Radial bone density and breast cancer risk in white and African-American women.

A number of different models for assessing individual risk of breast cancer use known risk factors such as age, age at menarche, age at first live birth, previous breast biopsies, and family history. High bone mass in white women is also associated with an increased breast cancer risk; however, bone mass as a risk factor has not been studied in African-American women. We conducted a case-control study to evaluate bone mineral density as a risk factor for breast cancer in white and African-American women. We recruited 221 women with newly diagnosed breast cancer from a comprehensive breast cancer center at a large university hospital, and 197 control women who were frequency matched for ethnicity and age. Odds ratios were based on proximal and distal radial bone density measured by peripheral bone densitometry (Norland pDEXA) and expressed as a standardized "Z-score" (age and ethnicity specific). Logistic regression models were fitted controlling for body mass index, menopausal status, age, and HRT use (ever/never and duration). With proximal bone density Z-score included in the model as a continuous variable, a one-unit increase in radial shaft bone density increased the risk of breast cancer by 25% (p=0.02). When proximal bone density Z-score was analyzed as a dichotomous variable (< or = 0, > 0) the odds ratio was 1.98 (95% CI, 1.32 to 2.97); that is, having an above average proximal bone density (age-specific) doubles the risk of breast cancer. There were no significant interactions with, and no appreciable confounding effects by, other covariates. An above-average radial shaft Z-score is a significant risk factor for breast cancer in both white and African-American women. The present study extends the association between bone mass and breast cancer risk to African-Americans, and suggests another potential application for bone density testing.

Surgical outcomes after breast cancer surgery: measuring acute lymphedema.

BACKGROUND: Studies of lymphedema have used inconsistent measures and criteria. The purpose of this pilot study was to measure the onset and incidence of acute lymphedema in breast cancer survivors using strict criteria for limb evaluation. MATERIALS AND METHODS: Eligible women were those undergoing breast cancer surgery that included axillary staging and/or radiation therapy of the breast. Arm volume, strength, and flexibility were measured preoperatively and quarterly. Lymphedema was defined as a greater than 10% increase in limb volume. Additional strength and flexibility assessments were done at these times. RESULTS: In 30 evaluable patients, half underwent modified radical mastectomy and half lumpectomy, with half of the lumpectomy patients undergoing axillary node staging. Of the 30 patients 27% were Stage 0; the rest were Stage I (27%), IIA (13%), IIB (23%), and IIIA (7%). One subject was IIIB postoperatively. There were 2 women with a 10% or greater change in limb volume; the change was detected in one woman at 3 months (5% incidence) and in the second woman at 6 months (11% incidence). Both had undergone mastectomy and axillary dissection and one of these two women had symptoms of tingling and numbness in the affected arm that began at 3 months. Overall, 35% of the sample experienced symptoms by 3 months, which included numbness, aching, and tingling of the entire upper extremity, but without volume changes. The relationship between undergoing modified radical mastectomy and experiencing symptoms in the affected limb at 3 months was significant (P = 0.05). CONCLUSIONS: In this interim report strict methods of measurement and limb volume comparisons detected acute lymphedema at 3 months in 5% of the sample, and at 6 months in 11% of the sample. Furthermore, symptoms were detected in 35% without volume changes at 3 months postoperatively, which may warn of lymphedema occurrence within the next 3 months. This may assist clinical evaluation of symptoms in the postoperative period and support early referral to lymphedema experts.

Physical activity as a predictor of weight maintenance in previously obese subjects.

We examined the association between exercise and weight loss maintenance in a group of 45 previously obese subjects 2 years post very-low-calorie diet (VLCD) to suggest exercise goals for this population. At baseline, subjects weighed a mean 100 kg and had a mean total cholesterol (TC) of 5.8 mmol/L. With VLCD they lost an average 28 kg and decreased their TC by 1.6 mmol/L. Two years post-VLCD their weight and lipids were measured and they completed a physical activity survey (Paffenbarger). Subjects were grouped into tertiles by reported exercise levels: low active (< 850 kcals per week), moderate active (850-1575 kcals per week) and high active (> 1575 kcals per week). Walking accounted for the greatest calorie expenditure (65%). Analysis of variance showed that baseline characteristics and weight and blood lipid changes during the VLCD did not differ (P > 0.05) among groups. At follow-up, high active patients maintained significantly greater weight loss, had a lower percent regain and a significantly greater decrease in total cholesterol (P < 0.05) than less active patients. Multiple regression analysis indicated that total exercise calories independently predicted overall weight loss and percent regain (r = 0.66 and r = 0.62, respectively). Exercise calories also predicted total cholesterol change (r = -0.37). The high active group walked more miles (16.2 per week) than the low and moderate active groups (4.8 and 9.1 per week, respectively) and exercised more days per week (5.3 vs. 1.9 and 3.7).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of cardiovascular risk factors in obese blacks and whites.

