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Biomedical subjects

J M Feldman

Publications and source records attributed to J M Feldman.

At least 127 records · Page 7Linked to original sources
PubMed1977

The practical use of thyroid function tests.

The diagnosis of thyroid disorders can usually be established by two tests: the serum T4 and the resin T3 uptake (RT3U). The T4 test measures both free and bound thyroxine; the RT3U reflects the number of binding sites available on thyroid-binding globulin. The values of these two tests can be used to calculate a free thyroxine index (FTI), which gives an approximation of the free T4 in the serum. Measurement of thyroid-stimulating hormone (TSH) is useful for the diagnosis of hypothyroidism, while the thyrotropin-releasing hormone (TRH) test may facilitate diagnosis of hyperthyroidism.

Female↗
PubMed1976

Plasma amino acids in patients with the carcinoid syndrome.

Plasma tryptophan (Trp) is reported to be decreased in some patients with the carcinoid syndrome. To determine if the plasma levels of other amino acids are also altered in the carcinoid syndrome, we used a fas-liquid chromatographic method to determine the plasma amino acid concentration of nine patients with the carcinoid syndrome and nine age-matched healthy control subjects. In comparison to the control subjects, the patients with the carcinoid syndrome had decreased plasma concentration of valine (Val), isoleucine (Ile), lysine (Lys), and ornithine (Orn), and an increased plasma concentration of methionine (Met). With the exception of a decrease in urinary excretion of proline (Pro) and hydroxyporline (Hyp), the patients with the carcinoid syndrome had normal quantities of amino acids in their urine. Plasma Met returned to normal when serotonin production by the tumor was reduced 60% by parachlorophenylalanine (PCPA); the other amino acid abnormalities persisted. Further studies are needed to determine the significance of these amino acid abnormalities.

Aged↗
PubMed1976

Effect of oral contraceptives on platelet monoamine oxidase, monoamine excretion, and adrenocortical function.

Studies with animals indicate that there are cyclical changes in the monoamine oxidase (MAO) activity of brain and uterus, and that these changes may be due to changes in estrogen and progesterone levels. To determine if oral contraceptives (OC) alter the tissue MAO activity of healthy women, we measured platelet MAO activity in 7 control women and in 7 women who were receiving combination estrogen-progesterone OC. The platelet MAO of the control women and the women receiving OC did not differ with the use of tryptamine and serotonin as MAO substrates. The two groups did not differ with respect to the following: serum serotonin, plasma tryptophan, plasma tyrosine, and the urinary excretion of tryptamine, tyramine, serotonin, 5-hydroxyindoleacetic acid, creatinine, 17-hydroxycorticosteroids, 17-ketosteroids, and urinary free cortisol. The subjects receiving OC had higher plasma cortisol concentrations than the controls. Two women in the seventh month of uncomplicated pregnancy, who underwent these studies, had higher plasma cortisol and urinary 17-ketosteroid excretion than control subjects. In the remaining tests the results of pregnant subjects did not differ from those of control subjects. We conclude that tissue MAO activity is not altered by OC or pregnancy.

Adrenal Cortex↗
PubMed1976

Effect of intravenous glucose and insulin on plasma tryptophan and tyrosine concentrations in normal subjects and patients with carcinoid tumors.

We evaluated the effect of intravenous (i.v.) glucose on the plasma tryptophan (TRP) and tyrosine (TYR) concentration of 12 normal subjects, six patients with carcinoid tumors and the carcinoid syndrome (carcinoid syndrome), and five patients with carcinoid tumors without the carcinoid syndrome (tumor.) Following i.v. glucose administration, the plasma Trp concentration of the normal subjects and the tumor patients incresed, while the plasma Trp concentration of the carcinoid syndrome patients decreased. Following i.v. glucose administration, the plasma Tyr concentration of the normal subjects and the tumor patients decreased, while the plasma Tyr concentration of the carcinoid syndrome patients did not change. The response to i.v. insulin differed in some respects from the response to i.v. glucose: the plasma Trp of normal subjects did not change while the plasma Trp of carcinoid syndrome patients decreased; the plasma Tyr of the normal subjects increased while the plasma Tyr concentration of the carcinoid syndrome patients did not change. The carcinoid syndrome patients had high serum serotonin concentrations and impaired glucose tolerance and insulin secretion as compared to both normal subjects and tumor patients. We conclude that under appropriate experimental conditions, glucose administration can increase the plasma Trp concentration of normal human subjects.

