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Aims/hypothesis: The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. Methods: A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which a continuous recording of the ECG was performed. The effect of insulin on cardiac autonomic balance was evaluated by performing power spectral analysis of heart rate variability. The low-to-high frequency ratio was calculated before and during the clamp and its modifications were expressed as % delta low-to-high frequency ratio (%Δ L: H). Results: Preoperative %Δ L: H showed a significant (p=0.0009, r 2=0.43), positive relationship to the reduction of body weight, measured 1 year after surgery and expressed as % excess weight loss (% EWL). Preoperative BMI was also significantly (p=0.0009, r 2=0.43) negatively related to the 12-month % EWL. In a multiple regression analysis, %Δ L: H remained a significant (p=0.003), independent predictor of body weight loss, even when preoperative BMI or age, % fat mass, insulinaemia and glucose disposal were taken into account. Conclusions/interpretation: The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic-hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reduction

Multiple insulin injection therapy can easily be adapted to the patient's needs. Therefore, it is supposed that more intensive insulin therapy is associated with better metabolic control and less hypoglycaemia compared with a conventional insulin strategy in patients with type 2 diabetes.HbA1c and incidence of non-severe and severe hypoglycaemia were analysed with regard to the strategy of insulin therapy [multiple insulin injection therapy with preprandial insulin with or without basal insulin or conventional insulin therapy with twice-daily premix insulin] from 20 943 visits of 1417 people treated with insulin with type 2 diabetes in a university outpatient department for endocrinology and metabolic diseases over a period of 22 years.Multiple insulin injection therapy was used in 13 896 (66.4%) of all 20 942 visits. Compared with conventional insulin therapy, these patients were younger (62.0 vs 68.7 years; p 0.001), had a slightly longer diabetes duration (16.5 vs 15.8 years; p 0.001) and higher body mass index (32.8 vs 30.9 kg/m(2) ; p 0.001), a higher insulin dose (76.4 vs 46.5 IU/day; p 0.001), more frequent blood glucose monitorings/week (24.2 vs 14.8; p 0.001), a slightly lower HbA1c [7.7 (61.2) vs 7.9% (62.9 mmol/mol); p 0.001] but more non-severe hypoglycaemic incidences per week (0.3 vs 0.2; p = 0.01). Episodes of severe hypoglycaemia were rare and comparable (0.01/patient/year) with both insulin therapy strategies.Multiple insulin injection therapy and conventional insulin therapy yielded comparable metabolic control with HbA1c below 8% (63.9 mmol/mol), but multiple insulin injection therapy is associated with higher body mass index and higher incidence of non-severe hypoglycaemia. Copyright © 2016 John WileySons, Ltd.

Objective: The gastric bypass-induced quantitative and qualitative modifications of energy intake (En In, kcal/day) and their impact on body weight (bw) loss were evaluated. The factors influencing energy intake and body weight loss were also investigated. Design: Longitudinal study. Setting: University Hospital of Geneva. Subjects: Fifty obese women undergoing a Roux-en-Y gastric bypass. Results: The reduction of EnIn was significantly related to bw loss expressed either in kg or as percentage correction of excess bw (P

The aim of this investigator-initiated trial is to evaluate the safety and efficacy of the novel Luminor® paclitaxel-coated drug-eluting balloon (DEB) catheter (iVascular, S.L.U., Barcelona, Spain) in inhibiting restenosis and in ensuring long-term vascular patency.This is a multicenter randomized controlled trial to evaluate the Luminor® paclitaxel-coated DEB catheter for stenotic or occlusive lesions (length ≤15 cm) in the superficial femoral artery (SFA) and the popliteal artery (PA) up to the P1 segment compared to the noncoated, plain old balloon angioplasty (POBA) catheter. In total 172 subjects will be treated with either the DEB catheter or the POBA catheter in 11 German study centers in a 1:1 randomization study design. The primary endpoint is late lumen loss (LLL) at 6 months. Secondary endpoints are patency rate, target lesion/vessel revascularization, quality of life (assessed with the Walking Impairment Questionnaire (WIQ) and the EQ-5D), change of Rutherford stage and ankle-brachial index, major and minor amputation rate at the index limb, number of dropouts and all-cause mortality.EffPac represents a randomized controlled trial that will provide evidence on the effectiveness of the Luminor® paclitaxel-coated DEB catheter for the reduction of restenosis compared to the POBA catheter for the SFA and the PA. The results of EffPac will allow direct comparison to other already-completed RCTs applying paclitaxel-coated DEBs from different manufacturers with different coating technologies in the same target vessel.ClinicalTrials.gov Identifier: NCT02540018 , registered on 17 August 2015. Protocol version: CIP Version Final04, 11 February 2016. EUDAMED No: CIV-15-03-013204.

