The relationship of cancer symptom clusters to depressive affect in the initial phase of palliative radiation.

Research on comorbidity across cancer symptoms, including pain, fatigue, and depression, could suggest if crossover effects from symptom-specific interventions are plausible. Secondary analyses were conducted on a survey of 268 cancer patients with recurrent disease from a northeastern U.S. city who were initiating palliative radiation for bone pain. Moderator regression analyses predicted variation in depressive affect that could be attributed to symptom clusters. Patients self-reported difficulty controlling each physical symptom over the past month on a Likert scale and depressive symptoms on a validated depression measure (Center for Epidemiologic Studies-Depression [CES-D]) over the past week on a four-category scale. An index of depressive affect was based on items of negative and positive affect from the CES-D. In predicting depressive affect, synergistic interactions of pain with fever, fatigue, and weight loss suggest separate pathways involving pain. A similar interaction with fever occurs when nausea was tested in place of pain. Further, the interaction between pain and fatigue is similar in form to the interaction between difficulty breathing and fatigue (when sleep is not a problem). Follow-up to the latter interaction reveals: 1) additional moderation by hypertension and palliative radiation to the hip/pelvis; and 2) a similar cluster not involving hypertension when appetite problems and weight loss were tested in place of fatigue. The significance and form of these interactions are remarkably consistent. Similar sickness mechanisms could be generating: 1) pain and nausea during fever; 2) pain and fatigue during weight loss; and 3) pain and breathing difficulty when fatigue is pronounced. Crossover effects from symptom-specific interventions appear promising.

Rats fed only during the light period are resistant to stress-induced weight loss.

Repeated restraint stress (3 h/day for 3 days) causes a chronic down-regulation of body weight in rats. This study determined whether weight loss was influenced by the time of day that rats had access to food or that stress was applied. Groups of male Sprague-Dawley rats were fed a 40% kcal fat diet with food given ad libitum, only during the light phase or only during the dark phase. After 2 weeks of adaptation, rats within each feeding treatment were divided into four groups. One was exposed to repeated restraint at the start of the light phase, another was restrained at the start of the dark phase and the remaining groups were nonstressed controls for restrained rats. Body weight was significantly reduced in ad libitum- and dark-fed restrained rats, compared with nonstressed controls, from Day 2 of restraint, regardless of the time of day that they were stressed. There was no significant effect of restraint on weight change of light-fed rats. Food intake was inhibited by stress in ad libitum- and dark-fed rats, but it was not changed in light-fed rats. Serum corticosterone was increased by restraint in all rats irrespective of feeding schedule. This study demonstrates that stress-induced weight loss only occurs when rats have food available during their normal feeding period (dark phase) and is not determined by increased corticosterone release.

Voluntary Weight Reduction in Older Men Increases Hip Bone Loss: The MrOS Study.

To test the hypothesis that weight loss in older men is associated with increased rates of hip bone loss irrespective of adiposity and intention to lose weight, we measured body weight, body composition, hip bone mineral density (BMD) and intention to lose weight in a cohort of 1,342 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study and followed them prospectively for an average of 1.8 yr for changes in weight and BMD. The adjusted average rate of change in total hip BMD was 0.1% per year in men with weight gain, -0.3% per year in men with stable weight and -1.4% per year in men with weight loss (P for trend < 0.001). Higher rates of hip bone loss were observed in men with weight loss irrespective of category of body mass index, body composition, or intention to lose weight. Even among obese (body mass index >/= 30kg/m(2)) men trying to lose weight, those with documented voluntary weight reduction experienced an increase in hip bone loss (average rate of change in total hip BMD 0.5% per year in those with weight gain, -0.1% per year in those with stable weight and -1.7% per year in those with weight loss, P for trend < 0.001). Older men who experience weight loss have increased rates of hip bone loss, even among overweight and obese men undergoing voluntary weight reduction.

Actions of immunosuppressor drugs on the development of an experimental ovarian tumor.

Immunosuppression has been related to the incidence of tumor apparition, including endocrine tumors. The intrasplenic ovarian tumor (luteoma) is a typical benign endocrine tumor that develops under high gonadotropin stimulation and, from the immunological perspective, is located in a critical organ involved in immune response. To establish if immunosuppression could alter the development of this experimental tumor, the effects of cyclosporin A (CsA) and dexamethasone (Dex) were evaluated. After surgery, tumor-bearing and sham animals were kept without treatment for 4 weeks; thereafter, they were distributed into CsA (25 mg/kg), Dex (0.1 mg/kg), or vehicle (75:25 castor oil:ethanol) groups and were injected on alternate days for 50 days. Body weight was evaluated weekly. Animals were sacrificed after a jugular vein blood sample was obtained. Thymi were weighed. Tumors were measured and placed in formaline for histological studies. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin (PRL), and estradiol were measured by radioimmunoassay. Hematological parameters were determined. CsA induced a significant decrease in survival rates both in tumor-bearing and sham animals (P < 0.01). Dex significantly impaired weight increase in both groups of animals. CsA induced a significant weight loss in sham animals, not observed in tumor-bearing animals. Dex induced thymus weight loss in both groups, whereas CsA induced thymus weight loss only in sham animals. Only Dex induced a decrease in lymphocyte number in both groups. CsA induced an increase in monocyte number only in sham animals. Treatments did not alter LH, FSH, or estradiol, whereas PRL was increased by CsA only in sham rats. Neither Dex nor CsA induced any significant variations in tumor volume, nor did they alter tumor histology. In addition, no visible metastases or alterations in other organs were observed. We conclude that, though immunological parameters were altered by the treatments, immunosuppressor drugs did not condition tumor development. In addition, tumors secrete one or more factor/s that counteract CsA effect.

