Biomedical subjects

D Heber

Publications and source records attributed to D Heber.

At least 73 records · Page 4Linked to original sources

PubMed1994

Role of insulin and norepinephrine in the hypertension of obesity.

The present study compares plasma norepinephrine (PNE), renin activity (PRA), aldosterone (PA), and insulin (RIAI) levels between 13 normotensive and 42 hypertensive obese subjects during weight maintenance, and in 19 of the 42 obese hypertensive subjects, these variables were measured during 16 weeks on a very low calorie diet (VLCD). Mean values for baseline RIAI and PNE were elevated in the 55 obese subjects compared to nonobese controls. However, when the normotensive and hypertensive groups were compared, mean values for PNE, PRA, PA, and RIAI were not different. In the 19 obese hypertensive subjects studied on the VLCD, there were significant reductions from baseline in mean body weight, blood pressure, RIAI, and PNE, but not for PRA or PA. Two phases of blood pressure, RAIA, and PNE responses to weight loss were noted. In the early phase (days 1-7), blood pressure and RAIA decreased dramatically, whereas PNE, PRA, and PA increased. During the late phase (weeks 2-16), further significant decreases in blood pressure and weight were accompanied by reductions in PNE (604 +/- 50 to 403 +/- 43 pg/mL, P < .01) and in RIAI (13.9 +/- 1.7 to 10.3 +/- 1.6 microU/mL, P < .05). As levels of insulin and norepinephrine were similar in normotensive and hypertensive obese individuals during weight maintenance, they may not contribute to the hypertension associated with obesity. During weight loss, however, the temporal changes in blood pressure, insulin, and norepinephrine suggest their mediation of the hypotensive response.

Adult↗

PubMed1994

Amino-substituted 1,8-naphthyridines and pyrido[2,3-d]pyrimidines: new compounds with affinity for A1- and A2-adenosine receptors.

Two novel classes of adenosine receptor (AR) antagonists, 4-amino-1,8-naphthyridines and 5-aminopyrido[2,3-d]pyrimidines, have been identified and investigated in radioligand binding assays. The compounds exhibit affinities for A1 and A2a AR of rat brain in the micromolar range. 1,8-Naphthyridines are non-selective, or somewhat selective for either A1- or A2 AR. Pyrido[2,3-d]pyrimidines are several-fold selective for A1 AR, the most potent and selective compound being 5-n-butylamino-1,3-dimethyl-1,2,3,4-tetrahydropyrido-[2,3-d]pyr imi dine-2,4-dione (12) with a Ki value of 1.8 microM at A1 AR and greater than 10-fold A1-selectivity.

Animals↗

PubMed1994

Synthesis and pharmacological evaluation of new esters of 2- and 4-alkylamino-1,8-naphthyridine-3-carboxylic acids endowed with positive inotropic properties.

In order to gain insight into structure-activity relationships concerning the positive inotropic effect of N-heterocycles, a series of 1,8-naphthyridines was synthesized by two different methods. First, 4-hydroxy substituted derivatives were accessible by cyclization of 2-vinylamino-1,8-naphthyridines using diphenyl-ether followed by chlorination and nucleophilic reactions with various amino compounds. Second, 2-amino-nicotinic acid was transformed to 2-alkylamino-1,8-naphthyridines involving a variation of the Friedländer synthesis as well as many subsequent steps. The effect of the compounds on myocardial contractility was assessed in guinea pig left atria paced at 3 Hz. In general, the concentrations for positive inotropism ranged in between 10(-6)-10(-4) mol/l. The compounds differed considerably with respect to the efficacy of the increase in contractile force. The pharmacological investigations appear to demonstrate the following requirements for the pharmacophoric structure. In connection with a lipophilic ester function in 3-position the target compounds have to contain an alkylamino side chain at C-4 bearing a pi-electron-rich center in a definite distance to the NH-function.

Animals↗

PubMed1994

Pharmacological characterization of positive inotropic derivatives of 4-amino-7-methyl-1,8-naphthyridine-3-carboxylic acid.

