Weight Loss,Weight Maintenance,and Improved Cardiovascular Risk Factors after 2 Years Treatment with Orlistat for Obesity

Objective: To determine the effect of orlistat, a new lipase inhibitor, on long‐term weight loss, to determine the extent to which orlistat treatment minimizes weight regain in a second year of treatment, and to assess the effects of orlistat on obesity‐related risk factors. Research Methods and Procedures: This was a 2‐year, multicenter, randomized, double‐blind, placebo‐controlled study. Obese patients (body mass index 28 to 43 kg/m²) were randomized to placebo or orlistat (60 or 120 mg) three times a day, combined with a hypocaloric diet during the first year and a weight maintenance diet in the second year of treatment to prevent weight regain. Changes in body weight, lipid profile, glycemic control, blood pressure, quality of life, safety, and tolerability were measured. Results: Orlistat‐treated patients lost significantly more weight (p < 0.001) than placebo‐treated patients after Year 1 (6.6%, 8.6%, and 9.7% for the placebo, and orlistat 60 mg and 120 mg groups, respectively). During the second year, orlistat therapy produced less weight regain than placebo (p = 0.005 for orlistat 60 mg; p < 0.001 for orlistat 120 mg). Several obesity‐related risk factors improved significantly more with orlistat treatment than with placebo. Orlistat was generally well tolerated and only 6% of orlistat‐treated patients withdrew because of adverse events. Orlistat leads to predictable gastrointestinal effects related to its mode of action, which were generally mild, transient, and self‐limiting and usually occurred early during treatment. Discussion: Orlistat administered for 2 years promotes weight loss and minimizes weight regain. Additionally, orlistat therapy improves lipid profile, blood pressure, and quality of life.     

Calcium intake and the outcome of short-term weight management

Experimental and epidemiological studies suggest that calcium intake is inversely related to weight gain. Calcium of dairy origin has been shown to be more effective in promoting weight loss. However, clinical studies yielded controversial results concerning the role of calcium intake in weight change. The aim of this study was to ascertain whether the addition of calcium can affect the outcome of 3-week weight management (WM) with a hypocaloric diet characterized by a decreased calcium intake. Overweight/ obese women (n=67; BMI 32.2+/-4.1 kg/m(2); age 49.1+/-12.1 years) underwent a 4-week comprehensive WM program. WM included a 7 MJ/day diet resulting in a stable weight during the first week and a 4.5 MJ/day diet with mean daily calcium intake 350 mg during the second to fourth week. Participants were divided into three age- and BMI-matched groups who received placebo or calcium (500 mg/day). Calcium was administered either as carbonate or calcium of dairy origin (Lactoval). There was no significant difference in weight loss in response to WM between the placebo-treated and calcium-treated groups. However, addition of calcium to the diet resulted in a lower hunger score in the Eating Inventory as well as a decrease in plasma resistin levels. Body composition measured by bioimpedance demonstrated that added calcium leads to preservation of fat-free mass. Nevertheless, a greater loss of fat-free mass in the placebo group might be partly due to a greater loss of water.     

Soy protein hydrolyzate with bound phospholipids reduces serum cholesterol levels in hypercholesterolemic adult male volunteers

This study was done to evaluate the effects of soy protein hydrolyzate with bound phospholipids (c-SPHP), on the serum cholesterol levels in hypercholesterolemic subjects over a three-month period. Subjects were Taiwanese adult male volunteers whose serum total cholesterol levels were above 220 mg/dl. Twenty-one subjects were divided into three groups randomly, and each group was given c-SPHP zero, 3, or 6 g per day. Test diets were orally administered in a powdered drink form that contained c-SPHP or casein hydrolyzate (placebo). The subjects were given the test diet four times daily. The study consisted of a two-week pre-feeding period, a three-month feeding period, followed by a two-week post-feeding period. After 3 months of c-SPHP administration, 3 g per day, serum total cholesterol decreased significantly from the initial level (15.0%, p<0.01) and compared with the placebo group (p<0.05). Furthermore, LDL-cholesterol decreased significantly (27.7%, p<0.01) and the LDL/HDL ratio also decreased significantly (47.4%, p<0.01) from the initial levels. These effects of c-SPHP were dose-dependent. This study suggests that c-SPHP has remarkable improving effects on the serum cholesterol levels in hypercholesterolemic subjects.     

Long term propranolol treatment and changes in body weight after myocardial infarction.

