Biomedical subjects

R Gleason

Publications and source records attributed to R Gleason.

At least 19 recordsLinked to original sources

PubMed2001

Self-reported hyperarousal traits among insomnia patients.

Hyperarousal Scale scores for certain self-reported behaviors reportedly correlate with EEG arousal measures. We tested whether an insomnia subject group had different Hyperarousal Scale scores compared with hypersomnia, delayed sleep phase syndrome, procrastinator or normal subject groups. Compared with 139 normal subjects, mean scores for a group of 256 insomnia subjects was significantly 1.2 S.D. higher on Hyperarousal total scale score, 0.82 S.D. higher on React subscale score and 0.85 S.D. higher on Introspectiveness subscale score. The insomnia group median Extreme score was 2.25 times that of the normal group. These self-report findings suggest that insomnia subjects may be more responsive generally. All sleep disorder groups had increased total Hyperarousal scores, although these increases were accounted for by different scale items. The procrastinator group had Hyperarousal score patterns that generally differed from those of the other groups.

Adult↗

PubMed1997

Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults.

There is evidence based on nitrogen balance that dietary cystine spares, from approximately 16% to 89%, the total methionine requirement. In a previous study we did not detect, by tracer techniques, a sparing effect of cystine when the diet provided methionine at a limiting intake (requirement level: 13 mg.kg-1.d-1). One reason could be that we used an intravenous infusion of the tracer, which may not, therefore, have labeled the carbon dioxide derived from the splanchnic oxidation of dietary methionine. The aim of this study was to compare methionine metabolism and oxidation in eight healthy adults given for 6 d each of three different diets: 13 mg (87.0 mumol) methionine.kg-1.d-1 and no cystine (diet A); 5 mg (33.5 mumol) methionine.kg-1.d-1 and no cystine (diet B); and 5 mg (33.5 mumol) methionine.kg-1.d-1 and 6.5 mg (52.4 mumol) cystine.kg-1.d-1 (diet C). On day 7, tracers ([1-13C, methyl-2H3]methionine and [2H2]cysteine) were administered orally at 30-min intervals for 8 h. Blood and breath samples were obtained for analysis during 3-h fasting and consecutive 5-h feeding periods. During fasting, methionine oxidation and methionine methyl (Qm) and carboxyl (Qc) fluxes and plasma concentrations were not affected by the amount of sulfur amino acids in the three diets. In the fed state methionine oxidation was significantly lower during diets B (3.0 +/- 0.5 mumol.kg-1.h-1) and C (2.8 +/- 0.6 mumol.kg-1.h-1) than during diet A (4.1 +/- 0.9 mumol.kg-1.h-1); there were no significant differences between diets B and C. Qm and Qc decreased with decreased methionine intake but no effect was observed by adding cystine. Cysteine flux (Qcys) was not affected by diet composition but it was lower during feeding than during fasting. In conclusion, replacing approximately 60% of the total requirement for methionine with cystine over a short diet period did not result in a detectable sparing of methionine oxidation.

Adult↗

PubMed1997

Age, gender, and non-modulation. A sexual dimorphism in essential hypertension.

The angiotensinogen gene is one of the very few related by linkage analysis to human hypertension, but the linkage has been consistently shown only among males. Moreover, polymorphisms in this gene predict an abnormal renal responsiveness to angiotensin II, a feature of non-modulation, but again, only among males. To pursue these related bridges between genetics and physiology, we evaluated the effects of sex on a second feature of non-modulation, the aldosterone response to infused angiotensin II during low sodium balance. We tested the resultant hypothesis-that non-modulation would be less frequent in women-by conducting identical protocols on 225 hypertensive inpatients (70 women, 155 men). Non-modulation was strikingly less frequent among women (26%; 95% confidence interval, 16% to 37%) than men (49%; 95% confidence interval, 40% to 57% (P = .001). We tested the hypothesis that sex steroids play a role by comparing young, premenopausal women (< 35 years) with women who were perimenopausal (45 to 55 years) and postmenopausal (> 55 years). Among the youngest women, the frequency of non-modulation was only 7%, significantly less than in young men (41%, P = .02). A steady increase in non-modulation frequency accompanied advancing age in women, reaching 47% in those older than 55 years, equal to the fraction of men affected. Age influenced non-modulation frequency in men far less. We conclude that a striking sex difference underlies the non-modulation phenotype and that female sex hormones may confer protection against a genotypic predisposition in women. This "override" of genotype, manifest by a very low frequency of non-modulation in young women, may participate in their known protection against cardiovascular disease.