In this study, we have retrospectively (2 years) assessed the efficacy of the nutritional education (NE) program provided to 83 diabetic patients during an in-hospital training week. Two years after NE, type 1 diabetic patients have decreased significantly their total caloric intake, protein (P

At the onset of menopause, weight-gain and the aggravation of certain cardiovascular risk factors are frequently observed. The aim of this study was to examine the metabolic effects of combined hormone replacement therapy (17beta-oestradiol transdermic 50 microg for 21 days and oral medroxyprogesterone acetate 5 mg from day 10 to 21) using, in particular, indirect calorimetry.Patients (21; 12 substituted and nine controls) were studied twice (3 months apart) during an oral glucose load (75 g).Total body weight was unaltered after 3 months in the control group, whereas a fat-loss of 2.1+/-0.2 kg and a decrease of the waist:hip ratio were observed in the substituted group. In the latter group, a significant increase in lipid oxidation was observed (0.58+/-0.06 mg/kg/min before and 0.75+/-0.04 mg/kg/min after substitution P0.05), whilst total energy expenditure and thermogenesis were also increased. Glucose, lipid and protein oxidation remained stable during three months in the control group. The insulin response to an oral glucose load diminished by 30% with hormone replacement therapy (102.3+/-32.8 mmicro/l versus 71.4+/-20.0 mmicro/l). Total and LDL-cholesterol improved after hormone replacement therapy whereas plasma triglycerides were not altered.Combined hormone replacement therapy not only prevented weight-gain, but favored weight-loss by significantly increasing lipid oxidation after 3 months of treatment. It also favourably influenced the insulin response, plasma lipids and energy expenditure.

OBJECTIVE: To investigate possible relationships between leptin and energy expenditure (EE), both in the condition of stable body weight and during weight loss. SUBJECTS: Seventy four Caucasian, adult obese women with stable body weight (including 10 obese women studied before and during a body weight-reducing program). MEASUREMENTS: Resting EE (REE) and substrate oxidation rates by indirect calorimetry; plasma leptin concentrations by radioimmunoassay (RIA). RESULTS: In conditions of stable body weight, leptin values showed a significant, negative relationship with REE, as expressed in absolute values (P = 0.030) and as adjusted for the variation in lean body mass (LBM) (P = 0.017). This negative relationship was independent of both LBM and fat mass (FM). Linear regression analysis was used to obtain the equation linking REE and LBM; then both predicted REE and the percent deviation from predicted REE were calculated for each subject. Leptin values were negatively related (P < 0.0001) to the deviation from predicted REE. During active body weight loss, the modifications of both REE (delta REE) and lipid oxidation (delta lipid oxidation) were significantly negatively related to leptin concentrations, which were measured before the dieting period (P < 0.03 for both). CONCLUSION: In obese women, high plasma leptin concentrations are associated with a low rate of REE, when body weight is stable, and with a reduction of REE and lipid oxidation, in response to a hypocaloric diet. This suggests that, in severely obese women, leptin is a marker of sparing energy mechanisms operating in both basal and reducing weight conditions.

