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Biomedical subjects

L Landsberg

Publications and source records attributed to L Landsberg.

At least 37 records · Page 2Linked to original sources
PubMed1994

Stimulatory influence of D(-)3-hydroxybutyrate feeding on sympathetic nervous system activity in the rat.

To examine the effect of ketone body utilization on sympathetic nervous system (SNS) activity, norepinephrine (NE) turnover was measured in heart and interscapular brown adipose tissue (IBAT) of rats fed diets enriched with D(-)3-hydroxybutyrate (3OHB), the naturally occurring isomer of hydroxybutyrate. Isoenergetic substitution of 3OHB for chow for 4 days increased cardiac [3H]NE turnover (P < .025), with a slightly less marked (P < .06) effect in IBAT. When [3H]NE turnover was measured in rats fed chow diets supplemented with 3OHB or sucrose and compared with that in animals fed chow alone, [3H]NE turnover rates in heart and IBAT were similar in the ketone-supplemented and chow-fed groups. Animals fed the sucrose-supplemented chow displayed lower rates of [3H]NE turnover in IBAT than rates found in those given the 3OHB-containing chow (-36%, P < .025 in IBAT). In addition, the stimulatory effect on SNS activity of a 4-day exposure to a sucrose-enriched diet after 2 days of fasting was significantly enhanced by concomitant ketone ingestion. Fractional NE turnover in IBAT was increased from 9.3% +/- 1.3%/h in control rats to 14.2% +/- 0.9%/h in rats refed with 3OHB (P < .005). These observations indicate that increased ketone body utilization does not suppress SNS activity and may stimulate it in a manner quantitatively similar to that seen with carbohydrate or fat ingestion.

3-Hydroxybutyric Acid↗
PubMed1994

Pathophysiology of obesity-related hypertension: role of insulin and the sympathetic nervous system.

Reviewed herein are data supporting the hypothesis that insulin and the sympathoadrenal system are involved in the pathogenesis of hypertension in the obese. Data from the Normative Aging Study, a population-based cohort followed in Boston, confirm other epidemiologic reports of a direct relationship between upper-body obesity, hyperinsulinemia, and hypertension. Because insulin is known to stimulate the sympathetic nervous system (SNS), the possibility that insulin-mediated sympathetic stimulation contributed to hypertension in the obese was investigated by the analysis of 24-h urinary norepinephrine (NE) excretion in this group. Urinary NE was directly correlated with body mass index and waist/hip ratio, supporting increased SNS activity in the obese. Epinephrine excretion, an index of adrenal medullary activity, was inversely related to obesity, and both high insulin and low epinephrine levels were independently correlated with lower levels of high-density lipoprotein cholesterol and higher levels of triglycerides. These results are consistent with the hypothesis that insulin-mediated sympathetic stimulation results in hypertension from concomitant sympathetic stimulation of the heart, vessels, and kidney. Reciprocal changes in adrenal medullary function contribute to the associated dyslipidemia. Therapeutic strategies aimed at diminishing insulin resistance and lowering insulin levels, and antagonizing the effects of sympathetic stimulation on the heart, the vessels, and the kidneys, would appear to have a solid physiological rationale in the obese.

Animals↗
PubMed1994

Unique problems in the treatment of the older hypertensive male. Introduction: increased sympathetic nervous system activity in the elderly.

Sympathetic activation increases blood pressure via effects on the heart, blood vessels and the kidney, and influences micturition and prostatic function via effects on the urinary sphincter and prostate muscular stroma. A systematic increase in sympathetic activity in older subjects would be expected to cause or exacerbate both hypertension and prostatism. Although assessment of sympathetic nervous system activity in humans is difficult, available evidence accumulated over the last decade strongly suggests that ageing is associated with increased sympathetic nervous system activity. There is general agreement that plasma norepinephrine levels are elevated in old, as compared with young, healthy human subjects. Furthermore, the rate of entry of norepinephrine into the circulation, a measure of sympathetic activity, is increased in older subjects. Plasma norepinephrine responses to both cardiovascular and metabolic stimuli are also accentuated in the aged so that the rise in plasma norepinephrine with upright posture and in response to oral glucose ingestion is greater in old than in young human subjects. As the clinical usefulness of selective alpha 1-adrenergic inhibitors is theoretically greater in states accompanied by increased sympathetic activity, the idea that selective alpha 1-adrenergic inhibition might be particularly useful in treating simultaneous hypertension and prostatism in older men has a sound physiological rationale.