Adolescent↗

PubMed1996

Calcium modulation of adrenocorticotropin levels in women--a clinical research center study.

In vitro calcium modulation of anterior pituitary hormone secretion has been well described. In addition, several investigations performed in human subjects have documented modulation of the circulating levels of pituitary hormones by supraphysiological calcium concentrations. Recent data from our laboratory document the existence of an extracellular calcium-sensing receptor that is thought to mediate the effects of variations in extracellular calcium on the secretion of PTH and calcitonin. We have also demonstrated the presence of this receptor in pituitary-derived, ACTH-secreting AtT-20 cells as well as in the anterior pituitary of rats and mice. In the present study we investigated the effect on anterior pituitary hormone levels of variations in serum calcium within the physiological range. We serially measured serum levels of ionized calcium (Cai), ACTH, cortisol, TSH, and PRL during 90-min iv infusions (on separate days) of calcium, citrate, and dextrose in 10 healthy women with a mean age of 55 +/- 5 yr. During the calcium infusion, the serum Cai level increased significantly from 4.32 +/- 0.10 mg/dL at baseline to 4.86 +/- 0.08 mg/dL at completion (P = 0.002), and this change was accompanied by a significant increment in the serum ACTH level from 9.87 +/- 1.32 to 16.31 +/- 2.84 pg/mL (P = 0.0008). There was no change in the serum ACTH level during the citrate infusion despite significant decrements in serum Cai, nor were there changes in either Cai or ACTH during the dextrose infusion. Finally, changes in Cai did not alter TSH or PRL levels. In summary, our dynamic studies are the first to demonstrate an increase in baseline serum ACTH levels in response to physiological increments in Cai (i.e. increments within the normal range). This effect was specific for increments and not decrements in serum Cai and was selective for ACTH, as TSH and PRL levels did not change with any of the infusions.

Adrenocorticotropic Hormone↗

PubMed1994

Long-term medical therapy for leiomyomata uteri: a prospective, randomized study of leuprolide acetate depot plus either oestrogen-progestin or progestin 'add-back' for 2 years.

Treatment of women with leiomyomata with gonadotrophin-releasing hormone agonists (GnRHa) for > 6 months is not recommended because of concerns regarding adverse sequelae of prolonged hypoestrogenism. It has been postulated that addition of low-dose sex steroids to GnRHa treatment, i.e. 'add-back' therapy, may avert some of these adverse effects (accelerated bone resorption, vasomotor flushes) without altering the efficacy of GnRHa therapy. To evaluate the effects of long-term GnRHa therapy on uterine size, bleeding patterns, bone mass and lipids, 51 pre-menopausal women with leiomyomata were treated with the GnRHa leuprolide acetate depot, 3.75 mg every 4 weeks for 2 years. After 3 months of leuprolide therapy, the women were randomized to receive either low-dose continuous oestropipate, 0.75 mg daily, plus cyclic norethindrone, 0.7 mg on days 1-14 each month (the oestrogen-progestin add-back group) or higher-dose norethindrone, 10 mg daily (the progestin add-back group), for the remaining 21 months. Mean uterine volume decreased by 40% in both treatment groups during the first 3 months on leuprolide treatment. There was no significant change in uterine size following oestrogen-progestin add-back. However, mean uterine volume in the progestin add-back group increased to 87% of pre-treatment size by treatment month 12 and 95% of pre-treatment size by treatment month 24. Mean bone density of the lumbar spine as measured by dual X-ray absorptiometry decreased significantly by 2.6% during the first 3 months in all patients, but did not change significantly following steroid add-back in both treatment groups during the final 21 treatment months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Racial differences in parathyroid hormone dynamics.