OBJECTIVE: To examine the relationships between the distribution and composition of subfractions of very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins and central fat deposition as measured by the waist-to-hip ratio (WHR). DESIGN: Participants (n=62, 44 women and 18 men; body mass index (BMI)≥25.0) were recruited from those consecutively attending the outpatient obesity clinic at the University Hospital, Geneva. MEASUREMENTS: Lipoprotein subfractions were isolated from fasting blood samples by cumulative flotation or density gradient ultracentrifugation. Concentration and composition were analysed as a function of obesity indices. RESULTS: There were significant correlations between the WHR and the profiles of the three major lipoprotein subclasses. Central obesity was associated with larger VLDL, small, dense LDL and lower levels of HDL-2 independently of other indices of obesity and plasma triglycerides. Central obesity was also significantly and independently associated with compositional anomalies, specifically an increased free cholesterol content of VLDL and LDL. CONCLUSIONS: Central body fat was associated with modifications of an atherogenic nature to lipoprotein distribution and composition. The data are consistent with an impact of body fat distribution on cardiovascular disease (CVD) via the agency of modified lipoprotein metabolism independently of raised triglycerides.

The prevalence of hyperostotic spurs (HS) in different areas of the shoulder was studied in 36 probands with and 58 probands without thoracospinal hyperostosis on lateral chest radiographs. Bilateral shoulder radiographs in three projections were analysed blindly, recording the presence of HS at six separate sites (glenoid, greater tuberculum, acromion, acromioclavicular joint, coracoid and humeral shaft) and applying defined grading criteria. The prevalence of HS ranged from 11.7% of the shoulders at the coracoid to 50.0% at the glenoid. The prevalence of HS was similar on both sides [right, 30.1% of the sites versus left, 27.0%, relative risk (RR) 1.12 (95% confidence interval [Cl] 0.93-1.35)] and was not related to sex and history of work. Classification for the presence of shoulder hyperostosis was identical on both sides with the exception of one individual. In probands with thoracospinal and shoulder hyperostosis all areas analysed contributed to the classification. However, this was particularly prominent at the humeral shaft [RR 5.3 (95% Cl 2.1-13.0)] and the coracoid [RR 8.4 (95% Cl 1.9-36.4)]. These results indicated that the prevalence of HS and the specificity for the presence of diffuse idiopathic skeletal hyperostosis (DISH) vary between different sites. We suggest that future grading criteria for shoulder hyperostosis take into account the localization of HS, in addition to their number and size.

In the process of risk stratification, a logistic calculation of mortality risk in percentage is easier to interpret. Unfortunately, there is no reliable logistic model available for postoperative intensive care patients. The aim of this study was to present the first logistic model for postoperative mortality risk stratification in cardiac surgical intensive care units. This logistic version is based on our previously presented and established additive model (CASUS) that proved a very high reliability.In this prospective study, data from all adult patients admitted to our ICU after cardiac surgery over a period of three years (2007-2009) were collected. The Log-CASUS was developed by weighting the 10 variables of the additive CASUS and adding the number of postoperative day to the model. Risk of mortality is predicted with a logistic regression equation. Statistical performance of the two scores was assessed using calibration (observed/expected mortality ratio), discrimination (area under the receiver operating characteristic curve), and overall correct classification analyses. The outcome measure was ICU mortality.A total of 4054 adult cardiac surgical patients was admitted to the ICU after cardiac surgery during the study period. The ICU mortality rate was 5.8%. The discriminatory power was very high for both additive (0.865-0.966) and logistic (0.874-0.963) models. The logistic model calibrated well from the first until the 13th postoperative day (0.997-1.002), but the additive model over- or underestimated mortality risk (0.626-1.193).The logistic model shows statistical superiority. Because of the precise weighing the individual risk factors, it offers a reliable risk prediction. It is easier to interpret and to facilitate the integration of mortality risk stratification into the daily management more than the additive one.

To assess the relationship between social status and quality of diabetes care in a tertiary care centre in Germany.Social status was assessed in 940 consecutive patients in a university outpatient department by a questionnaire. The assessment comprised three components: education, highest professional position and household net income (total score 3-21). Quality of diabetes care was measured by HbA(1c) , blood pressure and BMI. The influence of social status on quality measures was analysed at entry and last visit by fitting linear mixed models.At the entry visit, patients with lower social status had a higher HbA(1c) compared with patients with higher status (0.06% per each point of social score difference). After a mean follow- up of 6.0 years (Type 2 diabetes) and 9.4 years (Type 1 diabetes) no significant differences in HbA(1c) could be found. However, difference in BMI (-0.41 kg/m² per each point of social score) persisted at last observation. Blood pressure was only negligibly affected by the care programme.Low social status is associated with worse quality of diabetes care at entry in a tertiary care centre. The differences in HbA(1c) disappeared after treatment and structured education, whereas the difference in BMI persisted. There was no significant influence of social status or treatment on blood pressure.

Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is now an established therapy with a curative option for patients with gastrointestinal and gynecological peritoneal carcinomatosis as well as for primary peritoneal carcinomatous tumors. Decisive for the prognosis is a complete cytoreduction, which in most cases necessitates multi-organ resection in addition to a partial or subtotal parietal peritonectomy (PE). The highest priority is given to maintain an adequate quality of life for the patient while performing maximum tumor resection. The morbidity following PE and HIPEC in experienced centers lies between 25% and 35% with a mortality risk of5%. Consideration must be given not only to the technical surgical aspects and the intraoperative decision-making but also to the intraoperative management, intensive care therapy, pain therapy, management of complications, physiotherapy and many more. The greatest challenge in the management of peritoneal carcinomatosis is still patient selection. Computed tomography imaging together with (18)fluorodeoxyglucose positron emission tomography (FDG-PET) plays an important role in the assessment of operability.

There are conflicting data regarding the risk of osteoporosis in patients with Type 1 diabetes. We investigated an association between diabetes, bone mineral density and prevalent fractures.A single-centre, cross-sectional study of men and pre-menopausal women with Type 1 diabetes (n = 128) and a matched control group (n = 77) was conducted. The primary outcome measure was bone mineral density and secondary measures were markers of bone metabolism and prevalent fractures.Hip and total body bone mineral densities were significantly lower in women with diabetes compared with control subjects. In men, no difference in bone mineral density was found. A multivariate regression analysis in women with diabetes revealed higher BMI as the strongest predictor of higher total hip, femoral neck and total body bone mineral density, whereas previous fractures were inversely associated with total hip bone mineral density and C-terminal telopeptide of type I collagen with total body bone mineral density. Poor long-term glycaemic control was not associated with low bone mineral density. Fracture frequency was higher in patients with diabetes compared with control subjects (1.64 vs. 0.62 per 100 patient-years; P0.05). In a multivariable model, long-term HbA(1c) control was associated with increased clinical fracture prevalence (OR 1.92; 95% CI 1.09-2.75) in those with diabetes.Type 1 diabetes contributes to low bone mineral density in women. Previous fractures and low BMI were strong predictors of impaired bone mineral density and should therefore be considered in risk estimation. Fractures are more frequent in Type 1 diabetes. Long-term hyperglycaemia may account for impaired bone strength, independently from bone mineral density.

The study was conducted to assess the rate of suspected pulmonary embolism (PE) prior to death and the diagnostic and therapeutic procedures performed.Patients with autopsy-confirmed PE between 1998 and 2002 were included. Autopsy register and medical records were reviewed for history, diagnosis and therapy of PE. Patients were categorised into fatal and non-fatal PE according to the autopsy findings.102 patients with fatal and 247 patients with non-fatal PE were eligible for analysis (median age 68 years; 24-95). In 58.8% with fatal and in 32% with non-fatal PE, disease was suspected pre-mortal. Clinical suspicion of PE was significantly enhanced in venous thrombosis (Odds Ratio [OR] = 12.17, p=0.004) and significantly decreased for chronic vascular disease (OR = 0.30, p=0.002). Recurrent PE was demonstrated in 31.4% fatal and in 4.5% non-fatal PE (OR = 9.81, p=0.001). 7% of all PE were localised centrally, 19% centrally and peripherally and 74% peripherally. Dyspnoea and tachycardia were the most frequent symptoms in fatal PE. About half of all patients suffered from malignancies. Suspicion of PE decreased after day 14 of hospitalisation (OR = 0.33, p=0.021).PE often is not diagnosed pre-mortally. Patients with chronic vascular disease and tumours as well as those hospitalised for over 14 days are at particular risk for PE.

