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Biomedical subjects

J B Halter

Publications and source records attributed to J B Halter.

At least 163 records · Page 9Linked to original sources
PubMed1981

Effect of spinal anesthesia on adrenergic tone and the neuroendocrine responses to surgical stress in humans.

In order to quantitate the effect of spinal anesthesia on adrenergic tone, plasma levels of norepinephrine (NE) and epinephrine (EPI) were measured by radioenzymatic assay in 24 patients were then compared to those of 10 patients receiving inhalation anesthesia (halothane-nitrous oxide). High thoracic dermatome spinal anesthesia caused suppression of both arterial plasma NE and EPI and a fall of mean arterial pressure (MAP); in contrast, no changes of NE, EPI, or MAP were observed in patients receiving low spinal anesthesia. Overall, there was a relationship between the sensory dermatome anesthesia level and changes of both plasma NE (r = 0.71, P less than 0.001) and EPI (r = 0.52,P less than 0.02). In the inhalation anesthesia group, plasma NE increased during the operation and plasma levels of NE, EPI, growth hormone, and cortisol were elevated during the postoperative recovery period. These neuroendocrine responses to surgical stress were not observed in patients receiving either low or high spinal anesthesia. Thus, the effect of spinal anesthesia on adrenergic tone depends on the cord level of anesthesia and can be quantitated by measurement of plasma catecholamines. The neuroendocrine responses to surgical stress were prevented in patients who received low spinal anesthesia and who had no suppression of efferent adrenergic tone. These findings indicate that neural afferents from the site of tissue injury, which were blocked by low spinal anesthesia, mediated both the adrenergic and the hormonal responses to surgical stress in the inhalation anesthesia group.

Adrenergic Fibers↗
PubMed1981

Morphine: dual effects on plasma catecholamines.

The present studies demonstrate that morphine can increase, decrease, or not affect plasma catecholamines depending on the dose and on the experimental conditions under which it is given. In the conscious dog, morphine (30 mg s.c.) produces a marked elevation of plasma epinephrine but not norepinephrine. In contrast, morphine (15 mg i.v.) prevents the rise of both plasma epinephrine and norepinephrine in the anesthetized, laparotomized dog. Since neither dose of morphine changes plasma catecholamines significantly in the non-laparotomized, anesthetized dog, we suggest (a) that the catechol-lowering effect is due to the analgesic properties of morphine, and (b) that the catechol-raising effect is due to activation of separate central nervous system pathways which are suppressed by barbiturate anesthesia.

Animals↗
PubMed1981

Differential effects of tolbutamide on first and second phase insulin secretion in noninsulin-dependent diabetes mellitus.

Immunoreactive insulin responses to a 20-g iv glucose challenge during a 7.5 mg/m2/min tolbutamide infusion were studied in 21 untreated noninsulin-dependent male diabetics. All data were analyzed by paired t tests. During the tolbutamide infusion, compared to the saline control period in the same subjects, glucose levels were lowered [217 +/- 17 vs. 196 +/- 16 mg/dl (mean +/- SEM); P less than 0.005], and there was an increase in both first phase (2 +/- 1 vs. 16 +/- 4 micro U/ml; P less than 0.005) and second phase insulin responses (296 +/- 71 vs. 499 +/- 101 micro U. min/ml; P less than 0.05; n = 21). However, when the prestimulus glucose level was lowered by an insulin infusion (214 +/- 20 vs. 145 +/- 17 mg/dl; P less than 0.001), no effect on first phase insulin secretion was observed, and the second phase response decreased (290 +/- 78 vs. 124 +/ 55 micro U. min/ml; P less than 0.005; n = 11; saline control vs. insulin infusion). In 8 subjects, the plasma glucose level during the tolbutamide infusion was kept constant by a concurrent variable glucose infusion. First phase insulin secretion was still increased, though no more than in studies were plasma glucose was not kept constant. However, there was further augmentation of the second phase response (tolbutamide alone, 443 +/- 142 micro U. min/ml; tolbutamide plus glucose, 802 +/- 232 micro U. min/ml; P less than 0.05). These findings indicate that tolbutamide augments first phase insulin secretion in untreated diabetics independently of the prestimulus glucose level. However, changes in the glucose level significantly modulate the sulfonylurea influence on the second phase insulin response to glucose. This effect of glucose level is an important consideration when evaluating the insulinotropic effects of a sulfonylurea.

