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Biomedical subjects

D Heber

Publications and source records attributed to D Heber.

At least 73 records · Page 4Linked to original sources
PubMed1995

Topical fat reduction.

The fat on women's thighs is more difficult to mobilize due to increased alpha-2 adrenergic receptor activity induced by estrogen. Lipolysis can be initiated through adipocyte receptor stimulation (beta adrenergic) or inhibition (adenosine or alpha-2 adrenergic) or by inhibition of phosphodiesterase. Since many women desire regional thigh fat loss, a series of clinical trials were initiated using one thigh as a double-blinded control. Trial #1: Five overweight women had injections of isoproterenol at intervals around the thigh three times a week for 4 weeks with diet and walking. Trial #2: Five overweight woman had ointment containing forskolin, yohimbine and aminophylline applied to the thigh five times a week for 4 weeks after hypertonic warm soaks with a diet and walking. Trial #3: Eighteen overweight women were divided into three groups of six and trial #2 was repeated with each agent alone vs. placebo using forskolin, yohimbine or aminophylline in separate ointments. Trial #4: Thirty overweight women had 10% aminophylline ointment applied to the thigh five times a week for 6 weeks with diet and walking. Chemistry panel, theophylline level and patch testing were performed. Trial #5: Twelve women had trial #4 repeated with 2% aminophylline cream without a diet or walking. Trial #6: Trial #5 was repeated with 0.5% aminophylline cream. All trials except yohimbine ointment gave significantly more girth loss from the treated thigh (p < 0.05 to p < 0.001). Chemistry panel showed no toxicity. Theophylline was undetectable and patch testing was negative. We conclude that topical fat reduction for women's thighs can be achieved without diet or exercise.

Adipose Tissue↗
PubMed1995

Derivatives of 3-digitoxigenone amidinohydrazone: synthesis and effect on the digitalis receptor of several species. Part 7: Compounds with positive inotropic activity.

2-Digitoxigenone amidinohydrazone (1), a compound with known digitalis-like activity, and Schiff bases 2-11 of 3-digitoxigenone were synthesized and tested pharmacologically in order to further determine possible structural requirements at the 3-position of digitalis compounds. The inotropic activity was screened using guinea-pig atria, and the interaction with the digitalis receptor was further examined using [3H]ouabain binding to cardiac membranes from guinea pig, rat, pit and man. All compounds revealed activities intermediate between 3-digitoxigenone and ouabain, and the potency of the derivatives covered approximately one order of magnitude. The absolute potency varied among species, but the rank order of potency was rather similar, yielding good correlations between species. This indicates no pronounced preference of these compounds for a particular (Na+/K+)-ATPase isoform of any of the species studied.

Animals↗
PubMed1994

Clinical evaluation of a minimal intervention meal replacement regimen for weight reduction.

OBJECTIVE: The purpose of this study was to evaluate a simplified weight loss program in which subjects were provided a widely available meal replacement product and its package insert information (Ultra Slim-Fast). METHOD: Weekly follow-up visits were carried out by non-physician personnel for weight measurement, distribution of product, and completion of a subjective questionnaire. No dietary counseling was provided. A total of 273 of 301 subjects (91%) completed 12 weeks of study. Men lost 50% (from 119 to 108% of ideal body weight) and women lost 35% (from 122 to 111% of ideal body weight) of excess body weight. Thirty-five patients who lost < 9 lbs in 12 weeks were considered non-adherent and were excluded from the next phase of the study during which 238 subjects were followed biweekly. RESULTS: Despite a $25/week payment for participation nearly 44% of subjects dropped out or were judged non-compliant prior to the end of the study. At 116 weeks, 133 (97 females, 36 males) of 238 subjects remained in the study (44% of the initial population), with average weight loss from baseline of 13.6 +/- 10.5 lb in females and 14.0 +/- 10.5 lb in males. DISCUSSION: The weight loss observed (approximately 10% of body weight) is significant and has been associated with important health benefits particularly for patients with hypertension and non-insulin dependent diabetes. The potential advantages of using meal replacements for mild obesity include wide availability to aid compliance, low cost and minimal professional intervention.

Adult↗
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↗