Effects on tumor development and metastatic dissemination by the NKG2D lymphocyte receptor expressed on cancer cells.

The stimulatory NKG2D lymphocyte receptor together with its tumor-associated ligands enable the immune system to recognize and destroy cancer cells. However, with dynamic changes unfolding, cancers exploit NKG2D and its ligands for immune evasion and suppression. Recent findings have added yet another functional dimension, wherein cancer cells themselves co-opt NKG2D for their own benefit to complement the presence of its ligands for self-stimulation of parameters of tumorigenesis. Those findings are here extended to in vivo tumorigenicity testing by employing orthotopic xenotransplant breast cancer models in mice. Using human cancer lines with ectopic NKG2D expression and RNA interference (RNAi)-mediated protein depletion among other controls, we show that NKG2D self-stimulation has tumor-promoting capacity. NKG2D signals had no notable effects on cancer cell proliferation and survival but acted at the level of angiogenesis, thus promoting tumor growth, tumor cell intravasation and dissemination. NKG2D-mediated effects on tumor initiation may represent another factor in the observed overall enhancement of tumor development. Altogether, these results may have an impact on immunotherapy approaches, which currently do not account for such NKG2D effects in cancer patients and thus could be misdirected as underlying assumptions are incomplete.

Evaluation of a primary care-oriented brief counselling intervention for obesity with and without orlistat.

OBJECTIVE: There is a significant need for an obesity treatment model suitable for the primary care environment. We examined the effectiveness of a brief counselling intervention alone, in combination with orlistat, and drug-alone in a 12-month randomized-clinical trial at a medical school obesity centre. METHODS: Participants (N = 250) with body mass index (BMI) >or=27 were randomized. Changes in body weight, lipids, blood pressure and serum glucose were examined. Drug adherence and attendance were also evaluated. RESULTS: Completers analysis was conducted on 136 participants with data at baseline, 6 and 12 months and intention-to-treat analyses (ITT) for the total sample. Amongst completers, participants in the drug only (P = 0.012) and drug + brief counselling (P = 0.001) groups lost more weight (mean +/- SD: -3.8 +/- 5.8 kg and -4.8 +/- 4.4 kg, respectively) than participants in the brief counselling only group at 6 months (-1.7 +/- 3.3 kg), but there were no significant group differences at 12 months. ITT model results were similar to completers at 6 months and remained significant at 12 months, but the weight losses were more modest (<3 kg) for both groups receiving orlistat. For brief counselling alone, participants gained weight (1.7 +/- 4.2 kg). Cardiovascular disease (CVD) parameter changes were negligible. CONCLUSIONS: Pharmacotherapy alone or combined with brief counselling resulted in modest weight losses that had minimal impact on cardiovascular parameters, but were greater than brief counselling alone. Whilst brief interventions and primary pharmacotherapy have been suggested as viable treatments for implementation in primary care settings, our study suggests that such minimal interventions provide minimal benefits.

Does metabolic syndrome mitigate weight loss in overweight Mexican American women treated for 1-year with orlistat and lifestyle modification?

AIMS: To investigate the effects of a pharmacotherapy (orlistat) plus lifestyle management (OLM) intervention on weight loss in Mexican American women with and without metabolic syndrome (MS). METHODS: One hundred and seven female participants aged 21-65 years and of Mexican origin were randomized to either OLM or a wait-list control group (WLC) for one year. The lifestyle interventions were tailored to exhibit features of the Mexican culture. Within each group, subjects with MS were compared to those without MS to assess whether its presence mitigates weight loss. Risk factors for MS also were assessed. RESULTS: Participants with MS in the OLM group experienced significant decreases in weight and body mass index (BMI) as compared to participants without MS. Participants with MS in the OLM group and who completed the study lost 9.3+/-7.5 kg (20.5+/-16.5 lb) as compared to participants with MS in the WLC group, who only lost 0.2+/-3.1 kg (0.4+/-6.8 lb). Further, participants with MS in the OLM group who completed the study experienced a 3.1+/-3.9 kg/m2 decrease in BMI whereas participants with MS in the WLC group only experienced a 0.1+/-1.2 kg/m2 decrease in BMI. No changes in other MS risk factors were significant. CONCLUSIONS: Patients with MS experienced significant weight loss and decreases in BMI as a result of a lifestyle and pharmacotherapy intervention.

