Vibration-induced compaction of granular suspensions.

We investigate the compaction dynamics of vibrated granular suspensions using both digital imaging technique and MRI measurements. Starting from initialy loose packings, our experimental data suggest the existence of two stages in the compaction dynamics: a fast stage at short times where a rising compaction front propagates through the granular suspension and a slow stage at large times where the packing compacts slowly and homogeneously. The compaction dynamics in each stage can be well fitted to usual stretched exponential laws with stretching exponents equal to 2 and 0.45, respectively. The transition time between these two stages, τ c , depends on the fluid viscosity, vibration intensity and grain diameter. We show that τ c (-1) and the velocity of the front decrease roughly linearly with the lubrication Peclet number, Pe lub related to the competition between the lubrication stress induced by vibrations and the granular pressure.

Vibration-induced liquefaction of granular suspensions.

We investigate the mechanical behavior of granular suspensions subjected to coupled vibrations and shear. At high shear stress, whatever the mechanical vibration energy and bead size, the system behaves like a homogeneous suspension of hard spheres. At low shear stress, in addition to a dependence on bead size, vibration energy drastically influences the viscosity of the material that can decrease by more than 2 orders of magnitude. All experiments can be rationalized by introducing a hydrodynamical Peclet number defined as the ratio between the lubrication stress induced by vibrations and granular pressure. The behavior of vibrated wet and dry granular materials can then be unified by assimilating the hookean stress in dry media to the lubrication stress in suspensions.

[Rimonabant improves cardiometabolic risk profile in obese or overweight subjects: overview of RIO studies]. / Le rimonabant améliore le profit de risque cardio-métabolique chez le sujet obèse ou en surpoids: synthèse des etudes "RIO".

RIO (Rimonabant In Obesity and related disorders) is a large phase 3 programme (>6600 patients) evaluating the efficacy and safety of rimonabant (5 or 20 mg/day), a CBI receptor antagonist of endocannabinoid system, in obese or overweight patients with or without comorbidities (RIO-Europe and RIO-North America), with untreated dyslipidaemia (RIO-Lipids) or with type 2 diabetes treated with metformin or sulfonylurea (RIO-Diabetes). Compared to placebo, rimonabant 20 mg/day consistently increases weight loss, reduces waist circumference, increases HDL cholesterol, lowers triglyceride levels, diminishes insulin resistance, and reduces the prevalence of metabolic syndrome. Almost half of the metabolic effects, including adiponectin increase, occur beyond weight loss, suggesting a direct peripheral effect of rimonabant.

Long-term maintenance of weight loss after a very-low-calorie diet: a randomized blinded trial of the efficacy and tolerability of sibutramine.

BACKGROUND: Very-low-calorie diets are a well established method to achieve substantial short-term weight loss in obese patients, but long-term maintenance of the weight loss is very disappointing. A combined very-low-calorie diet and pharmacologic approach could be an effective means of prolonging its benefits. PATIENTS AND METHODS: Eligible patients had a body-mass index greater than 30 kg/m2; those who lost 6 kg or more during a 4-week treatment with a very-low-calorie diet were randomly assigned to 1 year of treatment with sibutramine (10 mg) or identical placebo. RESULTS: In an intention-to-treat analysis, mean (+/-SD) absolute weight change at 1 year (or study endpoint) was -5.2 (+/-7.5) kg in the 81 patients in the sibutramine group and +0.5 (+/-5.7) kg in the 78 patients in the placebo group (P = 0.004). When compared with their weight at study entry (before the very-low-calorie diet), 86% of patients in the sibutramine group had lost at least 5% of their weight, compared with only 55% of those in the placebo group (P <0.001) at the study endpoint. Similarly, at month 12, 75% of subjects in the sibutramine group maintained at least 100% of the weight loss achieved with a very-low-calorie diet, compared with 42% in the placebo group (P <0.01). CONCLUSION: Following a very-low-calorie diet, sibutramine is effective in maintaining and improving weight loss for up to 1 year.

Modalities of the food intake-reducing effect of sibutramine in humans.