Adult↗
PubMed1976

Effect of ether, chloroform and carbon dioxide on monoamine inactivation.

To determine if anaesthetic agents alter monoamine inactivation, we exposed tissue homogenates (liver, kidney and brain) from mice and rabbits to ether and chloroform vapors and carbon dioxide gas. These anaesthetic agents inhibited monoamine oxidase (MAO) activity against typtamine and serotonin. Concentrations of anaesthetic agents that are achieved in the plasma of man during general anaesthesia caused a 27% (ether) and 49% (chloroform) reduction in mouse liver MAO; higher concentrations caused a 95% inhibition mouse or rabbit liver MAO. Kinetic analysis with tryptamine as substrate indicate that ether and chloroform are noncompetitive, reversible MAO inhibitors that preferentially inhibit Type B MAO. Ether and chloroform cause noncompetitive inhibition of serotonin oxidation by mouse liver MAO and competitive inhibition of serotonin oxidation by mouse brain and kidney MAO. Ether or chloroform did not alter catechol-O-methyltransferase activity from tissues of mice. Isolated blood platelets (rabbit and human) were used as a model system for neuronal uptake. Ether caused an irreversible inhibition of serotonin uptake by platelets.

Amines↗
PubMed1976

Effect of age on intravenous glucose tolerance and insulin secretion.

Twenty-seven normal volunteers whose ages ranged from 22 to 67 (mean, 37 years) were given intravenous glucose tolerance tests (IVGTT). Age was not correlated with the glucose disposal rate constant (KG), incremental insulin secretion (deltaI), or the "insulinogenic index (deltaI/DELATG). The volunteers were divided into three age groups: 1) mean age 25 years, 2) mean age 42 years, and 3) mean age 62 years. Groups 2 and 3 did not differ from Group 1 with respect to the mean level of fasting plasma glucose, KG, or deltaI/AG. Group 2 (but not Group 3) had a greater mean deltaI than Group 1, and Group 3 (but not Group 2) had a higher mean fasting insulin concentration than Group 1. No significant deterioration was detected in the intravenous glucose tolerance of healthy volunteers up to age 67. This may be attributable to the previously described feed-back system that calibrates the pancreatic beta-cell response according to the insulin sensitivity of the peripheral tissues.

Adult↗
PubMed1976

Inhibitory effect of serotonin antagonists on growth hormone release in acromegalic patients.

We evaluated the effect of the serotonin antagonists cyproheptadine (Cypro) and methysergide (Methy) on growth hormone secretion in six patients with acromegaly. Two days administration of Cypro decreased the plasma GH concentration during oral glucose tolerance tests in four of the six patients evaluated; 2 days administration of Methy reduced the plasma GH levels of only one of the four patients evaluated. The one patient whose plasma GH concentration was lowered by Methy, did not have a decrease in plasma GH concentration after Cypro administration. Acromegalic patients have normal serum serotonin concentration and normal 5-hydroxyindoleacetic acid excretion. If Cypro lowers plasma GH by antagonizing serotonin, our data would suggest that serotoninergic neuronal pathways are important in the regulation of pituitary GH secretion in some patients with acromegaly.

Acromegaly↗
PubMed1975

Monoamine oxidase inhibitors: nature of their interaction with rabbit pancreatic islets to alter insluin secretion.