Adrenergic alpha-Antagonists↗
PubMed1994

Distinguishing hypothyroxinemia due to euthyroid sick syndrome from pituitary insufficiency.

Patients with severe nonthyroidal illness may have low serum levels of thyroid hormone and thyroid-stimulating hormone (TSH) indistinguishable from levels in patients with pituitary insufficiency. It is often difficult prospectively to rule out pituitary insufficiency in these patients. Our hypothesis was that patients sufficiently ill to have low free thyroxine index (FT4I) and TSH from nonthyroidal illness (euthyroid sick syndrome, or ESS) would have serum cortisol levels high enough to make pituitary insufficiency unlikely. Serum samples from all patients admitted to the Intensive Care Unit during 2 months were screened for low FT4I, and cortisol levels were measured on those samples. Five of five patients with a diagnosis of ESS had unequivocal elevations of serum cortisol (> 525 nmol/l), arguing against a diagnosis of pituitary insufficiency. Secondary hypothyroidism due to pituitary insufficiency can often be ruled out in patients with severe ESS by documenting appropriate elevated levels of serum cortisol.

Adult↗
PubMed1994

The relationships of abdominal obesity, hyperinsulinemia and saturated fat intake to serum lipid levels: the Normative Aging Study.

Abdominal obesity and hyperinsulinemia are associated with abnormalities in lipid metabolism and are important risk factors for coronary artery disease. Because hyperinsulinemia frequently accompanies abdominal obesity, it is unclear whether each is independently related to lipid abnormalities. Dietary saturated fat may influence these associations since it is associated with elevated lipid levels, obesity and hyperinsulinemia. Abdominal obesity (indexed as abdomen-to-hip circumference ratio), serum insulin level and dietary saturated fat intake were examined in relation to serum levels of lipids and lipoproteins in 878 male participants of the Normative Aging Study. Abdomen-to-hip ratio and insulin level were inversely related to high density lipoprotein cholesterol (HDL-C) (r = -0.17 and -0.21, respectively), and positively related to triglycerides (r = 0.25 and 0.36, respectively). Saturated fat intake was positively related to body mass index (r = 0.20), abdomen-to-hip ratio (r = 0.13), and insulin level (r = 0.10). In multiple linear regression models, abdomen-to-hip ratio was positively related to triglycerides and low density lipoprotein cholesterol (LDL-C) after adjusting for the effects of body mass index, alcohol intake, age, cigarette smoking and physical activity level, but was not significantly related to HDL-C. When serum insulin level was included as a covariate, abdomen-to-hip ratio remained significantly related to LDL-C and triglycerides, although its relationship with triglycerides was attenuated. Insulin level remained inversely related to HDL-C and triglycerides in multivariate models which adjusted for the effects of abdomen-to-hip ratio and BMI.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗
PubMed1993

Relation between blood lead and urinary biogenic amines in community-exposed men.