Weight loss with meal replacement and meal replacement plus snacks: a randomized trial.

OBJECTIVE: To evaluate whether snacking would improve weight loss and weight maintenance in overweight individuals within the context of a structured meal replacement (MR) weight loss program. DESIGN: A prospective 24 week, 2 (snacking vs nonsnacking) x 2 (MR vs meal replacement augmented with snacks (MRPS)) randomized trial. Participants were instructed to limit their total daily intake to 1200 (women) or 1500 (men) kcals. Those receiving the MR program were instructed not to snack while those in the MRPS program were told to snack three times per day. SUBJECTS: A total of 100 participants were block-randomized, based on prestudy snacking status (high vs low), to receive a standard meal replacement program (MR) or MRPS. MEASUREMENTS: Weight, height, blood pressure, lipid fractions, glucose, and insulin were assessed at the baseline, 12-, and 24 weeks. RESULTS: Completers analysis at 24 weeks demonstrated a significant time effect (F(1,46)=44.6, P<0.001), indicating that all participants lost significant amounts of weight regardless of group assignment. An intention-to-treat model resulted in similar results. By week 24, the average weight loss across groups was 4.6 kg. There also were significant improvements across all groups among completers for systolic blood pressure (P=0.047), cholesterol (P=0.001), LDL (P=0.001), glucose (P=0.004), and insulin (P=0.001) at week 12, and glucose (P=0.001) and insulin at week 24 (P=0.003). CONCLUSIONS: Our results suggest that a participant's preferences for snacking did not affect their response to treatment. Snackers and nonsnackers responded equally well whether they received a standard meal replacement program or one augmented with snacks.

Weight loss in obese Mexican Americans treated for 1-year with orlistat and lifestyle modification.

OBJECTIVE: To evaluate the effectiveness of a culturally appropriate lifestyle intervention combined with orlistat in producing weight loss with obese Mexican-American women. SUBJECTS: Mexican-American women (N=108), aged 21-65 y, with a body mass index (BMI) > or =27 kg/m(2) were randomized to 1 y of treatment with orlistat and a culturally tailored lifestyle modification intervention (OLM; n=56) or a wait-list control group (WLC; n=52). DESIGN: A randomized, controlled, open-label 12-month study. Orlistat was dosed at 120 mg, three times per day. The OLM intervention included behavior modification, a low-fat (< or =30% of total daily calories) diet, and moderate physical activity (> or =150 min/week). MEASUREMENT: Primary outcomes included changes in body weight (kg), BMI, waist circumference, blood pressure, glucose, and lipids. RESULTS: A total of 72 (37 OLM, 35 WLC) and 66 participants (32 OLM, 34 WLC) completed the 6- and 12-month follow-ups, respectively. Repeated-measures ANOVA demonstrated a significant time x treatment interaction (Wilks' lambda=12.61; P<0.001), indicating that OLM-treated patients achieved significant weight loss relative to the WLC group during the study (mean percentage weight loss+/-s.e.m.; -8.1%+/-1.2 vs -1.6%+/-0.7 at 6 months and -8.8%+/-1.5 vs -0.2%+/-1.0 at 12 months, respectively). OLM-treated patients also experienced significant reductions in waist circumference, low-density-lipoprotein, and total cholesterol. CONCLUSIONS: This study demonstrates the effectiveness of an intervention combining orlistat and lifestyle modification with Mexican-American women, a population with substantial risk for obesity.

Evaluation of a culturally appropriate intervention to increase physical activity.

OBJECTIVE: To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women. METHODS: Participants were randomly assigned to a physical activity program or wait-list control. RESULTS: Treated participants were not more active than controls at 6 or 12 months. In addition, we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups. CONCLUSION: The intervention did not increase physical activity in this population. Differences in baseline activity and contamination of the control group may partially account for the outcome.

Nutrient intake of obese female binge eaters.