Using an in vitro rabbit pancreas system, we studied the effect of monoamine oxidase (MAO) inhibitors on flucose-stimulated insulin secretion. We evaluated the effect of both brief (15 min) and prolonged (60 min) exposure of pancreas segments to non-hydrazine (harmine, alpha-methyltryptamine, tranylcypromine and pargyline) and hydrazine (phenelzine, nialamide, iproniazid) type MAO inhibitors. All of the hydrazine type MAO inhibitors potentiated glucose-stimulated insulin secretion. Of the non-hydrazine inhibitors, only harmine and alpha-methyltryptamine potentiated glucose-stimulated insulin secretion. Hydrazine, although not itself an MAO inhibitor, also potentiated insulin secretion. Sixty minutes of exposure to tranylcypromine or alpha-methyltryptamine caused a decrease in insulin secretion. These MAO inhibitors are primary amines and primary amines can inhibit insulin secretion. The dopamine (DA) or serotonin (5-HT) content of the B-cells was increased by incubating rabbit pancreas with L-3, 4-dihydroxyphenylalanine (L-Dopa) or 5-hydroxytryptophan (5-HTP) for forty-five minutes prior to stimulation with glucose. Non-hydrazine MAO inhibitors increased dopamine inhibition of insulin secretion and either did not alter, or decreased serotonin inhibition of insulin secretion. Rabbit pancreatic islets were isolated using the collagenase digestion technique. The MAO activity of islet homogenates was determined using 5-HT and DA as substrates. Rabbit islet MAO has only one-tenth the specific activity against 5-HT (35 +/- 8.7 mumumoles/mg/min, M +/- SEM) that it has against DA (357 +/- 62.3 mumumoles/mg/min). This suggests that one reason that MAT inhibitors do not increase serotonin inhibition of insulin secretion is because MAO is not the major pathway for 5-HT inactivation in rabbit pancreatic islets. These studies suggest that MAO inhibitors alter insulin secretion, by both decreasing B-cell monoamine degradation and by mechanisms that do not involve MAO inhibition.

5-Hydroxytryptophan↗
PubMed1975

Adrenal function in the carcinoid syndrome: effects of the serotonin antagonist cyproheptadine.

Results of evaluations of adrenal function in 11 patients with carcinoid tumors are presented. Nine patients had tumors that made and secreted serotonin resulting in elevated 5-hydroxyindoleacetic acid (5-HIAA), elevated serum serotonin, and the carinoid syndrome; while two patients had tumors that did not make serotonin and that did not cause elevated 5-HIAA excretion or elevated serum serotonin. All of the patients had normal 24-hr 17-hydroxycorticosteroid excretion. In the group of patients with tumors actively secreting serotonin, the correlation between 17-hydroxycorticosteroid and 5-HIAA excretion (r = 0.44) was not significant. Six of these patients pretreated with cyproheptadine (CYPRO), a serotonin antagonist, experienced a 36% mean decrease in 17-hydroxycorticosteroid excretion, a finding that was not present when three of them were treated with triprolidine (TPRO), an antihistamine. Serum cortisol at 8 a.m. was normal in all patients except two whose values were mildly elevated, and these two patients showed evidence of suppression of ACTH secretion secondary to dexamethasone treatment. There was a significant positive correlation between serum-cortisol concentrations and 5-HIAA excretions (r = 0.73, p less than .05). Normal diurnal variation was present in six patients in whom it was determined. The serum-cortisol response to insulin-induced hypoglycemia in six patients who had carcinoid tumors actively secreting serotonin was not statistically different from that of 12 normal volunteers. Comparisons between these two groups were difficult because the carcinoid patients' fall in blood sugar was 50%, whereas that of the control group was to 38% of the fasting glucose concentration. Six patients with actively secreting carcinoid tumors responded to standard metyrapone testing with a mean increment of 22.8 +/- 2.5 mg/day in 17-hydroxycorticosteroids. This response was statistically different from the increment of 13.8 +/- 5.3 mg/day in 17-hydroxycorticosteroid excretion found in 34 age-matched hospitalized control patients. When the tests were repeated in four of the patients with carcinoid tumors after pretreatment with CYPRO, the increment in 17-hydroxycorticosteroid excretion was reduced well below the mean increment of the control group. Peak serum 11-deoxycortisol (Compound S) values during the test were also reduced. This decrease in the metyrapone response after CYPRO pretreatment was not due to changed peripheral cortisol metabolism, altered adrenal responsiveness to ACTH, interference with recovery of 17-hydroxysteroids by the Porter-Silber reaction, altered metyrapone metabolism, or reduced renal clearance of Compound S. These changes in adrenal response to metyrapone were not seen when the patients were pretreated with TPRO. Our data suggest that the alterations in adrenal function in our patients may be related to elevated serum serotonin. If CYPRO acts by antagonizing serotonin, these data may give support to the idea of serotoninergic control of cortisol secretion.

