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Biomedical subjects

D Heber

Publications and source records attributed to D Heber.

At least 91 records · Page 5Linked to original sources
PubMed1990

Compounds with positive inotropic activity, III: Synthesis of 4-aminoquinoline derivatives as potential positive inotropic agents.

Anilinoacrylic acid derivatives 2-4 are the key intermediates from which 1-alkyl substituted 4-aminoquinoline 10-15 as well as 4-alkylaminoquinoline derivatives 16-23 are synthesized and examined for positive inotropic activity on isolated left atria and papillary muscles from guinea-pig. Structure activity relationships indicate that the effect depends on the alkyl side chain of the target compounds.

Aminoquinolines↗
PubMed1990

Nutritional and metabolic effects of gonadotropin-releasing hormone agonist treatment for prostate cancer.

Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy expenditure in 10 men with advanced stage C and D prostate cancer receiving a gonadotropin-releasing hormone (GnRH) agonist (Buserelin). Metabolic parameters and nutritional status were determined at 0, 2, 6, and 12 months of therapy. Baseline measurements of plasma leucine appearance (76.2 +/- 5.4 microM/kg/h) and HGP rates (80.1 +/- 2.9 mg/m2/min) were greater than previously reported for normal volunteers. GnRH agonist therapy in prostate cancer patients was associated with a significant reduction in serum testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), and cortisol, and significant increases in triiodothyronine (T3) and free triiodothyronine (free T3). Neither basal energy expenditure nor plasma leucine appearance rates were changed over time, but there were significant linear reductions in HGP rates (80.1 +/- 2.9 mg/m2/min, mean +/- SEM; 79.9 +/- 2.3, 73.7 +/- 3.4, 72.5 +/- 2.3; P less than .01; baseline, 2, 6, and 12 months, respectively, by repeated measures ANOVA). In all patients, significant increases in body weight, triceps skin fold, cholesterol, and fat mass were noted. Total body water content was not significantly increased after the 12-month period; therefore, the weight gain seen in these patients was water-free tissue, ie, fat mass.

Aged↗
PubMed1989

Prevalence and hemodynamic correlates of malnutrition in severe congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Whereas cardiac cachexia is well recognized, the frequency and hemodynamic correlates of malnutrition in severe congestive heart failure (CHF) have not been established. Anthropometric and serum albumin assessment of nutritional status was compared with hemodynamic, echocardiographic and serum chemistry evaluation in 48 patients with severe CHF (ejection fraction 0.17 +/- 0.05). Malnutrition, as defined by decreases in percent body fat determined from skinfold thicknesses, weight/height index or serum albumin, was present in 24 of 48 (50%) patients, who did not differ from the 24 well-nourished patients in cardiac index (1.9 +/- 0.6 vs 2.1 +/- 0.6 liters/min/m2) and pulmonary artery wedge pressure (30 +/- 6 vs 27 +/- 10 mm Hg), but had higher right atrial pressure (16 +/- 5 vs 9 +/- 6 mm Hg, p less than 0.01) and more severe tricuspid regurgitation by semiquantitative Doppler grading on a 0 to 3 scale (2.0 +/- 0.9 vs 0.9 +/- 0.8, p less than 0.01). Right atrial pressure was the only independent hemodynamic predictor of malnutrition (p less than 0.0002). Malnourished patients had lower serum sodium (134 +/- 4 vs 139 +/- 4 mEq/liter, p less than 0.01) and total triiodothyronine levels (89 +/- 30 vs 115 +/- 26 ng/dl, p less than 0.01) and higher creatinine levels (1.6 +/- 0.7 vs 1.2 +/- 0.4, p less than 0.03). None of the other biochemical markers of nutritional status differed between the groups except lower serum triglyceride levels (115 +/- 73 vs 186 +/- 97 mg/dl, p less than 0.05) in malnourished patients. Malnutrition is common in patients with severe CHF and is associated with increased right atrial pressure and tricuspid regurgitation.

Body Weight↗
PubMed1988

Nutrition in the elderly.

