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Biomedical subjects

M Heiman

Publications and source records attributed to M Heiman.

At least 19 recordsLinked to original sources
PubMed2001

Minireview: ghrelin and the regulation of energy balance--a hypothalamic perspective.

The recently discovered hormone, ghrelin, has been recognized as an important regulator of GH secretion and energy homeostasis. Orexigenic and adipogenic ghrelin is produced by the stomach, intestine, placenta, pituitary, and possibly in the hypothalamus. The concentration of circulating ghrelin, principally derived from the stomach, is influenced by acute and chronic changes in nutritional state. To date, most studies focused on the role of ghrelin in GH secretion or its function in complementing leptin action to prevent energy deficits. The potential significance of ghrelin in the etiology of obesity and cachexia as well as in the regulation of growth processes is the subject of ongoing discussions. A large quantity of information based on clinical trials and experimental studies with ghrelin and previously available synthetic ghrelin receptor agonists (GH secretagogues) must now be integrated with a rapidly increasing amount of data on the central regulation of metabolism and appetite. In this overview, we summarize recent findings and strategies on the integration of ghrelin into neuroendocrine networks that regulate energy homeostasis.

Animals↗
PubMed2000

Differential brain responses to satiation in obese and lean men.

Knowledge of how the brain contributes to the regulation of food intake in humans is limited. We used positron emission tomography and measures of regional cerebral blood flow (rCBF) (a marker of neuronal activity) to describe the functional anatomy of satiation (i.e., the response to a liquid meal) in the context of extreme hunger (36-h fast) in 11 obese (BMI > or =35 kg/m2, age 27+/-5 years, weight 115+/-11 kg, 38+/-7% body fat; mean +/- SD) and 11 lean (BMI < or =25 kg/m2, age 35+/-8 years, weight 73+/-9 kg, 19+/-6% body fat) men. As in lean men, satiation in obese men produced significant increases in rCBF in the vicinity of the ventromedial and dorsolateral prefrontal cortex and significant decreases in rCBF in the vicinity of the limbic/paralimbic areas (i.e., hippocampal formation, temporal pole), striatum (i.e., caudate, putamen), precuneus, and cerebellum. However, rCBF increases in the prefrontal cortex were significantly greater in obese men than in lean men (P < 0.005). rCBF decreases in limbic/paralimbic areas, temporal and occipital cortex, and cerebellum were also significantly greater in obese men than in lean men (P < 0.005), whereas rCBF decreases in the hypothalamus and thalamus were attenuated in obese men compared with lean men (P < 0.05). This study raises the possibility that the brain responses to a meal in the prefrontal areas (which may be involved in the inhibition of inappropriate response tendencies) and limbic/paralimbic areas (commonly associated with the regulation of emotion) may be different in obese and lean men. Additional studies are required to investigate how these differential responses are related to the pathophysiology of obesity.

Adult↗
PubMed1997

Markers for the gene ob and serum leptin levels in human morbid obesity.

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 +/- 7 kg/m2, and 151 lean controls with a mean BMI of 22 +/- 2 kg/m2, and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI > or = 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders.

Adult↗
PubMed1997

Novel polymorphism of the human ob gene promoter in lean and morbidly obese subjects.

OBJECTIVE: Leptin, the circulating product of the human ob gene, may play role in control of appetite and metabolic rate. We screened the proximal promoter area of the ob gene for mutations and common polymorphisms in order to find out whether genetic variation in the regulatory area of this gene plays a role in human obesity. DESIGN: The technique of single-strand-conformation polymorphism (SSCP) was applied to screen for the promoter area of the ob gene for genetic alterations in morbidly obese patients. SUBJECTS: A total of 249 morbidity obese (present or past body mass index [BMI] > or = 40 kg/m2) and 141 lean (BMI < or = 25 kg/m2) subjects. MEASUREMENTS: DNA analysis was carried out using a single-strand conformation polymorphism (SSCP) technique and PCR followed by digestion with the restriction enzyme BssHll. Leptin was determined by radioimmunoassay in obese subjects. Serum lipids, glucose and insulin concentrations in the obese subjects were also determined. RESULTS: A new polymorphism C(-188)A was identified in the promoter region of the ob gene. This polymorphism was detected with allelic frequencies of 0.06 in morbidly obese subjects and 0.09 in lean controls (P = 0.28). Initial studies failed to show an association of this polymorphism with serum leptin, response to treatment for obesity, history and extent of weight gain, or serum insulin, glucose of lipid concentrations. CONCLUSIONS: We have identified a common polymorphism in the promoter area of the human ob gene which appears to be very useful for genetic association and linkage studies. Further studies are needed to elucidate its potential role in the regulation of the human ob gene and in human metabolic disorders.