17-Hydroxycorticosteroids↗
PubMed1975

Characterization of pancreatic islet monoamine oxidase.

Monoamine oxidase (MAO) is present in isolated islets of Langerhans of rabbits, golden hamsters, and rats. Tryptamine, tyramine, serotonin, and dopamine can serve as substrates for this enzyme. We compared the properties of islet and liver MAO in the rabbit. The Michaelis constant (K(m)) for tryptamine of islet MAO (6.5 times 10-5M) is greater than the K(m) of liver MAO (3 times 10-5M). The K(m) for tyramine of islet MAO (1.5 times 10-4M) is similar to the K(m) of liver MAO (1.8 times 10-4M). Islet MAO appeared to be more susceptible to heat inactivation (50 degrees C) than did liver MAO. This may be an artifact produced by the collagenase technique used in the preparation of the islets, as collagenase treatment of liver increased the thermal lability of the MAO in this tissue. Liver and islet MAO have a comparable sensitivity to MAO inhibitors such as clorgyline, deprenyl, tranylcypromine, pargyline, and harmine. The present report, along with previous reports that MAO inhibitors alter insulin secretion, suggests that islet MAO may modify insulin secretion.

Animals↗
PubMed1975

The role of cortisol and growth hormone in the counter-regulation of insulin-induced hypoglycemia.

Four normal volunteers underwent a control insulin tolerance test (ITT) and an insulin tolerance test (ITT) after two days administration of the serotonin antagonist cyproheptadine (Cypro). Cypro administration resulted in an 81 +/- 11.4% (M +/- SEM) reduction in cortisol secretion and a 73 +/- 15.1% reduction in growth hormone (GH) secretion. Despite the reduction in hypoglycemia-induced cortisol and GH secretion, there was a similar decline and recovery of plasma glucose in the control ITT and the ITT after Cypro administration. Although previous studies indicate that normal basal levels of cortisol and growth hormone are needed for normal counter-regulation after insulin-induced hypoglycemia, augmented secretion of these hormones is probably not essential for this response. Hypoglycemia-induced increases in epinephrine and glucagon, secretion may contribute to the restoration of the normal plasma glucose concentration after insulin-induced hypoglycemia.

Blood Glucose↗
PubMed1975

Effect of cyproheptadine administration on insulin secretion in acromegalic, diabetic and normal subjects.

The effect of cyproheptadine (Cypro) and Placebo administration on insulin secretion and glucose utilization following i.v. glucose (IVGTT) was evaluated in 8 normal, 7 diabetic and 8 acromegalic subjects. Five of the diabetic subjects had overt diabetes and two of the diabetic subjects had "chemical" diabetes (oral GTT). One of the acromegalic subjects had overt diabetes, while one had borderline glucose tolerance and six had normal glucose tolerance (oral GTT). Cypro increased insulin secretion in the acromegalic but not in the diabetic or normal subjects. Methysergide (Methyl) increased insulin secretion in acromegalic and diabetic subjects but not in normal subjects. Methy and Cypro both increased insulin secretion in the same acromegalic subjects. None of the three groups of subjects had a modification in insulin secretion following Placebo administration. Neither Placebo, Cypro or Methy altered the glucose utilization rate contant (KG). There was no change in insulin half life or tissue sensitivity to insulin from Cypro (normal and acromegalic subjects) or Methy (normal subjects) administration. Despite their increase in insulin secretion in response to serotonin antagonists, acromegalic subjects have normal urinary 5-hydroxyindoleacetic acid excretion and normal serum serotonin concentrations. Their response cannot therefore be attributed to a generalized overproduction of serotonin.

