A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.
The use of megestrol acetate in the treatment of weight loss in gastrointestinal cancer patients has been disappointing. The aim of the present study was to compare the combination of megestrol acetate and placebo with megestrol acetate and ibuprofen in the treatment of weight loss in such patients. At baseline, 4-6 weeks and 12 weeks, patients underwent measurements of anthropometry, concentrations of albumin and C-reactive protein and assessment of appetite, performance status and quality of life using EuroQol-EQ-5D and EORTC QLQ-C30. Thirty-eight and 35 patients (median weight loss 18%) were randomized to megestrol acetate/placebo or megestrol acetate/ibuprofen, respectively, for 12 weeks. Forty-six (63%) of patients failed to complete the 12-week assessment. Of those evaluable at 12 weeks, there was a decrease in weight (median 2.8 kg) in the megestrol acetate/placebo group compared with an increase (median 2.3 kg) in the megestrol acetate/ibuprofen group (P<0.001). There was also an improvement in the EuroQol-EQ-5D quality of life scores of the latter group (P<0.05). The combination of megestrol acetate/ibuprofen appeared to reverse weight loss and appeared to improve quality of life in patients with advanced gastrointestinal cancer. Further trials of this novel regimen in weight-losing patients with hormone-insensitive cancers are warranted. (+info)
The influence of NO synthase inhibitor and free oxygen radicals scavenger--methylene blue--on streptozotocin-induced diabetes in rats.
The excessive production of nitric oxide (NO) and the subsequent increase of local oxidative stress is suggested as one of the pathophysiological mechanisms of streptozotocin-induced diabetes. It was reported that the administration of NO synthase inhibitors partially attenuated the development of streptozotocin-induced diabetes and reduced hyperglycaemia. Here we have studied the influence of methylene blue, which combines the properties of NO synthase inhibitor with antioxidant effects. The experiments were performed on male rats divided into four groups: control, diabetic (single dose of 70 mg of streptozotocin/kg i.p.), methylene blue (50 mg/kg in the food) and diabetic simultaneously fed with methylene blue. After 45 days the experiments were discontinued by decapitation. Serum glycaemia, glycated haemoglobin and oxidative stress parameters (plasma malondialdehyde concentration and erythrocyte superoxide dismutase activity) were significantly higher in the diabetic group. Simultaneous methylene blue administration partially reduced glycaemia and glycated haemoglobin, but did not decrease oxidative stress. We conclude that NO synthase inhibitor methylene blue partially attenuates the development of streptozotocin-induced diabetes in male rats, but does not reduce the development of oxidative stress in the diabetic group. (+info)
Prizes for weight loss.
A programme of weight loss competitions and associated activities in Tonga, intended to combat obesity and the noncommunicable diseases linked to it, has popular support and the potential to effect significant improvements in health. (+info)
Burden of infection on growth failure.
The high prevalence of infections among children living in poor areas of developing countries impairs linear growth in these populations. Acute, invasive infections, which provoke a systemic response (e.g., dysentery and pneumonia), and chronic infections, which affect the host over a sustained period (e.g., gut helminth infections), have a substantial effect on linear growth. Such infections can diminish linear growth by affecting nutritional status. This occurs because infections may decrease food intake, impair nutrient absorption, cause direct nutrient losses, increase metabolic requirements or catabolic losses of nutrients and, possibly, impair transport of nutrients to target tissues. In addition, induction of the acute phase response and production of proinflammatory cytokines may directly affect the process of bone remodeling that is required for long bone growth. Infection of cells directly involved in bone remodeling (osteoclasts or osteoblasts) by specific viruses may also directly affect linear growth. Many interventions are possible to diminish the effect of infection on growth. Prevention of disease through sanitation, vector control, promotion of breast-feeding and vaccination is crucial. Appropriate treatment of infections (e.g., antibiotics for pneumonia) as well as supportive nutritional therapy (again including breast-feeding) during and after recovery, is also important. Targeted therapeutic interventions to decrease the prevalence of gut helminth infections may also be appropriate in areas in which such infections are widespread. Such interventions are of public health benefit not only because they reduce the incidence or severity of infections, but also because they decrease the long-term detrimental effect of malnutrition on populations. (+info)
Report of a National Institutes of Health--Centers for Disease Control and Prevention workshop on the feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons.
A workshop was convened in 1997 by the National Institutes of Health and the Centers for Disease Control and Prevention to consider the need for and feasibility of conducting a randomized clinical trial to estimate the long-term health effects of intentional weight loss in obese persons. Although the benefits of weight loss in obese individuals may seem obvious, little information is available showing that intentional weight loss improves long-term health outcomes. Observational studies may be unable to provide convincing answers about the magnitude and direction of the health effects of intentional weight loss. Workshop participants agreed that a well-designed randomized clinical trial could answer several questions necessary for developing a rational clinical and public health policy for treating obesity. Such information will ultimately provide needed guidance on the risks and benefits of weight loss to health care providers and payers, as well as to millions of obese Americans. (+info)
Alterations of lipid and cholesterol metabolism in cachectic tumor-bearing rats are prevented by insulin.