The positive inotropic effect of a series of 4-amino-7-methyl-1,8-naphthyridine-3-carboxylic acid derivatives was compared with the effects of known inotropic agents (ouabain, dihydroouabain, isoproterenol, adrenaline, histamine and isobutylmethylxanthine) in guinea-pig atrial and ventricular myocardial preparations. With respect to their functional effects, the 1,8-naphthyridine compounds are clearly different from drugs acting on the cAMP system, whereas several similarities with cardiac glycoside effects were found. Their ability to inhibit [3H]ouabain binding in guinea-pig cardiac membranes correlates well with their effects on myocardial contractile force. However, the latter effect was exerted by tenfold lower concentrations. The dissimilarities found between the 1,8-naphthyridines and digitalis may be due to a different type of interaction with the binding site on the (Na(+) + K+)-ATPase.

Animals↗

PubMed1993

Compounds with positive inotropic activity, IV: Synthesis of N-methoxyquinolinium salts and their effects in heart muscles.

N-Methoxyquinolinium salts 3 are prepared as potential cardiotonic agents by alkylation of the corresponding N-oxides 2 synthesized by two different methods. 1. Oxidation of some quinoline derivatives 1 using 30% H2O2 or 3-chloroperbenzoic acid. 2. Nitration of the quinoline-N-oxides 2a, 2c, and 2m. Preparation of 2h and 2k requires subsequent nucleophilic ipso-substitution of the nitro group. The compounds 3 are tested for positive inotropic activity on isolated left atria and papillary muscles from guinea-pig. Structure activity relationships indicate that the effect depends on the N-methoxy group of the target compounds as well as on the presence of an electron-withdrawing substituent.

Adrenergic beta-Antagonists↗

PubMed1993

Biennial survey of physician clinical-nutrition training programs.

This is the fourth survey of physician clinical-nutrition training programs. As in previous reports, current fellowship training programs were identified, descriptive information obtained, and program content surveyed. In addition, a questionnaire developed by the American Board of Nutrition Committee on Fellowship Training Programs was used to determine the degree of emphasis given to content in the areas of basic nutrition science, clinical applications, and research training. Among the 38 programs identified, uniform ratings of importance were found in all major topic areas. There was also uniformity in most subtopics, with minor exceptions. As expected, in the area of nutrition in the life cycle, pediatric training programs emphasized infancy and childhood whereas medical-surgical programs emphasized adulthood and aging. Alcoholism was emphasized in medical-surgical training programs whereas cystic fibrosis and inborn errors of metabolism were emphasized in pediatric programs. Nutrition in burn patients received minor emphasis in all programs. The overall uniformity of curricular content in training programs confirms the contention that clinical nutrition has a defined clinical scope and should be considered for establishment as a recognized subspecialty in American medicine.

Education↗

PubMed1993

Obesity. Workshop III. AHA Prevention Conference III. Behavior change and compliance: keys to improving cardiovascular health.

The workshop provided the opportunity to discuss issues and develop and integrate ideas. The following recommendations for public policies, education programs, and high-priority research initiatives were developed: Recommendations for Public Policies: Focus on prevention by requiring school programs to emphasize appropriate diet, physical activity, and general health guidance to promote cardiovascular health and prevent disease through federal funding. Provide better access to exercise (city planning, work-site interventions). Influence food availability and accessibility. Influence reimbursement policies for effective early intervention and prevention strategies for obesity. Reevaluate policies for use of drugs in the treatment of obesity. Recommendations for Education Programs: Sponsor scientific workshop to: Define the most appropriate weight standards for prevention and treatment. Identify who should lose weight and why, when, and how. Promote the fact that obesity is an important health risk factor, even at moderate levels, and that excess visceral fat is particularly hazardous. Target health care professionals, consumers, and the media for education about: Nature of obesity as a heterogeneous syndrome. Recommendations for diet, exercise, behavioral interventions, drugs, and surgery. Recognition of special needs of populations of different ethnicity, gender, age, etc. State-of-the-art treatment and treatment programs. High-Priority Research Initiatives: Build better bridges between basic research and treatment/prevention practices. Acknowledge that obesity is a heterogeneous syndrome that may best be characterized as different obesities. Research on defining subtypes. Implications for etiology and treatment. Better characterization of genotypes and phenotypes. Study the effects of weight loss, weight gain,and weight cycling on medical and psychosocial outcomes and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Positive inotropic activity of 5-amino-6-cyano-1,3-dimethyl-1,2,3,4-tetrahydropyrido[2,3-d]pyrim idine-2,4-dione in cardiac muscle from guinea-pig and man. Part 6: Compounds with positive inotropic activity.