Adult↗
PubMed1981

Glucose disposal is not proportional to plasma glucose level in man.

Metabolic clearance rate (MCR) of glucose has been defined as the rate of glucose utilization divided by the glucose concentration. This model of glucose transport has been widely used as a measure of hormonally regulated glucose disposal, on the assumption that glucose disposal rate is proportional to glucose concentration. To test this assumption, the relationship between glucose concentration and disposal rate was studied in man during infusion of somatostatin +/- exogenous insulin to achieve fixed plasma insulin levels of 1, 18, and 46 microM/ml on separate days. When glucose concentration was increased to more than twice basal fasting levels, the glucose disposal rate increased significantly at all three insulin levels. However, the increase was not proportional to the rise in glucose concentration, and MCR fell by 38%, 16%, and 11% at the low, medium, and high insulin levels, respectively. These results are explained by an alternative model of glucose transport in which insulin-independent tissues such as brain have a relatively fixed glucose uptake, while other tissues have glucose transport systems which take up glucose at a rate proportional to its plasma concentration. We conclude that MCR of glucose is not a good measure of hormonally regulated glucose disposal because it is partially dependent on the glucose concentration, particularly at low insulin levels.

Adult↗
PubMed1981

Glycemic control and nerve conduction abnormalities in non-insulin-dependent diabetic subjects.

The influence of therapy of hyperglycemia on the progression of diabetic neuropathy is unclear. We studied variables of glycemia and motor and sensory nerve conduction velocity in a group of 18 non-insulin-dependent diabetic subjects before and after institution of diabetes therapy. Diabetes therapy significantly reduced variables of glycemia after 1, 3, 6, and 12 months. Conduction velocity of the median motor nerve was improved from baseline at each time tested during treatment. In addition, peroneal and tibial motor nerve conduction velocities improved in patients whose levels of hyperglycemia were lowered. Moreover, extent of improvement of conduction velocity of some motor nerves was related to the degree of reduction of hyperglycemia. Sensory nerve conduction velocity was not altered by diabetes therapy. These findings support the hypothesis of a metabolic component to diabetic neuropathy and suggest that optimal glycemic control may be beneficial to patients with this disorder.

Adult↗
PubMed1980

Effects of anesthesia and surgical stress on insulin secretion in man.

Surgical stress with inhalation anesthesia is associated with increased circulating catecholamines, hyperglycemia, and impaired insulin secretion. These changes do not occur during surgical stress with spinal anesthesia, suggesting that they are neurally mediated due to pain initiated afferents from the site of tissue trauma. Inhalation anesthesia alone was found to suppress basal insulin levels and the insulin response to intravenous glucose with no significant increase in plasma norepinephrine and a decrease in plasma epinephrine. Thus, these changes in insulin secretion are not attributable to adrenergic mechanisms. In the postoperative period, however, suppressed insulin secretion was found to be correlated with elevated plasma epinephrine concentrations and may, therefore, be mediated by adrenergic mechanisms. Thus, these findings indicate that impaired insulin secretion during surgical stress may have two etiologies--one related to the type of anesthesia used and the other due to adrenomedullary stimulation due to pain.

Anesthesia, Inhalation↗
PubMed1980

Arterial-venous differences of plasma catecholamines in man.

