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Prolonged survival of tumor-bearing rats with repetitive low-dose recombinant tumor necrosis factor.

Tumor necrosis factor may be a mediator of the syndrome of cancer cachexia. Tachyphylaxis or tolerance to the cachectic effects of recombinant tumor necrosis factor (rTNF) has been previously described. In this study, we investigate whether repetitive exposure to rTNF can induce similar tolerance in tumor-bearing (TB) rats and ameliorate cachexia induced by the tumor. In experiment 1, non-tumor-bearing (NTB) and TB rats were randomized to either escalating low doses of rTNF or saline i.p. twice daily for 9 consecutive days. NTB rats treated with rTNF demonstrated a significant decline in food intake and weight change (P less than 0.00001) but soon developed tolerance to the cachectic effects of rTNF; they consumed significantly more food than on the first day of treatment and had weight change similar to NTB rats treated with saline. TB rats treated with rTNF showed a similar significant decline in food intake and weight change (P less than 0.0001) and also demonstrated similar tolerance to the cachectic effects of rTNF with continued treatment. Following treatment, TB rats that had been treated with rTNF ate significantly more and lost less weight than TB rats that had been treated with saline (P less than 0.00001). rTNF treatment of TB rats also demonstrated antineoplastic activity, as estimated tumor weight of tumors from rats treated with rTNF were significantly less than controls (P = 0.003). The anticachexia and antineoplastic effects of rTNF resulted in prolonged survival of TB rats treated with rTNF compared to control TB rats (P = 0.015). Experiment 2 utilized two different rTNF treatment regimens in TB rats: one group received 12 days of escalating doses of rTNF, and another group received 15 days of rTNF treatment. TB rats treated with rTNF again had a significantly greater food intake (P less than 0.00001) and delayed weight loss (P = 0.0001) posttreatment that was further augmented by additional doses of rTNF. Antineoplastic activity of rTNF was less clear, and overall tumor growth curves were not affected by rTNF treatment. Survival of TB rats treated with rTNF was again significantly increased in a dose-dependent manner (P = 0.006). Repeated administration of low doses of rTNF to TB rats induces mild reduction in tumor growth, tolerance to the cachectic effects of rTNF that results in tolerance to the cachectic effects of tumor, and prolongation of survival.

Animals↗

Relationships between weight change and blood lipids in men and women: 'the Adelaide 1000'.

Relationships between changes in weight and blood lipids were examined in 655 subjects who had enrolled for a fitness programme. At entry data were obtained on weight, fitness, lipids, physical activity, diet, and smoking. On re-examination 2 years later approximately half the sample had maintained stable weight (+/- 2 kg), a quarter had lost (- greater than 2 kg), and a quarter had gained weight (+ greater than 2 kg). Analyses of weight change/lipid change relationships included comparisons of lipid changes in weight 'stable', 'losers', and 'gainers' groups, and multiple regression analyses controlling for the effects of age, diet, and fitness. It was found that changes in weight and lipids were significantly related, the relationship was stronger than between any other independent variable and changes in lipids, and it was stronger for men than for women. It was concluded that there is an independent cause and effect relationship between weight and lipids to an extent useful for clinical and public health purposes.

Adult↗

Heme overload inhibits the growth of normal rats.

We have developed a model with which to evaluate the direct metabolic effect of circulating heme in chronic hemolytic diseases. Normal rats were injected with heme intraperitoneally (IP) using different treatment schedules and then killed so their growth parameters could be measured; heme injections were well tolerated, but final body weight was decreased in the heme treated groups. In one experiment, we used heme 40 mg/kg IP 2x/d for 8 d and found that overall growth was significantly inhibited (weight increment in the heme-treated group +45 +/- 3g vs +65 +/- 3g in the controls, P less than .05); although serum somatomedin activity was significantly diminished, the liver extract somatomedin activity was not decreased. In another experiment, we compared the effect of heme 40 mg/kg versus heme 80 mg/kg IP 2x/d for 5 d: growth inhibition was dose-dependent (weight change +31 +/- 2g for vehicle-treated group versus +12 +/- 3 grams for heme 40 mg/kg group versus -6 +/- 5 grams for heme 80 mg/kg group) and related to serum heme levels (3.53 +/- 0.47 mcM for vehicle group versus 5.42 +/- 0.71 mcM for heme 40 mg/kg versus 10.91 +/- 0.84 mcM for heme 80 mg/kg group). Our data demonstrate that IP heme administration is feasible and provides a valid approach with which to identify the potential direct metabolic consequences of abnormally circulating heme and its contribution to the growth retardation associated with chronic hemolytic diseases.