OBJECTIVE: To compare the 6-month change in selected nutrients and number of binge days (from 7-day food records) between obese binge eaters randomly assigned to either a behavioral self-management (BSM) or waiting list control (WLC) group. Within each of the 2 groups, the average intake of selected nutrients on binge and nonbinge days at baseline and at 6 months were compared. DESIGN: A randomized, controlled, intervention study with assessments at entry and 6 months later. SUBJECTS: Forty-six women in the BSM group and 36 in the WLC group completed the 6-month measurement. Participants were 25 to 50 years of age, 30 to 90 pounds overweight, did not have a history of physical or psychological illnesses, and scored 20 or greater on the binge eating scale. INTERVENTION: Participants in the BSM intervention received 6 months of weekly, 1-hour classes taught by registered dietitians. Participants in the WLC group were not contacted during the 6 months. OUTCOME MEASURES: The main outcome measures were change in energy consumed (kilocalories); percentage of energy from fat, protein, and carbohydrate; grams of fiber/1,000 kcal; and change in the number of self-reported binge days. STATISTICAL ANALYSES: Weight at 6 months was compared using a 2-sample t test. The change in the number of binge days at 6 months and the amount of change in selected nutrients by group was compared using the 2-sample t test. The paired t test was used to compare the average nutrient intakes on binge and nonbinge days within groups. RESULTS: No significant difference was found in the 6-month change between groups in any of the selected nutrients. The BSM group reported a greater reduction in binge days between baseline and 6 months compared with the WLC group (mean 1.0 vs 1.7, P < 0.03). Within the BSM group at 6 months, energy intake and percentage of energy from fat on nonbinge days were significantly reduced compared with binge days. At baseline within the WLC group, energy intake increased and percentage of energy from protein decreased significantly on nonbinge days compared with binge days. Within the WLC group at 6 months, energy intake and percentage of energy from fat significantly decreased and percentage of energy from protein significantly increased on nonbinge days. CONCLUSIONS: Our results suggest that collecting dietary information from participants identified with binge eating disorder is challenging. Dietitians who conduct behavioral weight management programs may require additional training in identifying and understanding the psychological characteristics of participants with binge-eating disorder.

Negative stress and the outcome of treatment for binge eating.

This study investigated the ability of negatively versus positively perceived stress to predict outcome of treatment for binge eating disorder (BED). Participants were 62 obese women satisfying the DSMIV research criteria for BED. Stress was measured using an instrument based on the Recent Life Change Questionnaire (RLCQ). Participants experiencing high negative stress during the study period reported a binge eating frequency three times greater than that reported by subjects experiencing low negative stress (2.14 vs. 0.65 binge-days/week). Negative stress predicted how fast an individual would reduce binge eating and demonstrated more predictive power than positive stress.

Binge eating severity, self-concept, dieting self-efficacy and social support during treatment of binge eating disorder.

OBJECTIVE: In treatment of binge eating, measures of self-concept, eating self-efficacy, and social support were examined at 0, 6, and 18 months to determine if improvements in these variables were associated with reductions in binge eating severity. METHOD: Obese adult females (N = 125) were treated for 6 months, with 12 months of maintenance meetings. The Binge Eating Scale (BES), Tennessee Self-Concept Scale (TSC), Dieter's Inventory of Eating Temptations (DIET), and a social support measure (SocSup) were used. RESULTS: Over the first 6 months, improvements in BES were associated with improvements in the TSC and DIET. Over 18 months, improvements in BES were associated with improvements in the TSC, DIET, and SocSup. DISCUSSION: Therapy for binge eating should result in improvement in self-concept and eating self-efficacy, as well as reductions in binge eating. This study showed that self-concept and eating self-efficacy were associated with improvement in binge eating severity. The association with social support did not appear until long-term follow-up. Improvement in self-concept and eating self-efficacy may be processes leading to clinical improvement in this eating disorder, or they may result from changes in binge eating.

Nondieting versus dieting treatment for overweight binge-eating women.

This study evaluated the effectiveness of nondieting versus dieting treatments for overweight, binge-eating women. Participants (N = 219) were randomly assigned to 1 of 3 groups: diet treatment (DT), nondiet treatment (NDT), or wait-list control (WLC). DT received a balanced-deficit diet reinforced with behavioral strategies. NDT received therapy designed to help participants break out of their dieting cycles. Treatment in both conditions was administered in weekly groups for 6 months, followed by 26 biweekly maintenance meetings, for a total of 18 months of contact. At 6 months posttreatment, DT lost 0.6 kg while NDT gained 1.3 kg. Both treatment groups reduced their Binge Eating Scale scores significantly more than WLC. At 18-month follow-up, both treatment groups experienced weight gain but maintained similar reductions in binge eating. Results indicate that neither intervention was successful in producing short- or long-term weight loss. Therapist biases, which may have affected treatment integrity, and other methodological issues are discussed in relation to the small weight losses achieved.