Elevations in PTH levels have been reported in black subjects. Such observations have not been consistent, however, and seem paradoxical in view of the known bone-resorptive action of this hormone and the fact that black subjects have a higher bone mineral density and fewer fractures than their white counterparts. In this study, we used dynamic stimulation of the calcium-PTH axis to fully characterize potential racial differences in PTH dynamics. We, therefore, defined the inverse sigmoidal curve that describes the relationship between serum ionized calcium concentration and intact PTH levels in six normal white and six normal black volunteers and determined the four parameters that characterize this relationship. An elevation in any one of these parameters can result in hyperparathyroidism. Black subjects had higher maximal and minimal PTH responses to hypo- and hypercalcemia (mean intact PTH levels of 9.2 +/- 13 and 0.7 +/- 0.1 pmol/L respectively) than white subjects (6.9 +/- 0.6 and 0.3 +/- 0.1 pmol/L, respectively). There were no differences in the set-points or slopes of the curves. Despite the higher baseline and stimulated endogenous PTH levels in black subjects, their baseline and stimulated osteocalcin levels were lower. Our dynamic studies, therefore, document mild hyperparathyroidism in black subjects and suggest mild skeletal resistance to PTH.

Adult↗

PubMed1994

Aberrant snacking patterns and eating disorders in patients with obsessive compulsive disorder.

BACKGROUND: Appetitive symptoms, particularly carbohydrate craving, have been shown to occur in patients whose conditions responded to treatment with drugs that enhance serotonin-mediated neurotransmission. This suggested that patients with obsessive compulsive disorder (OCD) who also frequently respond to serotonergic drugs also might have similar distributions of appetitive and eating patterns. METHOD: A survey study of 170 OCD patients and 920 controls was conducted using a questionnaire that inquired about snacking behavior, including food preference, mood changes after eating, and previous diagnosis of eating disorders. The frequency responses in the two groups were tested for statistical significance. RESULTS: Significant differences were found between the OCD and control groups with respect to the reported incidence of eating disorders, snacking patterns, and mood response to food. CONCLUSION: This finding of different snacking patterns in OCD mirrors that found in other disorders that have been shown to be responsive to serotonergic drugs. The high incidence of carbohydrate snacking among OCD patients compared with the control group provides additional evidence that brain serotonin may be involved in this disorder.

Adult↗

PubMed1993

Dexfenfluramine, fluoxetine, and weight loss among female carbohydrate cravers.

The consumption of excess calories as carbohydrates (CHO)-rich, protein-poor snacks characterizes the overeating of obese CHO cravers, premenstrual women, patients with Seasonal Affective Disorder, and former smokers. This specific appetite for CHOs may involve brain serotonin, as the synthesis and release of this neurotransmitter can increase following consumption of CHO-rich foods. To examine whether weight loss produced by serotoninergic drugs involves a selective reduction in CHO intake, obese females who consumed at least 30% of their daily calories from CHO-rich snacks were treated with dexfenfluramine ([DF] 15 mg b.i.d.); fluoxetine ([FL] 20 mg t.i.d.); or placebo (PL) for 12 weeks. Weekly weight loss for 25 of 29 PL completers was 0.22 kg +/- 0.06 (mean +/- SEM); for 21 of 28 DF completers, 0.56 +/- 0.08 kg; and for 18 of 30 FL completers, 0.58 +/- 0.09 kg (PL < DF = FL; p = .039). Seven FL subjects, 2 PL subjects, and 1 DF subject withdrew from the study due to side effects; other withdrawals were due to intercurrent illness or personal problems. Prior to treatment, subjects consumed over 40% of their daily CHO intake from snacks. Both of the drugs selectively decreased CHO snack intake (p < 0.05); DF, but not FL, also decreased meal CHO intake (p < .025). These results suggest that weight loss following treatment with serotoninergic drugs may relate to a selective decrease in CHO appetite.

Adult↗

PubMed1993

An isotopic study of the effect of dietary carbohydrate on the metabolic fate of dietary leucine and phenylalanine.