Anemia, Hemolytic↗

Clinical and nutritional consequences of lactose feeding during persistent postenteritis diarrhea.

In a double-blind prospective trial, 64 children, 3 to 36 months of age, who had diarrhea for at least 14 days were randomly assigned to receive either a milk-based diet containing 6 g/kg of body weight per day of lactose or the same diet in which the lactose was greater than 95% prehydrolyzed with beta-galactosidase. Clinical and nutritional outcomes were compared. The groups were similar at the start of the study. Four of 33 patients (12.1%) in the lactose group were considered to have treatment failure because of excessive purging with or without refusal to accept the diet, compared with 1 of 31 patients (3.2%) in the hydrolyzed lactose group (P = .20). Among successfully treated boys, fecal excretion was initially similar, but on days 3 to 5 of the trial the lactose group purged a mean 74.4 g/kg per day (95% confidence limits 17.8, 131.0) compared with 42.0 g/kg per day (95% confidence limits 11.4, 72.6) in the hydrolyzed lactose group (P less than .01). Diarrhea stopped within 30 hours of hospital admission in 11 children in the hydrolyzed lactose group (35.5%) compared with 1 child in the lactose group (3.3%) (P less than .001). Fecal excretion of carbohydrate, nitrogen, and energy was significantly greater in lactose group (P less than .01), but there were no significant differences in fat excretion or in incremental weight change during hospitalization. Feeding lactose-containing nonhuman milk as the sole nutrient source to children with persistent diarrhea resulted in substantially greater purging which was sufficiently severe to increase the risk of dehydration in these children.

Animals↗

Changes of organ indices of CBA/Ca inbred mice as function of age.

Weight changes of seven organs: brain, heart, lungs, liver, spleen, small intestine, and kidneys, were analyzed during aging of male CBA/Ca inbred mice. Data were collected as absolute organ weights, organ weights related to body, as well as brain weights. It was established that most organs increase their weight up to nearly two years of age, after which there is a dramatic decline. Body weight shows a distinct plateau or constancy along the lifespan of the animals; consequently, body weight seems to be generally the most favorable reference point to express some of the physiological changes and parameters of the aging organism. Variation coefficients of the organ weights generally become higher with age.

Aging↗

Freedom from fat: a contemporary multi-component weight loss program for the general population of obese adults.

This report summarizes results for the first 2,037 participants in the Freedom from Fat (FFF) weight loss program. FFF combined nutrition education, a low-fat dietary pattern, exercise, behavioral self-management, and social support in a program designed to serve the general population of overweight and obese adults. Participants ranged in age from 18 to 84 and from ideal weight to massively obese. After enrolling, program participants attended professionally led weekly meetings as long as they wished. Participants were encouraged to keep daily food diaries, to reduce the proportion of calories from fat to 30% or less, to exercise at moderate intensity for 30 minutes a day 5 days a week, to keep graphic records of weight change and exercise, and to display their graphs at each weekly group meeting. Attrition rates were comparatively low for a large-scale program, with half of the participants still active in the fifth month and 22% still active after 1 year. Mean weight loss for obese participants (BMI 30 or greater) at 6 months was 7.3 kg (16.2 lb) for men and 5.3 kg (11.6 lb) for women. The best predictors of weight loss at 6 months were number of days per week in which food diaries were kept, baseline body mass index, number of minutes of exercise per week, and age.

Adult↗

Long-term follow-up of weight status of subjects in a behavioral weight control program.