Blacks are known to have higher blood pressure levels, a higher prevalence of hypertension, and higher body weights than whites. However, the interrelationships of these and other cardiac risk factors have not been analyzed in an obese population. We compared blood pressure (BP) and lipid levels in 174 obese blacks and 939 obese white patients who were entering a weight loss program; we also assessed the effects of weight loss on these factors. Prevalence of treated hypertension was similar in blacks and whites (28% vs. 25%, respectively). In patients not taking BP medication, black women weighed more (108 kg) than white women (102 kg) and black and white males' weights were similar (135 kg vs. 131 kg). Systolic and diastolic BP were similar in black and white women; black males had similar SBP but a significantly lower DBP than white males (83 mmHg vs. 89 mmHg, respectively). Lipid levels were similar in black and white women except black women had lower triglycerides (1.30 mmol/L) than white women (1.58 mmol/L, p < 0.05); and black males compared to white males had significantly lower total cholesterol (4.76 mmol/L vs. 5.56 mmol/L), LDL-cholesterol (3.15 mmol/L vs. 3.52 mmol/L) and triglycerides (1.31 mmol/L vs. 2.17 mmol/L, p < 0.05). Adult-onset obesity adversely affected a number of cardiovascular risk factors in whites, but not in blacks. Blacks lost significantly less weight (-13 kg) than whites (-19 kg). However, controlling for the difference in weight loss, blacks sustained comparable improvement in lipids and blood pressure, except for TC/HDL-C (whites improved significantly more, -0.36 kg/m2, than blacks, 0.03 kg/m2). Thus, the impact of obesity on cardiovascular risk factors seems ameliorated in blacks compared to whites.

Long-term follow-up of patients attending a combination very-low calorie diet and behaviour therapy weight loss programme.

We examined the effects of treatment with a very-low calorie diet (VLCD) combined with behaviour modification on weight loss and long-term maintenance of weight loss in 118 of 199 patients who completed eight weeks of VLCD. Those who began therapy in 1984 were surveyed by telephone an average of 3.3 years after ending the VLCD. Questionnaire data included reported weight, exercise, eating, work and sleep habits, emotional factors, and current use of behavioural techniques taught in the programme. Results showed that mean maximum weight loss during the time they attended the programme (average 51.6 weeks) was 31.3 kg, corresponding to a decrease in body mass index of 10.7 kg/m2. At follow-up a regain of 60.9% was reported yielding a net overall weight loss of 13.6 kg and decrease in body mass index of 4.4 kg/m2. Seventy-five per cent of subjects showed only a 37.5% regain of the weight they had lost. Those whose weight loss was better maintained at the time of follow-up reported exercising more, eating fewer high fat foods, and using more of the behavioural techniques taught in the programme. This study provides support for the conclusion that some patients treated with VLCD and behaviour modification can maintain significant weight losses over a relatively long period of time and that specific behaviours relate to this success.

Relationships between the amount of weight loss and post-heparin lipoprotein lipase activity in patients with type II diabetes.