Adiponectin before and after weight loss in obese children.

Adiponectin is decreased in obesity and seems to be involved in insulin resistance. The influences of age, gender, puberty, and weight loss on adiponectin have not been studied in obese children. We measured body fat mass based on skinfold thickness, age, pubertal stage, gender, adiponectin, and insulin resistance (homeostasis model assessment) in 42 obese children. We analyzed adiponectin and homeostasis model assessment 1 yr later in these obese children and separated them into two groups according to degree of weight loss (decrease in sd score for body mass index, >or=0.5 vs. <0.5). Adiponectin was negatively correlated to percentage body fat (r = -0.44; P = 0.002), insulin resistance (r = -0.33; P = 0.016), and age (r = -0.41; P = 0.003). Adiponectin levels were significantly (P = 0.017) higher in pubertal girls compared with boys, but there was no significant difference in prepubertal children in respect to gender (P = 0.833). Adiponectin was significantly (P < 0.001) lower in pubertal compared with prepubertal children. The significant weight loss in 16 children was associated with a significant increase in adiponectin (P = 0.010) and a decrease in insulin resistance (P = 0.013), whereas there were no changes in the 26 children without significant weight loss. Adiponectin levels in obese children were negatively correlated to age, body fat, and insulin resistance and were decreased in puberty. Significant weight loss led to an increase in adiponectin levels and an improvement of insulin resistance.

Energy and substrate metabolism in patients with chronic extensive graft-versus-host disease.

BACKGROUND: Allogeneic stem cell transplantation is frequently complicated by graft-versus-host disease (GVHD). weight loss is one of the characteristic features of GVHD. The etiology of weight loss in GVHD is not completely understood. METHODS: We measured resting energy expenditure (REE) and substrate oxidation rates by indirect calorimetry in patients with stable chronic extensive GVHD under immunosuppressive therapy (n=13) and sex-, age-, height-, and weight-matched healthy controls (n=13) in order to evaluate metabolic changes in these patients. Measurements were done on day 518+/-261 after allogeneic stem cell transplantation in the postabsorptive state. Serum concentrations of glucagon, norepinephrine, tumor necrosis factor-alpha, interleukin-6, and free fatty acids were determined. RESULTS: Patients showed a maximum weight loss of 22% during their course of GVHD; nevertheless, they regained 15% of total body weight (TBW) during successful treatment of GVHD. Indirect calorimetry showed an increase in REE per kilogram of TBW (patients, 21.8+/-3.1 kcal/kg TBW/day; controls, 19.9+/-2 kcal/kg TBW/day; P<0.05). Respiratory quotient (patients, 0.79+/-0.04, controls, 0.86+/-0.04; P<0.005) and non-protein respiratory quotient (0.78+/-0.05 and 0.87+/-0.05, respectively; P<0.005) were decreased in patients. GVHD patients had elevated serum glucagon and norepinephrine concentrations, whereas tumor necrosis factor-alpha and interleukin-6 were in the normal range. CONCLUSIONS: Patients with chronic extensive GVHD show an increase in REE and alterations in fat and carbohydrate oxidation rates. These changes seem to be the result of increased action of glucagon and norepinephrine.

Calorie intake and meal patterns up to 4 years after Roux-en-Y gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is the most popular surgical treatment for morbid obesity in the U.S.A., producing significant and durable weight loss with improvement in co-morbidities. Although a greater number of patients are undergoing surgical treatment for obesity, little data are available regarding their food intake after surgery. This study was undertaken to evaluate the caloric amount, nutrient composition and meal patterns of patients 18 months to 4 years after RYGBP. Ethnic differences in food intake were also investigated. METHODS: Questionnaires were mailed to 360 patients who had undergone RYGBP at least 18 months prior to the onset of the study. RESULTS: Data were available from 69 patients, 52% Caucasian, 25% African-American, 23% Hispanic. 30 months after surgery, the average daily calorie intake was 1733 +/- 630 kcal (n=68, range 624-3486 kcal), with 44% of calories from carbohydrates, 22% from protein and 33% from fat. Sugar-sweetened beverages represented 7% of total caloric intake. Patients consumed 3 meals and 3 snacks per day on average. Food intake from dinner and an evening snack represented 40% of the daily caloric intake. Snacks accounted for 37% of the daily intake. Percent excess weight loss (%EWL) was 58 +/- 17% and was not different among ethnic groups. However, Hispanics reported consuming fewer snacks and fewer calories. %EWL correlated with the total daily caloric intake (r= .446, P <0.001). Follow-up attendance was 54% at 1 year after surgery but fell to 10% at 3 years. Only 77% of patients were taking vitamin supplements. CONCLUSION: RYGBP resulted in significant weight loss. Caloric intake was quite variable. Long-term follow-up remained low, putting patients at risk for metabolic and vitamin deficiencies. The relationship between caloric intake and long-term weight changes remains to be studied.

Weight Loss reduces tissue factor in morbidly obese patients.

OBJECTIVE: To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome. RESEARCH METHODS AND PROCEDURES: Thirty-seven morbidly obese patients (4 men; BMI, 48 +/- 7 kg/m(2); range, 42 to 53 kg/m(2)), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 +/- 5 months postoperatively. RESULTS: weight loss significantly reduced circulating plasma TF (314 +/- 181 vs. 235 +/- 113 pg/mL, p = 0.04), coagulation factor VII (130 +/- 22% vs. 113 +/- 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 +/- 3.4 vs. 1.14 +/- 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 +/- 141.6 vs. 176.2 +/- 58.2, p < 0.001) and TF decrease after gastroplasty (DeltaTF: 164.7 +/- 51.4 vs. -81 +/- 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance. DISCUSSION: Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.