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Biomedical subjects

L Landsberg

Publications and source records attributed to L Landsberg.

At least 55 records · Page 3Linked to original sources
PubMed1992

Obesity and hypertension: experimental data.

BACKGROUND TO DATA REVIEW: Epidemiologic surveys have demonstrated that hypertension is associated with obesity in a substantial proportion of cases, particularly in young and middle-aged adults. Despite the clinical importance of this association the nature of the relationship between body weight and blood pressure remains obscure. CONCLUSION OF DATA REVIEW: The data reviewed here indicate that obesity-related hypertension involves insulin and the sympathetic nervous system, and may be part of a metabolic adaptation to the obese state.

Adaptation, Physiological↗
PubMed1992

Surrogate decision-maker preferences for medical care of severely demented nursing home patients.

BACKGROUND: In the absence of advanced directives, physicians treating demented patients rely on surrogates to help make medical care decisions. METHOD: We surveyed family members of severely demented nursing home residents to determine preferences for medical intervention in five hypothetical situations involving tube feeding, hospitalization, intensive care unit admission, mechanical ventilation, and cardiopulmonary resuscitation. RESULTS: Only 11.8% of surrogates rejected all interventions. Cardiopulmonary resuscitation and tube feeding were accepted least frequently (31.6% and 36.4%, respectively). Mechanical ventilation, hospitalization, and intensive care unit admission were accepted by 43.6%, 63.4%, and 75.2%, respectively. There was no correlation between previous surrogate experience with an intervention and its acceptance. Nearly 70% of surrogates indicated that decisions were independent of any previously expressed resident views. CONCLUSIONS: In this study, surrogates of even the most demented nursing home patients prefer hospital level services including intensive care unit care for the treatment of acute illness. Efforts to control access to services on ethical or economic grounds may meet with resistance.

Aged↗
PubMed1991

Changes in urinary catecholamine excretion after smoking cessation.

Excretion levels of norepinephrine, epinephrine, and dopamine were assessed in 17 habitual cigarette smokers while smoking and periodically during 30 days of abstinence to determine whether a pattern of transient change existed, suggestive of sympathetic nervous system (SNS) involvement in tobacco withdrawal. Excretion of all three catecholamines declined 1 day after abstinence but did not return to precessation levels during the rest of the follow-up period. The results suggest that postcessation declines in excretion may be permanent changes caused by loss of tobacco's agonist effects, rather than transient withdrawal phenomena resulting from SNS adaptation to the stimulatory effects of tobacco.

Adult↗
PubMed1991

Obesity, blood pressure, and the sympathetic nervous system.

Obesity has long been recognized as a major risk factor for the development of hypertension. Recently, insulin level has been shown to correlate with blood pressure in clinical and population-based studies. Since insulin is a major signal in the relationship between dietary intake and sympathetic nervous system activity, the possibility that insulin-mediated sympathetic stimulation is involved in the pathogenesis of hypertension in the obese has been raised. This hypothesis, developed on the basis of studies in laboratory rodents and normal human subjects, is currently being tested in the Normative Aging Study in Boston. Utilizing epidemiologic techniques applied to this defined population, evidence in support of this hypothesis has been accumulated. The preliminary results indicate that in this population, the abdominal form of obesity is associated with higher insulin levels and increased 24-hour urinary norepinephrine excretion (an index of sympathetic activity).

Animals↗
PubMed1991

Blood pressure, pulse, and neurohumoral responses to nitroprusside-induced hypotension in normotensive aging men.

In order to assess the effects of age on blood pressure, pulse, and neurohumoral responses to hypotensive stress, we infused nitroprusside into healthy young and old men until mean arterial blood pressure was reduced 20% from basal. Elderly subjects were much more sensitive to nitroprusside. Pulse increases in response to this hypotensive stress were markedly reduced in the elderly, but renin, vasopressin, and norepinephrine responses were not different between young and old. We conclude that cardioacceleration, one of the primary defenses against hypotension, is impaired with age. However, neurohumoral responses to hypotension are intact in the elderly.