Adolescent↗
PubMed1996

Twenty-four-hour ambulatory electrocardiography in elderly subjects: prevalence of various arrhythmias and prognostic implications (report from the Bronx Longitudinal Aging Study).

Functional, ambulatory, community-dwelling subjects (n = 423, aged 75 to 85 years) underwent baseline 24-hour ambulatory electrocardiography (ECG) examinations as part of the Bronx Aging Study, a 10-year prospective cohort study designed to identify risk factors and disease markers for cardiovascular, cerebrovascular, and dementia illnesses in old people. Premature ventricular contractions were the most commonly observed arrhythmia noted (93% of subjects), with a low prevalence of nonsustained ventricular tachycardia (5%), paroxysmal atrial tachycardia (13%), atrial fibrillation (4%), and atrioventricular blocks (4%). A 24-hour sinus rate of < 60 beats/min was noted in 13% of subjects, and 11% of subjects were noted to have transient episodes of severe bradycardia (< 40 beats/min). In a multivariate analysis, nonsustained ventricular tachycardia was an independent predictor of death (p = 0.015; relative risk [RR] 2.8; 95% confidence interval [CI] 1.4 to 5.8) and myocardial infarction (p = 0.031; RR 3.2; CI 1.2 to 9.4). Transient atrioventricular block was an independent predictor of stroke (p - 0.0006; RR 9.7; CI 3.3 to 28.9), as was sinus bradycardia over a 24-hour period (p = 0.033; RR 2.7; CI 1.2 to 6.4). Ventricular tachycardia approached significance as an independent predictor of multiinfarct dementia (p = 0.052; RR 6.3; CI 1.4 to 28.7). Episodes of paroxysmal atrial fibrillation, a trial tachycardia, and severe bradycardia were not associated with adverse outcomes. Some arrhythmias found on the ambulatory ECG in very old subjects can predict an increased risk for subsequent death, myocardial infarction, stroke, and multiinfarct dementia.

Aged↗
PubMed1993

Nisoldipine: a new dihydropyridine calcium-channel blocker.

Nisoldipine is a new calcium-channel blocker of the dihydropyridine subclass, with a chemical structure similar to nifedipine. It has been used in clinical trials to assess its efficacy and safety in patients with hypertension, angina pectoris, and congestive heart failure. Similar to other dihydropyridines, nisoldipine is a potent peripheral and coronary dilator. The most optimal dosage regimen has not been established in clinical trials. The drug appears to have a favorable side-effect profile.

Angina Pectoris↗
PubMed1992

Cardiomegaly on chest x-ray: prognostic implications from a ten-year cohort study of elderly subjects: a report from the Bronx Longitudinal Aging Study.

This report is from a 10-year cohort study of community-dwelling elderly men and women. Mean age at the time of entry into the study was 79 years. Annual chest x-ray studies were performed, and data are presented regarding prevalence, incidence, and prognosis of cardiomegaly. Cardiomegaly was defined as a transverse diameter of the cardiac silhouette greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio). At the time of entry into the study 110 subjects (23%) had cardiomegaly. After 10 years, 51% of the subjects with cardiomegaly at baseline died compared with 33% of the subjects without cardiomegaly (mortality rate = 9.1 vs 4.8/100 person-years respectively; p = 0.014). Cardiovascular disease incidence was also higher for those with preexisting cardiomegaly at baseline (rate 9.1 vs 6.1/100 person-years; p = 0.0001). According to the Cox proportional hazards regression analysis, age, cardiomegaly, diabetes, and prior evidence of myocardial infarction were independent predictors for death in this cohort. Similarly, the best predictive variables for cardiovascular disease were age, diabetes, prior evidence of myocardial infarction, and cigarette smoking. Of the 359 subjects without cardiomegaly at baseline, 108 (30%) showed evidence of new cardiomegaly, and their risk of cardiovascular disease was 1.8 times that of subjects whose test results were negative for cardiomegaly throughout the study (p = 0.003). Thus cardiomegaly, as defined by an increased cardiothoracic ratio on x-ray films, irrespective of cause, is associated with a poor prognosis in very elderly men and women.

