non-insulin-dependent diabetes in whom glycemic control was stable. During nine weeks of treatment with 250 mg per day of sorbinil, nerve conduction velocity was faster in the three tested nerves when compared with the velocities during the placebo period (peroneal motor nerve conduction velocity: +0.70 +/- 0.24 m per second, mean +/- SEM, p less than 0.008; median motor nerve conduction velocity: +0.66 +/- 0.27 m per second, p less than 0.005; median sensory nerve conduction velocity: +1.16 +/- 0.50 m per second, p less than 0.035). Although the effect of an improvement in glycemic control and administration of sorbinil in increasing nerve conduction velocity in two groups of neurologically asymptomatic patients with diabetes was small, the findings are consistent with the hypothesis that polyol pathway activity contributes to slowed large-fiber nerve conduction velocity in these patients.

Aldehyde Reductase↗
PubMed1985

Glucose regulation in non-insulin-dependent diabetes mellitus. Interaction between pancreatic islets and the liver.

The degree of fasting hyperglycemia in patients with non-insulin-dependent diabetes mellitus is dependent on the rate of hepatic glucose production. The basal rate of hepatic glucose production is increased in patients with non-insulin-dependent diabetes mellitus, and there is a positive correlation between hepatic glucose production and fasting glucose levels. Diminished secretion of insulin, impaired hepatic sensitivity to insulin's effects, or a combination of these factors could contribute to the elevated hepatic glucose production in patients with non-insulin-dependent diabetes mellitus. The relationship between insulin secretion and hepatic glucose production is regulated by a closed feedback loop operating between glucose levels and pancreatic beta cells. Although fasting insulin levels are usually comparable between patients with non-insulin-dependent diabetes mellitus and normal subjects, insulin secretion is markedly impaired in non-insulin-dependent diabetes mellitus in relation to the degree of hyperglycemia present. In fact, the degree of fasting hyperglycemia in a given patient with non-insulin-dependent diabetes mellitus is closely related to the degree of impaired pancreatic beta-cell responsiveness to glucose. Such findings suggest that impaired insulin secretion leads to increased hepatic glucose production, which raises the plasma glucose level. The resulting hyperglycemia helps to maintain relatively normal basal insulin output. Chronic sulfonylurea drug therapy of patients with non-insulin-dependent diabetes mellitus enhances pancreatic islet sensitivity to glucose, leading to increased insulin secretion, suppression of hepatic glucose production, and a decline in the steady-state fasting glucose level.

Arginine↗
PubMed1985

Pentobarbital suppresses basal and reflexive pancreatic polypeptide release in dogs.

We sought to determine in overnight-fasted dogs whether basal or 2-deoxy-D-glucose (2-DG)-stimulated levels of pancreatic polypeptide (PP) could be reliably used as an index of cholinergic activity at the pancreas and thereby determine the effect of pentobarbital anesthesia on this cholinergic outflow. At low basal PP levels, either atropine or pentobarbital had a small effect on PP levels; at higher basal levels, both atropine and pentobarbital had a larger effect. Thus both drugs decreased PP in proportion to its initial basal level, suggesting that basal PP levels have a variable cholinergic component. Atropine abolished the PP response to intravenous 2-DG, confirming in our animal model that the PP response to neuroglucopenia is entirely cholinergically mediated. Pentobarbital also abolished the PP response to 2-DG, suggesting that anesthesia either suppresses cholinergic outflow to the pancreas or the response of the pancreatic F-cell to it. To test the latter hypothesis, the acetylcholine analogue bethanechol was administered before and during pentobarbital anesthesia. The PP response to direct cholinergic stimulation was not abolished by pentobarbital, although it was reduced modestly. We conclude that only part of the basal level of PP is under cholinergic control; all of the PP response to 2-DG is cholinergically mediated; pentobarbital anesthesia abolishes the cholinergic input to the pancreas; and if the endogenous cholinergic input influences certain pancreatic endocrine and exocrine responses, then its contribution would be seriously underestimated when studied in pentobarbital-anesthetized animals.

Animals↗