Influence of methylphenidate on eating in obese men

OBJECTIVE: Rapid synaptic dopamine transport or reduced brain dopamine receptor signaling may influence energy intake. Methylphenidate, a dopamine reuptake inhibitor, increases brain synaptic dopamine and produces anorexia, suggesting that it may reduce energy intake. We investigated the effects of two doses of short-acting methylphenidate on energy intake over one meal in obese adult males. RESEARCH METHODS AND PROCEDURES: Nine obese males (>85th BMI percentile) ingested a placebo or a moderate dose (0.5 mg/kg) or a high dose (1.0 mg/kg) of methylphenidate in a within-subject double-blind acute laboratory study. One hour after ingestion, pizza consumption was measured in a naturalistic laboratory setting. RESULTS: Participants reduced energy intake by 23% for the moderate dose vs. the placebo (p < 0.02), but there was no significant difference for the high dose vs. the moderate dose (p > 0.05). Participants consumed 34% fewer kilocalories after ingesting the lowest effective dose of methylphenidate compared with placebo (725.7 +/- 404.5 vs.1095 +/- 271.1 kcal, p < 0.01). Seven of nine subjects responded to the moderate dose. The increase in perceived drug effect above placebo was correlated with the reduction in energy intake for both the moderate (r = -0.85, p = 0.004) and the high (r = -0.75 p = 0.021) doses. Hunger scores were not different across drug doses or placebo before drug administration. DISCUSSION: Methylphenidate reduced energy intake of a highly palatable food over one meal by one-third in obese adult males. Dopamine transport inhibition may be an effective component of a comprehensive treatment for obesity.     

Timed flat infusion of 5-fluorouracil increases the tolerability of 5-fluorouracil/docetaxel regimen in metastatic breast cancer: a dose-finding study

A dose-finding study was undertaken to determine the maximum-tolerated dose, and the recommended dose of docetaxel in combination with 12-h timed (22:00-10:00) flat infusion of 5-fluorouracil (5-FU) in metastatic breast cancer patients. This schedule seems to reduce the occurrence of stomatitis of the docetaxel and infusional 5-FU regimen.     

Linear relationship between Wnt activity levels and apoptosis in colorectal carcinoma cells exposed to butyrate

We have reported that butyrate, a fatty acid produced by dietary fiber that induces cell cycle arrest, differentiation and/or apoptosis in colorectal carcinoma (CRC) cells in vitro, modulates Wnt activity in 2 CRC cell lines (Bordonaro et al., Int. J. Cancer, 2002; 97:42-51). Our study determines how changes in the levels of Wnt activity induced by butyrate relate to the effects of butyrate on apoptosis, cell cycle arrest and differentiation of CRC cells. In 10 human CRC cell lines a direct relationship was shown between apoptosis and butyrate-induced increase in Wnt activity, as well as between suppressed clonal growth and increased Wnt activity. No correlation existed between butyrate-induced increase in Wnt activity and differentiation. The direct relationship between apoptosis and Wnt activity was supported by analyses of DLD-1 and HCT-116 cells expressing a dominant negative form of Tcf4, and therefore, with repressed Wnt activity, as well as by measuring the ratio of apoptotic to live cells in flow cytometry-sorted cell fractions with high and low Wnt activity. Novel flow cytometric methodology was utilized to show that butyrate differentially increases the number of cells with Wnt activity in different CRC cell lines. Thus, CRC cell lines in which butyrate upregulated Wnt activity to relatively high levels were most susceptible to the apoptotic effects of butyrate, whereas cell lines in which butyrate modestly modulated Wnt activity were less affected.     

Seasonal pattern of onset in lymphocytic colitis

BACKGROUND: The etiology of lymphocytic colitis, a microscopic colitis syndrome, has remained elusive. Because 1) many infectious enteritides exhibit seasonal variability in incidence and 2) a few investigators have proposed some infectious mechanism in lymphocytic colitis, our aim was to determine if any variability in symptom onset existed among lymphocytic colitis patients diagnosed at our institution. STUDY: We identified 71 nonduplicated, consecutive patients with lymphocytic colitis over a 4-year period using rigorous clinicopathologic inclusion criteria: 1) chronic watery diarrhea, 2) endoscopically normal colon, 3) no evidence for celiac sprue or drug-induced colitis, 4) diffuse colitis with increased intraepithelial lymphocytes of at least 10 lymphocytes per 100 epithelial cells, 5) evidence of surface epithelial damage, and 6) no significant neutrophilic infiltrates, architectural distortion of the mucosa, or subepithelial collagen deposits. The date of diagnosis was corrected for month of onset of symptoms. RESULTS: The distribution of month of onset of symptoms showed a statistically significant (chi test of homogeneity, P = 0.0008) temporal variability and seasonal incidence pattern with excess cases during summer and fall and a paucity of cases during colder months. CONCLUSIONS: To our knowledge, this is the first study to examine systematically and report a significant seasonal incidence pattern of lymphocytic colitis. Our observations may support a potential link to an infectious source in lymphocytic colitis.     

The challenge of identifying behavioral alternatives to food: clinic and field studies

Background: One of the basic principles of behavioral economics interventions is identification of alternative behaviors to compete with the reinforcing value of a highly rewarding commodity.Purpose: Two experiments that attempt to increase alternatives to eating in obese youth are presented.Methods: A randomized, controlled trial was used in Study 1 to compare a comprehensive family-based behavioral treatment program or an experimental treatment that incorporated reinforcing children for engaging in alternative behaviors to eating for 41 overweight 8-to 12-year-old children. Study 2 used a within-subject design with baseline, enriched environment and a second baseline phase to determine the influence of providing activities that compete with eating for 13 overweight 8-to 12-year-old children. Measurements included body mass index (BMI) change, alternatives to eating, eating, and physical activity.Results: In Study I both treatments were associated with significant (p < .05) and maintained reductions in z-BMI over the 24 months of observation. The experimental group showed a significantly (p < .05) greater increase in alternatives to eating, and both groups showed significant (p < .05) increases in physical activity. In Study 2 alternative behaviors to eating were increased by almost I hr/day (p < .001) but were not associated with significant changes in energy intake or physical activity.Conclusion: These results suggest that using the methods studied, increasing behaviors that could compete with eating did not influence relative weight in a clinical outcome study or energy intake in a controlled field study. Dr. Richard Stein is now at the Center for Human Nutrition, Washington University School of Medicine. Dr. Leonard Epstein is a consultant to Kraft Foods. This research was supported in part by grant HD 39792 awarded to Leonard Epstein. Appreciation is expressed to Rekha Trivakram for coordinating the implementation of Experiment 2.