The objective of this study was to investigate the changes in plasma post-heparin lipoprotein lipase activity, as it relates to the total amount of weight loss and the changes in plasma lipoproteins, during acute weight reduction and after weight maintenance in type II diabetic patients. Twenty-eight severely obese (mean weight = 106 +/- 21.7 kg, BMI = 36.4 +/- 6.0 kg/m2), diabetic patients lost, on the average, 13.3 kg on a 500 kcal (2100 kJ) diet in eight weeks. Weight loss was maintained throughout the study, which lasted 24 weeks. At the baseline, post-heparin lipoprotein lipase activity did not correlate with degree of obesity, but correlated inversely with fasting plasma glucose (r = -0.64, P less than 0.0001) and triglyceride (r = -0.63, P less than 0.0001). Both during acute caloric restriction and after weight maintenance suppression in post-heparin lipoprotein lipase activity correlated directly with the amount of weight reduction (r = 0.37, P less than 0.05 during weight loss and r = 0.42, P less than 0.03 during weight maintenance). At the end of the study patients were divided into tertiles according to the amount of weight loss achieved and baseline characteristics of the highest and lowest weight loss groups were compared. Before weight loss, despite having similar weights, the highest weight loss group had higher lipoprotein lipase activity (211 +/- 32 mU/ml vs 166 +/- 35 mU/ml, P less than 0.05) and lower plasma triglyceride (1.64 +/- 0.62 mmol/l vs 2.81 +/- 1.28 mmol/l, P less than 0.05) as compared to the lowest weight loss group.(ABSTRACT TRUNCATED AT 250 WORDS)

Fluoxetine's effect on weight loss in obese subjects.

Forty-five obese subjects with a mean weight of 102.9 kg and a body mass index (in kg/m2) of 37.6 were randomly assigned to a fluoxetine-diet group (n = 23) or a placebo-diet group (n = 22) for 52 wk. At week 29, 14 subjects on fluoxetine who completed the study attained their maximum weight loss of 12.4 kg, an amount significantly greater than the maximum weight loss of 4.5 kg for the 16 on placebo who completed the study. The fluoxetine group's significantly greater mean weight loss continued through week 45. However, those on fluoxetine regained a mean of 4.2 kg from their lowest weight (P less than 0.001) whereas the placebo group did not. By the end of the study, each group weighed significantly less than they did at baseline (fluoxetine: -8.2 kg; placebo: -4.5 kg; P less than 0.05) although the difference between groups was no longer significant (P greater than 0.05). Several factors were considered as possible causes for the regain with fluoxetine.

Comparison of the effects of guanadrel sulfate and propranolol on blood pressure, functional capacity, serum lipoproteins and glucose in systemic hypertension.

In a controlled, double-blind, crossover study, the effects of guanadrel sulfate and propranolol on blood pressure (BP) and selected cardiopulmonary and metabolic variables were compared in 15 physically active and moderately hypertensive subjects. Guanadrel sulfate reduced systolic and diastolic BP at rest by -16 and -15 mm Hg, and at maximal exercise by -33 and -13 mm Hg, respectively (p less than 0.005), without affecting submaximal oxygen consumption (VO2), maximal VO2, ventilatory threshold, forced vital capacity, forced expiratory volume in 1 second, or fatigue, as assessed by perceived exertion. In contrast, propranolol significantly decreased diastolic BP at rest (-16 mm Hg) and systolic BP at maximal exercise (-44 mm Hg); however, it significantly decreased submaximal VO2 (-3.9 ml.kg-1.min-1), maximal VO2 (-3.9 ml.kg-1.min-1), ventilatory threshold (-0.3 liters.min-1), minute ventilation at submaximal exercise (-7.3 liters.min-1), forced expiratory volume in 1 second (-0.27 liters), and concomitantly increased the rating of perceived exertion at maximal exercise (1.9 U). Guanadrel sulfate was also associated with significant decreases in mean fasting plasma glucose and total serum cholesterol, whereas propranolol resulted in an increase in serum triglycerides (p less than 0.05). In contrast to propranolol, guanadrel sulfate appears to decrease BP without evoking negative metabolic consequences or impairing exercise tolerance.

Endurance Training in Middle-Aged Male Physicians.

In brief: Vigorous exercise has been associated with reduced cardiovascular risk factors and a lower incidence of coronary heart disease. To determine the effects of endurance training on middle-aged men, a group that is at risk for heart disease, two groups of Physicians were surveyed: 1,269 runners (members of the American Medical Joggers Association who had been running at least 10 miles per week) and 683 nonrunners (members of the AMA). These groups were chosen because they are similar in age, sex, life-style, profession, socioeconomic position, and knowledge about health. Results showed that the runners had lower body weight and reduced cardiovascular risk factors, and that they smoked fewer cigarettes. However, prospective studies are needed to determine both the risks and benefits of endurance exercise.