Comparison of 2-year weight loss trends in behavioral treatments of obesity: diet, exercise, and combination interventions.

OBJECTIVE: The effects of three cognitive-behavioral weight control interventions for adults were compared: diet only, exercise only, and a combination of diet and exercise. This article reports 2-year follow-up data. DESIGN: The three interventions were compared in a randomized, experimental design. SUBJECTS: A total of 127 men and women who were at least 14 kg overweight (according to height-weight tables) were recruited from an urban community and assigned randomly to the experimental conditions. INTERVENTION: The dietary intervention was a low-energy eating plan adjusted to produce a 1 kg/week loss of weight. The exercise component involved training in walking and a home-based program of up to five exercise periods per week. There were 12 weekly instructional sessions, followed by 3 biweekly and 8 monthly meetings. All sessions were led by registered dietitians. OUTCOME MEASURES: Changes in body weight. STATISTICAL ANALYSES: Analysis of variance for weight changes and repeated measures analysis of variance for weight change trends. RESULTS: At 1 year, no significant differences were noted among the three groups. The diet-only group lost 6.8 kg, the exercise-only group lost 2.9 kg, and the combination group lost 8.9 kg (P=.09). During the second year, the diet-only group regained weight--reaching 0.9 kg above baseline; the combination group regained to 2.2 kg below baseline; and the exercise-only group regained slightly to 2.7 kg below baseline (P=.36). Repeated measures analysis of variance showed a group-by-time interaction (P=.001); data for the dieting groups best fit a U-shaped regain curve (P=.001). APPLICATIONS: The results suggest that dieting is associated with weight loss followed by regain after treatment ends, whereas exercise alone produced smaller weight losses but better maintenance. The large outcome variability and unequal difficulty of the regimens across groups limit the generalizability of the findings.

Crescentic fibrillary glomerulonephritis associated with intermittent rifampin therapy for pulmonary tuberculosis.

This case study reveals an unusual finding of rapidly proliferative crescentic glomerulonephritis in a patient treated with rifampin who had no other identifiable causes for developing this disease. This patient underwent a 10-month regimen of rifampin and isoniazid for pulmonary tuberculosis and was discovered to have developed signs of severe renal failure five weeks after completion of therapy. Renal biopsy revealed severe glomerulonephritis with crescents, electron dense fibrillar deposits and moderate lymphocytic interstitial infiltrate. Other possible causes of rapidly progressive glomerulonephritis were investigated and ruled out. This report documents the unusual occurrence of rapidly progressive glomerulonephritis with crescents and fibrillar glomerulonephritis in a patient treated with rifampin.

Effect of alcohol and exercise on postprandial lipemia and triglyceride clearance in men.

Alcohol intake and exercise have both been found to be related to increased plasma levels of high density lipoprotein cholesterol (HDLC). Exercise training results in decreased postprandial lipemia, and clearance rate of infused lipids is related to plasma lipoprotein levels in physically active men. The effect of alcohol intake on plasma triglyceride (TG) clearance has not been studied in relation to the exercise status of subjects. Plasma TG change over 8 h was determined following a liquid fatty meal in 14 male habitual runners (R) and 13 physically inactive men (I) after 3 weeks of alcohol abstinence and 3 weeks of drinking approximately 41 g (1.44 oz) of ethanol per day. Fasting total cholesterol and apolipoprotein A-1 (apo A-1) were not different between groups, but TG was lower and HDLC, HDL2C, and HDL3C were higher in the runners. After abstinence, I had slower TG clearance (P = 0.07) compared with R; with alcohol, TG clearance was unchanged in R, but was significantly retarded in I. With alcohol, both groups had increased HDLC levels, but this mainly was due to an increase in HDL3C in R and HDL2C in I; apo A-1 increased similarly in both groups and fasting TG increased significantly only in I. Alcohol-induced increases in postprandial lipemia and retardation of TG clearance appear to occur in inactive, but not exercise-trained subjects and the effect of alcohol on plasma HDL subfractions may differ between these groups.

Family versus individually oriented intervention for weight loss in Mexican American women.

