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Biomedical subjects

G A Bray

Publications and source records attributed to G A Bray.

At least 55 records · Page 3Linked to original sources
PubMed2000

Clinical evaluation of the overweight patient.

Evaluation of an overweight patient is the first step in any therapeutic program. The syndromes of obesity can be classified in several ways. The first is an anatomic classification based on the size, number, and distribution of fat cells and fat tissue. The second is an etiologic classification based on identification of specific diseases and settings that produce obesity. Hypothalamic injury and endocrine disease such as Cushing's disease and the polycystic ovary syndrome are three identifiable causes of obesity. In this medicated society drugs are always candidates to produce weight gain. The most common causes, however, are stopping smoking, overconsumption of high-fat foods, a decrease in the level of activity, and aging. The natural history of obesity provides a useful framework in which to view both preventive and therapeutic strategies. Some individuals will never become overweight, but of those who do, about one-third will do so during the first two decades, and the remaining two-thirds will become overweight after age 20. A number of epidemiological and metabolic factors can serve as a guide to those individuals who are at high risk. Having overweight parents tops the list, but multiple births, cessation of smoking, and a sedentary lifestyle are additional factors. Therapeutic decisions should be based on risk-benefit decisions. The risk can be assessed from the body mass index, the distribution of fat in upper or lower body obesity, the rate of weight gain, and the degree of physical inactivity. After assessing risk, the therapeutic choices can be selected from the age category of the patient. With any therapeutic activity, involvement of the patient in a realistic approach to the treatment process is essential.

Adipose Tissue↗
PubMed1999

A dietary approach to prevent hypertension: a review of the Dietary Approaches to Stop Hypertension (DASH) Study.

BACKGROUND: Populations eating mainly vegetarian diets have lower blood pressure levels than those eating omnivorous diets. Epidemiologic findings suggest that eating fruits and vegetables lowers blood pressure. HYPOTHESIS: Two hypotheses were tested: (1) that high intake of fruits and vegetables lowers blood pressure, and (2) that an overall dietary pattern (known as the DASH diet, or DASH combination diet) that is high in fruits, vegetables, nuts, and low-fat dairy products, emphasizes fish and chicken rather than red meat, and is low in saturated fat, cholesterol, sugar, and refined carbohydrate lowers blood pressure. METHODS: Participants were 459 adults with untreated systolic blood pressure < 160 mmHg and diastolic blood pressure 80-95 mmHg. After a 3-week run-in on a control diet typical of Americans, they were randomized to 8 weeks receiving either the control diet, or a diet rich in fruits and vegetables, or the DASH diet. The participants were given all of their foods to eat, and body weight and sodium intake were held constant. Blood pressure was measured at the clinic and by 24-h ambulatory monitoring. RESULTS: The DASH diet lowered systolic blood pressure significantly in the total group by 5.5/3.0 mmHg, in African Americans by 6.9/3.7 mmHg, in Caucasians by 3.3/2.4 mmHg, in hypertensives by 11.6/5.3 mmHg, and in nonhypertensives by 3.5/2.2 mmHg. The fruits and vegetables diet also reduced blood pressure in the same subgroups, but to a lesser extent. The DASH diet lowered blood pressure similarly throughout the day and night. CONCLUSIONS: The DASH diet may offer an alternative to drug therapy in hypertensives and, as a population approach, may prevent hypertension, particularly in African Americans.

Adult↗
PubMed1999

Serial echocardiographic and clinical evaluation of valvular regurgitation before, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine.

