Patient expectations of obesity treatment-the experience from a day-care unit.

BACKGROUND: Unrealistic patient weight loss expectations in treatment of obesity may hamper the modest success which can actually be achieved. SETTING: Academic obesity Unit Day Care Centre. OBJECTIVE: Description of weight loss expectations and weight loss concerns by questionnaire analyses. RESULTS: Patients were severely obese, with a median initial body mass index (BMI) of 40.7 kg/m(2). weight loss expectations were generally unrealistic, with women hoping for a loss up to 42%, and men for 29% of their baseline weight (P<0.001). No effects of age on actual weight loss or weight loss expectations were observed. CONCLUSION: Gender differences in weight loss expectations may be important to acknowledge in future development of obesity treatment programmes. Realistic treatment outcome should be described early in a programme to facilitate compliance.

The proportion of CD45RA(+)CD62L(+) (quiescent-phenotype) T cells within the CD8(+) subset increases in advanced weight loss in the protein- or energy-deficient weanling mouse.

Male and female C57BL/6J mice, initially 19 d old, had free access to a complete purified diet, were fed this diet in restricted daily quantities, or had free access to a low-protein diet. Three separate studies were conducted with feeding periods of 14, 9 or 6 d (n = 7-8 per dietary group and feeding period; 6 d: restricted intake and age-matched controls only). A zero-time control group (19 d old) was included in each study. Malnourished mice lost approximately 2% of initial body weight daily. Naive-phenotype (quiescent) CD8(+) T cells of the blood, spleen and mesenteric lymph nodes were identified on the basis of surface coexpression of CD45RA and CD62L. Relative to age-matched controls, the percentage of naive-phenotype CD8(+) T cells was high in energy-restricted groups after 9 d and 14 d of weight loss and in the protein-restricted groups after 14 d (P < or = 0.05). No ontogenetic change was apparent (age-matched vs. zero-time control). Other studies have demonstrated depression in cell-mediated immune competence in both malnutrition models within the first week of weight loss. An overabundance of quiescent-phenotype T cells within the involuted CD8(+) compartment may contribute to established immune depression but not to its initiation in weight loss pathologies.

Cerebrospinal fluid and plasma concentrations of leptin, NPY, and alpha-MSH in obese women and their relationship to negative energy balance.

Leptin and its principal mediators, NPY and alpha-MSH are postulated to play a pivotal role in energy balance. To determine the possibility of the disturbance in neuropeptides in human obesity and their consequent changes in response to negative energy balance, we evaluated plasma and cerebrospinal fluid (CSF) leptin, NPY, and alpha-MSH levels in obese women before and after weight loss in comparison with normal control women. Subjects included 16 obese women [mean body mass index (BMI), 35.6 kg/m(2)] before and after weight loss induced by a 2-wk very low caloric diet (800 kcal/d) and 14 normal weight women (mean BMI, 20.4 kg/m(2)). The CSF to plasma leptin ratio in normal weight subjects was 2.3-fold higher than that in obese subjects. After weight loss in obese subjects, plasma leptin levels decreased by 40% and CSF levels decreased by 51%. There was a positive linear correlation between CSF and plasma leptin levels at baseline in obese subjects (r = 0.74, P < 0.05) and a positive logarithmic correlation in normal weight subjects (r = 0.89, P < 0.05) and in obese subjects after weight loss (r = 0.64, P < 0.05). The BMI was negatively correlated with the CSF to plasma leptin ratio (r = -0.86, P < 0.05) in all subjects. Neither the baseline plasma levels nor the baseline CSF levels of NPY were different between normal weight subjects and obese subjects. After weight loss, the CSF NPY level decreased significantly compared with baseline values in obese subjects. The alpha-MSH levels in plasma and CSF did not differ significantly from controls in obese subjects at baseline or after weight loss. Baseline CSF leptin level correlated with neither the baseline CSF NPY level nor the baseline CSF alpha-MSH level. In conclusion, this study demonstrated that the efficiency of brain leptin delivery is reduced in human obesity and central nervous system leptin uptake involves a combination of a saturable and an unsaturable mechanism. CSF NPY and alpha-MSH did not differ from controls in human obesity, and the CSF NPY level decreased significantly whereas alpha-MSH did not differ after weight loss in obese subjects compared with baseline. There was no significant correlation between CSF leptin and CSF NPY or alpha-MSH. This could be the result of leptin resistance present in human obesity and/or the more complex mechanisms involved in modulating appetite and regulating energy balance in human obesity.

Effect of Lap-Band-induced weight loss on type 2 diabetes mellitus and hypertension.