Acromegaly↗
PubMed1975

Glucose intolerance in the carcinoid syndrome.

We assayed glucose tolerance and insulin secretion in ten patients with metastatic carcinoid tumors and the carcinoid syndrome ("active tumors") and in seven patients with metastatic carcinoid tumors without the carcinoid syndrome ("inactive tumors"). The patients with "active tumors" had elevated serum serotonin levels while the patients with "inactive tumors" had normal serum serotonin levels. Of the ten patients with "active tumors," five had diabetic and three had borderline intravenous glucose disposal rate constants (KG = 0.88 +/- 0.07, M. +/- S.E.M.). Their KG was significantly lower (p less than 0.01) than a group of age-matched normals. All of the patients with "inactive tumors" had normal KG values (KG = 1.67 +/- 0.24). Their KG did not differ from that of age-matched normal subjects. Both groups of carcinoid patients had a comparable decrease in their insulinogenic index. Two days' administration of the serotonin antagonist cyproheptadine (Cypro) to eight of the patients with "active tumors" resulted in a significant increase in the "insulinogenic index" (50%) but a nonsignificant increase in the KG (12%). Administration of p-chlorophenylalanine, a compound that blocks serotonin synthesis, resulted in an increase in both the KG (60%) and the "insulinogenic index" (55%). The insulin half-life (t1/2) of patients with "active tumors" (6.1 +/- 0.4 min.) did not differ from the t1/2 of normal subjects (6.6 +/- 0.4 min.), suggesting that the decreased plasma insulin levels following intravenous glucose were due to impaired insulin secretion rather than accelerated insulin destruction. Seven of the patients received treatment with the antitumor agent streptozotocin (Strepto). The patients received cumulative doses of from 70 to 300 mg. of Strepto per kilogram body weight with no impairment in glucose tolerance or insulin secretion. We conclude that there is high incidence of glucose intolerance (80%) and impaired insulin secretion in patients with the carcinoid syndrome and that serotonin plays a role in producing these alterations.

Adult↗
PubMed1975

Inhibition of pancreatic islet monoamine oxidase by adrenergic antagonists and ethanol.

Although the alpha-adrenergic antagonist phentolamine potentiates glucose-stimulated insulin secretion of intact animals, it either does not alter, or it inhibits in vitro insulin secretion. This may be because in the higher concentration used in in vitro studies, phentolamine exerts a second pharmacological effect that counterbalances its primary effect of blocking monoamine action. We recently demonstrated that pancreatic islets contain substantial amounts of monoamine oxidase (MAO), and that MAO inhibitors such as iproniazid and tranylcypromine can alter insulin secretion. In the present study, we determined if other drugs that affect insulin secretion, alter the MAO activity of homogenates of rabbit pancreatic islets (collagenase technique) or liver. Phentolamine, phenoxybenzamine and propranolol (10 muM and 100 muM) inhibit islet and hepatic MAO. Haloperidol (10muM) inhibits hepatic but not islet MAO, while haloperidol (10muM) does not inhibit MAO in either tissue. Ethanol (270 to 2.7mM) inhibits islet MAO. Hepatic MAO is inhibited by high (270 to 180mM) but not by low (27 to 2.7mM) concentrations of ethanol. Collagenase digestion does not increase the sensitivity of islet and liver MAO to inhibition by phentolamine or ethanol. In the absence of added monoamines, phentolamine and phenoxybenzamine do not alter basal or glucose-stimulated insulin secretion from rabbit pancreas. Preincubation of rabbit pancreas with the serotonin precursor 5-hydroxytryptophan (5-HTP) increases the beta cell serotonin content and inhibits glucose-stimulated insulin secretion. Alpha adrenergic antagonists not only fail to block, but actually potentiate the serotonin inhibition of insulin secretion. We conclude that inhibition of islet MAO may cause an increase in islet monoamine content and these monoamines may alter in vitro insulin secretion. One mechanism through which adrenergic antagonists and ethanol modify in vitro insulin secretion may be by inhibiting pancreatic islet MAO.

5-Hydroxytryptophan↗