OBJECTIVE: The prevalence of cardiac valvular regurgitation demonstrated by echocardiography in patients who took appetite-suppressant medication for weight loss has been assessed at 5%-30%. We studied 86 patients who had echocardiograms before treatment with appetite suppressants to determine the incidence of new cases and to evaluate the clinical implication of the echocardiographic findings. RESEARCH METHODS AND PROCEDURES: We studied 69 men [Mean+/-Standard Deviation (S) age 49+/-8] and 17 women (mean+/-S age 50+/-7) who had 233 echocardiograms before, during, and after a weight-loss program that used predominantly fenfluramine (or dexfenfluramine) with mazindol (or phentermine). Mean drug exposure was 17 months. Blinded echocardiographic readings were performed to identify and grade aortic regurgitation (AR) or mitral regurgitation (MR). RESULTS: Seven of 86 patients (8%) had pre-existing regurgitation with five (6%) meeting our case definition. Thirteen (16.5%) of initially normal patients developed valvular regurgitation and were new cases. Of the new cases, 12 were grade I/IV AR and one was both grade II/III MR and II/IV AR. All 13 patients were asymptomatic, and only two aortic insufficiency murmurs could be auscultated. There was significantly greater risk for developing valvulopathy for those who took medications longer than 6 months (p = 0.03), and no new cases were observed in patients exposed for less than 8 months. No increased risk associated with age, presence of hypertension, or exposure to fenfluramine-phentermine combination was demonstrated. Although there was a higher incidence of new regurgitation in women (31% vs. 13% for men), this was not statistically significant (p = 0.093). DISCUSSION: Some patients who had normal echocardiograms at baseline developed cardiac valvular regurgitation after exposure to fenfluramine or dexfenfluramine with mazindol or phentermine. The development of valvulopathy was significantly correlated with duration of exposure. The clinical implications of echocardiographically demonstrated regurgitation are uncertain, since there were only two audible murmurs and no other clinically relevant signs or symptoms among the patients.

Aortic Valve Insufficiency↗
PubMed1999

Sibutramine produces dose-related weight loss.

OBJECTIVE: Sibutramine is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. In animals, it reduces food intake and increases thermogenesis and preliminary data in human beings showed weight loss. This paper reports a 24-week dose-ranging study to determine the effect of sibutramine on body weight of patients with obesity. RESEARCH METHODS AND PROCEDURES: Seven clinical centers screened 1463 patients with obesity and randomized 1047 to 24 weeks of treatment with 1 of 6 doses of sibutramine (1, 5, 10, 15, 20, or 30 mg) or placebo once daily. Six hundred eighty-three patients completed the study. A two-week placebo run-in period was used to initiate a standardized program of diet, physical activity, and lifestyle changes. RESULTS: Weight loss was dose-related and statistically significant vs. placebo (p<0.05) across all time-points for a 5 mg/day to 30 mg/day dosage of sibutramine. At week 24, percent weight loss from baseline for completers was: placebo, 1.2%; 1 mg, 2.7%; 5 mg, 3.9%; 10 mg, 6.1%; 15 mg, 7.4%; 20 mg, 8.8%; and 30 mg, 9.4%. Weight loss achieved at week 4 was predictive of weight loss achieved at week 24. Patients losing weight demonstrated an increase in serum high density lipoprotein cholesterol and reductions in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, and uric acid. Small mean increases in blood pressure and pulse rate (with considerable individual variability) were observed in patients treated with sibutramine. The most frequent adverse events were dry mouth, anorexia, and insomnia. DISCUSSION: Sibutramine administered once daily for 24 weeks in the weight loss phase of treatment for uncomplicated obesity produced dose-related weight loss and was well tolerated. Improvements in serum lipids and uric acid accompany sibutramine-induced weight loss. Most of the adverse events observed on sibutramine are related to its pharmacology, including small mean increases in blood pressure and heart rate.

Adult↗
PubMed1999

Pharmaceutical cost savings of treating obesity with weight loss medications.