Few studies have examined the long-term effectiveness of behavioral weight control programs. Interpretation of the results from these studies has been limited due to small sample size, use of only one sex, and the number of evaluation parameters. A 2-year follow-up study was designed to assess the effectiveness of a behavioral weight control program on 123 obese male and 386 obese female subjects. Body weights were measured by dietitians at baseline and after an 8-week treatment program. Two-year follow-up weights were self-reported from a mailed questionnaire. The subjects' mean weight at baseline was 185.6 +/- 43.4 lb (no. = 509). Their mean percent over ideal body weight at baseline was 29.7%. Following an 8-week treatment period, mean weight was 176.4 +/- 41.3 lb (no. = 509), yielding a mean weight loss of 9.2 +/- 6.4 lb. Weight change after the 8-week treatment period ranged from a loss of 37 lb to a gain of 5 lb. The 2-year follow-up study showed that mean weight of the 498 subjects was 179.8 +/- 42.9 lb, yielding a mean weight loss of 5.8 +/- 15.5 lb. Weight change ranged from a loss of 71 lb to a gain of 47 lb. After 2 years, 325 subjects (65.3%) were still below their baseline weights, 182 subjects (36.6% of the entire study group) had maintained or enhanced the weight loss achieved during treatment, and 80 subjects (16.1%) weighed at least 10% less than their baseline weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

An analysis of genotype effects and their interactions by using the apolipoprotein E polymorphism and longitudinal data.

We investigate the interaction between the apolipoprotein E polymorphism and changes in weight and height as they affect the longitudinal profile of total cholesterol, triglyceride, beta lipoprotein, and glucose levels. Data were available on a sample of 466 individuals in 158 nuclear families from Nancy, France. Longitudinal data analyses were carried out on 128 unrelated adults and 56 unrelated children. We estimate the relative frequencies of the epsilon 2, epsilon 3, and epsilon 4 apolipoprotein E alleles in this population to be .120, .764, and .116, respectively. There is no significant evidence from these data that supports an effect of the apolipoprotein E polymorphism on the longitudinal profile of any of the variables considered. There is a significant interaction between the effects of this gene and weight change on the longitudinal change of serum triglyceride and beta lipoprotein levels in adults. In conjunction with weight gain, individuals with an epsilon 4 allele are expected to show a larger increase in triglyceride levels (0.15 +/- 0.03 mmol/L/kg) compared with individuals with no epsilon 4 allele. An increased production of very-low-density lipoprotein (VLDL) as one gains weight, along with retarded VLDL clearance attributable to the effects of the epsilon 4 allele, may account for this results. The significant interaction between the apolipoprotein E polymorphism and changes in weight on the longitudinal change in triglyceride levels corroborates epidemiological studies reporting that the epsilon 4 allele increases the risk of hypertriglyceridemia among obese individuals.

Apolipoproteins E↗

The effects of a new beta-adrenoceptor agonist BRL 26830A in refractory obesity.

Beta-adrenoceptor agonists have recently been shown to promote substantial loss of adipose tissue in laboratory animals. One of these BRL, 26830A, increases thermogenesis in human volunteers and has been shown to enhance the rate of weight reduction in patients adhering to a strict reducing regimen. Forty-three post-menopausal or sterilized female subjects suffering from refractory obesity participated in a double-blind placebo-controlled study, the treatment group receiving BRL 26830A 50 mg qid. Two subjects were withdrawn because they developed an unpleasant sensation of tremor and in all, 17 of the 20 who received BRL 26830A mentioned this side effect. There was no change in erect or supine blood pressure or in resting heart rate. There was no significant difference in weight change during the 6-week study. It is concluded that BRL 26830A does not appear to promote weight reduction in subjects unable to adhere strictly to their dietary regime.

Adrenergic beta-Agonists↗

Dietary habits, weight history, and vitamin supplement use in elderly osteoarthritis patients.