OBJECTIVE--To determine the effect of long term propranolol treatment on body weight. DESIGN--Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial). PATIENTS--3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits. MAIN OUTCOME MEASURE--Changes in body weight. RESULTS--At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages. CONCLUSION--Long term beta blockade results in a sustained weight gain.     

Randomized controlled trials of the D1/D5 antagonist ecopipam for weight loss in obese subjects

Objective: To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity. Research Methods and Procedures: Four randomized, double‐blind, multicenter trials compared ecopipam (n = 1667) and placebo (n = 1118) in obese subjects including type 2 diabetic subjects. Subjects received oral ecopipam 10, 30, or 100 mg daily for 12 weeks (Phase 2) or 50 or 100 mg daily for 52 weeks (Phase 3) combined with a weight loss program. Primary efficacy variables were the proportion of subjects with ≥5% weight loss from baseline at 12 weeks (Phase 2) or the distribution of percentage weight loss from baseline at 52 weeks (Phase 3). Results: In the Phase 2 study, 26% of subjects administered ecopipam 100 mg vs. 6% of placebo subjects achieved ≥5% weight loss after 12 weeks (p < 0.01). In the Phase 3 studies, ecopipam 100 mg produced a 3.1% to 4.3% greater weight loss than placebo at 52 weeks. More subjects administered ecopipam vs. placebo achieved a 5% to 10% or >10% weight loss in two non‐diabetic phase 3 trials. Ecopipam‐treated subjects also maintained more weight loss compared with placebo subjects at 52 weeks. Phase 3 studies were discontinued because of unexpected psychiatric adverse events (ecopipam 31% vs. placebo 15%), including depression, anxiety, and suicidal ideation. Discussion: Ecopipam was effective for achieving and maintaining weight loss in obese subjects, including type 2 diabetic subjects; however, the adverse effects on mood observed in the Phase 3 studies exclude its projected use in weight management.     

Metformin Decreases Food Consumption and Induces Weight Loss in Subjects with Obesity with Type II Non-Insulin-Dependent Diabetes

Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3times3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity.     

Effect of ethyloestrenol on fibrinolysis in the vessel wall.

Forty-nine patients with decreased fibrinolytic activity in the vessel walls or a decreased release mechanism, or both, were treated with ethyloestrenol for three to 17 months. Forty-five of the patients had had recurrent, phlebographically verified, deep venous thrombosis (DVT) and four had arterial thrombosis. Ethyloestrenol 8 mg/day was given to 31 patients and 4 mg/day was given to 12. The remaining six patients had been treated with a combination of phenformin and ethloestrenol. The phenformin was withdrawn but they were kept on ethyloestrenol 8 mg/day. Another 15 patients with a normal fibrinolytic system--four with recurrent DVT and 11 with severe arteriosclerosis--were given ethyloestrenol 8 mg/day. The spontaneous fibrinolytic activity, local fibrinolytic activity during standardised venous occlusion of the arms, and fibrinolytic activity of the vessel walls increased significantly after treatment with ethyloestrenol 8 mg/day for three months. No further increase occurred after three months, and ethyloestrenol 4 mg/day had no effect. No values rose significantly in the patients with a normal fibrinolytic system. One patient suffered a recurrence within three months of treatment, before the fibrinolytic system became normal. In one patient the fibrinolytic defect reappeared after 10 months in spite of continued treatment. Two of the three women of fertile age developed irregular cycles and intermenstrual bleeding, which disappeared when the treatment was withdrawn. No other side effects were observed.     

Clinical and Laboratory Double-blind Investigation on Effect of Fibrinolytic Therapy in Patients with Cutaneous Vasculitis

The effects of phenformin and ethyloestrenol and phenformin and stanozolol on the clinical state, plasma fibrinolytic activity, and fibrinogen-fibrin-related antigen (F.R.-antigen) were compared with placebo in 13 patients with cutaneous vasculitis. Eight patients showed considerable clinical improvement when taking phenformin and an anabolic steroid; an impaired fibrinolytic activity before treatment favoured clinical improvement.     

Pharmacological and Clinical Studies of Ephedrine and Other Thermogenic Agonists

When given as a supplement to an energy restricted diet the sympathomimetic agent ephedrine, in combination with methylxanthines such as caffeine, improves fat loss by dual actions: a central suppression of appetite and peripheral stimulation of energy expenditure covered by fat oxidation. Mean weight loss was found to be 16.6 kg after 6 months when E+C was given as an adjuvant to an efficient hypoenergetic diet, which was 3.4 kg higher than in the placebo group. An additional 24 weeks treatment with E+C prevented relapse. In the first weeks of treatment E+C offset the hypotensive effect of energy restriction and weight loss, but the effect was transient, and after 8 weeks blood pressures were indistinguishable from those of the placebo group. E+C has no adverse effect on glucose and lipid metabolism, but has been shown to prevent the decline in HDL-cholesterol caused by weight loss. In a comparative trial the weight loss produced by E+C was similar to that of dexfenfluramine. More research on sympathomimetics and methylxanthines should be carried out to identify combinations with improved efficiency and safety. Moreover, more long-term trials and studies in males are required.     