Mexican Americans are more likely to be obese than non-Hispanic whites, yet little research has been conducted on the treatment of obesity in Mexican Americans. The purpose of this study was to compare a family-based intervention with a traditional program oriented to the individual for achieving weight loss by obese Mexican American women. A total of 168 obese women were randomly assigned to one of three groups. Group 1 served as a comparison group and received only printed materials on nutrition, exercise, and behavioral principles for weight loss. Subjects in the individual group (group 2) received the same printed information, but they also attended classes led by bilingual registered dietitians. Subjects in the family group (group 3) received materials and attended classes that emphasized a family-oriented approach to making changes in eating habits and exercise behavior. Spouses and children attended classes with subjects in this group. Results revealed a significant linear trend in both body mass index and weight reduction across the groups, with losses greatest in the family group, followed by the individual group, and least in the comparison group. Both the individual and the family groups lost significantly more weight than the comparison group, although the difference between these two groups was not statistically significant. The results suggest that a culturally and linguistically appropriate program can achieve significant weight reduction among Mexican Americans. More research should be conducted on the effects of family and other types of social support on weight loss by Mexican Americans.

Ethics of obesity treatment: implications for dietitians.

Dietitians face both a responsibility and an opportunity to address the ethical issues of obesity treatment and to promote weight management strategies that are beneficial and effective. The Code of Ethics for the Profession of Dietetics, which was adopted in 1989 to provide guidance to dietetics practitioners in their professional practice and conduct, can serve as a guide in an evaluation of current obesity treatments. Dietitians must help clients be realistic about their weight loss goals and address emotional conflicts that may be undermining weight management efforts. Referrals to therapists may be indicated, and dietitians must be prepared to recognize the need and make the recommendations. Dietitians should take the lead in developing more ethical and beneficial treatments by collaborating with government and industry to protect the consumer from ineffective or potentially harmful practices.

Effect of alcohol dose on plasma lipoprotein subfractions and lipolytic enzyme activity in active and inactive men.

Controversy as to which lipoprotein subfraction of high-density lipoprotein (HDL) increases during alcohol consumption prompted the current study of the effects of two alcohol doses over varying time intervals on plasma lipoproteins and lipolytic enzymes. Measurements were made in 49 healthy men before and after three weeks of abstinence from alcohol and after consumption of one or three 12-ounce cans of beer per day. We found that HDL (10%), HDL2 (14%), and HDL3 (9%) cholesterol, and apolipoprotein A-I (7%) decreased with abstinence from alcohol and then increased with its consumption. These increases were not significant until after 3 weeks of daily alcohol intake, but they were significant in both the one-can and three-cans of beer per day groups. In the 23 inactive subjects HDL and HDL2 cholesterol decreased with abstinence but did not increase significantly with alcohol intake. Lipolytic enzymes were not changed by alcohol manipulation, but the level of lipoprotein lipase was higher and that of hepatic lipase was lower at each measurement point in the 26 habitually active versus the 23 inactive subjects. Adjustment for weight or skinfold thickness did not affect lipoprotein changes over time within groups but did eliminate many of the differences between activity groups. Alcohol consumption seems to be related to possibly beneficial influences on plasma HDL and HDL2 cholesterol, and may thus impact the risk of heart disease.

Effect of alcohol intake and exercise on plasma high-density lipoprotein cholesterol subfractions and apolipoprotein A-I in women.

Abstinence from alcohol consumption for 3 weeks was followed by 3 weeks of wine intake in 18 inactive and 18 physically active premenopausal women (runners). The runners weighed less and had higher plasma high-density lipoprotein (HDL) cholesterol and lower low-density lipoprotein cholesterol levels than the inactive women. There were no differences between groups in plasma total cholesterol, triglyceride and apolipoprotein A-I concentrations. Runners had higher plasma HDL2 cholesterol concentrations than inactive women (34 +/- 17 vs 19 +/- 12 mg/dl), but HDL3 cholesterol concentration did not differ between the groups (41 +/- 10 vs 39 +/- 9 mg/dl). Addition of 35 g/day of ethanol for 3 weeks did not result in a significant change in either group for any of the variables measured. The amount of exercise appears to be a more important determinant of plasma lipoproteins and apolipoprotein A-I than alcohol intake in premenopausal women.