Search PubMed⌕ Search

Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 73 records · Page 4Linked to original sources
PubMed1990

Age-related differences in norepinephrine kinetics: effect of posture and sodium-restricted diet.

We used compartmental analysis to study the influence of age on the kinetics of norepinephrine (NE) distribution and metabolism. Plasma NE and [3H]NE levels were measured in 10 young (age 19-33 yr) and 13 elderly (age 62-73 yr) subjects in the basal supine position, during upright posture, and after 1 wk of a sodium-restricted diet. We found that the basal supine release rate of NE into the extravascular compartment, which is the site of endogenous NE release (NE2), was significantly increased in the elderly group (young, 9.6 +/- 0.5; elderly, 12.3 +/- 0.8 nmol.min-1.m-2; means +/- SE; P = 0.016), providing direct evidence for an age-related increase in sympathetic nervous system (SNS) tone. Although upright posture led to a greater increase in plasma NE in the young (0.90 +/- 0.07 to 2.36 +/- 0.16 nM) than in the elderly (1.31 +/- 0.11 to 2.56 +/- 0.31 nM; age group-posture interaction, P = 0.02), the increase in NE2 was similar between the young (9.6 +/- 0.6 to 16.2 +/- 1.5 nmol.min-1.m-2) and the elderly (11.6 +/- 1.4 to 16.1 +/- 2.4 nmol.min-1.m-2; posture effect, P = 0.001; age group-posture interaction, P = 0.15). Thus the increase in SNS tone resulting from upright posture was similar in young and elderly subjects. Plasma NE levels increased similarly in both groups after a sodium-restricted diet (diet effect, P = 0.001; age group-diet interaction, P = 0.23). However, NE2 did not increase significantly in either group (diet effect, P = 0.26), suggesting that SNS tone did not increase after a sodium-restricted diet. Compartmental analysis provides a description of age-related differences in NE kinetics, including an age-related increase in the extravascular NE release rate.

Adult↗
PubMed1990

Glucagon, catecholamine and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts.

Successful pancreas transplantation in type I diabetic patients restores normal fasting glucose levels and biphasic insulin responses to glucose. However, virtually no data from pancreas recipients are available relative to other islet hormonal responses or hormonal counterregulation of hypoglycemia. Consequently, glucose, glucagon, catecholamine, and pancreatic polypeptide responses to insulin-induced hypoglycemia and to stimulation with arginine and secretin were examined in 38 diabetic pancreas recipients, 54 type I diabetic nonrecipients, and 26 nondiabetic normal control subjects. Glucose recovery after insulin-induced hypoglycemia in pancreas recipients was significantly improved. Basal glucagon levels were significantly higher in recipients compared with nonrecipients and normal subjects. Glucagon responses to insulin-induced hypoglycemia were significantly greater in the pancreas recipients compared with nonrecipients and similar to that observed in control subjects. Glucagon responses to intravenous arginine were significantly greater in pancreas recipients than that observed in both the nonrecipients and normal subjects. No differences were observed in epinephrine responses during insulin-induced hypoglycemia. No differences in pancreatic polypeptide responses to hypoglycemia were observed when comparing the recipient and nonrecipient groups, both of which were less than that observed in the control subjects. Our data demonstrate significant improvement in glucose recovery after hypoglycemia which was associated with improved glucagon secretion in type I diabetic recipients of pancreas transplantation.

Arginine↗
PubMed1990

Role of the central nervous system in hemodynamic and sympathoadrenal responses to cocaine in rats.

These studies were undertaken to examine the contribution of central nervous system mechanisms to the cardiovascular and sympathoadrenal effects of cocaine. Changes in systolic and diastolic blood pressure, heart rate and plasma catecholamine concentrations were determined in response to cocaine injected i.a. or i.c.v. in conscious unrestrained rats. Systemically administered cocaine produced brisk, transient dose-related increases in systolic and diastolic pressure at doses of 0.05 to 5 mg/kg i.a. Plasma catecholamine concentrations increased in a dose-related manner, reaching peak levels at 5 to 10 min after i.a. cocaine injection. Only the higher doses of cocaine induced reflex vagal bradycardia that was blocked by atropine (0.4 mg/kg i.a.). Propranolol (1 mg/kg i.a.) prolonged the duration of cocaine-induced hypertension and bradycardia. Ganglionic blockade with chlorisondamine (7.5 mg/kg i.a.) antagonized completely the cardiovascular and sympathoadrenal effects of cocaine, indicating that intact ganglionic transmission is required for full expression of the autonomic responses. Antagonist drugs selective for the D-1 or D-2 dopamine receptors attenuated effects of cocaine on plasma catecholamine concentrations but not on cardiovascular parameters. Intracerebroventricular injection of cocaine (50-250 micrograms) increased systolic pressure and plasma catecholamine concentrations, providing direct evidence for an action of cocaine in the central nervous system. These results demonstrate that cocaine acts centrally to increase sympathetic outflow leading to hypertension and reflex bradycardia in conscious rats.

