Stimulated sweating as a therapy to reduce interdialytic weight gain and improve potassium balance in chronic hemodialysis patients: a pilot study.

Controlling the extracellular volume in hemodialysis patients is a difficult task. The aim of this study was to evaluate the capacity of different methods of stimulated sweating to reduce mean interdialytic weight gain (IWG), to improve blood pressure regulation, and potassium/urea balance. Two center, crossover pilot study. In Lausanne, hemodialysis patients took four hot-water baths a week, 30 minutes each, on nondialysis days during 1 month. In Sfax, patients visited the local Hammam Center four times a week. Hemodynamic parameters were recorded, and weekly laboratory analysis was performed. Results were compared with a preceding 1-month control period. In Lausanne, five patients (all men, median age 55 years) participated. Bathing temperature was (mean ± standard deviation) 41.2 ± 3°C and sweating-induced weight loss 600 ± 500 g. Mean IWG (control vs. intervention period) decreased from 2.3 ± 0.9 to 1.8 ± 1 kg (P = 0.004), Systolic blood pressure from 139 ± 21 to 136 ± 22 mmHg (P = 0.4), and diastolic blood pressure form 79 ± 12 to 75 ± 13 mmHg (P = 0.08); antihypertensive therapy could be reduced from 2.8 ± 0.4 to 1.9 ± 0.5 antihypertensive drugs per patient (P = 0.01). In Sfax (n = 9, median age 46 years), weight loss per Hammam session was 420 ± 100 g. No differences were found in IWG or BP, but predialysis serum potassium level decreased from 5.9 ± 0.8 to 5.5 ± 0.9 mmol/L (P = 0.04) and urea from 26.9 ± 6 to 23.1 ± 6 mmol/L (P = 0.02). Hot-water baths appear to be a safe way to reduce IWG in selected hemodialysis patients. Hammam visits reduce serum potassium and urea levels, but not IWG. More data in larger patient groups are necessary before definite conclusion can be drawn.

Predicted effects of small decreases in energy expenditure on weight gain in adult women.

Small daily positive energy imbalances of 200 to 800 kJ (about 50 to 200 kcal) due to reduced resting energy expenditure (REE), reduced diet-induced thermogenesis, or physical inactivity are believed to predispose to obesity. However, estimates of the magnitude of the weight gain often fail to account for concurrent changes in body composition and increases in maintenance energy requirements as weight increases and energy equilibrium is re-established. Using previously reported data on body composition and REE in women and the energy cost of tissue deposition, we used mathematical models to predict the theoretical effect of a persistent reduction in energy expenditure on long-term weight gain, assuming no adaptation in energy intake. The analyses indicate the following effects of a reduced level of energy expenditure in lean and obese women: (i) REE rises more slowly with increasing degrees of obesity due to a declining proportion of the more metabolically active fat-free mass; so, for the same positive energy balance, a significantly greater weight gain is expected for obese than for lean women before energy equilibrium is re-established; (ii) due to the greater energy density of adipose tissue, the time course of weight gain to achieve energy balance is longer for obese subjects: in general, this is approximately five years for lean and ten years for obese women; (iii) the magnitude of weight gain of lean women in response to a reduced energy expenditure of 200 to 800 kJ/day is only about 3 to 15 kg, amounts insufficient to explain severe obesity.

Meal-induced thermogenesis and obesity: is a fat meal a risk factor for fat gain in children?