Fluoxetine: A Randomized Clinical Trial in the Maintenance of Weight Loss

Because current weight-reduction treatments have considerable recidivism, a therapy that could help patients maintain weight loss would be of benefit. A six-center, randomized, double-blind trial compared the effects of the specific serotonin uptake inhibitor, fluoxetine hydrochloride, and placebo on maintenance of weight loss. Obese outpatients who had lost ≤3.6 kg after 8 weeks of single-blind fluoxetine 60 mg/day in the qualification phase (N=317 [70.4% of patients entered]; mean ± standard deviation [SD] weight loss, 6.8 ± 2.8 kg) were randomly assigned to fluoxetine 20 mg/day (N=104), fluoxetine 60 mg/day (N=106), or placebo (N=107) for 40 weeks (maintenance phase). Patients received minimal nutrition/dietary counseling. Qualification phase clinic visits were biweekly; maintenance phase visits were monthly for 4 months, then bimonthly for 6 months. Patients treated with fluoxetine 60 mg/day continued to lose weight for 8 additional weeks (16 weeks total; maximum mean ± SD weight loss, 7.2 ± 4.6 kg); those treated with fluoxetine 20 mg/day or placebo began to regain weight. Mean weights remained below baseline values at week 48 (all groups); treatment differences were not statistically significant. Study completion rates were comparable (fluoxetine 20 mg/day, 67.3%; fluoxetine 60 mg/day, 56.6%; placebo, 67.3%; p = 0.175). Among commonly reported adverse events (>10% incidence), only asthenia was reported statistically significantly (p< 0.050) more frequently with fluoxetine than with placebo. Few patients discontinued for any single adverse event. Fluoxetine 60 mg/day was effective for a longer period than fluoxetine 20 mg/day or placebo in maintaining weight loss. Overall, fluoxetine was safe and well tolerated.     

Effects of "natural oestrogen" replacement therapy on menopausal symptoms and blood clotting.

In a double-blind study on the value of equine ("natural") oestrogens 30 patients presenting with menopausal symptoms in a group practice were monitored for possible adverse effects on blood clotting, weight, and blood pressure. The women were randomly allocated to two groups and given either three months'' hormone treatment followed by three months'' placebo or vice versa. An appreciable amelioration of all symptoms on placebo made it difficult to asses the genuine value of oestrogen treatment during the period of study. Both groups made a dramatic clinical improvement during the first three months. Nevertheless, the symptoms of the 15 women who received oestrogen first returned after the cross-over to placebo without any suggestion of a placebo response. In contrast, the other group who took placebo first did not deteriorate after changing to oestrogen. The menopausal index and the karyopyknotic index were not reliable guides to the need for oestrogen treatment. Hot flushes, however, were proportionately reduced on oestrogen and they seemed to be more readily eliminated in individual cases by oestrogen. The results of blood clotting studies indicated that natural oestrogen administration raised the levels of the extrinsic clotting factors VII and X and accelerated the prothrombin time. The findings were similar to those observed after three months synthetic oestrogen administration with oral contraception. Long-term studies and epidemiological surveys of the clinical incidence of thrombotic and other sequelae are needed before large-scale oestrogen replacement treatment can be recommended.     

Weight Loss Expectations in Obese Patients and Treatment Attrition: An Observational Multicenter Study