Animals↗
PubMed1989

Altered norepinephrine metabolism in Shapiro's syndrome.

We studied a 66-year-old woman with spontaneous periodic hypothermia (Shapiro's syndrome) to determine the mechanisms that result in increased plasma norepinephrine (NE) levels. In comparison with age-matched control subjects, compartmental analysis of NE kinetics revealed an increased NE release rate into the extravascular compartment and decreases in NE clearance and volume of distribution of NE in the intravascular compartment. Clonidine therapy was associated with an initial dramatic decrease in the frequency of diaphoretic episodes as well as with a fall in NE release rate and increases in NE clearance and volume of distribution. We conclude that increased NE release and decreased plasma NE clearance result in elevated plasma NE levels in Shapiro's syndrome. Clonidine, which was associated with changes in NE kinetics, may provide effective treatment for this disorder.

Aged↗
PubMed1989

Impaired sympathetic nervous system response to cognitive effort in early Alzheimer's disease.

Sympathetic nervous system responses to a cognitive challenge and a physiologic stimulus (upright posture) were compared in 10 patients with early Alzheimer's Disease and a group of healthy older adults. Plasma catecholamine and cardiovascular responses to upright posture were similar in the two groups. However, sympathetic activation during mental effort was impaired in the patient group; this difference did not appear to be attributable to motivational factors. Alzheimer's Disease is associated with a defect in sympathetic nervous system function that is specifically linked to cognitive effort and appears early in the course of the disease.

Aged↗
PubMed1989

Effects of low-sodium diet on regulation of platelet alpha 2-adrenergic receptors in young and elderly humans.

To examine whether there are age differences in agonist-mediated alpha 2-adrenergic receptor (alpha 2-AR) regulation, we studied the effect of a sustained increase in plasma norepinephrine (pNE) during a 7-day 10-meq Na+/day diet on platelet alpha 2-AR binding and its linked adenylate cyclase (AC) activity in 11 elderly and 11 young healthy subjects. In the young, a 41% increase in mean pNE after a low-sodium diet was correlated with a decline in receptor density (Bmax; r = -0.816; P less than 0.01) and was accompanied by a reduction in the maximal percent inhibition of sodium fluoride-stimulated AC activity by epinephrine (%AC INH; 33 +/- 4 vs. 24 +/- 4%, mean +/- SE; P less than 0.05 vs. normal diet). Despite a comparable 39% increase in mean pNE in the elderly, neither Bmax nor %AC INH was significantly reduced after a low-sodium diet. The amount of pertussis toxin substrate (Gi protein) was similar in both groups before and after dietary sodium restriction. At comparable pNE, %AC INH in the groups was similar (young, 24 +/- 4 vs. elderly, 18 +/- 4%; P = NS). We postulate that higher basal pNE levels in the elderly on normal diet may account for the lack of further downregulation of platelet alpha 2-AR density and response after low-sodium diet.

Adult↗
PubMed1989

Downregulation of beta-adrenergic receptor-mediated function during sodium restriction in humans.

Mononuclear leukocyte (MNL) beta 2-adrenergic receptor (beta 2-AR) binding and its linked adenylate cyclase sensitivity to isoproterenol were measured in nine healthy humans prior to and after 7 days of dietary sodium restriction to determine whether chronic physiological increases in plasma norepinephrine (NE) are associated with the downregulation of beta-AR-mediated function. Sodium restriction resulted in an increase in the plasma NE concentration (P less than 0.02) and decreases in MNL beta 2-AR density (P less than 0.001), affinity for antagonist (P less than 0.001), and adenylate cyclase sensitivity to isoproterenol (ANOVA, P less than 0.01). To determine whether this downregulation of MNL beta 2-AR-mediated function is related to the increased plasma NE concentration or to increased extravascular NE release, NE kinetics was assessed using compartmental analysis in each subject prior to and after sodium restriction. Sodium restriction caused a decrease in the plasma NE metabolic clearance rate (P less than 0.005) and in the volume of distribution of NE in the intravascular compartment (P less than 0.005), whereas the extravascular NE release rate was unchanged. Our data suggest that the downregulation of MNL beta 2-AR-mediated function in humans during dietary sodium restriction is a response to the increase in plasma NE.