In screening experiments, several 5-aminopyrido[2,3-d]-pyrimidine derivatives 1-14 were found to possess a positive inotropic action in guinea-pig left atria. The size of the effect varied between 10 and 60% of the maximum response to isoprenaline (3 x 10(-7) mol/l). Of these compounds, only 7 and 14 increased force of contraction also in papillary muscles. The latter effect was not accompanied by any changes in the shapes of the transmembrane action potentials and was reversible after addition of carbachol indicating that an increase in intracellular levels of cAMP might be involved. In Langendorff-perfused hearts of the guinea-pig 7 (10(-5) mol/l) increased force of contraction and spontaneous beating frequency like isoprenaline, but unlike isoprenaline, reduced perfusion pressure. Like 3-isobutyl-1-methylxanthine (IBMX) and milrinone, 7 also increased force of contraction of isolated right atrial trabeculae obtained from man during cardiac surgery. The influence of 7 on phosphodiesterase (PDE) activity was investigated in partially purified isoenzymes from guinea-pig ventricles. Compound 7 inhibited preferably PDE III with an IC50 value of 15.2 +/- 4.5 mumol/l. More than tenfold higher concentrations were needed to inhibit PDE II. The IC50 value was 198 +/- 91 mumol/l. PDE I and IV were inhibited by 7 only by a minor extent. At a drug concentration of 1 mmol/l PDE activity was reduced to 83 +/- 30 and 55 +/- 8% of control value, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗

PubMed1993

Synthesis and positive inotropic activity of several 5-aminopyrido[2,3-d]pyrimidines. Part 5: Compounds with positive inotropic activity.

Starting from 6-amino-1,3-dimethyluracil two approaches were developed for the preparation of 5-amino-pyrido[2,3-d]pyrimidine derivatives as potential cardiotonic agents. 1. Gould-Jacobs reaction followed by chlorination of the intermediate 5-hydroxypyrido-[2,3-d]pyrimidine using DMF/POCl3. 2. Cyclization of C-acetylated as well as C-cyano acetylated 6-amino-1,3-dimethyluracil by an application of the Vilsmeier reaction yielding 5-chloropyrido[2,3-d]pyrimidines. Subsequent nucleophilic substitution reactions formed the target compounds which were examined for positive inotropic activity on isolated left atria and papillary muscles from guinea-pig hearts. Structure-activity relationships indicated that the effect depended on the 4-aminopyridine-3-carboxylic acid derivative structure.

Action Potentials↗

PubMed1992

Assessment of adherence to a low-fat diet for breast cancer prevention.

BACKGROUND: The relationships between self-reported adherence to a low-fat diet in healthy women between the ages of 44 and 69 and a number of correlates of this self-reported behavior were examined in an attempt to improve monitoring of adherence to nutritional intervention trials for breast cancer prevention. METHODS: Dietary fat intake in 87 women who completed 6 months of nutritional intervention was reduced from 38.2 +/- 5.9% to 21.7 +/- 7.8% of total energy intake (P less than 0.005). Reported total calorie intake was reduced by approximately 20%. RESULTS: Body weight decreased by 2.7% from 68.1 +/- 11.2 kg to 66.3 +/- 11.9 kg (P less than 0.05). Fasting total plasma cholesterol levels decreased from 205 +/- 31 mg/dl to 184 +/- 29 mg/dl (P less than 0.05). Fasting plasma triglyceride levels did not change significantly (97 +/- 44 mg/dl vs 101 +/- 55 mg/dl). Relative percentage changes in body weight correlated with percentage changes in dietary fat intake (r = 0.23, P less than 0.05). CONCLUSION: Self-reported changes in dietary behavior correlated significantly with objective changes in body weight and fasting cholesterol in these healthy women encouraged to consume a low-fat diet for prevention of breast cancer.