Objective: To investigate the influence of weight loss expectations (expected 1‐year BMI loss, dream and maximum acceptable BMI) on attrition in obese patients seeking treatment. Research Methods and Procedures: Obese subjects (1785; 1393 women; median age, 46 years; median BMI, 36.7 kg/m²) seeking treatment in 23 medical Italian centers were evaluated. Baseline diet and weight history, weight loss expectations, and primary motivation for seeking treatment (health or improving appearance) were systematically recorded. Psychiatric distress, binge eating, and body image dissatisfaction were tested at baseline by self‐administered questionnaires (Symptom Check List‐90, Binge Eating Scale, and Body Uneasiness Test). Attrition and BMI change at 12 months were prospectively recorded. Results: At 12 months, 923 of 1785 patients (51.7%) had discontinued treatment. Compared with continuers, drop‐outs had a significantly lower age, a lower age at first dieting, lower dream BMI, a higher expected 1‐year BMI loss, and a higher weight phobia. At logistic regression analysis, the strongest predictors of attrition at 12 months were lower age and higher expected 1‐year BMI loss. The risk of drop‐out increased systematically for unit increase in expected BMI loss at 12 months (hazard ratio, 1.12; 95% confidence interval, 1.04 to 1.20; p = 0.0018). The risk was particularly elevated in the first 6 months. Discussion: Baseline weight loss expectations are independent cognitive predictors of attrition in obese patients entering a weight‐losing program; the higher the expectations, the higher attrition at 12 months. Unrealistic weight goals should be tackled at the very beginning of treatment.     

The Bacon Chow study: Genetic analysis of physical growth in assessment of energy–protein malnutrition

Estimates of the prevalence of energy–protein malnutrition almost universally employ physical growth measurements. In this study we focus on this disease and the role of body size of relatives as mediators of responses in individuals to one type of nutrition intervention: supplementation of pregnant and lactating women. In this study, initiated by Dr. Bacon Chow and others in 1967, during gestation of a first infant a mother was untreated, while during the lactation of the first infant and the gestation and lactation of a second infant she was treated with either a calorie supplement or a placebo. Supplement–placebo group differences were sought in sibling and mother–child correlations in growth from birth to 30 months, in order to assess the role of heredity as a mediator of supplement effects. There were 108 pairs of siblings whose mothers had received a high-calorie–high-protein supplement as described above and 105 pairs of siblings whose mothers had received a placebo. Among the latter, sibling correlations for most measurements are statistically significant at birth, and of the same magnitude seen in previous studies (～0.5), while among supplemented siblings, birth correlations are unusually low and often insignificant. The sibling correlations in Rohrer's index (wt/L³) differed the most between groups (p < 0.01). Group differences in the sibling correlation tended to disappear over the first 2.5 years of life. Correlations between mothers and their second children in subscapular skinfold tended to be higher in the supplemented than in the placebo group, birth to 30 months. In both supplement groups mother–second child correlations for body weight were higher than mother–first child correlations, suggesting the occurrence of secular changes in the environment unconnected with the treatment. The results suggest that: (1) genetic analysis of components of anthropometric variation may be a more sensitive method than the more conventional comparison of group means in detecting supplement effects; and (2) infant relative weight (Rohrer index), particularly the addition of subcutaneous fat, may be more affected by maternal supplementation than growth in weight or length alone.     

The beta cell function in NIDDM patients with secondary failure: a three year follow-up of combined oral hypoglycemic and insulin therapy.

Eleven Type 2 (non-insulin-dependent) diabetic patients, islet cell autoantibodies negative, nonobese with secondary failure to oral hypoglycemic agents (OHA) [glyburide (7.5 mg/day) and phenformin (75 mg/day)] and HbA1c 10.2 +/- 0.6% were studied. Insulin receptors on circulating monocytes, glucose utilization at supraphysiological insulin concentrations, and plasma C-peptide after i.v. glucagon were evaluated before and after 2 months of combined therapy with OHA and insulin (Ultratard HM Novo). A significant improvement was demonstrated in HbA1c and glycemia after two months of treatment. Glucose MCR was increased after two months of treatment whilst basal C-peptide was decreased as well as receptor binding to monocytes. After three years of combined therapy, body weight, glycemia and HbA1c did not increase. After three years the C-peptide basal values were significantly increased with respect to values found after 2 months of therapy. These results demonstrate that insulin treatment may restore insulin sensitivity in NIDDM patients resistant to OHA treatment and that after three years there is no exhaustion of B-cell function.     