Adenylyl Cyclases↗
PubMed1989

Atrial natriuretic factor in the elderly: diminished response to epinephrine.

We have previously found that epinephrine (EPI) increases plasma immunoreactive atrial natriuretic factor (irANF) in young human subjects. Because elderly humans have decreased sensitivity to adrenergic stimulation, we compared plasma irANF responses to intravenous infusion of EPI, 5 micrograms/min for 80 min in six young (ages 20-29) and nine old (ages 62-75) healthy subjects. In addition, we measured plasma irANF responses of the nine old subjects to 1 liter of normal saline infused over 30 min. Young and old subjects had similar basal EPI levels [108 +/- 18 vs. 106 +/- 10 (SE) pg/ml], but basal irANF levels tended to be higher in the old (32 +/- 7 vs. 50 +/- 8 pmol/l, P = 0.15). The young subjects had a significant increase in irANF levels after the EPI infusion (32 +/- 7 vs. 59 +/- 11 pmol/l, P less than 0.02), but there was no change in irANF in the old (50 +/- 8 vs. 48 +/- 7 pmol/l) despite similar plasma EPI levels in young and old (1,125 +/- 57 vs. 1,183 +/- 52 pg/ml). In contrast, the irANF response of the old subjects to saline infusion was striking: all nine subjects demonstrated a rise in irANF (P less than 0.01); mean levels increased from 54 +/- 4 pmol/l to a peak of 122 +/- 23 pmol/l. We conclude that healthy elderly subjects have a defect in EPI-stimulated ANF secretion, a finding compatible with other evidence for diminished sensitivity to adrenergic stimulation in aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Epinephrine kinetics in humans: radiotracer methodology.

The use of the plasma epinephrine (EPI) level as an index of adrenomedullary activity in humans is complicated by the rapid removal of EPI from plasma by many tissues. To determine whether the kinetics of distribution and metabolism of EPI could be best quantified using the isotope dilution method or a mathematical modeling technique, eight human subjects received a [3H]EPI infusion for 50-60 min. Analysis of the steady state arterialized plasma levels of EPI and [3H]EPI using the isotope dilution technique showed that the basal plasma EPI appearance rate is 0.87 +/- 0.11 nmol/m2.min, and the basal plasma EPI clearance rate is 1.63 +/- 0.14 L/min.m2. Mathematical modeling of the [3H]EPI levels revealed that a biexponential curve fit was superior to monoexponential and triexponential curve fits. A two-compartment model was the minimal compartment model that accurately described EPI kinetics. The basal plasma EPI appearance (0.82 +/- 0.16 nmol/m2.min) and EPI clearance (1.67 +/- 0.15 L/min.m2) rates that were estimated from this two-compartment model are similar to the results derived from the isotope dilution method. Mathematical modeling revealed a large extravascular mass of EPI. We conclude that the isotope dilution and mathematical modeling techniques similarly describe plasma EPI kinetics in humans. Kinetic analysis using mathematical modeling provides new insights into adrenomedullary function in humans.

Adult↗
PubMed1988

Endocrine markers of aging.

Sophisticated methods available to quantitate hormone secretion and hormone action provide opportunities to identify potential endocrine biomarkers of aging. However, there are many challenges facing the investigator who wishes to establish an endocrine biomarker. Circulating levels of many hormones fluctuate on a circadian rhythm, and a variety of other short-term fluctuations may occur. Hormone secretion is generally tightly regulated and often affected by multiple, redundant feedback mechanisms. Interpretation of circulating hormone levels must also take into account factors affecting hormone metabolism and degradation which may be influenced by age. The rate of hormone secretion and circulating hormone levels are related to the sensitivity to hormone action by feedback control mechanisms. Thus interpretation of potential circulating endocrine markers of aging must take into account changes in sensitivity to that hormone as well.

Aging↗
PubMed1988

Electrophysiologic effects of epinephrine in humans.