To investigate the relationship between forearm venous levels of catecholamines and systemic levels, simultaneous arterial and forearm vein blood samples were obtained from 14 subjects undergoing elective dental procedures and assayed with a sensitive and specific radioenzymatic assay. Baseline venous levels of norepinephrine were greater than arterial levels (305 +/- 30 pg/ml versus 221 +/- 18; +/- SEM, p less than .005). Conversely, arterial epinephrine levels were higher than venous (132 +/- 17 pg/ml versus 80 +/- 10; p less than .005). There was a significant relationship between arterial and venous levels of both norepinephrine (r = .77, p less than .01) and epinephrine (r = .67, p less than .01). The arterial-venous epinephrine difference increased from the baseline value of 44 +/- 14 pg/ml to 108 +/- 16 (p less than .005) by 3 min after subcutaneous injection of epinephrine (18 microgram), but the arterial-venous difference returned to 65 +/- 24 by 5 min after injection (p = NS versus baseline). These findings indicate that under the conditions of this study, forearm tissues produced more norepinephrine than they removed, but removed more epinephrine than they produced. Baseline venous and arterial levels were related; when epinephrine production was augmented, there was a short time lag for the venous epinephrine increase.

Arteries↗
PubMed1980

Effects of clonidine on hormone and substrate responses to hypoglycemia.

We have reported that clonidine (CLON) reduces basal norepinephrine (NE) levels but has no effect on basal epinephrine (E) levels. To study the effects of CLON on stimulated NE and E secretion, six normal men received a single dose of CLON followed by induction of hypoglycemia with insulin. Despite the presence of a mean hypolygemic nadir of 44 mg/100 ml, there was no rise in E and NE levels during CLON treatment. To determine the effects of such catecholamine inhibition on the counterregulation of hypoglycemia, additional experiments were performed since the mean glucose nadir during CLON in the initial studies was slightly (9 ml/100 ml) less deep than in controls. When subjects on CLON received higher doses of insulin, gluose responses were identical to control responses; CLON still reduced the 0 to 60-min catecholamine response by 83% (p < 0.02). Glucagon secretion was not impaired, but CLON blunted the early rate of glucose recovery in the first 15 min after the glucose nadir. We conclude that CLON inhibits the catecholamine (but not the glucagon) rise during insulin-induced hypoglycemia. Selective inhibiton of catecholamine secretion does not inhibit the glucogan response but leads to definite, although transient, inhibiton of glucose recovery after hypoglycemia.

Adult↗
PubMed1980

Relationship of impaired insulin secretion during surgical stress to anesthesia and catecholamine release.

Impaired insulin secretion has been observed during surgical stress in man. To determine the relationship between insulin secretion during anesthesia and surgical stress and plasma levels of norepinephrine (NE) and epinephrine (Epi), studies were performed in 16 patients before and during elective minor surgical procedures. In 8 patients studied during halothane inhalation anesthesia before operation, the acute insulin response (AIR) to glucose (5 g, IV) fell to 51 +/- 3% of the preanesthesia AIR (mean +/- SEM; P < 0.001). This inhibition of AIR appeared unrelated to increased adrenergic activity, since during anesthesia alone, plasma NE did not change significantly and plasma Epi fell from 94 +/- 11 to 34 +/- 10 pg/ml (P < 0.01). During the postoperative recovery period in these patients, after discontinuation of the anesthesia, the AIR to glucose was 50 +/- 5% of the preanesthesia baseline response (P < 0.001). At this time, both plasma NE and Epi were increased compared to preanesthesia levels [NE: 240 +/- 40 (preanesthesia) vs. 340 +/- 43 (postoperative); Epi: 219 +/- 43 (preanesthesia) vs. 94 +/- 11 (postoperative); both P < 0.05]. In eight patients undergoing similar operations during low spinal anesthesia, no inhibition of the AIR to glucose occurred, and plasma NE and Epi did not increase significantly during or after the operation. During the recovery period, there was a relationship between plasma Epi and the degree of inhibition of the AIR to glucose (r = 0.70; n = 11; P < 0.05). Thus, inhibition of insulin secretion during surgical stress may be mediated both by direct effect of the anesthesia used and by activation of the sympathetic nervous system.

Anesthesia, Inhalation↗
PubMed1980

Potentiation of insulin secretion to nonglucose stimuli in normal man by tolbutamide.