The fate of dietary leucine and phenylalanine was studied in five healthy, young adult men, by using a dual, stable isotope-tracer infusion approach to estimate amino acid fluxes, splanchnic (Sp) uptake, and dietary of absorbed amino acid to the peripheral circulation. Subject received two, 4-h tracer infusions of [1-13C]leucine and [15N]phenylalanine infused through a feeding tube placed in the duodenum, and [5,5,5-2H3]leucine, [ring-2H5]phenylalanine, and [6,6-2H2]glucose infused simultaneously by vein. In one experiment subjects received an amino acid mixture (83 mg amino acid.kg-1.h-1) via the feeding tube and in the other experiment amino acids were supplied with carbohydrate (CHO) (167 mg.kg-1.h-1). Sp uptake of dietary leucine decreased with added dietary CHO (29% of ingested leucine for amino acids alone vs 20% with CHO; P < 0.05) but was not different for phenylalanine (P > 0.05). Addition of CHO decreased both release of leucine via protein breakdown and leucine oxidation and increased body leucine balance (P < 0.05).

Adult↗

PubMed1993

A prospective, randomized trial of gonadotropin-releasing hormone agonist plus estrogen-progestin or progestin "add-back" regimens for women with leiomyomata uteri.

Treatment of women with myomas with GnRH agonists (GnRH-a) for 3-6 months will result in profound hypoestrogenism, a significant but temporary reduction in uterine volume, and menstrual suppression. Long-term (i.e. > 6 months) treatment with a GnRH-a is not recommended because of accelerated bone resorption and the presence of hypoestrogenic symptoms. In this 2-yr study, women with myomas were treated with GnRH-a plus one of two steroid "add-back" regimens to minimize adverse sequelae of chronic hypoestrogenism. Fifty-one premenopausal women with large, symptomatic uterine myomas all received the GnRH-a, leuprolide acetate depot (LAD), every 4 weeks for 12 weeks at which time the women were randomized to receive LAD plus either an estrogen-progestin or progestin-only add-back regimen for an additional 92 weeks. Efficacy parameters assessed included serial uterine volumes, hemoglobin concentrations, and hematocrits; safety parameters evaluated included serial bone mineral density measurements, lipid profiles, and medication-related symptoms. This report analyzes the first 52 weeks of study data. Mean uterine volume decreased to 64% of pretreatment size at 12 weeks of LAD treatment in both groups. The estrogen-progestin add-back group had no significant regrowth of uterine volume, which was 75% of pretreatment size at treatment week 52; in contrast, the progestin add-back group had a mean uterine volume of 92% of pretreatment size by treatment week 52. Both groups demonstrated significant improvements in mean hemoglobin concentrations and hematocrits. The progestin add-back group had a significant decline in mean high density lipoprotein-cholesterol concentration, which was not seen in the estrogen-progestin add-back group. Finally, after a significant 3% bone loss during the first 12 weeks of treatment, bone mineral density stabilized in both add-back regimen groups. GnRH-a/steroid add-back regimens provide a useful long-term treatment strategy in women with large, symptomatic uterine myomas and may obviate the need for surgical intervention in selected cases. The estrogen-progestin add-back regimen was superior or equal to the progestin add-back regimen in all efficacy and safety parameters assessed.

Adult↗

PubMed1992

Study of a Fenton type reaction: effect of captopril and chelating reagents.

The purpose of this study was to determine if captopril, an angiotensin-converting enzyme inhibitor, could interact with iron ions and so modify a Fenton type reaction. Results indicate that different degrees of thiobarbituric acid-reactive substance from deoxyribose are obtained in an ascorbate-driven Fenton system depending on the order of addition of captopril and iron to the incubation medium. Similar results were obtained with the chelating reagents ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid, indicating that the buffer solution plays a relevant role when a particular iron complex is formed with a chelating agent. These metal complexes produce oxidizing species in a Fenton type system whose nature is discussed.

Captopril↗

PubMed1992

Effect of sequential and daily continuous hormone replacement therapy on indexes of mineral metabolism.