Aged↗
PubMed1991

Usefulness of oral nisoldipine for stable angina pectoris. The Nisoldipine Multicenter Angina Study Group.

The duration and extent of antianginal effects of nisoldipine, a dihydropyridine calcium antagonist, were assessed in 178 patients with chronic stable angina pectoris. Using a placebo run-in, placebo-controlled, randomized, parallel study design, patients received placebo twice daily for 2 to 3 weeks and were then randomized to receive either placebo (n = 42), nisoldipine 10 mg once daily (n = 44), nisoldipine 10 mg twice daily (n = 47) or nisoldipine 20 mg once daily (n = 45) for 5 weeks. Frequency of angina and nitroglycerin consumption were assessed by weekly patient diaries. Exercise tolerance time was assessed at baseline and at weeks 1, 3 and 5 in the double-blind phase. Peak effects after 5 weeks of double-blind medication showed significant or nearly significant improvements with nisoldipine over placebo in time-to-termination of exercise, time to onset of angina, and time to onset of 1 mm ST-segment depression. There were no significant improvements in trough effects with nisoldipine. Also, placebo was not significantly different from nisoldipine in either the number of anginal attacks or nitroglycerin consumed. Although significantly more drug-related, adverse effects were observed with the nisoldipine regimen, 20 mg once daily, compared with placebo, nisoldipine appears to be an effective and well-tolerated antianginal drug. However, its duration of antianginal action, as measured by exercise stress testing, is relatively short. The drug needs to be examined using shorter dosing intervals and higher daily doses, or in a longer-acting sustained-release formulation.

Administration, Oral↗
PubMed1991

Comparison of celiprolol and propranolol in stable angina pectoris. Celiprolol International Angina Study Group.

The comparative antianginal effects and safety of propranolol and celiprolol, a highly beta 1-selective adrenoceptor blocker with selective partial beta 2-adrenoceptor agonist activity, were assessed in an international multicenter, placebo run-in, active control, double-blind, randomized, titration-to-effect study of 140 patients with stable, exercise-induced angina pectoris. At baseline, all patients received placebo for 2 weeks, then titrated doses of once-daily celiprolol (200, 400, 600 mg) or twice-daily propranolol (total daily dose 80, 160, 320 mg) over 4 weeks, followed by a 2-week maintenance period. Heart rate and blood pressure, at rest and with exercise, weekly anginal attack frequency, nitroglycerin consumption and symptom-limited treadmill exercise times (modified Bruce protocol) were assessed. Compared with their respective baselines, both celiprolol and propranolol reduced anginal attack and nitroglycerin consumption rates to a comparable degree, while improving exercise tolerance (p less than 0.05). Treatment with propranolol compared with celiprolol, however, was associated with a significantly lower heart rate at rest (p less than 0.01). The double-product at the conclusion of exercise testing was significantly reduced by both drugs. Celiprolol and propranolol had similar effects on blood pressure, and were well tolerated. More symptomatic bradycardia occurred with propranolol. Despite the differences in their hemodynamic actions, once-daily celiprolol is as effective as twice-daily propranolol in the treatment of patients with stable angina pectoris.

Adrenergic beta-Antagonists↗
PubMed1990

Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The Bronx Aging Study.