Variable effects of weight loss on serum lipids and lipoproteins in obese patients.

After a 500 calorie diet and 6 months of low fat, maintenance diet, weight, serum lipid, and lipoprotein levels were compared to baseline in 46 obese patients. Mean weight decreased by 25.9 percent (29.2 kg). Mean total (TC) and low density lipoprotein cholesterol (LDL-C), and triglycerides (TG) decreased by 5.5 percent (12.1 mg/dl), 11 percent (15.5 mg/dl) and 23.6 percent (34.5 mg/dl); mean high density lipoprotein cholesterol (HDL-C) increased by 20.6 percent (10.3 mg/dl) and TC/HDL-C decreased by 25 percent (1.2), P less than 0.01. Females and males had equal increases in HDL-C. The decrease in TG and TC in patients who continued to lose 4.2 kg during the 6 month maintenance period was significantly greater than in those who regained 7.8 kg (P less than 0.015). Greater changes in HDL-C and TC/HDL-C occurred in younger individuals (r = -0.35 and r = -0.37); in those with more abnormal initial values (r = -0.60, r = 0.64); and for HDL-C, a larger increase occurred in those with greater weight loss (r = 0.32; P less than 0.04).

Achieving therapeutic goals in insulin-using diabetic patients with non-insulin-dependent diabetes mellitus. A weight reduction-exercise-oral agent approach.

Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes in the civilized world. Its consequences include microvascular and macrovascular disease, both of which appear to evolve from a common background of obesity and physical inactivity. The current study was undertaken in obese patients with NIDDM to see whether improvements could be made in glycemic control as well as in many cardiovascular risk factors (obesity, hypertension, lipid abnormalities, and physical inactivity) that are typical of this condition. Fifteen obese insulin-using patients with NIDDM (average body mass index, 34.0) were treated with a 500-calorie formula diet for eight to 12 weeks. Administration of insulin and diuretics was discontinued at the onset of the study. A eucaloric diet was begun at eight to 12 weeks and maintained until Week 24. A behaviorally oriented nutrition-exercise program was instituted at the beginning of the study. Glipizide or placebo was added (randomized) at Week 15 if the fasting plasma glucose level in patients exceeded 115 mg/dl. Patients lost an average of 22 pounds over the course of 24 weeks. Frequency and duration of physical activity increased significantly from baseline, as did the maximal oxygen consumption rate. Glycemic control by 15 weeks (without insulin) was similar to baseline (with insulin). With the addition of glipizide at Week 15, both fasting plasma glucose and glucose tolerance improved significantly. This improvement was not observed with placebo. In addition, both systolic and diastolic blood pressure decreased by about 10 mm Hg. There were no significant changes in the levels of serum lipids or glycosylated hemoglobin. In conclusion, a multifaceted intervention program, employing weight reduction, exercise, diet, and glipizide therapy, can be instituted in insulin-using patients with NIDDM, with improvement in glycemic control and in certain risk factors (hypertension, obesity, physical inactivity) for cardiovascular disease.

The short- and long-term effects of a low-fat, cholesterol-free, hypocaloric diet on serum triglyceride and cholesterol distribution in severely obese humans.

The effect of weight loss on serum triglycerides (TG), and total, HDL, and LDL cholesterol was measured retrospectively over a 9-month period in 14 obese patients who lost at least 90 lbs on a very-low-calorie, nearly fat-free, formula diet of 300-450 cal/day. These measurements were repeated in seven of these patients during the first 3 months of stable weight maintenance. Changes in total, LDL and HDL cholesterol were biphasic during the hypocaloric diet, showing a decrease during the first 3 months, and subsequently approaching or reaching baseline values. No further change occurred in total cholesterol, LDL cholesterol, or HDL cholesterol during the subsequent weight maintenance phase. Triglycerides decreased by the first month of this diet and remained low throughout the entire 9-month period of caloric restriction and during a 3-month period of weight maintenance. Percentage changes in TG and HDL-C during the first 3 months of hypocaloric diet were inversely correlated with their baseline values, those with the highest initial values showing the greatest decrease, and those with the lowest values showing an increase. These results demonstrate the importance of obtaining multiple specimens over time in interpreting the effect of hypocaloric diets on serum lipids.