The cross-sectional relation between levels of urinary biogenic amines (dopamine, epinephrine, norepinephrine, and serotonin) and levels of blood lead was examined in a study of 645 male participants from a longitudinal study of aging. This stable population of men had initially been recruited from communities in and around Boston, Massachusetts, and had not been selected with regard to lead exposure. Blood lead samples and 24-hour and 2-hour urine specimens were collected during regularly scheduled clinic visits. In multivariate linear regression step-forward models, 24-hour epinephrine excretion was significantly and positively associated with blood lead (beta = 0.101 microgram(microgram/dl)-1 blood lead, SE (standard error) (beta) = 0.045, p = 0.026). Twenty-four-hour norepinephrine excretion was positively associated with blood lead (beta = 0.023 microgram(microgram/dl)-1 blood lead, SE(beta) = 0.029, p = 0.425), and both 24-hour dopamine (beta = -4.35 microgram(microgram/dl)-1 blood lead, SE(beta) = 6.90, p = 0.529) and 2-hour serotonin (beta = -0.348 microgram(microgram/dl)-1 blood lead, SE(beta) = 0.277, p = 0.210) excretion were negatively associated with blood lead; however, these relations did not achieve statistical significance. An increase of 10 micrograms/dl in blood lead was associated with an increase in epinephrine excretion of 11 micrograms/24 hours. These results support the hypothesis that epinephrine metabolism is influenced by low levels of lead exposure.

Adult↗
PubMed1993

Relationship of dietary saturated fatty acids and body habitus to serum insulin concentrations: the Normative Aging Study.

The purpose of this study was to examine the relationship of body mass index, abdomen-hip ratio, and dietary intake to fasting and postprandial insulin concentrations among 652 men aged 43-85 y, followed in the Normative Aging Study. Log-transformed fasting insulin was significantly associated with body mass index, abdomen-hip ratio, total fat energy, and saturated fatty acid energy, with correlation coefficients ranging from 0.14 for total fat to 0.45 for body mass index. When multivariate models were used, body mass index, abdomen-hip ratio, and saturated fatty acid intake were statistically significant independent predictors of both fasting and postprandial insulin concentrations, after age, cigarette smoking, and physical activity were adjusted for. If saturated fatty acids as a percentage of total energy were to decrease from 14% to 8%, there would be an 18% decrease in fasting insulin and a 25% decrease in postprandial insulin. These data suggest that overall adiposity, abdominal obesity, and a diet high in saturated fatty acids are independent predictors for both fasting and postprandial insulin concentrations.

Adipose Tissue↗
PubMed1993

Sympathoadrenal activity and obesity: physiological rationale for the use of adrenergic thermogenic drugs.

The sympathetic nervous system is a major regulator of dietary thermogenesis in laboratory animals and humans. Since a lowered metabolic rate predisposes to the development of obesity, and since caloric restriction suppresses sympathetic activity, a role for adrenergic agonists in the treatment of obesity has a well established physiological rationale. Although diminished sympathetic activity does not appear to underlie obesity in most circumstances in humans, to the extent that adrenergic agonists increase metabolic rate in the obese they may be useful as pharmacologic adjuncts to low energy diets. During caloric restriction the significant diminution in sympathetically mediated thermogenesis antagonizes weight loss; this decrease in metabolic rate may be overcome by sympathomimetic amines thereby increasing the effectiveness of low energy diets. Since smoking stimulates the sympathoadrenal system and increases thermogenesis, smoking cessation, with its attendant fall in sympathoadrenal activity and decrease in metabolic rate, fosters weight gain. Adrenergic agonists may be useful in this circumstance as well.

Adrenal Glands↗
PubMed1993

Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity.

The safety and efficacy of a mixture of ephedrine (75-150mg), caffeine (150mg) and aspirin (330mg), in divided premeal doses, were investigated in 24 obese humans (mean BMI 37.0) in a randomized double blind placebo-controlled trial. Energy intake was not restricted. Overall weight loss over 8 weeks was 2.2kg for ECA vs. 0.7 kg for placebo (p < 0.05). 8 of 13 placebo subjects returned 5 months later and received ECA in an unblinded crossover. After 8 weeks, mean weight loss with ECA was 3.2 kg vs 1.3 kg for placebo (p = 0.036). 6 subjects continued on ECA for 7 to 26 months. After 5 months on ECA, average weight loss in 5 of these was 5.2 kg compared to 0.03 kg gained during 5 months between studies with no intervention (p = 0.03). The sixth subject lost 66 kg over 13 months by self-imposed caloric restriction. In all studies, no significant changes in heart rate, blood pressure, blood glucose, insulin, and cholesterol levels, and no differences in the frequency of side effects were found. ECA in these doses is thus well tolerated in otherwise healthy obese subjects, and supports modest, sustained weight loss even without prescribed caloric restriction, and may be more effective in conjunction with restriction of energy intake.