Diet composition, in particular fat intake, has been suggested to be a risk factor for obesity in humans. Several mechanisms may contribute to explain the impact of fat intake on fat gain. One factor may be the low thermogenesis induced by a mixed meal rich in fat. In a group of 11 girls (10.1 +/- 0.3 yr), 6 obese (body mass index, 25.6 +/- 0.6 kg/m(2)), and 5 nonobese (body mass index, 19 +/- 1.6 kg/m(2)), we tested the hypothesis that a mixed meal rich in fat can elicit energy saving compared with an isocaloric and isoproteic meal rich in carbohydrate. The postabsorptive resting energy expenditure and the thermic effect of a meal (TEM) after a low fat (LF; 20% fat, 68% carbohydrate, and 12% protein) or an isocaloric (2500 kJ or 600 Cal) and isoproteic high fat (HF; 48% fat, 40% carbohydrate, and 12% protein) meal were measured by indirect calorimetry. Each girl repeated the test with a different, randomly assigned menu (HF or LF) 1 week after the first test. TEM, expressed as a percentage of energy intake was significantly higher after a LF meal than after a HF meal (6.5 +/- 0.7% vs. 4.3 +/- 0.4%; P < 0.01). The postprandial respiratory quotient (RQ) was significantly higher after a LF meal than after a HF meal (0.86 +/- 0.013 vs. 0.83 +/- 0.014; P < 0.001). The HF low carbohydrate meal induced a significantly lower increase in carbohydrate oxidation than the LF meal (20.3 +/- 6.2 vs. 61.3 +/- 7.8 mg/min; P < 0.001). On the contrary, fat oxidation was significantly higher after a HF meal than after a LF meal (-1.3 +/- 2.4 vs. -15.1 +/- 3.6 mg/min; P < 0.01). However, the postprandial fat storage was 8-fold higher after a HF meal than after a LF meal (17.2 +/- 1.7 vs. 1.9 +/- 1.8 g; P < 0.001). These results suggest that a high fat meal is able to induce lower thermogenesis and a higher positive fat balance than an isocaloric and isoproteic low fat meal. Therefore, diet composition per se must be taken into account among the various risk factors that induce obesity in children.

Gain of function mutations in CgPDR1 of Candida glabrata not only mediate antifungal resistance but also enhance virulence.

CgPdr1p is a Candida glabrata Zn(2)-Cys(6) transcription factor involved in the regulation of the ABC-transporter genes CgCDR1, CgCDR2, and CgSNQ2, which are mediators of azole resistance. Single-point mutations in CgPDR1 are known to increase the expression of at least CgCDR1 and CgCDR2 and thus to contribute to azole resistance of clinical isolates. In this study, we investigated the incidence of CgPDR1 mutations in a large collection of clinical isolates and tested their relevance, not only to azole resistance in vitro and in vivo, but also to virulence. The comparison of CgPDR1 alleles from azole-susceptible and azole-resistant matched isolates enabled the identification of 57 amino acid substitutions, each positioned in distinct CgPDR1 alleles. These substitutions, which could be grouped into three different "hot spots," were gain of function (GOF) mutations since they conferred hyperactivity to CgPdr1p revealed by constitutive high expression of ABC-transporter genes. Interestingly, the major transporters involved in azole resistance (CgCDR1, CgCDR2, and CgSNQ2) were not always coordinately expressed in presence of specific CgPDR1 GOF mutations, thus suggesting that these are rather trans-acting elements (GOF in CgPDR1) than cis-acting elements (promoters) that lead to azole resistance by upregulating specific combinations of ABC-transporter genes. Moreover, C. glabrata isolates complemented with CgPDR1 hyperactive alleles were not only more virulent in mice than those with wild type alleles, but they also gained fitness in the same animal model. The presence of CgPDR1 hyperactive alleles also contributed to fluconazole treatment failure in the mouse model. In conclusion, this study shows for the first time that CgPDR1 mutations are not only responsible for in vitro/in vivo azole resistance but that they can also confer a selective advantage under host conditions.

Composition of weight gain during the neonatal period and longitudinal growth follow-up in premature babies.

Changes in the rate of growth and adiposity index (Quetelet index), calculated as weight/(length)2, kg/m2, were monitored from birth to 3 years in 19 premature babies (post-conceptional age 31.2 +/- 2 weeks) who were subjected during rapid growth (16 +/- 4 g/kg.day) to initial metabolic balance studies in the first weeks of life. These studies showed that the rate of fat accretion in these infants (3.3 +/- 0.9 g/kg.day) was substantially greater than that observed in fetuses of the same gestational age (2 g/kg.day) but the adiposity index was lower (9.6 +/- 1 kg/m2) than intrauterine values (11 kg/m2). Since at 6 months of age (corrected for gestational age at birth) the adiposity index was close to normality (103% of standard), the greater rate of fat accretion in early life contributed to progressively restore total body fat in premature babies. It is concluded that despite substantial fat deposition during the first weeks of life, the future evolution of these premature babies is favourable as judged from the normalization of adiposity index within the first 2 years of life.

A Heterozygous Deletion Mutation in the Cardiac Sodium Channel Gene SCN5A with Loss- and Gain-of-Function Characteristics Manifests as Isolated Conduction Disease, without Signs of Brugada or Long QT Syndrome.