The purpose of this study was to analyse metabolic control in patients with diabetes mellitus in primary care in Thuringia and to evaluate HbA1c mapping as a newly proposed method for population-based continuous monitoring of metabolic control in primary care.A cross-sectional study (2nd quarter 2005) using the electronic data bases of Thuringian medical laboratories (HbA1c, postal code of GP) was undertaken. The study population comprised all Thuringian patients with diabetes mellitus who were treated in ambulatory care. A comparison was made between data from HbA1c mapping and data collected by GPs (general practitioner) of two selected areas.We collected 89,407 HbA1c tests by HbA1c mapping: the following values were obtained - mean HbA1c: 6.73+/-1.27%; HbA1c/=7%: 32.6%; HbA1c/=10%: 2.4% of all HbA1c tests. The mean HbA1c was 0.2% lower in HbA1c mapping compared to data collection in GPs (HbA1c 6.8+/-1.32% vs. 7.02+/-1.26%, p0.001). The percentage of HbA1c tests below 7% was higher, HbA1c test results between 7% and 9% were less frequent in HbA1c mapping. Patient data were as follows: type 2 diabetes 98.7%, female gender: 57%, age 69.8+/-11.6 years, insulin therapy 28.8%.The Thuringian cross-sectional study 2005 showed acceptable results for metabolic control in ambulatory care. The results of HbA1c mapping were comparable to the data on glycaemic control of patients with diabetes mellitus in ambulatory care.

To assess the outcome of a Diabetes Treatment and Teaching Programme (DTTP) on glycated haemoglobin (HbA1c), severe hypoglycaemia (SH) and severe ketoacidosis (SKA) in adolescents and young adults with Type 1 diabetes.Quality-assurance project with assessment of participants 1 year after participation in a DTTP (5-day inpatient course, groupsor = 10 patients, fixed curriculum of education/training, introduction of dietary freedom). Before-after analyses of participants aged 12-15, 15-18, 18-21 and 21-24 years. Main outcome measures were HbA1c, SH and SKA.For the 1592 participants, aged 12 to 24 years, mean age at enrolment was 19 +/- 3 years, mean duration of diabetes was 7.3 +/- 5.4 (range 0.3-24) years, mean baseline HbA1c declined from 8.8 +/- 2.3% to 8.1 +/- 2.0%. The incidence of SH was 0.31 vs. 0.11 events/patient/year; the incidence of SKA 0.17 vs. 0.07 events/patient/year. In mixed effects models taking into account effects of centres, age and diabetes duration, the mean difference was -0.64%[P0.001, 95% confidence interval (CI) -0.79 to -0.5] for HbA1c, -0.2 events/patient/year (P0.0001, 95% CI -0.28 to -0.12) for SH and -0.1 events/patient/year (P0.0001, 95% CI -0.14 to -0.06) for SKA.Adolescents and young adults with Type 1 diabetes benefit from participation in a standard DTTP for flexible, intensive insulin therapy and dietary freedom.

Adipose tissue secretes a variety of cytokines, some of which are increased in the serum of obese patients. The anti-inflammatory interleukin-1 receptor antagonist (IL-1Ra) is the most highly elevated known cytokine in human obesity, and its serum levels are strongly associated with the degree of insulin resistance in non-diabetic patients. AIM: The present study examined serum levels of IL-1Ra in type 2 diabetic patients (T2DM) and their relationships with three other adipokines (leptin, interleukin-6 [IL-6], adiponectin). Their correlation with anthropometric and biochemical variables was examined, as well as their intraindividual fluctuations. METHODS: Fifty T2DM patients, aged 58+/-13 years, were consecutively recruited among those electively hospitalized for a one-week intensive training course with our Diabetes Education Service. Anthropometric measurements and blood samples were taken after an overnight fast on admission (baseline) and after four days. RESULTS: Mean serum levels of IL-1Ra and leptin, but not of IL-6 and adiponectin, were significantly higher in women than in men (P