BACKGROUND: Continuous regimens of estrogen-progesterone have recently been favored over sequential regimens because of a lower incidence of withdrawal bleeding. To determine whether the beneficial effects of sequential hormonal therapy on bone metabolism are preserved with the newer continuous regimens, we studied indexes of skeletal metabolism and changes in bone mineral density during a 1-year prospective trial. METHODS: Our subjects were randomized to one of three treatment groups: those in group C-2.5 were treated with 0.625 mg of conjugated estrogen with 2.5 mg of micronized medroxyprogesterone acetate daily continuously; group C-5 received 0.625 mg of conjugated estrogen and 5.0 mg of micronized medroxyprogesterone acetate daily continuously; and group S-5 received 0.625 mg of conjugated estrogen on days 1 through 25 and 5 mg of micronized medroxyprogesterone acetate on days 14 through 25. RESULTS: At 1 year, all groups demonstrated a significant decrease in indexes of bone formation turnover, including decrements in alkaline phosphatase levels of 11% to 30% and in osteocalcin levels of 45% to 60%. Intact parathyroid hormone levels rose 10% to 20%, with a concomitant near-significant decrement in ionized calcium levels at 12 months. In addition, there were significant decrements in the 24-hour urinary calcium-creatinine ratios and hydroxyproline-creatinine ratios of 13% to 28%, measures of bone resorption. Linear regression analyses showed that the subjects with the high bone resorption achieved the greatest increment in bone mineral density in response to hormone therapy. CONCLUSION: The daily continuous estrogen-progesterone regimens are as efficacious as sequential hormonal therapy in decreasing indexes of bone turnover and stabilizing bone mineral density of the spine and proximal femur.

Bone Density↗

PubMed1992

Non-modulation as an intermediate phenotype in essential hypertension.

Non-modulation is a trait characterized by abnormal angiotensin-mediated control of aldosterone release and the renal blood supply. To determine whether non-modulation defines a specific subgroup of the hypertensive population and its utility as an intermediate phenotype, we have studied the distribution of this quantitative trait, whether its features are reproducible on repeated testing, and whether there is concordance of its multiple features. Essential hypertensive patients (224) and normotensive subjects (119) received an infusion of angiotensin II (Ang II) at 3 ng.kg-1.min-1 for 30-45 minutes. p-Aminohippurate (PAH) clearance was assessed as an index of renal plasma flow while the subjects were on a 200 meq sodium diet; plasma aldosterone levels were measured while the subjects were on a 10 meq sodium diet. In 54 subjects, diuretic-induced volume depletion superimposed on a low salt diet was substituted for the Ang II infusion. The results of each study were submitted to maximum likelihood analysis to assess bimodality. In response to both diuretic-induced volume depletion (p < 0.000023) and Ang II infusion (p < 0.0009), aldosterone responses were bimodally distributed in the essential hypertensive but not in the normotensive subjects, suggesting that this trait identifies a discrete subgroup. In the 59 subjects who had both an adrenal and renal study, 50 (85%) were concordant. Finally, in 27 subjects studied two to six times over a span of 1-60 months, the intraclass correlations of the adrenal, PAH, or both responses were highly significant (p values between 0.001 and 0.00007), indicating high reproducibility of results on repeated testing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1991

Captopril does not scavenge superoxide: captopril prevents O2-. production by chelating copper.

The purpose of this study was to use a direct method, that of electron spin resonance spectroscopy, to evaluate the ability of captopril, an angiotensin-converting enzyme inhibitor, to prevent the superoxide-mediated formation of phenyl radicals. Results indicate that, under certain conditions, captopril is a potent inhibitor of the generation of phenyl radicals, produced by the autoxidation of phenylhydrazine. The inhibitory effect of captopril, however, was better understood as a direct interaction of the drug with the metals that catalyze the autoxidation process rather than as a reaction of captopril with the free radicals generated. This last conclusion was supported by the finding that captopril was not able to inhibit the superoxide anion-mediated reduction of nitroblue tetrazolium.

Captopril↗

PubMed1991

Study of the interaction of cadmium with membrane-bound succinate dehydrogenase.

Cadmium ions inhibit membrane-bound succinate dehydrogenase with a second-order rate constant of 10.42 mM-1 s-1 at pH 7.35 and 25 degrees C. Succinate and malonate protect the enzyme against cadmium ion inhibition. The protection pattern exerted by succinate and malonate suggests that the group modified by cadmium is located at the active site. The pH curve of inactivation by Cd2+ indicates the involvement of an amino acid residue with pKa of 7.23.