Treatment of Obese Female and Male SHHF/Mcc-facp Rats with Antihypertensive Drugs,Nifedipine and Enalapril: Effects on Body Weight,Fat Distribution,Insulin Resistance and Systolic Pressure

Little is known about the effects of common antihypertensive drugs in obese, insulin-resistant females. Nine-month-old obese female SHHF/Mcc-fn^cp rats that received either nifedipine, a calcium channel antagonist, or enalapril, an angiotensin-converting-enzyme inhibitor, for three months were compared with untreated SHHF/Mcc-fa^cp rats (controls). After one month, nifedipine significantly decreased body weight in obese females compared to either enalapril or controls. After three months of treatment, total, abdominal, and subcutaneous fat masses were decreased in obese females given nifedipine compared to either enalapril or controls. Enalapril treatment was associated with a redistribution of fat mass from abdominal to subcutaneous depots. Nifedipine reduced plasma triglyceride and fasting glucose levels and improved insulin response to an oral glucose load in obese females, whereas enalapril did not appear to affect glycemic control. Systolic pressure was not significantly decreased until after two months of treatment with nifedipine or three months of treatment with enalapril in obese females and may have coincided with improvement in insulin-resistance. Similarly, plasma atrial natriuretic peptide concentrations were significantly lower in obese females given nifedipine. To determine how obese males responded to a calcium channel antagonist, six-month-old obese male SHHF/Mcc-fa^cp rats were treated for three months with either nifedipine or placebo (controls). Nifedipine-treated obese males showed a mild but significant decrease in weight gain that was due to a decrease in fat deposition in both subcutaneous and abdominal depots and systolic blood pressure was significantly reduced after one month of treatment. Nifedipine did not affect other plasma biochemical parameters in obese males. In conclusion, nifedipine improved systolic pressure and glycemic control in obese female SHHI;/Mcc-fa^cp rats, effects that may be associated with a marked loss in body weight and fat mass and improved lipid metabolism. Nifedipine-treated obese males exhibited only a diminished weight gain that was not associated with changes in diabetic characteristics.     

Effect of Two or Six Doses 800 mg of Albendazole Every Two Months on Loa loa Microfilaraemia: A Double Blind,Randomized, Placebo-Controlled Trial

BackgroundLoiasis is a parasitic infection endemic in the African rain forest caused by the filarial nematode Loa loa. Loiasis can be co-endemic with onchocerciasis and/or lymphatic filariasis. Ivermectin, the drug used in the control of these diseases, can induce serious adverse reactions in patients with high L loa microfilaraemia (LLM). A drug is needed which can lower LLM below the level that represents a risk so that ivermectin mass treatment to support onchocerciasis and lymphatic filariasis elimination can be implemented safely.MethodologySixty men and women from a loiasis endemic area in Cameroon were randomized after stratification by screening LLM (≤30000, 30001–50000, >50000) to three treatment arms: two doses albendazole followed by 4 doses matching placebo (n = 20), six doses albendazole (n = 20) albendazole or 6 doses matching placebo (n = 20) administered every two months. LLM was measured before each treatment and 14, 18, 21 and 24 months after the first treatment. Monitoring for adverse events occurred three and seven days as well as 2 months after each treatment.

Principal Findings

None of the adverse events recorded were considered treatment related. The percentages of participants with ≥ 50% decrease in LLM from pre-treatment for ≥ 4 months were 53%, 17% and 11% in the 6-dose, 2-dose and placebo treatment arms, respectively. The difference between the 6-dose and the placebo arm was significant (p = 0.01). The percentages of participants with LLM < 8100 mf/ml for ≥4 months were 21%, 11% and 0% in the 6-dose, 2-dose and placebo treatment arms, respectively.

Conclusions/ Significance

The 6-dose regimen reduced LLM significantly, but the reduction was insufficient to eliminate the risk of severe and/or serious adverse reactions during ivermectin mass drug administration in loiasis co-endemic areas.     

Safety of treatment for subclinical osteomalacia in the elderly.

Forty one elderly patients admitted to hospital for acute illnesses were also found to have subclinical osteomalacia. Immediately before discharge, therefore, all were randomised to receive either vitamin D2 25 micrograms daily, alfacalcidol 0.5 micrograms daily, or placebo. Treatment was given for at least three months, those allocated to placebo then being switched to an active drug. Within the first three months of treatment with either of the active drugs most patients had exhibited a fall to normal in osteoid values. In only four treatment periods was there a mild increase in serum calcium concentration, and in no patient was this accompanied by deterioration in renal function. Any increase in serum creatinine concentration was invariably attributable to the underlying disease for which the patient had been admitted in the first place. Subclinical osteomalacia in the elderly may be corrected by relatively low doses of alfacalcidol (0.5 micrograms daily) or vitamin D2 (25 micrograms daily) given for three months. Such treatment is safe and not accompanied by a serious risk of hypercalcaemia or renal impairment.     