Knowledge of ecological differences between the molecular forms of Anopheles gambiae Giles (Diptera: Culicidae) might lead to understanding of their unique contribution to disease transmission, to better vector control, and to identification of the forces that have separated them. We compared female fecundity measured as egg batch size in relation to body size between the molecular forms in Mali and contrasted them with their sibling species, Anopheles arabiensis Patton. To determine whether eggs of different egg batches are of similar "quality," we compared the total protein content of first-stage larvae (L1s), collected2 h after hatching in deionized water. Egg batch size significantly varied between An. gambiae and An. arabiensis and between the molecular forms of An. gambiae (mean batch size was 186.3, 182.5, and 162.0 eggs in An. arabiensis and the M and the S molecular form of An. gambiae, respectively). After accommodating female body size, however, the difference in batch size was not significant. In the S molecular form, egg protein content was not correlated with egg batch size (r = -0.08, P0.7) nor with female body size (r = -0.18, P0.4), suggesting that females with more resources invest in more eggs rather than in higher quality eggs. The mean total protein in eggs of the M form (0.407 microg per L1) was 6% higher than that of the S form (0.384 microg per L1), indicating that the M form invests a greater portion of her resources into current (rather than future) reproduction. A greater investment per offspring coupled with larger egg batch size may reflect an adaptation of the M form to low productivity larval sites as independent evidence suggests.

The prevalence of Toxoplasma gondii in free-ranging chickens can be considered a good indicator of the prevalence of T. gondii oocysts in the environment because chickens feed from the ground. In the present study, prevalence of T. gondii in 29 free-range chickens (Gallus domesticus) from Argentina was investigated. Blood, heart, and brain from each chicken were examined for T. gondii infection. Antibodies to T. gondii, assayed with the modified agglutination test (MAT), were found in 19 of 29 (65.5%) chickens. Hearts and brains of seropositive (MATor = 1:5) chickens were bioassayed in mice. Toxoplasma gondii was isolated from 9 of 19 seropositive chickens. Genotyping of chicken isolates of T. gondii using the SAG2 locus indicated that 1 was type I, 1 was type II, and 7 were type III. This is the first report of isolation of T. gondii from chickens from Argentina.

Mesenteric inflammatory veno-occlusive disease (MIVOD) is a rare cause of intestinal ischemia of unknown etiology. Histologically, MIVOD is characterized by extended thrombophlebitis and fibrous organized thrombosis of multiple veins. The arteries are by definition not involved. Management includes surgery in all cases described. Recurrence has not been described until now.We describe the case of a 64-year-old woman operated with the suspicion of intestinal ischemia. Clinical and histopathological characteristics are reported.The patient underwent a right hemicolectomy and segmental resection of the terminal ileum 15 months later for a recurrence. The histological examination of the resected specimen confirmed the diagnosis of MIVOD and a recurrence thereof.MIVOD is a rare cause of colonic ischemia. Recurrence of the disease, which is described here for the first time, is unusual after surgical resection.

Chlamydia pneumoniae is a common cause of acute infections within the upper respiratory tract. It is less well known that chlamydia pneumoniae, just like chlamydia trachomatis, may also trigger reactive arthritis. We describe three patients with arthritis possibly triggered by chlamydia pneumoniae. The patients showed the typical symptoms of reactive arthritis like asymmetric oligo- or polyarthritis, dactylitis, enthesiopathies and tendovaginitis. The course of the disease was quite different. The first patient developed persistent polyarthritis which required longterm treatment with a rheumatic disease modifying drug; the second patient improved after several weeks and the third patient experienced a full remission within a few days.