Adult↗

PubMed1992

Clinical aspects of nutrition in advanced cancer.

Nutritional assessments of our patients with disseminated malignancies have revealed that the incidences of reported anorexia, decreased food intake, and weight loss range between 49 and 64%. It is therefore essential that a planned approach to the nutritional needs of patients with advanced cancer be part of routine oncology care. Our first step is a clinical assessment of the patient's nutritional state and diet, and a determination of caloric and nutrient needs. The potential tools available to the oncologist in the management of the undernourished cancer patient are many and include dietary counseling, food supplements (which contain vitamins and other micronutrients), stimulation of appetite, enteral nutrition, total parenteral nutrition, or a combination of these. The dietitian can be an invaluable component of the cancer care team, both in the inpatient and outpatient settings. An understanding of the role of each intervention will enable the physician to use available resources rationally and efficiently.

Adult↗

PubMed1992

Pathophysiology of cancer: hormonal and metabolic abnormalities.

Despite the development of advanced nutritional support technology, malnutrition remains a significant morbid and mortal complication of cancer. A number of metabolic abnormalities have been demonstrated in malnourished cancer patients, including increased protein breakdown, increased glucose production, increased lipolysis, hypogonadism in male patients, and insulin resistance. Previous studies conducted under metabolic ward conditions have demonstrated that metabolic abnormalities interfere with efforts at renutrition of patients with localized head and neck cancer. Efforts to correct these abnormalities by treatment with hydrazine sulfate, anabolic androgens, and insulinotropic drugs have been ineffective. An improved understanding of the pathophysiology of cancer malnutrition may lead to improved therapies of this vexing clinical problem.

Cachexia↗

PubMed1992

The role of nutrition in cancer prevention and control.

Evidence has accumulated from the study of populations and from animal feeding studies that strongly implicates dietary patterns and some specific nutrients in the process of promotion of cancers of the breast, colon, uterus and prostate. Nutritional factors may also complement smoking in the promotion of head and neck and lung cancer. Population studies indicate that lifestyle, which includes diet, tobacco use and alcohol consumption, may account for up to 70% of avoidable cancer mortality in this country. The development of effective dietary interventions to reduce some of these risks promises to reduce the age-adjusted incidence and mortality from these common forms of cancer. The biological mechanisms and hypotheses related to the principal dietary components of prevention and control of common cancers is presented together with a review of recent trials testing these ideas.

Dietary Fats↗

PubMed1992

Assessment and maintenance of nutrition in older cancer patients.

Variables that the clinician can assess to determine the nutritional status of cancer patients include percent and rate of weight loss from usual body weight, current weight compared to calculated ideal body weight, and levels of appetite and food intake. Our studies show that two-thirds of patients with advanced cancer over the age of 65 have had some degree of weight loss, and that more than half are underweight, have loss of appetite, or complain of a decrease in food intake. Ongoing support and education, food supplementation, and attention to activity level may all contribute to preserve the patient's nutritional status and quality of life. Severe, persistent anorexia that does not respond to dietary counseling can be reversed with megestrol acetate. Enteral and parenteral nutrition have specific indications but should not be routinely used in anorectic patients.

Aged↗

PubMed1991

The ability of cationic amphiphilic compounds to depress the transition temperature of dipalmitoylphosphatidic acid liposomes depends on the spatial arrangement of the lipophilic moiety.