Adult↗
PubMed1992

POEMS syndrome with myocardial infarction: observations concerning pathogenesis and review of the literature.

A 27-year-old white man with no significant risk factors for coronary artery disease presented with a 9-month history of progressive impotence, gynecomastia, lower extremity paresthesias, and extensive myocardial infarction and subsequently developed ulcerative proctitis. A diagnosis of POEMS syndrome was made based on the clinical presentation; additional physical findings of papilledema, clubbing, and hyperpigmentation; and laboratory findings of an immunoglobulin G M component of the lambda subtype, elevated cerebrospinal fluid protein, and typical sclerotic bone lesions. Abnormal in vitro binding of the patient's serum immunoglobulin to testicular tissue was also seen. Cardiac catheterization showed evidence of diffuse coronary artery narrowing and left ventricular wall motion abnormalities. Diffuse coronary involvement and ulcerative proctitis have not been previously described in POEMS syndrome. It is hypothesized that an abnormal immunoglobin (or fragment) is responsible for both findings. Furthermore, the detection of antitesticular autoantibodies suggests the possibility of an interaction between the antibody and Leydig cells, leading to an alteration in the synthesis and release of sex steroids and thereby explaining the gonadal failure seen in this syndrome. Long-term glucocorticoid therapy for the past 5 years has resulted in marked subjective and objective improvement.

Adult↗
PubMed1992

Phaeochromocytoma: diagnosis and management.

The incidence, symptoms, signs and differential diagnosis of phaeochromocytoma have been discussed in detail. Current methods of biochemical diagnosis and anatomical localization of the tumour have been reviewed, the appropriate pharmacotherapy and other aspects of medical management have been outlined. Also detailed herein are anaesthetic management and surgical approach, the pitfalls of drug administration in known or suspected phaeochromocytoma, and particular considerations when phaeochromocytoma is malignant or when it coexists with pregnancy. Three decades ago, the diagnosis and management of phaeochromocytoma was succinctly summarized as follows: 'think of it, confirm it, find it and remove it' (Manger and Gifford, 1977; Ross, 1962). Despite the availability of sophisticated diagnostic tests and the significant progress in management, where phaeochromocytoma is concerned, a high index of suspicion ('thinking of it') remains the physician's most valuable tool.

Adrenal Gland Neoplasms↗
PubMed1992

Relationship of catecholamine excretion to body size, obesity, and nutrient intake in middle-aged and elderly men.

Catecholamine release from sympathetic nerves and the adrenal medulla is influenced by diet under controlled research conditions. To test whether diet affects catecholamine excretion in free-living men, the urinary content of dopamine (DA), epinephrine (Epi), or norepinephrine (NE) was measured in 24-h collections provided by 572 participants of the Normative Aging Study of the Veterans Administration. Average daily intakes of energy and macronutrients were assessed by means of a semiquantitative food frequency questionnaire and sodium intake by quantitation of sodium excretion. Catecholamine excretion was also examined in relation to anthropometric variables. Because DA and Epi excretion were inversely related to age, all subsequent analyses included adjustments for age. Although DA and NE were positively related to measures of body size and fatness, Epi was negatively related to body fatness. Excretion rates of all three catecholamines were directly related to total energy intake and inversely related to energy-adjusted CHO consumption.

Adult↗
PubMed1992

Effect of cold exposure and nutrient intake on sympathetic nervous system activity in rat kidney.