Nutritional modulation is one approach to successful aging. In animals, dietary restriction increases life span. Alterations in the macronutrient and micronutrient constituent of the diet can modulate gene expression. Anorexia is common in elderly persons. The results of studies in animals suggest that aging is associated with a decrease in the opioid feeding drive and an increase in the satiating effect of cholecystokinin. Unrecognized depression is a common, treatable cause of anorexia and weight loss in elderly persons. Protein synthesis decreases in elderly persons; nevertheless, nitrogen balance can be maintained in patients with fairly low intakes of protein. Carbohydrate intolerance is common and may be modulated by nutritional intervention and physical activity. The role of cholesterol in the development of heart disease in very old persons is controversial. Homebound and institutionalized elderly persons often do not expose their skin to sunlight; because the skin of older persons has a decreased ability to form vitamin D, the vitamin D status in these persons is precarious and they are at risk for osteopenia. Vitamins are often abused by elderly persons. Drug administration alters the vitamin requirements of persons. Borderline zinc state has been associated with deteriorating immune function, especially in persons who have diabetes mellitus or who abuse alcohol. Zinc administration appears to protect against the deteriorating vision associated with age-related macular degeneration. Selenium deficiency seems to be associated with an increased prevalence of cancer.

Aged↗
PubMed1987

Low density lipoprotein receptor regulation and the cellular basis of atherosclerosis: implications for nutritional and pharmacologic treatment of hypercholesterolemia.

Blood levels of lipids and lipoproteins are prominent among the factors identified as contributing to the development of coronary artery disease. Studies have demonstrated that reduction of low density lipoprotein (LDL) levels lowers the risk of coronary events and retards the progression of atherosclerotic lesions. LDL receptors play a central role in the metabolism of LDL: they maintain cellular cholesterol homeostasis by effects on cholesterol synthesis, modulate the plasma level of lipoproteins by clearing LDL from the circulation and deliver cholesterol to the adrenal glands and gonads for steroid hormone synthesis and to the liver for bile acid synthesis. The 2 major strategies that have been developed so far to lower LDL levels involve the use of bile acid-binding resins, which bind cholesterol in the intestinal lumen, thereby leading to a decrease in intracellular cholesterol, which increases the rate of synthesis of LDL receptors and increases the rate of LDL clearance; and, more recently, the use of inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the biosynthesis of cholesterol. Further studies are required to assess whether HMG-CoA reductase inhibitors, used alone or concomitantly with bile acid-binding resins, are safe and effective for long-term use in patients with elevated LDL levels.

Arteriosclerosis↗
PubMed1987

Effect of hydrazine sulphate on whole-body protein breakdown measured by 14C-lysine metabolism in lung cancer patients.

In a prospective double-blind trial twelve malnourished patients with lung cancer were randomised to receive either placebo or hydrazine sulphate (60 mg three times daily) for 30 days. Fasting lysine flux was determined by a primed 4-hour continuous infusion of 14C-lysine before and after one month of hydrazine treatment. Baseline plasma lysine flux was 2580 (SD 580) mumol/h for the placebo group and 2510 (440) mumol/h for the hydrazine group. After one month the placebo group showed a slight rise to 2920 (450) mumol/h (p = 0.08) and the hydrazine group showed a significant fall to 1840 (750) mumol/h (p less than 0.05); serum albumin fell in the placebo group and was unchanged in the hydrazine group. Administration of hydrazine sulphate to reduce aminoacid flux may favourably influence the metabolic abnormalities in cancer cachexia.

Adult↗
PubMed1987

Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience.

Hydrazine sulfate was evaluated using 24-hour dietary recalls and body weight determinations before and after 30 days of either placebo or hydrazine (60 mg, 3 times/d) oral administration in 101 heavily pretreated cancer patients with weight loss. After 1 month, 83% of hydrazine and only 53% of placebo patients completing repeat evaluation maintained or increased their weight (P less than 0.05). In addition, appetite improvement was more frequent in the hydrazine group (63% versus 25%, P less than 0.05). Although caloric intake was only slightly greater in hydrazine-treated patients, an increased caloric intake was more commonly associated with weight gain in patients receiving hydrazine compared with those receiving placebo (81% versus 53%, respectively). Hydrazine toxicity was mild, with 71% of patients reporting no toxic effects. Hydrazine sulfate circulatory levels were obtained from a subset of 14 patients who completed 30 days of treatment, with a single sample obtained in the morning at least 9 hours after the last dose. Mean maintenance hydrazine sulfate levels, determined using a spectrofluorometric assay, ranged from 0 to 89 ng/ml (mean 45 +/- 16 ng/ml). These data, which demonstrate an association between 1 month of hydrazine sulfate administration and body weight maintenance in patients with cancer, suggest future clinical trials of hydrazine sulfate are indicated to definitively assess its long-term impact on important clinical outcome parameters in defined cancer populations.

Appetite↗
PubMed1987

Effects of exercise training on resting energy expenditure during caloric restriction.