OBJECTIVE: To evaluate, in compliant patients, the pharmaceutical costs of treating obesity with fenfluramine/mazindol, fenfluramine/phentermine, caffeine/ephedrine, or mazindol relative to the pharmaceutical costs of treating obesity-related comorbid conditions and reducing cardiovascular risk. METHODS AND PROCEDURES: Subjects were between 18 and 60 years of age with a BMI of >30 kg/m2. Pharmaceutical costs were evaluated in 73 of 220 subjects taking medications for diabetes, hyperlipidemia, or hypertension before and after treatment using fenfluramine with mazindol or phentermine. The pharmaceutical cost of weight loss, cardiac risk reduction, and low-density lipoprotein (LDL) cholesterol reduction was calculated for fenfluramine with mazindol or phentermine, caffeine with ephedrine, or mazindol alone, and compared to approved lipid-lowering medications. RESULTS: Losses of 6% to 10% of initial body weight reduced pharmacy costs $122.64/month for insulin treated diabetes, $42.92/month for sulfonylurea-treated diabetes, $61.07/month for hyperlipidemia treated with medication, and $0.20/month for hypertension treated with medication. Blood pressure and laboratory evidence of insulin resistance improved in all medication groups. Caffeine/ephedrine was most cost-effective of the three treatments in reducing weight, cardiac risk, and LDL cholesterol. DISCUSSION: Obesity medications produced a substantial weight loss in compliant patients and resulted in a net pharmaceutical cost savings compared to treating obesity related comorbid conditions.

Adolescent↗
PubMed1999

Methods to maximize retention in weight loss studies.

OBJECTIVE: Dropouts from clinical trials decrease quality and increase costs. Free participation, paid participation, and contingency contracting are three study retention methods. Contingency contracting, or depositing a fee to be refunded contingent upon attendance in a clinical trial, has been reported to decrease dropouts without affecting weight loss. These three methods of retention were compared with a commercial weight loss clinic's practice of charging nonrefundable fees. METHODS AND PROCEDURES: Dropouts were compared in two studies testing mazindol, with one study using free care and the other using contingency contracting; two studies testing phenylpropanolamine, one using free care and the other using contingency contracting; and in studies with phenylpropanolamine on file with Thompson Medical Company using free care, paid participation, and contingency contracting. RESULTS: The dropout rate was 50% at 8 weeks in a trial of mazindol with free care vs. 7% for contingency contracting (p<0.001). The two phenylpropanolamine studies gave the same weight losses, but the dropouts were 37% at 8 weeks for free care vs. 11% for contingency contracting (p<0.001). The studies of phenylpropanolamine on file at the Thompson Medical Company had 28% dropouts at 8 weeks using free care vs. 19% for paid participation (p<0.001), and 11% for contingency contracting (p<0.005). Dropouts with contingency contracting (11%) were not different from the commercial weight loss program (13%). DISCUSSION: Contingency contracting can decrease dropouts, improve quality, and decrease costs without affecting weight loss in clinical trials for obesity.

Appetite Depressants↗
PubMed1999

Flexible vs. Rigid dieting strategies: relationship with adverse behavioral outcomes.

This study was designed to test the hypothesis that different types of dieting strategies are associated with different behavioral outcomes by investigating the relationship of dieting behaviors with overeating, body mass and mood. A sample of 223 adult male and female participants from a large community were studied. Only a small proportion of the sample (18%) was seeking weight loss treatment, though almost half (49.3%) of the subjects were significantly overweight (body mass index, BMI>30). Subjects were administered questionnaires measuring dietary restraint, overeating, depression and anxiety. Measurements of height and weight were also obtained in order to calculate BMI. Canonical correlation was performed to evaluate the relationship of dietary restraint variables with overeating variables, body mass, depression and anxiety. The strongest canonical correlation (r=0.65) was the relationship between flexible dieting and the absence of overeating, lower body mass and lower levels of depression and anxiety. The second strongest canonical correlation (r=0.59) associated calorie counting and conscious dieting with overeating while alone and increased body mass. The third canonical correlation (r=0.57) found a relationship between low dietary restraint and binge eating. The results support the hypothesis that overeating and other adverse behaviors and moods are associated with the presence or absence of certain types of dieting behavior.

Adult↗
PubMed1999

Dietary Approaches to Stop Hypertension: rationale, design, and methods. DASH Collaborative Research Group.

Epidemiologic studies across societies have shown consistent differences in blood pressure that appear to be related to diet. Vegetarian diets are consistently associated with reduced blood pressure in observational and interventional studies, but clinical trials of individual nutrient supplements have had an inconsistent pattern of results. Dietary Approaches to Stop Hypertension (DASH) was a multicenter, randomized feeding study, designed to compare the impact on blood pressure of 3 dietary patterns. DASH was designed as a test of eating patterns rather than of individual nutrients in an effort to identify practical, palatable dietary approaches that might have a meaningful impact on reducing morbidity and mortality related to blood pressure in the general population. The objectives of this article are to present the scientific rationale for this trial, review the methods used, and discuss important design considerations and implications.