The hypothesis was tested with the help of model compounds that the ability of cationic amphiphilic drugs to depress the phase-transition temperature Tt of dipalmitoylphosphatidic acid (DPPA) liposomes depends on the spatial arrangement of the lipophilic moiety. The main structure of the compounds with identical cationic side chain was 1-dimethylamino-3-phenylpropane (compound I). A further phenyl ring was introduced either at C3 of the propane chain (compound II) to broaden the lipophilic moiety, or in para-position of the phenyl ring (compound III) to elongate it. As shown by differential scanning calorimetry, the reduction of Tt (control 64 degrees) amounted for compound I to 29 degrees, for compound II to 28 degrees and for compound III to 53 degrees. In order to assess the binding affinity of the compounds to DPPA, their inhibitory effect on 45Ca(2+)-binding to DPPA films was measured. The IC50 values were 2100 microM for compound I, 40 microM for compound II, and 9 microM for compound III. Thus, binding affinity corresponded with the hydrophobicity of the compounds. In contrast, the depressing effect on the transition temperature was only augmented by the additional phenyl ring when substituted in the elongating position.

Calcium↗

PubMed1991

Insulin action and metabolism in patients with head and neck cancer.

Cachexia is a phenomenon commonly observed in patients with cancer, but its etiology is poorly understood. Abnormalities of insulin action and metabolism that have been hypothesized to promote cancer cachexia were investigated in this study using a computerized euglycemic clamp and modified frequently sampled intravenous glucose tolerance test (FSIGT) in a group of malnourished patients with localized head and neck cancer, and in healthy, well-nourished, age- and, sex-matched controls. Glucose disposal rates, determined by the euglycemic clamp at three different rates of insulin infusion did not differ significantly between the two groups. However, mean plasma insulin concentrations at each level of insulin infused were significantly lower in the patients with cancer than in the control subjects resulting in unexpectedly higher calculated insulin metabolic clearance rate in the patients with cancer. Peripheral insulin sensitivity calculated from the slope of glucose disposal versus plasma insulin concentration did not differ between the two groups. Results from the FSIGT demonstrated no difference in insulin sensitivity or insulin-independent glucose disappearance between the two groups. However, whole body glucose appearance was significantly elevated in the patients with cancer. Thus, increased whole body glucose utilization in the absence of insulin resistance or increased insulin-dependent glucose disposal was observed. These data are consistent with the concept of a localized tumor acting as a glucose drain in which case increased glucose appearance and increased insulin clearance would defend against hypoglycemia.

Blood Glucose↗

PubMed1991

Nutrition training in graduate medical (residency) education: a survey of selected training programs.

Because limited information exists about nutrition training of residents, we studied the teaching practices of nationally recognized nutrition programs. Two hundred thirty-eight nutrition educators and 787 residency-program directors identified 160 institutions with strong nutrition training. The 23 highest-ranked programs were surveyed and 7 were visited. The results showed that 1) clinically active physician-nutritionist role models are the key elements in teaching residents clinical nutrition; 2) multidisciplinary nutrition support teams are valuable learning resources unless they function primarily as technical support services; 3) nutrition elective rotations, although highly effective, are taken by a minority of residents; 4) the nutrition curriculum should include practical learning materials and conferences; and 5) a research environment is important to attract qualified physician-nutritionist role models. A major deficit is teaching nutritionally based approaches to disease prevention in the ambulatory setting. Finally, a shortage of nutrition-oriented physician role models is probably the major constraint in teaching nutrition to residents.

Curriculum↗

PubMed1991

Treatment of anorexia and weight loss with megestrol acetate in patients with cancer or acquired immunodeficiency syndrome.

Anorexia is a symptom of cancer and a cause of decreased caloric intake and weight loss. Successful treatment for anorexia can improve the patient's well-being and prevent or reverse the effects of anorexia on nutrition. Following reports of appetite enhancement and weight gain in uncontrolled studies of high-dose (320 to 1,600 mg/d) megestrol acetate in patients with cancer or AIDS (acquired immunodeficiency syndrome), several randomized, placebo-controlled trials have been completed. These trials demonstrate that megestrol acetate therapy improves appetite and food intake in patients with anorexia and advanced cancer, leading to weight gain in a subset of patients. The mechanisms of action of megestrol acetate (a progesterone derivative) probably include both behavioral and metabolic effects. Several carefully designed randomized trials are under way to establish the optimal dose and to determine the mechanism of weight gain. Patients with cancer or AIDS who complain of anorexia and whose nutritional status is compromised may benefit from megestrol acetate therapy.

Acquired Immunodeficiency Syndrome↗