Sibutramine Produces Dose-Related Weight Loss

BRAY, GEORGE A., GEORGE L. BLACKBURN, JAMES M. FERGUSON, FRANK L. GREENWAY, ADESH K. JAIN, CARL M. MENDEL, JOSEPH MEN-DELS, DONNA H. RYAN, SHERWYN L. SCHWARTZ, MONTE L. SCHEINBAUM, AND TIMOTHY B. SEATON. Sibutramine produces dose-related weight loss. Obes Res. Objective Sibutramine is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. In animals, it reduces food intake and increases thermogenesis and preliminary data in human beings showed weight loss. This paper reports a 24-week dose-ranging study to determine the effect of sibutramine on body weight of patients with obesity. Research Methods and Procedures Seven clinical centers screened 1463 patients with obesity and randomized 1047 to 24 weeks of treatment with 1 of 6 doses of sibutramine (1, 5, 10, 15, 20, or 30 mg) or placebo once daily. Six hundred eighty-three patients completed the study. A two-week placebo run-in period was used to initiate a standardized program of diet, physical activity, and lifestyle changes. Results Weight loss was dose-related and statistically significant vs. placebo (p <0.05) across all time-points for a 5 mglday to 30 mglday dosage of sibutramine. At week 24, percent weight loss from baseline for completers was: placebo, 1.2%; 1 mg, 2.7%; 5 mg, 3.9%; 10 mg, 6.1%; 15 mg, 7.4%; 20 mg, 8.8%; and 30 mg, 9.4%. Weight loss achieved at week 4 was predictive of weight loss achieved at week 24. Patients losing weight demonstrated an increase in serum high density lipoprotein cholesterol and reductions in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, and uric acid. Small mean increases in blood pressure and pulse rate (with considerable individual variability) were observed in patients treated with sibutramine. The most frequent adverse events were dry mouth, anorexia, and insomnia. Discussion Sibutramine administered once daily for 24 weeks in the weight loss phase of treatment for uncomplicated obesity produced dose-related weight loss and was well tolerated. Improvements in serum lipids and uric acid accompany sibutramine-induced weight loss. Most of the adverse events observed on sibutramine are related to its pharmacology, including small mean increases in blood pressure and heart rate.     

Increased memory load-related frontal activation after estradiol treatment in postmenopausal women

Prior research shows that menopause is associated with changes in cognition in some older women. However, how estrogen loss and subsequent estrogen treatment affects cognition and particularly the underlying brain processes responsible for any cognitive changes is less well understood. We examined the ability of estradiol to modulate the manipulation of information in working memory and related brain activation in postmenopausal women. Twenty healthy postmenopausal women (mean age (SD) = 59.13 (5.5)) were randomly assigned to three months of 1 mg oral 17-β estradiol or placebo. At baseline and three months later each woman completed a visual verbal N-back sequential letter test of working memory during functional magnetic resonance imaging (fMRI). The fMRI data showed that women who were treated with estradiol for three months had increased frontal activation during the more difficult working memory load conditions compared to women treated with placebo. Performance on the verbal working memory task showed no difference between estradiol and placebo treated subjects. These data are consistent with prior work showing increases in frontal activation on memory tasks after estrogen treatment. However, this is the first study to show that estrogen-induced increases in brain activity were tied to cognitive load during a verbal working memory task. These data suggest that estradiol treatment effects on cognition may be in part produced through modulation of frontal lobe functioning under difficult task conditions.     

Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vaginosis and vulvovaginal candidiasis

This randomized double-blind placebo controlled study assessed the vaginal colonization of lactic acid bacteria and clinical outcome. Vaginal capsules containing L gasseri LN40, Lactobacillus fermentum LN99, L. casei subsp. rhamnosus LN113 and P. acidilactici LN23, or placebos were administered for five days to 95 women after conventional treatment of bacterial vaginosis and/or vulvovaginal candidiasis. Vulvovaginal examinations and vaginal samplings were performed before and after administration, after the first and second menstruation, and after six months. Presence of LN strains was assessed using RAPD analysis. LN strains were present 2–3 days after administration in 89% of the women receiving LN strains (placebo: 0%, p < 0.0001). After one menstruation 53% were colonized by at least one LN strain. Nine percent were still colonized six months after administration. Ninety-three percent of the women receiving LN strains were cured 2–3 days after administration (placebo: 83%), and 78% after one menstruation (placebo: 71%) (ns). The intervention group experienced less malodorous discharge 2–3 days after administration (p = 0.03) and after the second menstruation (p = 0.04), compared with placebo. In summary, five days of vaginal administration of LN strains after conventional treatment of bacterial vaginosis and/or vulvovaginal candidiasis lead to vaginal colonization, somewhat fewer recurrences and less malodorous discharge.