The prevalence, incidence and prognosis of recognized and unrecognized Q-wave myocardial infarction (MI) was assessed in an 8-year prospective study of 390 community-based subjects (age 75 to 85 years at entry, mean 79 years). Subjects were studied at baseline and with annual follow-up electrocardiographic (ECG) exams. At baseline, 7.9% had a history of MI without ECG evidence, 6.4% had ECG evidence of Q-wave MI without clinical history, 4.1% had both clinical history and ECG evidence and 81.5% had neither history nor ECG evidence (control subjects). After an average follow-up period of 76.2 months, the total mortality rate was 5.9/100 person-years for subjects with some evidence of MI at baseline versus 3.9 in the control group (p = 0.059). The incidence of cardiovascular disease in subjects with evidence of MI was 8.8/100 person-years versus 4.7 among control subjects (p = 0.002). During the follow-up period, 115 new Q-wave MIs occurred (50 unrecognized, rate 2.4/100; 65 recognized, rate 3.2/100). There was no difference in mortality and morbidity outcome between subjects with recognized and unrecognized MIs. Those with only a history of MI at baseline had a threefold greater risk of a new MI (recognized and unrecognized) than the control group (p = 0.003). Unrecognized Q-wave MI is a common occurrence in the "old old" with subsequent morbidity and mortality prognosis comparable to that of recognized MI. History of MI alone in this age group is also associated with an increased risk of MI, suggesting the need for better diagnostic markers of myocardial ischemia in the old.

Aged↗
PubMed1989

Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: evidence for attenuation of effect over time.

The safety and efficacy of using continuous high-dose transcutaneous nitroglycerin in doses up to 100 mg/24 hours in chronic stable angina was assessed in 20 patients using serial treadmill testing. Patients had first to show a response to sublingual nitroglycerin with a 20% improvement in exercise time. All patients were then titrated with 20 mg (40 cm2), 60 mg (120 cm2), 80 mg (160 cm2) or 100 mg (200 cm2) patches, until intolerable headache in association with a 10 mmHg reduction in blood pressure and a ten-beat increment in heart rate. Drug was then discontinued for 2 days and patients underwent three repeat stress tests to reestablish a consistent drug-free baseline. Patients were then randomized in double-blind fashion to receive either active patch (N = 11) in previous titration dose or placebo patch (N = 9), with treadmill tests performed at 0 (1 hour after previous patch removal), 4, and 24 hours after patch application at baseline and at weeks 1 and 2. Venous blood was obtained for measurement of plasma nitroglycerin levels. After the first 24 hours of active patch therapy, there was a significant reduction in systolic blood pressure (P = .05), a significant increase in heart rate (P = .01), and a minor increase in exercise tolerance (P = .06) compared to placebo. At weeks 1 and 2, there was an attenuation of drug effect in all of these parameters. Plasma nitroglycerin levels demonstrated consistently high plasma levels over each 24-hour dosing interval, on day 1, week 1, and week 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1976

Sleep orgasm in women.

Some of the recent most challenging contributions to our knowledge of female sexuality were provided by direct observations as early as during the second year of life concerning genital self-stimulation and masturbation in girls. Other investigators have advanced the proposition that girls are capable of vaginal masturbation and possibly of experiencing vaginal sensation and stimulation very early in life. Our own clinical study on sleep orgasm, based mainly on data obtained from the analysis of one woman, leads to formulating the hypothesis that in some instances the nursing situation may provide sensations in the genitals (vagina), not only for the mother, but also for the baby. We assume that such sensations in the genitals of the infant female are not the result of mechanical stimulation of the genital organs--as described during the second year and later--but are the result of a "resonance" phenomenon whereby the infant's genitals, including the vagina, are stimulated from within. The observations of orgasm made by others and by the author should be considered the first tentative steps toward an understanding of the complex nature of female orgasm. Eventually, further studies might lead to distinguishing more clearly a sexual orgasm in a narrower sense from a sucking orgasm, from an anger orgasm, and from a stress orgasm--i.e. an unspecific genital discharge. Sleep orgasm can represent gratification of unacceptable disguised sexual wishes and can therefore occur after intercourse and orgasm experienced when awake. The study of sleep orgasm might be of value in relation to the general problems of female orgasm. I would like to close with a reminder that some of the formulations presented in this paper are quite obviously largely speculative.

Adult↗