The electrophysiologic effects of circulating epinephrine in humans were examined in four study groups of 10 subjects each. In 10 subjects without structural heart disease (Group 1) and in 10 patients with coronary disease or dilated cardiomyopathy (Group 2) epinephrine infusion at 25 and 50 ng/kg body weight per min for 14 min resulted in an elevation of the plasma epinephrine concentration in the physiologic range. In both groups it produced a dose-dependent decrease in the effective refractory period of the atrium, atrioventricular (AV) node and ventricle and improvement in AV node conduction. Epinephrine facilitated the induction of sustained ventricular tachycardia in 3 of the 20 subjects. In Group 3, a beta-adrenergic blocking dose of propranolol was added to the infusion of 50 ng/kg per min of epinephrine. Propranolol not only reversed the effects of epinephrine, but also lengthened these variables compared with baseline values. In Group 4, propranolol was administered first, followed by 50 ng/kg per min of epinephrine. Propranolol alone slowed AV node conduction and mildly prolonged the refractory periods. In the presence of beta-blockade, epinephrine had no effect on AV node properties but resulted in a lengthening of the atrial and ventricular effective refractory periods. In conclusion, epinephrine in physiologic doses shortens the effective refractory period of the atrium, AV node and ventricle, improves AV node conduction and may facilitate the induction of sustained ventricular tachycardia. The overall electrophysiologic effects of epinephrine result from stimulation of beta-receptors. Stimulation of alpha-receptors by epinephrine has no effect on the AV node but prolongs the effective refractory period of the atrium and ventricle, partially offsetting the shortening of refractory periods mediated by beta-receptor stimulation.

Adult↗
PubMed1988

Daily symptoms and behavioral responses. Results of a health diary with older adults.

Research on the health care behavior of older adults in response to symptoms will benefit from having data collection methods that can monitor health actions as they occur on a daily basis. In the present study, symptom experiences over a 2-week period and the actions taken in response to them were studied with a self-kept daily diary. Participants were 142 community-resident older persons, aged 62-94. Diary information about number of daily symptoms and the accompanying pain/discomfort was correlated with health perceptions and psychosocial indices obtained in an interview prior to the diary period. Women tended to take a more active response to symptoms than men, particularly in the area of personal care actions. Preventive health behaviors were not strongly related to symptom-related actions. Satisfaction with one's income was the only predictor of seeking professional assistance. Overall, the diary method is feasible to use with older adults, although certain groups may require special consideration (e.g., the visually impaired, persons with multiple symptoms per day, or those with a limitation on writing ability).

Age Factors↗
PubMed1988

Effect of sodium-restricted diet and posture on norepinephrine kinetics in humans.

We used compartmental analysis to analyze the kinetics of distribution and metabolism of norepinephrine (NE) and to determine whether the increase in plasma norepinephrine concentration (PNE) during sodium restriction in humans is due to sympathetic nervous system (SNS) activation. [3H]-NE infusion and postinfusion decay were measured in young subjects in the supine position and during 60 min of standing during normal sodium (NS) diet and after 7 days of 10 meq/day sodium-restricted (SR) diet. The mean supine PNE was greater during SR diet compared with NS diet (154 +/- 9 vs. 185 +/- 12 pg/ml, P = 0.02, n = 10). During both NS and SR diets, upright PNE increased (163 +/- 4 vs. 359 +/- 38 pg/ml and 182 +/- 8 vs. 401 +/- 26 pg/ml, respectively, multivariate one-way analysis of variance, P less than 0.001, alpha = 0.05). The increases of PNE with both SR diet and upright posture were accompanied by a fall in NE metabolic clearance rate (MCR1). During SR diet this was due to a fall in the volume of distribution of NE (6.1 +/- 0.4 vs. 5.0 +/- 0.4 liters, P = 0.003, n = 10). In contrast to the effect of upright posture to increase NE release into the extra-vascular compartment (NE2), during SR diet there was no change in NE2 (1.63 +/- 0.09 vs. 1.62 +/- 0.1 micrograms.min-1.m-2, P = 0.97, n = 10). Thus the increase in PNE during SR diet in humans can be explained by a fall in the volume of distribution of NE, resulting in a decrease in MCR1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Increased plasma and cerebrospinal fluid norepinephrine in older men: differential suppression by clonidine.