To determine how sulfonylureas affect beta cell function, insulin release in response to isoproterenol and arginine was assessed in 32 normal subjects before and during a tolbutamide infusion. When the plasma glucose was allowed to decrease during tolbutamide, the acute insulin response (AIR) to isoproterenol was not changed (delta AIR = 4 +/- 8 MicroU/ml, mean +/- SEM, n = 8,p = NS) and was enhanced slightly for arginine (delta AIR = +61 +/- 26 microU/ml, n = 6, p less than 0.05). When plasma glucose levels were maintained by means of a concomitant variable glucose infusion during tolbutamide, the insulin responses to both isoproterenol and arginine were enhanced (isoproterenol: delta AIR = +55 +/- 15 microU/ml, n = 6, p less than 0.001; arginine: delta AIR = +137 +/- 34 microU/ml, n = 8, p less than 0.001). Regression analysis demonstrated a linear relationship between change in the prestimulus glucose level and the change in the AIR to isoproterenol during tolbutamide (r = 0.66, n = 14, p less than 0.02). Since the slope of his relationship is not significantly different from a similar relationship in the absence of tolbutamide, the potentiating effect of tolbutamide is an amplification of an established physiologic relationship. We conclude that tolbutamide augments the insulin response to nonglucose stimuli. However, this potentiating effect of tolbutamide may be masked by a decrease in the prestimulus glucose level.

Arginine↗
PubMed1979

Glucose infusion potentiates the acute insulin response to nonglucose stimuli during the infusion of somatostatin.

These studies assessed the ability of glucose infusions to potentiate the acute insulin response (AIR) to iv isoproterenol (12 micrograms), arginine (750 mg), or glucose (5 g) that was previously inhibited by an infusion of somatostatin (SRIF). SRIF (1.7 micrograms/min) markedly inhibited the AIR to isoproterenol (AIR before SRIF, 28 +/- 1 microU/ml; AIR during SRIF, 8 +/- microU/ml; P less than 0.025), arginine (AIR before SRIF, 6 +/- 2 microU/ml; AIR during SRIF, 1 +/- 1 microU/ml; P less than 0.01), and glucose (AIR before SRIF, 19 +/- 7 microU/ml; AIR during SRIF, 1 +/- microU/ml; P less than 0.05). The administration of a glucose infusion of 105 mg/min partially restored the AIR to isoproterenol and arginine. Glucose infused at 440 mg/min fully restored the AIR to both isoproterenol (AIR during SRIF plus glucose, 31 +/- 4 microU/ml) and arginine (AIR during SRIF plus glucose, 9 +/- 2 microU/ml). In contrast, the AIR to glucose was not affected by infusion of glucose (AIR during SRIF plus glucose, 0 +/- 1 microU/ml). In the absence of SRIF, glucose infusion potentiates the AIR to isoproterenol and arginine but not to glucose. Therefore, during SRIF infusion, glucose retains the ability to potentiate the AIR to nonglucose stimuli despite the loss of the ability to stimulate insulin release directly. These data suggest that the potentiating effects of glucose and the inhibiting effects of SRIF may be mediated by a common mechanism affecting insulin release.

Animals↗
PubMed1979

Comparison of a colorimetric assay for glycosylated hemoglobin with ion-exchange chromatography.

Because levels of glycosylated hemoglobin (GHb) are increased in diabetes and reflect the previous metabolic control, clinicians and clinical investigators are finding increasing applications for measurements of GHb in diabetic patients. We report the characterization of a colorimetric assay procedure for GHb and compare its performance with that of a commonly used assay by ion-exchange chromatography. Although results of GHb determination by both methods correlate highly (r = 0.946, P less than 0.001), the two procedures estimate different glycosylated fractions. The colorimetric procedure is nonstoichiometric, requiring careful standardization of assay conditions, including the concentration of total hemoglobin in the assayed aliquot, to achieve precision and permit comparison of results. We characterized the effect of storage of hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes on the subsequent determination of GHb by both methods. Determinations of GHb by the colorimetric method, but not by column chromatography, are reproducible on hemolysates or packed erythrocytes stored frozen for at least 5 mo. A unique advantage of the colorimetric procedure is the capability to estimate GHb levels when variant hemoglobins, including fetal and sickle hemoglobins, are present.

Chromatography, Ion Exchange↗
PubMed1979

Nerve conduction abnormalities in untreated maturity-onset diabetes: relation to levels of fasting plasma glucose and glycosylated hemoglobin.