Renal sympathetic nervous system (SNS) responses to environmental temperature and diet were evaluated using [3H]norepinephrine ([3H]NE) turnover as the index of sympathetic activity. Pharmacological studies first demonstrated that renal NE was localized principally within storage granules of renal sympathetic nerves and regulated by central sympathetic outflow. Acute exposure to cold (4 degrees C), which increased cardiac SNS activity (P < 0.00005), had no effect on renal SNS. A 48-h fast suppressed renal [3H]NE turnover by 37% (P = 0.00024) and cardiac [3H]NE turnover by 48% (P = 0.00608). Dietary supplementation with sucrose did not affect [3H]NE turnover in kidney in either of two separate experiments, although it increased cardiac NE turnover in both. On the other hand, lard feeding significantly increased [3H]NE turnover in both kidney and heart, whereas dietary protein supplementation exerted no effect on either renal or cardiac [3H]NE turnover. These studies demonstrate a unique pattern of sympathetic regulation in kidney, one which is highly responsive to fasting and dietary fat, but not to cold exposure or dietary sucrose.

Animals↗
PubMed1992

Hyperinsulinemia: possible role in obesity-induced hypertension.

Data in support of the hypothesis that insulin-mediated sympathetic stimulation contributes to the hypertension that occurs in association with obesity are presented. The relation between insulin and the sympathetic nervous system derives from the effect of diet on sympathetic activity. Fasting suppresses but overfeeding stimulates the sympathetic nervous system. Insulin-mediated glucose metabolism within central neurons sensitive to insulin and glucose appears to be one important signal in this relation between diet and sympathetic activity. In the obese, hyperinsulinemia and hypertension track together in epidemiological studies. Evidence from a human population-based study (the Normative Aging Study) indicates that the abdominal form of obesity is associated with both hyperinsulinemia and increased urinary norepinephrine excretion. Elevations in urinary norepinephrine excretion, moreover, were highest in those with the highest fasting levels of insulin and glucose. These observations are consistent with the hypothesis that insulin-mediated sympathetic stimulation is a mechanism recruited in the obese to increase metabolic rate and restore energy balance; concomitant increases in sympathetic stimulation of the heart, vasculature, and kidney result in hypertension, which, according to this formulation, is an unfortunate by-product of the cardiovascular response to a metabolic adaptation.

Animals↗
PubMed1992

Altered dopaminergic responses in hypertension.

Biogenic amine metabolism may be altered in hypertension and thus contribute to its pathophysiology. This report describes an abnormality in dopamine excretion in hypertensive subjects in the postabsorptive state that persists despite an increase in dietary precursors for dopamine supplied by a protein meal. We studied seven normotensive and six nonmedicated hypertensive men after two different meals: 60 g protein and a noncaloric electrolyte-equivalent broth. Overall mean sodium excretion was 56% higher in the hypertensive group throughout both meal studies (p less than 0.01), implying higher chronic dietary sodium intake. Despite this, overall urinary excretion of dopamine tended to be lower in hypertensive than in normotensive subjects (p = 0.06). Hypertensive also differed from normotensive subjects in their response to protein feeding. In the normotensive subjects there was a 23% increase in urinary dopamine excretion (p less than 0.05), which was not seen after the noncaloric meal. In the hypertensive subjects, there was no change in urinary dopamine after the protein meal. In the normotensive subjects there was a 74% increase in sodium excretion (p less than 0.01) after the protein meal, but no significant change was seen in the hypertensive subjects. There were no differences in baseline renal plasma flow or glomerular filtration rate between the groups and no statistically significant differences between the groups in their renal hemodynamic responses to the meals. In summary, hypertensive subjects have less renal dopamine production for the amount of sodium ingested and a decreased renal dopamine production in response to a protein load as compared with normotensive subjects, consistent with a renal defect in conversion of DOPA to dopamine.

Aged↗