Adult↗
PubMed1999

The DASH Diet, Sodium Intake and Blood Pressure Trial (DASH-sodium): rationale and design. DASH-Sodium Collaborative Research Group.

The DASH Diet, Sodium Intake and Blood Pressure Trial (DASH-Sodium) is a multicenter, randomized trial comparing the effects of 3 levels of sodium intake and 2 dietary patterns on blood pressure among adults with higher than optimal blood pressure or with stage 1 hypertension (120-159/80-95 mm Hg). The 2 dietary patterns are a control diet typical of what many Americans eat, and the DASH diet, which, by comparison, emphasizes fruits, vegetables, and low-fat dairy foods, includes whole grains, poultry, fish, and nuts, and is reduced in fats, red meat, sweets, and sugar-containing beverages. The 3 sodium levels are defined as higher (typical of current US consumption), intermediate (reflecting the upper limit of current US recommendations), and lower (reflecting potentially optimal levels). Participants are randomly assigned to 1 of the 2 dietary patterns using a parallel group design and are fed each of the 3 sodium levels using a randomized crossover design. The study provides participants with all of their food during a 2-week run-in feeding period and three 30-day intervention feeding periods. Participants attend the clinic for 1 meal per day, 5 days per week, and take home food for other meals. Weight is monitored and individual energy intake adjusted to maintain baseline weight. The primary outcome is systolic blood pressure measured at the end of each intervention feeding period. Systolic blood pressure is compared across the 3 sodium levels within each diet and across the 2 diets within each sodium level. If effects previously observed in clinical trials are additive, sodium reduction and the DASH diet together may lower blood pressure to an extent not as yet demonstrated for nonpharmacologic treatment. The DASH-Sodium results will have important implications for the prevention and treatment of high blood pressure.

Adult↗
PubMed1999

Differential satiating effects of fats in the small intestine of obesity-resistant and obesity-prone rats.

The effects of duodenal infusions of fats on sham feeding was measured in two strains of rats that differ in their susceptibility to fat-induced obesity. Osborne-Mendel rats are prone to developing obesity on a high-fat diet and preferentially choose fats over carbohydrates in macronutrient selection paradigms. In contrast, S 5B/PL rats are resistant to developing obesity when eating a high-fat diet, and preferentially choose carbohydrates in macronutrient selection paradigms. To test the hypothesis that differences in the satiating potency of fats in the small intestine contributed to these differences between the two strains, we measured the effects of duodenal infusions of Intralipid and sodium linoleate on sham-feeding intakes. The results were consistent with the hypothesis. Duodenal infusions of either of these fats decreased intake significantly more in S5B/PL rats than in Osborne-Mendel rats. Both rat strains sham fed similar amounts when intestinally infused with 0.15 M NaCl. These results suggest that differences in responses to intestinal satiating mechanisms may contribute to the differences in susceptibility to fat-induced obesity in these rat strains.

Animals↗
PubMed1999

The effects on feeding of galanin and M40 when injected into the nucleus of the solitary tract, the lateral parabrachial nucleus, and the third ventricle.

Several reports indicate that central injection of galanin stimulates feeding, and that there is macronutrient specificity in this response. In addition, the galanin receptor antagonist, M40, reduces food intake when injected centrally. The nucleus of the solitary tract (NTS) and the lateral parabrachial nucleus (PBN) contain galanin receptors, and are involved in the control of food intake. Hence, we sought to compare the feeding response to galanin injection into these areas with that of third ventricle (3V) galanin injection. The feeding response to injection of galanin was greatest for the 3V. Hindbrain injection of galanin stimulated food intake only at the beginning of the dark period. NTS injection of M40 inhibited intake of a macronutrient diet in food-deprived rats, but was ineffective at reducing dark-onset feeding or deprivation-induced chow intake. 3V injection of M40 did not reduce deprivation-induced intake. PBN injection of galanin at dark onset had no effect in a group of fat-preferring rats. These results suggest that hindbrain galanin may contribute to feeding by inhibiting satiety, and that hypothalamic galanin receptors are involved with stimulation of intake. Furthermore, the absence of a consistent pattern of the stimulation of macronutrient intake suggests that galanin may not be a significant effector of macronutrient selection during individual meals.