Animals↗

PubMed1991

Weight gain and withdrawal symptoms after smoking cessation: a preventive intervention using d-fenfluramine.

Directly measured food intake in 31 overweight female smokers to test whether (a) calorie and carbohydrate intakes increase after smoking cessation and (b) double-blind d-fenfluramine (30 mg), a serotonin-releasing drug, suppresses weight gain, overeating, and dysphoric mood associated with stopping smoking. Placebo-treated patients grew dysphoric after smoking withdrawal and ate 300 kcal/day more from 2 to 28 days after, showing a 3.5-lb weight gain. Fat and protein intakes did not change, but carbohydrate intake increased (30% to 40%). D-fenfluramine prevented postcessation dysphoria. Although drug-treated patients ate more carbohydrate snacks just after quitting, they returned to baseline by 4 weeks, showing a 1.8-lb weight loss. Agents that enhance brain serotonin-mediated neurotransmission may help prevent weight gain, overeating, and dysphoric mood after smoking withdrawal.

Adult↗

PubMed1991

Dissociation in plasma renin and adrenal ANG II and aldosterone responses to sodium restriction in rats.

In rats, plasma renin activity (PRA) increases sharply, reaching a plateau within hours of sodium restriction. Plasma aldosterone increases gradually, not reaching a plateau for 1-2 days. To determine whether this dissociation is secondary to the time needed to modify adrenal sensitivity to angiotensin II (ANG II) and to assess the role of locally produced ANG II in this process, rats were salt restricted for 0-120 h. Plasma hormone levels were assessed, adrenal ANG II was measured, and basal and ANG II (1 x 10(-8) M)-stimulated steroidogenesis were determined in vitro. Although PRA attained an elevated plateau within 8 h, plasma aldosterone did not peak until after 48 h of sodium depletion. The in vitro aldosterone sensitivity to exogenous ANG II was not apparent until rats had been salt restricted for 16 h. A plateau (4-fold increase above the ANG II response on high salt) was achieved between 24 and 48 h. Adrenal ANG II also exhibited a similar delayed response that correlates significantly with changes in aldosterone biosynthesis and late pathway activity. Thus the dissociation between PRA and plasma aldosterone may be secondary to a lag in the zona glomerulosa's (ZG) steroidogenic response to ANG II as well as a parallel lag in tissue ANG II production, suggesting that changes in tissue ANG II may mediate ZG sensitivity to ANG II during sodium deprivation.

Aldosterone↗

PubMed1991

Renal and endocrine responses to a renin inhibitor, enalkiren, in normal humans.

Interpretation of renin-angiotensin blockade with angiotensin converting enzyme inhibitors is potentially confounded by their multiple effects. We used a selective renin inhibitor (enalkiren, A-64662) to explore the renal and endocrine effects of angiotensin II in healthy men. Each received 90-minute enalkiren infusions at 2-day intervals, on a low (10 mmol, 16 subjects) and high (200 mmol, 12 subjects) salt diet. Plasma renin activity, immunoreactive plasma angiotensin II and aldosterone concentrations, inulin, and p-aminohippurate clearance were measured by standard methods. Plasma renin activity fell at 0.1 micrograms/kg, but the threshold for biologic effect was 256 micrograms/kg, where plasma immunoreactive angiotensin II and aldosterone concentration fell, and renal plasma flow rose (p less than 0.01). The maximal renal vascular response (+152 +/- 23 ml/min/1.73 m2) occurred at 512 micrograms/kg (p less than 0.01). Diastolic and mean blood pressure fell modestly but significantly (p less than 0.05). Responses were limited on a high salt diet. We confirm that conventional plasma renin activity measurement is misleading in humans receiving a renin inhibitor. The renal vascular response to renin inhibition in this study appeared to substantially exceed reported responses to angiotensin converting enzyme inhibition, perhaps reflecting a crucial and relatively inaccessible intrarenal locus.

Adult↗