The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressive body weight loss, associated with reduced food intake, and protein and lipid hypercatabolism. Because insulin regulates glucose as well as lipid and protein metabolism, we suggest that the observed alterations are at least in part secondary to hypoinsulinemia and/or to the increase of counterregulatory hormones in AH130-bearing rats. To verify this hypothesis, controls with free access to food (n = 4), controls with free access to food plus insulin (107 micromol. kg body wt-1. d-1) (n = 4), controls pair-fed to the tumor-bearing rats (n = 4), pair-fed controls treated with insulin (n= 4), tumor hosts (n = 9), and tumor hosts treated with insulin (n = 6) were used. The Yoshida ascites hepatoma cells ( approximately 10(8) cells/rat) were inoculated intraperitoneally. Daily food intake and body weight were measured; insulin was injected starting the day of tumor implantation for 6 d. The metabolism of both cholesterol and lipids was investigated in tumor cells, and ascitic fluid and blood serum were investigated at the end of treatment. Insulin prevented the reduction of food intake (19 +/- 0.6 vs. 13 +/- 0.4 g/d, P < 0.01; AH130 hosts treated and not treated with insulin, respectively), the loss of body weight (202 +/- 12 vs. 135 +/- 9 g, P < 0.01), lowered the circulating triglycerides (48.3 +/- 4.9 vs. 84.5 +/- 7.1 mmol/L, P < 0.01), and free fatty acids (561 +/- 47 vs. 989 +/- 54 mmol/L (P < 0.01), while corrected the decrease of adipose lipoprotein lipase activity (1,240 +/- vs. 300 +/- pmol FA, P < 0.01) observed in AH130 hosts. Moreover, insulin prevented the decrease in HDL cholesterol (13.2 +/- 0.8 vs. 9.3. +/- 0.7 mmol/L, P < 0.01) and significantly increased hepatic cholesterol synthesis as evaluated by 14C-acetate incorporation into cholesterol, in both liver (3,337 +/- 245 vs. 830 +/- 115 Bq/g, P < 0.01) and AH130 cells (11,676 +/- 1,693 vs. 4,196 +/- 527 Bq/10(6) cells, P < 0.01). Thus insulin treatment ameliorated many metabolic derangements, with a lengthening of rats survival time (7 +/- 1 vs. 11 +/- 1 d, P < 0.05) without significantly stimulating tumor growth. These data, together with our previous observations on the effectiveness of insulin on protein turnover perturbations, suggest that many metabolic alterations occurring during cancer cachexia can be avoided by the administration of this hormone. (+info)
Prospective study of intentional weight loss and mortality in overweight white men aged 40-64 years.
Although 25% of US men indicate that they are trying to lose weight, the association between intentional weight loss and longevity in men is unknown. The authors analyzed prospective data from 49,337 overweight (initial body mass index > or =27) white men aged 40-64 years who, in 1959-1960, answered questions on weight change direction, amount, time interval, and intent. Vital status was determined in 1972. Proportional hazards regression estimated mortality rate ratios for men who intentionally lost weight compared with men with no weight change. Analyses were stratified by health status and adjusted for age, initial body mass index, smoking status, alcohol intake, education, physical activity, health history, and physical symptoms. Among men with no reported health conditions (n = 36,280), intentional weight loss was not associated with total, cardiovascular (CVD), or cancer mortality, but diabetes-associated mortality was increased 48% (95% confidence interval (CI) -7% to +133%) among those who lost 20 pounds (9.1 kg) or more; this increase was largely related to non-CVD mortality. Among men with reported health conditions (n = 13,057), intentional weight loss had no association with total or CVD mortality, but cancer mortality increased 25% (95% confidence interval -4% to +63%) among those who lost 20 pounds or more. Diabetes-associated mortality was reduced 32% (95% confidence interval -52% to -5%) among those who lost less than 20 pounds and 36% (95% confidence interval -49% to -20%) among those who lost more than 20 pounds. These results and those from our earlier study in women (Williamson et al., Am J Epidemiol 1995;141:1128-41) suggest that intentional weight loss may reduce the risk of dying from diabetes, but not from CVD. In observational studies, however, it is difficult to separate intentional weight loss from unintentional weight loss due to undiagnosed, underlying disease. Well-designed observational studies, as well as randomized controlled trials, are needed to determine whether intentional weight loss reduces CVD mortality. (+info)
Prospective study of intentionality of weight loss and mortality in older women: the Iowa Women's Health Study.
Several epidemiologic investigations have suggested that weight loss is associated with increased mortality risk but have not examined whether the weight loss was intentional or unintentional. The authors examined whether the association between weight loss and mortality differs by whether the weight loss was intentional or unintentional as part of the Iowa Women's Health Study, a prospective cohort study of health risk factors in postmenopausal women. Women aged 55-69 years completed questions about intentional and unintentional weight losses since age 18 years via mail survey in 1992 and were followed through 1995. One or more intentional weight loss episodes of 20 or more pounds (> or =9.1 kg) during adulthood was not significantly associated with higher total or cardiovascular disease mortality risk compared with never losing > or =20 pounds. One or more unintentional weight loss episodes of 20 or more pounds was associated with a 26-57% higher total mortality risk and a 51-114% higher cardiovascular disease mortality risk, compared with never losing 20 or more pounds. Associations between unintentional weight loss and increased mortality risk were confined mostly to women with prevalent disease, hypertension, or diabetes. Patterns of association did not vary by overweight status. These findings suggest that the association between weight loss and increased mortality risk observed in epidemiologic studies may be due to unintentional weight loss that reflects existing disease and not due to intentional weight loss. (+info)