Resting energy expenditure (REE), maximum oxygen uptake (VO2max), and body composition were measured in seven moderately obese women during 9 wk of dietary restriction (800 kcal/d). During weeks 4-6, subjects underwent exercise training (30 min cycling/d, 5 d/wk, at 70% VO2max). The first 3 wk of caloric restriction decreased REE by 13% (from 1437 +/- 76 to 1254 +/- 66 kcal/24 h, means +/- SEM, p less than 0.05). Exercise training increased VO2max (from 1717 +/- 108 to 1960 +/- 120 mL/min, means +/- SEM, p less than 0.05) but did not elevate the dietary-depressed REE (from 1254 +/- 66 to 1262 +/- 62 kcal/24 h). The greatest decrease in body fat (3.7 +/- 0.4 kg) occurred during exercise training, resulting in a small apparent increase in REE when expressed per kilogram total body weight. However, expressed per unit lean body mass, REE remained suppressed throughout the period of caloric restriction. We conclude that exercise training of sufficient intensity to substantially increase VO2max does not reverse the dietary-induced depression of REE.

Adult↗
PubMed1986

Pathophysiology of malnutrition in the adult cancer patient.

A number of common metastatic cancers are associated with marked weight loss at the time of diagnosis. Cancer patients with weight loss at the time of diagnosis have decreased mean survival compared to similar cancer patients without weight loss. Provision of excess calories alone does not appear to change median survival in patients with advanced cancer and many patients either maintain body weight or lose weight while receiving calories which would be predicted to result in weight gain. The authors recently have extended their studies to head and neck cancer patients without detectable metastatic disease in order to detect systemic metabolic effects of a localized tumor. These patients failed to gain weight despite the administration of apparently adequate calories by continuous enteral alimentation. Abnormalities of carbohydrate metabolism with secondary effects on fat and protein metabolism have been identified in several populations of patients with common cancers. These abnormalities offer potential points of intervention which may enhance nutritional therapy as rehabilitation and as a potential biological modifier of the response of specific cancers to chemotherapy, radiation therapy, or surgery.

Adult↗
PubMed1986

Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer.

The short term addition of nandrolone decanoate to combination chemotherapy given to patients with unresectable non-small cell lung cancer was evaluated in a randomized, prospective trial. Patients were treated with doxorubicin 50 mg/M2 intravenously, cyclophosphamide 300 mg/M2 intravenously, CCNU 50 mg/M2 orally, vincristine 1.4 mg/M2 intravenously, with and without cisplatin 50 mg/M2 intravenously, all given every 28 days. In addition, patients were randomized to receive either nandrolone decanoate 200 mg intramuscularly weekly for 4 weeks or no additional therapy. Patient age, disease extent, performance score, and pretreatment weight loss were similar in the two treatment arms. Objective antitumor response frequency was comparable on both treatment arms with median survival somewhat longer for patients receiving the androgen (median survival 5.5 months without and 8.2 months with nandrolone decanoate). There was a trend for less severe weight loss on the nandrolone decanoate arm (average weight loss 0.8 +/- 0.15 kg versus 0.21 +/- 0.18 kg, respectively), with half as many patients experiencing weight loss on nandrolone decanoate (25% versus 12%). A separate concurrent study has demonstrated decreased free testosterone levels in 66% of patients with advanced cancer studied prior to chemotherapy treatment, therefore, further prospective studies in which pretreatment testosterone levels are used to guide androgen administration are needed to define more precisely a role for androgen replacement therapy in non-small cell lung cancer.

Anabolic Agents↗
PubMed1986

Metabolic abnormalities in cancer patients: carbohydrate metabolism.

Weight loss in patients with a variety of cancers is associated with a poor prognosis. Consistent abnormalities of carbohydrate metabolism are seen in cancer patients with weight loss and appear to represent derangements in host metabolism that are induced by the presence of cancer. To define therapeutic strategies to improve the poor clinical outcome for patients with cancer cachexia, investigations are under way to define the relationships among glucose metabolism, altered energy expenditure, caloric intake, weight loss, and clinical outcome.

Animals↗
PubMed1985

Metabolic abnormalities in the cancer patient.

Many malnourished patients with cancer fail to gain weight with what appears to be adequate nutritional support. Metabolic abnormalities resulting from remote effects of the tumor on host metabolism have been postulated to increase energy requirements in such cancer patients. In the current study, 44 patients with lung cancer who had significant weight loss (16 +/- 2% of usual body weight) were studied under metabolic ward conditions. Whole body glucose production rates were significantly elevated in cancer patients compared to age-matched healthy controls. Blood glucose levels 2 hours after a standard oral glucose challenge were also significantly increased, but insulin levels were not different at this time. Fasting glucose and insulin levels were not different. Fasting plasma alanine levels were significantly decreased in these patients, while branched-chain amino acids were not different. Increased alanine flux for gluconeogenesis is likely to reflect a basic metabolic abnormality in patients with cancer and could be explained on the basis of a resistance to insulin action in such patients.