BACKGROUND: The SCN5A gene encodes for the α-subunit of the cardiac sodium channel NaV1.5, which is responsible for the rapid upstroke of the cardiac action potential. Mutations in this gene may lead to multiple life-threatening disorders of cardiac rhythm or are linked to structural cardiac defects. Here, we characterized a large family with a mutation in SCN5A presenting with an atrioventricular conduction disease and absence of Brugada syndrome. METHOD AND RESULTS: In a large family with a high incidence of sudden cardiac deaths, a heterozygous SCN5A mutation (p.1493delK) with an autosomal dominant inheritance has been identified. Mutation carriers were devoid of any cardiac structural changes. Typical ECG findings were an increased P-wave duration, an AV-block I° and a prolonged QRS duration with an intraventricular conduction delay and no signs for Brugada syndrome. HEK293 cells transfected with 1493delK showed strongly (5-fold) reduced Na(+) currents with altered inactivation kinetics compared to wild-type channels. Immunocytochemical staining demonstrated strongly decreased expression of SCN5A 1493delK in the sarcolemma consistent with an intracellular trafficking defect and thereby a loss-of-function. In addition, SCN5A 1493delK channels that reached cell membrane showed gain-of-function aspects (slowing of the fast inactivation, reduction in the relative fraction of channels that fast inactivate, hastening of the recovery from inactivation). CONCLUSION: In a large family, congregation of a heterozygous SCN5A gene mutation (p.1493delK) predisposes for conduction slowing without evidence for Brugada syndrome due to a predominantly trafficking defect that reduces Na(+) current and depolarization force.

Socio-demographic and behavioural determinants of weight gain in the Swiss population.

BackgroundIn Switzerland, socio-demographic and behavioural factors are associated with obesity, but no study ever assessed their impact on weight gain using prospective data.MethodsData from 4,469 participants (53.0% women), aged 35 to 75 years at baseline and followed for 5.5 years. Weight gain was considered as a rate (kg/year) or as gaining ¿5 kg during the study period.ResultsRate of weight gain was lower among participants who were older (mean¿±¿standard deviation: 0.46¿±¿0.92, 0.33¿±¿0.88, 0.21¿±¿0.86 and 0.06¿±¿0.74 kg/year in participants aged [35-45[, [45-55[, [55¿65[and [65+ years, respectively, P<0.001); physically active (0.27¿±¿0.82 vs. 0.35¿±¿0.95 kg/year for sedentary, P¿<¿0.005) or living in a couple (0.29¿±¿0.84 vs. 0.35¿±¿0.96 kg/year for living single, P¿<¿0.05), and higher among current smokers (0.41¿±¿0.97, 0.26¿±¿0.84 and 0.29±0.85 kg/year for current, former and never smokers, respectively, p<0.001). These findings were further confirmed by multivariable analysis. Multivariable logistic regression showed that receiving social help, being a current smoker or obese increased the likelihood of gaining ¿5Kg: Odds ratio (OR) and 95% confidence interval (CI) 1.43 (1.16-1.77); 1.63 (1.35-1.95) and 1.95 (1.57-2.43), respectively, while living in couple or being physically active decreased the risk: 0.73 (0.62-0.86) and 0.72 (0.62-0.83), respectively. No association was found between weight gain and gender, being born in Switzerland or education.ConclusionsIn Switzerland, financial difficulties (indicated by receiving social help) and current smoking were associated with increases in body weight over a 5 years follow-up. Living in couple, being older or physically active were protective against weight gain.

Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population.

PURPOSE: To describe the weight gain-related side-effects of psychotropic drugs and their consequences on metabolic complications (hypercholesterolemia, obesity) in a Swiss cohort of psychiatric patients. METHOD: This cross-sectional observational study was performed in an out-patient psychiatric division with patients having received for more than 3 months the following drugs: clozapine, olanzapine, quetiapine, risperidone, lithium, and/or valproate. Clinical measures and lifestyle information (smoking behaviour, physical activity) were recorded. RESULTS: 196 inclusions were completed. Weight gain (≥10% of initial weight) following drug treatment was reported in 47% of these patients. Prevalence of obesity (BMI ≥ 30), hypercholesterolemia (≥6.2 mmol/L) and low HDL-cholesterol (<1.0 mmol/L in men, <1.3 mmol/L in women) were present in 38%, 21%, and 27% of patients, respectively. A higher standardised dose, an increase of appetite following medication introduction, the type of medication (clozapine or olanzapine > quetiapine or risperidone > lithium or valproate), and the gender were shown to be significantly associated with evolution of BMI. CONCLUSION: High prevalence of obesity and hypercholesterolemia was found in an out-patient psychiatric population and confirms drug-induced weight gain complications during long-term treatment. The results support the recently published recommendations of monitoring of metabolic side-effects during treatment with atypical antipsychotics. Moreover, the weight gain predictors found in the present study could help to highlight patients with special health care management requirement.