Analysis of Variance↗
PubMed1999

Macronutrient diet intake of the lethal yellow agouti (Ay/a) mouse.

To examine the effect of chronic endogenous melanocortin receptor (MC-R) antagonism on macronutrient diet selection, Ay/a mice that ectopically overexpress the MC-R antagonist, agouti, were fed a three-choice macronutrient diet of pure fat, carbohydrate, and protein. Ay/a mice gained more weight and consumed a greater proportion of their daily intake from fat and less from carbohydrate than wild-type littermates did. The increased fat preference was present immediately, and persisted throughout the 7-week long experiment. Protein intake was greater for Ay/a mice; however, the proportion of protein intake to total intake was similar between mouse types. Ovarian fat pads of Ay/a mice comprised a greater percentage of total body weight that that from wild-type littermates. These results suggest that endogenous inhibition of MC-Rs mediate the increased fat intake in growing mice.

Animals↗
PubMed1999

Etiology and pathogenesis of obesity.

Obesity results from a greater consumption of energy than is used by the body. As this energy is stored, fat cells enlarge, producing the characteristic pathology of obesity. The pathologic enlargement of fat cells, in turn, produces altered levels of many peptide and nutrient signals that are responsible for the disease we call "obesity." The genetic makeup of human beings, which reflects a long history of relative scarcity of foodstuffs, has run into an age of surfeit, and many people cannot readily adapt. Thus, the increased intake of food does not signal satiety, and there is a gradual increase in energy stores as intake of energy outpaces need as we grow older. Against this background of struggle between nature and nurture, it is possible to identify an increasing number of defects or etiologies that produce obesity. For most patients, however, it is not possible to connect obesity to a specific cause. Leptin deficiency and defects in the leptin receptor both produce human obesity. Defects in the pro-opiomelanocortin receptor system, the peroxisome proliferator-activated receptor-gamma, the agouti-related peptide, and a few other rare genetic syndromes are also associated with human obesity. Of the genetic causes, Prader-Willi syndrome is the most common. Hypothalamic injury following craniopharyngioma is the most common neuroendocrine cause. Endocrine disorders such as Cushing's disease, polycystic ovary disease, and growth-hormone deficiency can lead to increased body fat. In the modern world, exposure to a high-fat diet predisposes many people to obesity, and this problem is compounded by the low levels of activity now required for daily living. Treatment strategies must be developed against this background.

Energy Intake↗
PubMed1999

Clinical evaluation of the obese patient.

An appropriate evaluation is the first step in developing a treatment plan for the overweight individual. The medical history should evaluate aetiological factors that may have played a role in the development of obesity. The physical examination and laboratory tests should extend this evaluation to risk factors associated with obesity. The natural history of the development of obesity then provides a guide to selecting appropriate treatment algorithms.

Adolescent↗
PubMed1999

Drug treatment of obesity.

Drugs to treat obesity can be divided into three groups: those which reduce food intake, those which alter metabolism and those which increase thermogenesis. Monoamines acting on noradrenergic receptors, serotonin receptors, dopamine receptors and histamine receptors can reduce food intake. A number of peptides also affect food intake. The noradrenergic drugs phentermine, diethylpropion, mazindol benzphetamine and phendimetrazine are approved only for short-term use. Sibutramine, a norepinephrine-serotonin re-uptake inhibitor, is approved for long-term use. Orlistat inhibits pancreatic lipase and can block 30% of triglyceride hydrolysis in subjects eating a 30% fat diet. The only thermogenic drug combination that has been tested is ephedrine and caffeine, but this treatment has not been approved by regulating agencies. Leptin is currently in clinical trials and other drugs that may modulate peptide-feeding systems are being developed.

Androgen Antagonists↗