Alanine↗
PubMed1985

Identification and partial characterization of gonadotropin-releasing hormone-like factors in human seminal plasma.

Gonadotropin-releasing hormone (GnRH)-like material was measured by radioimmunoassay in acid-ethanol-extracted human seminal plasma using radiolabeled D-[Leu6] GnRH ethylamide as labeled ligand, authentic GnRH as standard, and antibody raised against D-[Lys6] GnRH analog. The mean amount of GnRH-like material measured in the seminal plasma of semen samples with sperm counts greater than 20 X 10(6)/ml was 229.0 +/- 66 pg/ml, with sperm counts less than 20 X 10(6)/ml was 213 +/- 42 pg/ml, and from vasectomized samples was 252 +/- 36 pg/ml. There was no significant difference among the three groups. Scatchard analysis of radioreceptor binding data demonstrated significant displacement of GnRH agonist ligand from castrated male rat pituitary membrane preparations. Ultrafiltration and gel column chromatography of pooled extracted seminal plasma identified two compounds with apparent molecular weights of 2600 and 5000 that differ chemically and immunologically from native GnRH. Further characterization using affinity column chromatography suggests that at least one of these GnRH-like factors is a glycosylated protein.

Chromatography, Gel↗
PubMed1985

Postcastration rise in plasma gonadotropins is blocked by a luteinizing hormone-releasing hormone antagonist.

The dependence of the acute increases in plasma gonadotropins following castration on luteinizing hormone-releasing hormone (LHRH) was assessed with the use of a potent LHRH antagonist [ALHRH; (Nac-L-Ala1,p-Cl-D-Phe2,D-Trp3,6) LHRH]. Blood samples were collected from male and female rats at the time of castration and 2, 4, 8, 12, 24 and 48 h following and plasma gonadotropin levels were determined. Immediately following castration (diestrus I for females) animals received one of the following treatments: females-vehicle, 100 micrograms ALHRH, 50 micrograms estrogen benzoate (EB), or 100 micrograms ALHRH + 50 micrograms EB; males-vehicle, 100 micrograms ALHRH, 500 micrograms testosterone propionate (TP), or 100 micrograms ALHRH + 500 micrograms TP. ALHRH blocked the selective increase in plasma follicle-stimulating hormone (FSH) observed in female rats as well as the parallel increases in both gonadotropins seen in male rats following castration. Administration of EB or ALHRH + EB to females significantly suppressed both gonadotropins compared with control levels. However, EB alone did not completely block the rise in plasma FSH in females. In males, all three treatments significantly suppressed the increases in both gonadotropins when compared with control levels. These data demonstrate that hypothalamic LHRH plays an essential role in the acute elevations of plasma gonadotropins following castration in rats. In addition, these data suggest that the selective rise of FSH in females is dependent on LHRH stimulation of pituitary gonadotropes.

Animals↗
PubMed1985

Lactate, pyruvate, and lactate-to-pyruvate ratio during exercise and recovery.

The pattern of lactate increase and its relation to pyruvate and lactate-to-pyruvate (L/P) ratio were studied during exercise and early recovery in 10 normal subjects for incremental exercise on a cycle ergometer. Gas exchange was measured breath by breath. Lactate and pyruvate were measured by enzymatic techniques. Lactate and log lactate changed only slightly at low levels of O2 uptake (VO2) but both began to abruptly increase at approximately 40-55% of the maximal VO2. However, the point of abrupt increase in pyruvate occurred at higher work rates and the rate of increase was not as great as that for lactate. Thus L/P ratio increased at the same VO2 as the log lactate increase. Following the exercise, pyruvate continued to increase steeply for at least the first 5 recovery min, whereas at 2 min lactate increased only slightly or decreased. Thus arterial L/P ratio reversed its direction of change and decreased toward the resting value by 2 min of recovery. Lactate, as well as L/P ratios, decreased in all subjects by 5 min. This study demonstrates that lactate and pyruvate concentrations increase slightly at low levels of exercise without a change in L/P ratio until a threshold work rate at which lactate abruptly increases without pyruvate. The resulting increase in L/P ratio is progressive as work rate is incremented and abruptly reverses when exercise stops.

Adult↗