To evaluate the effect of advanced age on central nervous system noradrenergic activity, cerebrospinal fluid (CSF) and plasma norepinephrine (NE) concentrations were measured concurrently in 14 older [mean, 65 +/- 9 (+/- SD) yr] and 33 younger (25 +/- 2 yr) normal men. CSF NE was significantly higher in older men than in young men [214 +/- 75 (+/- SD) vs. 164 +/- 56 pg/mL (1.26 +/- 0.44 vs. 0.97 +/- 0.33 nmol/L); P less than 0.02] as was plasma NE [282 +/- 103 vs. 211 +/- 63 pg/mL (1.67 +/- 0.61 vs. 1.25 +/- 0.37 nmol/L); P less than 0.02]. Subgroups of young and older men underwent two lumbar punctures, one of which was performed 100 min after the administration of 5 micrograms/kg oral clonidine. The young (n = 7) and older (n = 7) men had similar plasma clonidine levels [1.0 +/- 0.1 vs. 0.8 +/- 0.1 ng/mL (4.35 +/- 0.43 vs. 3.48 +/- 0.78 nmol/L)] and CSF clonidine levels [0.18 +/- 0.02 vs. 0.22 +/- 0.03 ng/mL (0.78 +/- 0.09 vs. 0.96 +/- 0.13 nmol/L)]. The suppression of CSF NE by clonidine was significantly greater (P less than 0.015) in young men [189 +/- 44 to 104 +/- 26 pg/mL (1.12 +/- 0.26 to 0.62 +/- 0.15 nmol/L)] than in older men [190 +/- 49 to 164 +/- 58 pg/mL (1.12 +/- 0.29 to 0.97 +/- 0.34 nmol/L)]. In contrast, the suppression of plasma NE by clonidine did not significantly differ between young [242 +/- 72 to 93 +/- 24 pg/mL (1.43 +/- 0.43 to 0.55 +/- 0.14)] and older men [285 +/- 102 to 167 +/- 84 pg/mL (1.68 +/- 0.60 to 0.99 +/- 0.50 nmol/L)]. These data suggest that decreased sensitivity of alpha 2-adrenergic mechanisms regulating CNS noradrenergic activity may contribute to increased CNS noradrenergic activity with aging.

Adult↗
PubMed1988

Pancreatic islet defects in NIDDM.

While circulating insulin levels may at times appear to be normal or even elevated in patients with NIDDM, depending on the control group for comparison and the glucose level at which subjects are studied, a profound impairment of pancreatic B-cell function is characteristic of NIDDM and contributes to the hyperglycemia in this condition (Halter, et al., 1985). Table I lists some of the defects of pancreatic islet function that have been observed in NIDDM.

Diabetes Mellitus, Type 2↗
PubMed1988

Diabetes mellitus in the older adult.

Diabetes mellitus is common in the elderly, and the incidence of new cases is 10 times greater for this age group than for persons under age 45. Increased ratio of fat to body weight, a low-carbohydrate diet, lack of exercise, drug regimens, and coexisting illness may all contribute to this population's predisposition to diabetes. The older individual, who may be less capable of coping physiologically with complications of diabetes, faces greater risks; the mortality rate for the elderly diabetic patient is 11%. Since there is no optimal therapy program, management must be individualized. There are advantages and disadvantages to each major approach to therapy: diet, exercise, oral sulfonylurea drugs, and insulin.

Aged↗
PubMed1987

The interplay between endogenous catecholamines and induced ventricular tachycardia during electrophysiologic testing.

Plasma epinephrine and norepinephrine concentrations were measured before, during, and shortly after induced ventricular tachycardia (VT) in 22 selected patients. Sustained, unimorphic VT was induced by programmed ventricular stimulation and terminated after 45 to 384 seconds by overdrive pacing in all patients. In no patient did VT result in loss of consciousness. The baseline plasma catecholamine concentrations did not correlate with the baseline right ventricular effective refractory period, the cycle length of induced VT, or the number of extrastimuli required to induce VT. Induced VT was not associated with a significant increase in the mean plasma epinephrine concentration. In contrast, the plasma norepinephrine concentration increased from a mean baseline level of 317 +/- 136 pg/ml (mean +/- standard deviation) to 418 +/- 220 pg/ml during VT (p less than 0.01) and increased further to 569 +/- 387 pg/ml shortly after VT (p less than 0.01). The plasma norepinephrine concentration shortly after VT correlated with the rate and duration of VT and with the magnitude of decrease in mean blood pressure during VT (p less than 0.05 for each). In eight patients the same configuration of VT was induced on two sequential attempts; in five patients the same number of extrastimuli were required for the second induction of VT as for the first, whereas in three patients fewer extrastimuli were required. Plasma catecholamine concentrations were not higher in patients requiring fewer extrastimuli to induce the second episode of VT, either shortly after the first episode of VT or shortly after the second episode of VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