BACKGROUND: Severe obesity is associated with type 2 diabetes and hypertension. Improvement in these comorbidities after surgically-induced weight loss has been documented, and laparoscopic adjustable gastric banding (LAGB) is an effective weight loss operation. METHODS: Of 840 patients who underwent Lap-Band, data are available in 402 out of 413 patients whose surgery took place at >/= 1 year ago. Preoperative and follow-up data were studied retrospectively to examine the effect of Lap-Band-induced weight loss on diabetes and hypertension. RESULTS: Of 413 patients with at least 1 year postoperative follow-up, 53 (12.8%) were taking medications for type 2 diabetes preoperatively and 189 (45.7%) were on antihypertensive medications. 66% (n=35) of diabetic patients were also hypertensive. Resolution of diabetes was observed in 66% at 1-year and 80% at 2-year follow-up. HbA1c dropped from 7.25% (5.6-11.0, n=53) preoperatively to 5.58% (5.0-6.2, n=15) at 2 years after surgery. Hypertension resolved in 59.8% and 74% at 1 and 2 years, respectively. Percent excess weight loss (%EWL) was lower for diabetic patients than for our cohort population (39.2% vs 41.2% at 1 year, 46.7% vs 54.2% at 18 months, and 52.6% vs 63.3% at 2 years, respectively). Patients in whom diabetes was improved but not resolved had lower %EWL than did those whose diabetes went into remission (27.0% at 1 year and 26.5% at 2 years). Patients with the shortest duration of diabetes (<5 years) and better weight loss after surgery achieved higher resolution rates. CONCLUSIONS: Dramatic improvement in - and frequent resolution of - diabetes and hypertension have been observed as a result of weight loss after Lap-Band surgery.

Weight change, weight fluctuation, and mortality.

OBJECTIVE: To examine the relation between weight change and weight fluctuation (cycling) and mortality in middle-aged men. METHODS: A prospective study of 5608 men aged 40 to 59 years at screening, drawn from one general practice in each of 24 British towns. Changes in weight observed during a 12- to 14-year period were related to mortality during the subsequent 8 years. RESULTS: There were 943 deaths from all causes: 458 cardiovascular disease (CVD) and 485 non-CVD deaths. Those with stable weight or weight gain had the lowest total, CVD, and non-CVD mortality. Sustained weight loss or weight fluctuation (loss-gain or gain-loss) showed a significantly higher mortality risk than stable weight even after adjustment for lifestyle variables (relative risk [95% confidence interval], 1.60 [1.32-1.95], 1.50 [1.17-1.91], and 1.63 [1.24-2.14], respectively). Adjustment or exclusion of men with preexisting disease markedly attenuated the increased risk of CVD and total mortality associated with sustained weight loss and weight gain-weight loss. In long-term nonsmokers, any weight loss since screening was associated with an increased risk of mortality, but this was markedly attenuated by adjustment for preexisting disease. Recent ex-smokers showed the most marked increase in mortality associated with sustained weight loss. CONCLUSIONS: The increased mortality in middle-aged men with sustained weight loss and weight fluctuation (cycling) is determined to a major extent by disadvantageous lifestyle factors and preexisting disease. The evidence suggests that weight loss and weight fluctuation (cycling) in these men does not directly increase the risk of death.

Patupilone (epothilone B, EPO906) and imatinib (STI571, Glivec) in combination display enhanced antitumour activity in vivo against experimental rat C6 glioma.

PURPOSE: The microtubule-stabilizing agent patupilone (epothilone B, EPO906) and the tyrosine kinase inhibitor imatinib (STI571, Glivec) which primarily inhibits Bcr-Abl, PDGF and c-Kit tyrosine kinase receptors, were combined in vivo to determine if any interaction would occur with respect to antitumour effect and tolerability using rat C6 glioma xenografted into nude mice. METHODS: Patupilone and imatinib were administered alone or in combination at suboptimal doses. Imatinib treatment (orally once daily) was initiated 4 days after s.c. injection of rat C6 glioma cells into athymic nude mice and patupilone administration (i.v. once per week) was started 3 or 4 days after imatinib treatment. RESULTS: As a single agent, imatinib was inactive in the regimens selected (100 mg/kg: T/C 86% and 116%; 200 mg/kg: T/C 68% and 84%; two independent experiments), but well tolerated (gain in body weight and no mortalities). Patupilone weekly monotherapy demonstrated dose-dependent antitumour effects (1 mg/kg: T/C 67% and 70%; 2 mg/kg: T/C 32% and 63%; 4 mg/kg: T/C 3% and 46%). As expected, dose-dependent body weight losses occurred (final body weight changes at 1 mg/kg were -7% and -3%; at 2 mg/kg were -23% and -13%; and at 4 mg/kg were -33% and -15%). Combining 2 mg/kg patupilone and 200 mg/kg per day imatinib in one experiment produced a non-statistically significant trend for an improved antitumour effect over patupilone alone (combination, T/C 9%), while in the second experiment, enhancement was seen with the combination and reached statistical significance versus patupilone alone (combination, T/C 22%; P=0.008). Reduction of the imatinib dose to 100 mg/kg per day resulted in no enhancement of antitumour activity in combination with 2 mg/kg patupilone. Reduction of the patupilone dose to 1 mg/kg resulted in a reduced antitumour effect, and only a trend for synergy with either imatinib dose (combination, T/C 46% and 40%). Pooling the data from the two experiments confirmed a significant synergy for the combination of 2 mg/kg patupilone and 200 mg/kg per day imatinib (P=0.032), and a trend for synergy at the 1 mg/kg patupilone dose. Reduction in the imatinib dose to 100 mg/kg per day resulted only in additivity with either dose of patupilone. Body weight losses were dominated by the effect of patupilone, since no greater body weight loss was observed in the combination groups. CONCLUSION: Combining patupilone with high-dose imatinib produced an increased antitumour effect without affecting the tolerability of treatment in a relatively chemoresistant rat C6 glioma model. Such results indicate that further evaluation is warranted, in particular to elucidate possible mechanisms of combined action.