Sibutramine is a serotonin and noradrenaline reuptake inhibitor exerting a weight reducing effect partly via its anorectic properties. We investigated the effects of 15 mg sibutramine on objective (intake) and subjective (sensations) parameters of eating behavior in 24 young male subjects. At 0830 h subjects took either placebo or sibutramine in a counterbalanced order, followed by a fixed amount of breakfast. Intake was covertly recorded in the laboratory until the dinner meal, and then until the next morning using diary reports. Sibutramine induced a highly significant reduction in energy (1304 kJ, p < 0.001), protein (294 kJ, p < 0.001), fat (414 kJ, p < 0.01), and carbohydrate (CHO, 594 kJ, p < 0.001) intakes compared to placebo. This reduction was further enhanced when 24-h intake was analyzed (1601 kJ, p < 0.001). The effect of sibutramine occurred mainly at lunch (637 kJ, p = 0.005). Throughout the test day the number of items consumed and the weight of food were reduced by sibutramine (1.6, p < 0.01 and 222 g, p < 0.001, respectively), whereas energy density was not changed. Meals minus dessert items were the most altered by sibutramine. A specific CHO reduction was found in the dinner meal, although the proportions of macronutrients in total daily energy intake were not changed by sibutramine. Hunger ratings began to be lower than placebo 240 min after sibutramine. These results show that a single dose of sibutramine in lean humans induces a potent reduction in intake, and that its action is modulated according to the time of occurrence and the structure of the meal.

[Prescription of non-steroidal anti-inflammatory agents and risk of iatrogenic adverse effects: a survey of 1072 French general practitioners]. / Prescription des anti-inflammatoires non stéroïdiens et pratiques à risque de iatrogènie: étude chez 1072 médecins généralistes français.

As a group, non-steroidal anti-inflammatory drugs (NSAIDs) rank first among commonly prescribed drugs for serious adverse reactions. We conducted a cross-sectional survey in which 1072 French general practitioners (GPs) were evaluated for their basic pharmacological knowledge and practice of NSAIDs prescription. Results suggest that GPs have insufficient pharmacological knowledge and provide inadequate management of adverse reaction risk. Well-established risk factors for serious adverse reactions, such as age, are not taken enough into account, and tolerance is not correctly monitored. Drugs allegedly protecting against peptic ulcers are frequently associated but, most of the time, without any relevant justification, such as the patient's risk level or drug's efficacy. Our findings demonstrate a need for greater information among GPs about prescription and tolerance monitoring of NSAIDs.

Two-state model to describe the rheological behavior of vibrated granular matter.

In this paper, we present a model aimed at predicting the rheological response of a 3D dry granular system to nonstationary mechanical solicitations, subjected or not to vibrations. This model is based on a phenomenological two-state approach related to the inherent bimodal behavior of chain forces in granular packing. It is set up from a kinetic equation describing the dynamics of the contact network. To allow experimental assessment, the kinetic equation is transformed into a differential constitutive equation, relating stress to strain, from which rheological properties can be derived. Its integration allows predicting and describing several rheological behaviors, in stationary and nonstationary conditions, including viscous (Newtonian) and frictional (Coulombian) regimes, as well as elastic linear (Hookean and Maxwellian) and nonlinear behaviors. Despite its simplicity, since it involves only three independent parameters, the model is in very close agreement with experiments. Moreover, within experimental errors, the values of these parameters are independent of the type of test used to determine them, evidence of the self-consistency of the model.

Efficacy of rimonabant in obese patients with binge eating disorder.

In obesity, a dysregulation of the endocannabinoid system has been shown. The endocannabinoid receptor blockage by rimonabant demonstrated interesting metabolic effects. However, the role of rimonabant in weight loss of patients with binge eating disorder has not been investigated. Thus, our aim was to evaluate the effects of rimonabant on body weight in obese patients with binge eating disorders. This multicenter, randomized, double-blind, placebo-controlled study included 289 obese subjects (age 18-70 years, body mass index 30-45 kg/m(2)) with binge eating disorders. Subjects were randomized (1:1) to receive rimonabant 20 mg/day or placebo for 6 months. In total, 289 participants (age: 43.2±10.5 yrs, 91% of women) were randomized. The completer rate was similar (71%) in both treatment and placebo groups. Participants treated with rimonabant lost 4.7±5.2% of their initial body weight, vs. 0.4±4.5% in the placebo group (difference between both groups: 4.4±0.6 kg, p<0.0001). The rimonabant group showed a greater reduction on the binge eating scale total score (mean±SD - 40.9±35.2%) vs. placebo ( - 29.9±34.6%, p=0.02). The incidence of treatment emergent adverse events was comparable in both the rimonabant (82.5%) and placebo (76.0%) group. Discontinuations due to treatment emergent adverse events occurred in 13.3% rimonabant-treated vs. 6.2% placebo-treated participants. In conclusion, this is the only randomised, placebo-controlled, double-blind trial having assessed the effect of rimonabant in patients with binge eating disorders. The rimonabant treatment reduced body weight significantly more than placebo in obese subjects with binge eating. Trial registration number (clinicaltrials.gov): NCT00481975.

Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study.

OBJECTIVES: To assess the weight-reducing effects and tolerability of 5 mg, 10 mg and 15 mg daily doses of sibutramine, a novel serotonin and noradrenaline reuptake inhibitor (SNRI). DESIGN: Multicentre, double-blind, and placebo-controlled study. After a one week run-in period, patients were randomized to receive placebo or sibutramine over a 12-week period. Advice on diet and behaviour modification was provided. One follow-up was conducted four weeks after cessation of treatment. SUBJECTS: 235 obese outpatients, aged 18-65 y with a body mass index (BMI) within the range 27-40 kg/m2. MEASUREMENTS: Weight, height, waist and hip circumference, and medical history, assessment of hunger, satiety, appetite and craving for sweet, savoury and carbohydrate foods, and also for carbohydrate snacking, standard laboratory assessments, blood pressure, heart rate and ECG. RESULTS: The group mean (+/- s.e.m.) weight loss at end-point was 1.4 +/- 0.5 kg for placebo (n = 59), 2.4 +/- 0.5 kg for 5 mg sibutramine (n = 56), 5.1 +/- 0.5 kg for 10 mg sibutramine (n = 59) and 4.9 +/- 0.5 kg (n = 62) for 15 mg sibutramine. The difference observed between the placebo and the 10 mg and 15 mg groups was statistically significant from week 2 onwards (P < 0.01), but there was no significant difference between these sibutramine groups. The percentage of patients losing > 5% of initial bodyweight was significantly greater for 15 mg sibutramine (55%) and 10 mg sibutramine (49%) than for treatment with placebo (19%), (P < 0.001). During the double-blind period, 41 patients (17%) withdrew prematurely and 168 patients (71%) reported 453 adverse events. The incidence and type of adverse event and the rates of withdrawal, were not significantly different in the four groups. No significant differences between the groups were observed, in respect of changes in systolic and diastolic blood pressure, but a significant increase in heart rate (about 4 beats/min) was noted for patients who received 10 mg or 15 mg sibutramine, compared with the placebo (P < 0.001). CONCLUSION: These data demonstrate dose-related weight loss with sibutramine treatment for up to 12 weeks in obese patients. Doses of 10 mg and 15 mg once daily were shown to be similarly effective, well tolerated and significantly more effective than the placebo.

A comparison of sibutramine and dexfenfluramine in the treatment of obesity.

OBJECTIVE: Because long-term weight reduction is often unsuccessful with dietary restriction alone, pharmacological agents have been used to promote weight loss. We have compared the novel (multiple monoamine neurotransmitter reuptake inhibitor) antiobesity drug sibutramine (10 mg once daily) with the extensively studied serotonin-releasing antiobesity agent dexfenfluramine (15 mg twice daily). RESEARCH METHODS AND PROCEDURES: 226 healthy outpatients (aged 18 to 65 years; body mass index > or =27 kg/m2) were included in a 12-week, randomized, double-blind, parallel group study. The main outcome measures were changes in weight, body mass index, waist and hip circumference and ratio, and safety profiles. RESULTS: Mean (+/-SEM) absolute weight loss was 4.5 +/- 0.4 kg in the sibutramine group (n = 112) and 3.2 +/- 0.3 kg in the dexfenfluramine group (n = 112) (endpoint analysis); 4.7 +/- 0.4 kg in the sibutramine group (n = 101); and 3.6 +/- 0.3 kg in the dexfenfluramine group (n = 94) (completers analysis). Comparing the two treatments under the conventional null hypothesis of equality as a secondary analysis, weight loss at endpoint in patients receiving sibutramine was significantly greater than that achieved with dexfenfluramine (p<0.05). Both drugs had similar adverse events profiles: 174 patients (77%) experienced adverse events; 17 patients withdrew due to adverse events (sibutramine, n = 6; dexfenfluramine, n = 11). Pulse rate increased significantly in sibutramine-treated patients (3.6 bpm), but decreased in dexfenfluramine-treated patients (-0.9 bpm). DISCUSSION: Sibutramine (10 mg once daily) is at least as effective as dexfenfluramine (15 mg twice daily) in achieving weight loss in patients with obesity.