The role of metabolic abnormalities in the development of diabetic neuropathy is controversial. To investigate the influence of hyperglycemia on nerve conduction, we studied 20 untreated maturity-onset diabetic patients and 23 normal control subjects of similar age. Nerve conduction velocity of motor (median, peroneal, and tibial) and sensory (median and sural) nerves in diabetic patients was significantly slowed and H-reflex latency time prolonged. Levels of fasting plasma glucose in diabetic subjects were correlated with slowed motor conduction velocity of the median, peroneal, and tibial nerves but not with sensory nerve conduction velocities. Levels of glycosylated hemoglobin, an index of long-term glycemia, were correlated with slowing of peroneal motor conduction velocity in diabetic patients. These associations could not be explained by patient age or duration of diabetes. These findings suggest that the degree of hyperglycemia of untreated maturity-onset diabetes contributes to the motor nerve conduction abnormalities in this disease.

Adult↗
PubMed1978

Suppression of plasma catecholamines and flushing by clonidine in man.

Administration of the anti-hypertensive agent clonidine as a single (0.5 mg) oral dose or as multiple doses (0.2-0.4 mg/day for 4 days) markedly reduced plasma catecholamines (decrement = 81 +/- 3% and 68 +/- 5%, respectively; X +/- SE, % of basal; both P less than 0.001) in normal male volunteers. Five patients with various metabolic disorders showed similar responses. The absolute decrements in plasma catecholamines correlated significantly with basal catecholamine levels (P less than 0.001). Clonidine-induced decrements in mean arterial blood pressure correlated significantly with decrements in plasma catecholamines (P less than 0.001). The clonidine effect upon catecholamine levels was reversed by phentolamine (clonidine = -68 +/- 5%; clonidine with phentolamine = -1 +/- 16%). The decrements in catecholamines induced by clonidine in normal subjects were associated with increased sensitivity to the pressor effect of infusion of exogenous norepinephrine. In an analogous fashion flushing associated with endogenous adrenergic discharge was blocked by clonidine, whereas that due to exogenous catecholamines was intensified. These data are compatible with data in experimental animals suggesting that clonidine acts at least in part by interaction with a central alpha adrenergic receptor.

Adenoma, Islet Cell↗
PubMed1978

Mechanisms of impaired acute insulin release in adult onset diabetes: studies with isoproterenol and secretin.

Previous work has suggested that impaired islet glucose recognition occurs in patients with adult onset diabetes, as acute insulin release is absent after iv glucose but present after beta adrenergic stimulation with isoproterenol (Iso). However, insulin responses to Iso were variably reduced as compared to normal in the diabetics. In order to evaluate the importance of the Iso dose, dose-response studies were performed in 9 diabetics (fasting plasma glucose greater than 150 mg/dl) and 10 age-matched controls. In both control subjects and diabetics, 0.5 microgram Iso produced no insulin response; 2 micrograms Iso produced an intermediate response; and 8 and 12 micrograms Iso produced a higher response. The insulin responses to the larger doses of Iso were lower in diabetics than control subjects (8 micrograms, 20 +/- 5 vs. 39 +/- 6 (P less than 0.025); 12 micrograms, 21 +/- 6 vs. 37 +/- 4 (P less than 0.05); means +/- SEM, microU/ml). Of 16 diabetics who received 12 micrograms Iso, 5 had insulin responses greater than 2 SD below the control mean, while others had responses that spanned the entire range of normal. Seven diabetics also were given iv secretin (150 U). Their insulin responses to secretin correlated with the responses to Iso (r = 0.83, P less than 0.02). Thus, patients with subnormal responses to Iso also had low secretion responses. The abnormalities of acute insulin secretion in diabetics can be explained by a lesion variably affecting islet membrane receptors; some patients may have glucose receptor damage, but intact responses to other stimuli, and others may have more widespread damage affecting beta-adrenergic and secretin responses as well. Alternatively, there may be heterogeneity in adult onset diabetes, as patients with low responses to all stimuli could have a qualitatively different lesion affecting insulin secretory capacity rather than membrane receptors.

Aged↗