Adult↗
PubMed1991

The treatment of orthostatic hypotension with dihydroxyphenylserine.

Neurogenic orthostatic hypotension is an incapacitating symptom of central and peripheral autonomic nervous system degeneration. It occurs in such clinical conditions as multiple system atrophy, pure autonomic failure, and small-fiber peripheral neuropathies. Although many treatments are available, their effects are inconsistent, unsustained, and complicated by side effects. 3,4-Dihydroxyphenylserine is a synthetic, unnatural amino acid that is an immediate norepinephrine precursor. There is theoretical and clinical evidence supporting the use of this agent in the treatment of neurogenic orthostatic hypotension in patients with peripheral and central autonomic nervous system dysfunction. We review the biochemistry, pharmacokinetics, and possible mechanisms of action and clinical utility of this agent in the treatment of neurogenic orthostatic hypotension.

Droxidopa↗
PubMed1991

Relation of obesity and diet to sympathetic nervous system activity.

The hypothesis that dietary intake and obesity stimulate the sympathetic nervous system was investigated in a cross-sectional study of 572 men aged 43-85 years from the Normative Aging Study. Habitus was represented by body mass index, as a measure of overall adiposity, and by the ratio of abdomen-to-hip circumference (abdomen/hip ratio), as a measure of centripetal fat distribution. Sympathetic activity was assessed by measurement of 24-hour urinary norepinephrine excretion. Increased body mass index and total caloric intake were independently associated with increased 24-hour urinary norepinephrine excretion (p = 0.0001 and p = 0.0055, respectively). In addition, mean urinary norepinephrine excretion was higher in subjects classified as either hyperglycemic (serum fasting glucose greater than or equal to 113 mg/dl) and hyperinsulinemic (serum fasting insulin greater than or equal to 19 microIU/ml) (p = 0.0023) or in subjects classified as either hyperglycemic or hyperinsulinemic (p = 0.0063) than the mean urinary norepinephrine excretion in normal subjects. These relations were demonstrated to be independent of age, smoking status, and physical activity. Our results are consistent with the hypothesis that insulin mediates sympathetic stimulation in response to dietary intake and increases sympathetic nervous system activity in the obese.

Adipose Tissue↗
PubMed1991

Hypertension in obesity and NIDDM. Role of insulin and sympathetic nervous system.

An important link exists between obesity, noninsulin-dependent diabetes mellitus (NIDDM), and hypertension. Most patients with NIDDM are obese; the incidence of hypertension in obesity and NIDDM is substantial, approaching 50% in some studies. Furthermore, hypertension is known to contribute to the increased cardiovascular morbidity and mortality in patients with obesity and NIDDM. Despite the obvious clinical importance, the pathogenesis of hypertension in obesity and NIDDM remains poorly understood. Recent studies have identified hyperinsulinemia and insulin resistance as important threads that tie hypertension, obesity, and NIDDM together. The hypothesis is developed that insulin-mediated sympathetic stimulation contributes to blood pressure elevation in both obesity and NIDDM. Recruited as a mechanism to limit weight gain and restore energy balance, insulin resistance and sympathetic stimulation increase blood pressure by enhancing renal Na+ reabsorption and stimulating the cardiovascular system. In this article, we review the evidence on which this hypothesis is based.

Diabetes Complications↗
PubMed1990

The sympathoadrenal system, obesity and hypertension: an overview.

Obesity-related hypertension is a clinical problem of major significance. The nature of the relationship between blood pressure and body weight has not been elucidated. Recent studies suggest that insulin (and/or insulin resistance) may be involved. An hypothesis is developed, based on the relationship between dietary intake and sympathetic activity, that attributes obesity-related hypertension to sympathetic stimulation.

Adrenal Glands↗
PubMed1990

Insulin resistance, energy balance and sympathetic nervous system activity.