Cold air provocation of airway hyperreactivity in patients with cystic fibrosis.

Thirty-four patients with cystic fibrosis (CF) were assessed for baseline pulmonary functions before, and 5 and 15 minutes after cold air challenge (CACh). Most of the patients had no change in forced expiratory volume in 1 second (FEV1) and maximum expiratory flow at 25% vital capacity (Vmax25%VC) post-CACh. Five patients responded with reduced FEV1 and 13 with reduced Vmax25%VC. However, paradoxical increases were noted in 10 patients for FEV1 and in 5 for Vmax25%VC. Paradoxical responses were most frequent in patients with severe lung disease. The explanation for this variability may lie in the varying degrees of airway instability and volume of airway contribution (VAC) to early flows, resulting from the damage caused by chronic infection. Conventional challenges may be useless in determining the true incidence of bronchial hyperreactivity in patients with CF.

Insulin and blood pressure in obesity.

To assess factors in overweight persons that account for a tendency toward hypertension, 33 very obese women, 26 to 77 years of age, were studied. Blood pressures in these 33 women varied from low normal to mildly hypertensive. None of them had taken medication for high blood pressure, and none had diabetes mellitus. The effect of independent variables--age, body mass index (weight/height2), fasting serum glucose levels, fasting serum insulin levels, and 24-hour urinary sodium excretion--on systolic and diastolic blood pressure was assessed. There was no correlation between sodium excretion and blood pressure. Age did not correlate with diastolic blood pressure but did correlate with systolic blood pressure when body mass index, serum glucose level, and insulin level were controlled. Diastolic blood pressure correlated with body mass index and serum glucose level, but only the latter remained significant when all independent variables were considered together. Both systolic and diastolic blood pressure were found to be significantly related to fasting serum insulin level (r = 0.47, p = 0.005 and r = 0.68, p less than 0.001) even when age, weight, and serum glucose level were controlled (r = 0.41, p = 0.025 and r = 0.62, p less than 0.001 respectively). The relation between serum insulin and blood pressure was more pronounced in those women with a family history of hypertension. These data indicate that insulin may play a major role in the regulation of blood pressure in obesity and that the previously accepted relation of weight to blood pressure may depend on blood levels of insulin.

Evolution of cytochrome C investigated by the maximum parsimony method.

Rates of evolution for cytochrome c over the past one billion years were calculated from a maximum parsimony dendrogram which approximates the phylogeny of 87 lineages. Two periods of evolutionary acceleration and deceleration apparently occurred for the cytochrome c molecule. The tempo of evolutionary change indicated by this analysis was compared to the patterns of acceleration and deceleration in the ancestry of several other proteins. The synchrony of these tempos of molecular change supports the notion that rapid genetic evolution accompanied periods of major adaptive radiations. Rates of change at different time in several structural-functional areas of cytochrome c were also investigated in order to test the Darwinian hypothesis that during periods of rapid evolution, functional sites accumulate proportionately more substitutions than areas with no known functions. Rates of change in four proposed functional groupings of sites were therefore compared to rates in areas of unknown function for several different time periods. This analysis revealed a significant increase in the rate of evolution for sites associated with the regions of cytochrome c oxidase and reductase interaction during the period between the emergence of the eutherian ancestor to the emergence of the anthropoid ancestor.

Immunodiffusion systematics of the primates. Part V. The Platyrrhini.

Evolutionary relationships between New World monkeys and marmoset genera and the place of the Ceboidea within the primates are considered in terms of the immunological specificity of ceboid proteins. Antigenic distances between the New World primates are measured using antisera produced in rabbits to nine ceboid genera: Alouatta, Aotes, Ateles, Callicebus, Cebus, Chiropotes, Lagothrix, Saimiri and Saguinus. A cladogram constructed on the basis of increasing degrees of antigenic distance between branches depicts Ceboidea as a monophyletic assemblage within which Alouatta is grouped with the Atelinae genera, Lagothrix and Ateles, Chiropotes joins Cacajao and Cebus joins Saimiri. The joining of the cebid genera Aotes and Callicebus with callithricid genera Callimico and Saguinus into a single complex lineage suggests that Cebidae is a paraphyletic or polyphyletic taxon. A phylogenetic taxonomy for Platyrrhini is proposed.