Osteoarthritis is a chronic disabling disease in the elderly, but few studies have examined nutritional parameters of osteoarthritis patients. For 82 ambulatory elderly osteoarthritis patients, a registered dietitian assessed the following: consumption of 72 food items, using a food-frequency questionnaire; weight history, by measuring current weight and asking the weight at age 20, maximum adult weight, and minimum adult weight; dietary habits; and vitamin supplement consumption. Joint pain and activities of daily living (ADL) were assessed by a physician. On the basis of the Four Food Group guidelines, dietary intakes were suboptimal in the dairy and grain groups, which are important sources of calcium, vitamin D, thiamin, iron, and riboflavin. Eighty percent of the sample were obese (BMI greater than or equal to 27). The average weight change since early adulthood was a gain of 59 lb. Current joint pain and ADL restrictions were not related to obesity or weight gain. Vitamin/mineral supplements were consumed by 37% of the sample.

Activities of Daily Living↗

Mechanisms from models--actual effects from real life: the zero-calorie drink-break option.

Animal and human laboratory models show that the suppression of appetite by a modest amount of readily assimilable energy, such as a caloric sweetener, is not likely to last longer than an hour. The transience of their satiating effect constitutes a mechanism whereby the sugars, starch, alcohol and fats in drinks and the snackfoods eaten with them could add to energy intake which is subsequently uncompensated and so contributes to weight gain. Conversely, if those in the habit of consuming such energy-containing drinks and accompaniments avoided such items or replaced them by low-calorie substitutes, this might help in weight reduction and even perhaps in prevention of obesity. The effectiveness of this "zero-calorie drink-break option" can be tested by correlating separately reported real-life eating habits and weight changes across people whose circumstances are similar. The existing field data indicate that the fatter a person is the more likely they are to use the conventional undifferentiated sugar-substitution strategies and also that these usually do not help weight reduction.

Appetite↗

Weight maintenance in pediatric burned patients.

Weight change, defined as the difference between the preadmission and discharge weights, has often been used as an indicator of the adequacy of nutrition support. Weight change has been found to be uninterpretable in burned patients because excision and grafting contribute to weight loss but do not reflect systemic physiology. Also, normal growth during hospitalization contributes to weight gain but is not included in traditional methods of assessing weight change of children. We examined weight change corrected for escharectomies and growth in 42 adult and pediatric burned patients. Thirty-five of the patients had weight loss within 10% of their premorbid weight. Moreover, weight loss was correlated with three observable patient characteristics: age, percent initial burn size, and preburn weight. It was concluded that the dietary regimen of providing twice the predicted basal metabolic rate in terms of calories, based on ideal body weight, was adequate to prevent significant weight loss in most patients but that further refinement is necessary to improve individual reliability. Furthermore, significant weight losses may not affect morbidity/mortality as previously thought.

Adolescent↗

[Relations between weight changes and various biological parameters. Results of a longitudinal epidemiological survey].

Weight changes over a three year period were measured on a group of about 1400 working men aged 46 to 52 years and related to several biological parameters (cholesterolemia, triglyceridemia, uricemia, glycemia and blood pressure). We observed: a) a slight increase in mean weight over the three year period; b) significant correlations between weight change and changes in these biological parameters. These results are compared to those found in cross sectional studies. Their implications for public health and prevention of ischemic heart disease are discussed.

Blood Glucose↗

Some effects of uninfected laboratory-reared tsetses (Glossina morsitans morsitans westw.) (diptera: glossinidae) on host-rabbits.

Rabbits (Flemish giant x French lop-eared) exposed to 300 to 500 tsetses (Glossina morsitans morsitans Westw.) a day, 2 or 3 days a week, did not show significant differences from littermates receiving no exposure, with respect to weight changes, haematocrits, red and white blood cell counts or whole blood clotting times. In other rabbits, the same daily exposure, 6 days a week, resulted in sharp decreases in haematocrit levels and in some, changes in weights, but no change in citrated plasma thrombin times. Rabbit haematocrit levels correlated negatively with estimated weekly blood loss. Weights and haematocrits of most rabbits exposed to 1,200 to 1,500 flies on a single occasion were not affected. However, following heavy exposure, ears were cold and blood letting difficult, indicating the possibility of arteriolar vasoconstriction.