Insulin resistance and hyperinsulinemia are commonly associated with hypertension in the obese. The nature of this association is obscure. An hypothesis is developed that attributes obesity-related hypertension to sympathetic stimulation. The relationship between insulin and the sympathetic nervous system (SNS) has its origins in the mediation of dietary thermogenesis. Fasting suppresses while carbohydrate and fat feeding stimulate sympathetic activity. Insulin-mediated glucose metabolism within critical central neurons links dietary intake and central sympathetic outflow. The sympathetic nervous system, in turn, contributes to changes in metabolic rate that accompany alterations in dietary intake. It is hypothesized that insulin resistance is a mechanism recruited in the obese to limit further weight gain and stabilize body mass. Insulin-mediated sympathetic stimulation is one mechanism that may restore energy balance in the obese since the obese are not resistant to the stimulatory effect of insulin on the SNS. Sympathetically mediated stimulation of the heart, vasculature and kidney contributes, in genetically predisposed individuals, to the development of hypertension. Viewed in this light, obesity-related hypertension is the unfortunate by-product of an adaptive mechanism (insulin resistance) recruited to restore energy balance in the obese. Possible implications of this formulation are discussed.

Adipose Tissue↗
PubMed1990

The relationship of body fat distribution to blood pressure in normotensive men: the normative aging study.

Body fat distribution may be a more specific marker than obesity for risk of cardiovascular disease and diabetes. The relationship between body fat distribution and sitting systolic and diastolic blood pressure was examined in a cross-sectional analysis of 1936 normotensive men aged 21 to 80 years. In this analysis body fat distribution was represented by the ratio of abdomen circumference to hip breadth (denoted as WHbR). Pearson product-moment correlations adjusted for age revealed a positive correlation between WHbR and both systolic and diastolic blood pressure (r = 0.13 and r = 0.14, respectively). In a multiple linear regression model controlling for age, smoking status and body mass index (BMI), WHbR was associated with systolic blood pressure [regression coefficient (standard error) = 3.58 (1.8), P = 0.048)], but had much less of an association with diastolic blood pressure [regression coefficient (standard error) = 1.90 (1.3), P = 0.141]. Further adjustment for alcohol intake decreased the association between WHbR and systolic blood pressure [regression coefficient (standard error) = 2.90 (1.81), P = 0.110]. Body fat distribution, as represented by WHbR was associated with level of systolic blood pressure independently of overall level of obesity (BMI) in normotensive men; adjustment for alcohol intake attenuated the relationship. These data suggest that dietary factors, notably alcohol intake, may influence the effect of body fat distribution on blood pressure.

Adipose Tissue↗
PubMed1989

Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy.

Phenytoin sodium has been used to treat muscle cramps of diverse causes, and is known to increase insulin sensitivity during long-term use. We have previously described a syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy with continual muscle cramping. The effect of 300 mg/d of phenytoin (Dilantin) on muscle cramping and carbohydrate economy was studied in three affected patients and four control subjects. Oral glucose tolerance tests, euglycemic insulin infusion studies, and monocyte insulin binding tests were conducted before and after phenytoin administration. All three patients had notable improvement in muscle cramps. In response to phenytoin, metabolic improvements were variable, with improvement characteristically better in patients with less severe baseline metabolic abnormalities. Patient 1, with the mildest degree of glucose intolerance, had decreased fasting insulin and blood glucose levels, improved glucose tolerance, and insulin-mediated glucose disposal, associated with an increase in monocyte insulin receptors. Patient 2 had reduced fasting plasma glucose and insulin levels and improved oral glucose tolerance, suggesting a beneficial effect on carbohydrate metabolism. Patient 3, with the most severely impaired carbohydrate economy, showed no metabolic improvement despite marked lessening of muscle pain. These clinical characteristics were unaffected in control subjects. We conclude that phenytoin is of value in the therapy of muscle cramps and glucose intolerance in patients with this syndrome.

Acanthosis Nigricans↗
PubMed1989

Differential catecholamine responses to dietary intake: effects of macronutrients on dopamine and epinephrine excretion in the rat.