Congenital ataxia and hemiplegic migraine with cerebral edema associated with a novel gain of function mutation in the calcium channel CACNA1A.

Mutations in the CACNA1A gene, encoding the α1 subunit of the voltage-gated calcium channel CaV2.1 (P/Q-type), have been associated with three neurological phenotypes: familial and sporadic hemiplegic migraine type 1 (FHM1, SHM1), episodic ataxia type 2 (EA2), and spinocerebellar ataxia type 6 (SCA6). We report a child with congenital ataxia, abnormal eye movements and developmental delay who presented severe attacks of hemiplegic migraine triggered by minor head traumas and associated with hemispheric swelling and seizures. Progressive cerebellar atrophy was also observed. Remission of the attacks was obtained with acetazolamide. A de novo 3bp deletion was found in heterozygosity causing loss of a phenylalanine residue at position 1502, in one of the critical transmembrane domains of the protein contributing to the inner part of the pore. We characterized the electrophysiology of this mutant in a Xenopus oocyte in vitro system and showed that it causes gain of function of the channel. The mutant CaV2.1 activates at lower voltage threshold than the wild type. These findings provide further evidence of this molecular mechanism as causative of FHM1 and expand the phenotypic spectrum of CACNA1A mutations with a child exhibiting severe SHM1 and non-episodic ataxia of congenital onset.

Metabolic predictors of obesity. Contribution of resting energy expenditure, thermic effect of food, and fuel utilization to four-year weight gain of post-obese and never-obese women.

This prospective study was designed to identify abnormalities of energy expenditure and fuel utilization which distinguish post-obese women from never-obese controls. 24 moderately obese, postmenopausal, nondiabetic women with a familial predisposition to obesity underwent assessments of body composition, fasting and postprandial energy expenditure, and fuel utilization in the obese state and after weight loss (mean 12.9 kg) to a post-obese, normal-weight state. The post-obese women were compared with 24 never-obese women of comparable age and body composition. Four years later, without intervention, body weight was reassessed in both groups. Results indicated that all parameters measured in the post-obese women were similar to the never-obese controls: mean resting energy expenditure, thermic effect of food, and fasting and postprandial substrate oxidation and insulin-glucose patterns. Four years later, post-obese women regained a mean of 10.9 kg while control subjects remained lean (mean gain 1.7 kg) (P < 0.001 between groups). Neither energy expenditure nor fuel oxidation correlated with 4-yr weight changes, whereas self-reported physical inactivity was associated with greater weight regain. The data suggest that weight gain in obesity-prone women may be due to maladaptive responses to the environment, such as physical inactivity or excess energy intake, rather than to reduced energy requirements.

Cognitive behavioural therapy for weight gain associated with antipsychotic drugs

BACKGROUND: Overweight and obesity are common concerns in individuals with severe mental disorders. In particular, antipsychotic drugs (AP) frequently induce weight gain. This phenomenon lacks current management and no previous controlled studies seem to use cognitive therapy to modify eating and weight-related cognitions. Moreover, none of these studies considered binge eating or eating and weight-related cognitions as possible outcomes. AIM: The main aim of this study is to assess the effectivity of cognitive and behavioural treatment (CBT) on eating and weight-related cognitions, binge eating symptomatology and weight loss in patients who reported weight gain during AP treatment. METHOD: A randomized controlled study (12-week CBT vs. Brief Nutritional Education) was carried out on 61 patients treated with an antipsychotic drug who reported weight gain following treatment. Binge eating symptomatology, eating and weight-related cognitions, as well as weight and body mass index were assessed before treatment, at 12 weeks and at 24 weeks. RESULTS: The CBT group showed some improvement with respect to binge eating symptomatology and weight-related cognitions, whereas the control group did not. Weight loss occurred more progressively and was greater in the CBT group at 24 weeks. CONCLUSION: The proposed CBT treatment is particularly interesting for patients suffering from weight gain associated with antipsychotic treatment