Animals↗

Effects of social and environmental change on institutionalized mentally retarded persons: the relocation syndrome reconsidered.

The "relocation syndrome" in multiply-handicapped, institutionalized mentally retarded residents was examined in an observational study. Weight change and the initiation and duration of constructive and nonconstructive behavior was observed, as well as resident-staff interactions before and after relocation to a new living unit. The hypothesis that there would be an increase in behavior deleterious to the health of clients after relocation, when compared to two premove baseline periods of crowding, was not totally supported. Although relocation did cause significant changes in a variety of behaviors, not all were deleterious (i.e., no mortalities, weight gains). Results were discussed in terms of a social-situational model.

Adolescent↗

Ingestive behavior and composition of weight change during cyproheptadine administration.

The effect of cyproheptadine on spontaneous energy intake was studied by means of an automated (liquid diet) food-dispensing apparatus in two nonobese adults confined to a metabolic ward. The experimental design included both single and double-blind periods. Throughout, the composition of daily weight change was determined by the energy-nitrogen balance method. While on cyproheptadine, both subjects exhibited increases in energy intake with the following average composition of weight gain: protein 16%, fat 14% and water 70% (first subject), and protein 5%, fat 49% and water 46% (second subject). The cyproheptadine-induced increase in energy intake was statistically significant in one of the subjects, who was at his desirable weight level at the outset. The other subject was underweight initially and tended to gain throughout the experiment, although rate of weight gain appeared to be more rapid during the periods of cyproheptadine administration. Energy output in both subjects remained fairly constant throughout. We conclude that cyproheptadine induces weight gain of 'normal' composition by stimulating increased energy intake.

Adult↗

Plasma corticosterone level of rats after bilateral lesion of the globus pallidus and elimination of the sex-dependence of the body weight loss following pallidal lesion by bilateral adrenalectomy.

Plasma corticosterone (CST) level and body weight were studied in male and female rats after bilateral pallidal lesion (GPL). The effect of high dose of glycocorticoids on body weight of food and water deprived, non-lesioned rats was also studied since high CST levels due to the stress caused by the aphagia and adipsia could be anticipated. Weight changes in lesioned-adrenalectomized animals were in investigated as well. A weight loss, higher in males than females, developed after the pallidal lesion and the CST level was higher in lesioned females than in lesioned males. This sex-difference was present in non-lesioned, food and water deprived animals as well. The weight loss was higher in lesioned males than in food and water deprived male/female controls. Adrenalectomy eliminated weight loss differences between the sexes after lesion, by reducing the weight loss in males. CST administration reduced body weight loss in food and water deprived males but not in familes, and cortisol facilitated it in both sexes.

Adrenal Cortex↗

The perinatal rat: body weight, hematocrit and regional changes in heart weight and lactate dehydrogenase isozyme composition and activity.

Body weight (BW), hematocrit (Hct), heart weight (HW) and cardiac lactate dehydrogenase (LDH) activity and isozyme pattern were studied in the perinatal rat. BW increased linearly, from 5 days before birth till 10 days after birth, while Hct increased from 30 to 34% within 1 day of birth. HW increased in step with BW. However, the relative contribution to total HW of right ventricle (RV), interventricular septum (S) and atria declined relative to the left ventricle free wall (LVW) beginning 2 to 3 days before birth. RV/LVW declined steadily throughout the study period. LDH specific activity in LVW, RV, S and atria increased greatly prior to birth and less so afterwards, with atria showing the lowest values throughout the study. Total LDH activity in each portion of the heart paralleled the respective regional weight changes. LDH isozyme composition (percent M subunit) declined at the time of birth in LVW, RV and S from 63 to 43%; change in atrial M subunit was smaller. The change in LDH isozyme composition could be accounted for in LVW, RV and S by increasing H subunit activity alone. In atria, both M and H subunit activity increased.

Animals↗