Sympathetic nervous system (SNS) function responds to changes in diet in animals and humans; whether alterations in peripheral dopaminergic activity or in adrenal medullary secretion also occur with dietary manipulation is unclear. The present studies in rats demonstrate that casein supplementation of a lab chow diet raised urinary excretion of dopamine (DA) and epinephrine (E); both sucrose and lard feeding suppressed urinary DA, though only lard appeared to exert any effect on E excretion (reduction). Addition of tyrosine to the chow diet in an amount equivalent to the tyrosine content of casein increased DA output comparably to that seen in casein-fed rats, but did not reproduce the effects of casein on E excretion. Oral administration of carbidopa, an inhibitor of 3,4-dihydroxyphenylalanine (DOPA) decarboxylation in kidney reduced the DA response to casein, but chemical sympathectomy, which lowered urinary norepinephrine (NE), and adrenal denervation, which diminished E excretion, did not. Thus, the patterns of response of the peripheral dopaminergic system in kidney and of the adrenal medulla to short-term nutrient and tyrosine ingestion are distinct from those observed for the SNS and for each other, suggesting that all three peripheral catecholamine systems may be governed by separate regulatory mechanisms.

Animals↗
PubMed1989

Obesity, metabolism, and the sympathetic nervous system.

The association of hypertension and obesity is poorly understood. Studies conducted in our laboratory over the last decade, in conjunction with recent clinical and epidemiological observations, suggest that hypertension in the obese is derived from a fundamental relationship between dietary intake and sympathetic nervous system (SNS) activity. The application of kinetic techniques to the measurement of norepinephrine (NE) turnover rate in sympathetically innervated tissues of laboratory rodents has defined a relationship between the SNS and dietary intake. Fasting or caloric restriction suppresses sympathetic activity in a variety of organs of the rat, including heart and interscapular brown adipose tissue. Overfeeding a mixed, palatable, "cafeteria" diet stimulates sympathetic activity in these same tissues. The stimulatory effect of mixed diets is due to the carbohydrate and fat content, because these two latter nutrients stimulate sympathetic activity even when total caloric intake is not increased. Insulin-mediated glucose metabolism within central neurons associated with the ventromedial hypothalamus (VMH) plays an important role in the relationship between dietary intake and SNS activity as indicated by the following observations: (1) Hypoglycemia (noninsulin-mediated) is associated with suppression of the SNS (despite concomitant adrenal medullary stimulation); (2) 2-deoxyglucose, an intracellular inhibitor of glucose metabolism, decreases sympathetic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Eating↗
PubMed1988

Mechanisms in obesity-related hypertension: role of insulin and catecholamines.

Although the association of obesity and hypertension is well recognized, the mechanisms involved in the pathogenesis of increased blood pressure in the obese are poorly understood. Recent studies addressing the impact of 1) body fat distribution on blood pressure and 2) dietary intake on sympathetic nervous system (SNS) activity suggest a plausible hypothesis that relates the hypertension of the obese to hyperinsulinemia and SNS stimulation. Hypertension in the obese is associated with fat accumulation in the upper body segments; this type of obesity is also characterized by hyperinsulinemia and insulin resistance. Insulin, moreover, is an important signal in the relationship between dietary intake and SNS activity: increased insulin levels are associated with SNS stimulation. The hyperinsulinemia of obesity may, therefore, increase blood pressure by 1) direct effects of insulin to stimulate renal sodium reabsorption, and 2) sympathetic stimulation of the heart, blood vessels, and kidney. Conversely, SNS suppression and diminished insulin following caloric restriction may explain the hypotensive effects of caloric restriction in obese hypertensive subjects. The hypothesis presented here emphasizes the important role of diet in the treatment of obese hypertensive subjects. The efficacy of caloric restriction, weight loss, and exercise in reducing blood pressure in the obese is linked to diminished insulin and SNS activity and may be viewed as evidence in favor of this hypothesis.

Blood Pressure↗