Relationship of a large weight loss to long-term weight change among young and middle-aged US women.

OBJECTIVE: To assess the prevalence of clinically significant weight loss among women and whether this is associated with smaller long-term weight gains. DESIGN: Six-year follow-up of young and middle-aged women in the Nurses' Health Study II. SUBJECTS: A total of 47,515 women who did not report a pregnancy, or a diagnosis of cancer or cardiovascular disease any time between 1989 and 1995. MEASUREMENTS: Self-reported weights in 1989, 1991, 1993 and 1995, dietary intake, physical activity, inactivity, history of weight cycling and smoking. RESULTS: Between 1989 and 1991, 9% of the women lost > or =5% of their 1989 weight (6% lost 5--9.9% and 3% lost > or =10%). The proportion who lost > or =10% of their weight increased with category of body mass index (BMI, kg/m(2)) from 0.4% among women with a BMI <22 to 9% among women with a BMI > or =30 in 1989. Women who lost > or =5% of their weight between 1989 and 1991 gained more weight between 1991 and 1995 than their peers and the difference increased across categories of BMI in 1989. However, due to their large weight losses, women who lost > or =5% of their weight between 1989 and 1991 overall gained less weight than their peers between 1989 and 1995 (P<0.001). Moreover, women who engaged in 5 or more hours per week of vigorous physical activity gained approximately 0.5 kg less than their inactive peers (P<0.001). CONCLUSION: Although most women who lost a clinically significant amount of weight regained most of it, they gained less weight over the entire 6 y period than their peers.

Synergy of Sibutramine ( Meridia ) and low-dose leptin in treatment of diet-induced obesity in rats.

Tachyphylaxis to the effects of anorexigenic agents, such as Sibutramine ( Meridia ) (S), may be due, in part, to counterregulatory decreases in energy expenditure (EE) and increases in hunger that result from reduced circulating leptin (L) due to loss of body fat and lowered L production/adipocyte. The present study was conducted to test the hypothesis that L administered at low doses sufficient to restore ambient L to preweight loss concentrations would enhance the intercurrent efficacy of S by reducing the strength of physiologic counterregulation to weight loss. Forty male Sprague-Dawley rats were fed a high-fat (HF) diet (45% energy) to induce obesity. After 8 weeks, the obese rats (600 +/- 58 g) were weight-matched into 4 groups (N = 8/group) and implanted subcutaneously (SC) with 2 mL, 7-day Alzet mini-pumps that provided: vehicle (V, saline), L (0.5 mg/kg/d), S (3 mg/kg/d), or L+S. Food intake (FI) on the HF diet was measured daily. On day 7, 24-hour EE was measured by indirect calorimetry, and the animals then killed for body composition analysis. Compared with vehicle, treatment with S alone, but not L alone, produced significant weight loss (-23 +/- 26 v -6 +/- 16 g, P <.01). L alone, or with S, increased fat oxidation (decreased respiratory quotient [RQ]) compared with V (P <.05). The lack of decline in EE with S may be due to its documented effect to stimulate thermogenesis. Administration of L with S synergistically decreased FI and increased weight loss and fractional fat loss. A reduction in plasma L concentration may contribute to the "plateau phenomenon" observed in studies of weight loss therapies. Replacement doses of L during S administration increased weight loss and fractional fat loss by (1) decreasing food intake and (2) by increasing fat oxidation. Such drug combinations may be useful in the treatment of human obesity. Copyright 2001 by W.B. Saunders Company