To determine the effects of synovial fluids (SF) on DNA binding activity of transcription factor nuclear factor-kappaB (NF-kappaB) in the Mono Mac 6 monocytic/macrophage cell line as a model for the interaction between SF and synovial tissue macrophages in arthritis.Mono Mac 6 cells were incubated with SF from the knee joints of human subjects with rheumatoid arthritis (RA), undifferentiated seronegative oligoarthritis, and osteoarthritis (OA). Nuclear extracts prepared from the Mono Mac 6 cells and RA synovial tissue were analyzed by electrophoretic mobility shift analysis (EMSA) for NF-kappaB DNA binding proteins.Induction of NF-kappaB DNA binding by the p65(RelA)/p50 heterodimer was observed in response to incubation of Mono Mac 6 cells with SF (20% in culture medium) from 5 of 8 subjects with RA, 4 of 5 with OA, and none of 3 with undifferentiated seronegative oligoarthritis. Incubation of SF with neutralizing antibodies against tumor necrosis factor-alpha (TNF-alpha), but not antibodies against interleukin 6 (IL-6), significantly reduced the induction of p65/p50 binding activity in SF from subjects with RA and OA. Unexpectedly, a slowly migrating SF inducible NF-kappaB-binding complex was observed in EMSA of Mono Mac 6 cells after incubation with SF from 5 of 8 RA and 2 of 5 OA subjects. The induction of this complex by SF was not affected by neutralization of TNF-alpha or IL-6 in SF, and the complex was not inducible by TNF-alpha, IL-1beta, TNF-alpha/IL-1beta, IL-6, platelet derived growth factor, lipopolysaccharide, or tetradecanoyl phorbol acetate. The slowly migrating complex could not be supershifted with antibodies against NF-kappaB, Jun, or the transcriptional coactivators p300 or CBP. A NF-kappaB-binding complex with similar slow mobility was observed in nuclear extracts prepared from fresh human RA synovial tissue.Biological activity of TNF-alpha in SF from RA and OA subjects is capable of inducing p65/p50 NF-kappaB DNA binding activity in macrophages. A property of SF that is independent of TNF-alpha and other cytokines is responsible for the induction of a novel slowly migrating NF-kappaB-binding complex. Soluble mediators in SF of subjects with RA and OA can therefore modulate binding of nuclear proteins to the NF-kappaB binding site in macrophages and may play a role in inflammatory gene expression in arthritis.

OBJECTIVE: The pharmacokinetics and pharmacodynamics of high-dose intravenous (i.v.), oral and rectal diacetylmorphine (diamorphine, heroin, DAM) preparations were compared. METHOD: Two heroin-dependent patients participating in a heroin-assisted treatment program received single or repeated doses of 200 - 690 mg DAM i.v., orally (capsules, controlled-release tablets) and rectally. Plasma and urine profiles of DAM and metabolites were monitored by high-performance liquid chromatography and gas chromatography mass spectrometry, flash and high effects by visual analog scaling (VAS). RESULTS: DAM was only detectable in plasma after i.v. administration. With a t 1/2 beta of 1.3 - 2.2 min it was rapidly desacetylated to 6-acetylmorphine which was further metabolized to morphine and its 3- and 6-O-glucuronide. Morphine-3-glucuronide was the dominating metabolite in plasma and urine independent of the administration route. Oral and rectal doses and dosage intervals were adequate to produce flash and high effects without any cardiovascular and respiratory side-effects nor withdrawal symptoms. CONCLUSIONS: Oral and rectal DAM should further be tested and validated on a wider patient group for the non-invasive, long-term application of high-dose DAM within heroin-assisted treatment programs as alternative to the harmful i.v. application.

The impact of energy economy on body weight loss was investigated in 20 obese women, submitted to Roux-en-Y gastric bypass. Resting energy expenditure (REE), substrate oxidation rates, plasma glucose, free fatty acid, and insulin and leptin levels were measured before and 3, 6, and 12 months after surgery. Predicted REE was obtained from linear regression analysis of REE and fat free mass, in a group of 85 women, whose body mass index ranged between 20 and 60 kg/m2. The deviation from predicted REE, calculated as area under the curve (AUC) over the 12-month period for each patient, was considered as the expression of energy economy. Energy economy AUC was significantly (P < 0.005) negatively related to the weight lost during 12 months after surgery.Energy intake, calculated from self-reported food consumption, was also expressed as AUC. Energy intake AUC showed a significant (P < 0.002) positive correlation with weight loss.Lipid oxidation rate, also calculated as AUC, significantly correlated, negatively, with energy economy (P < 0.001) and, positively, with energy intake (P < 0.002). Preoperative leptin values were significantly (P < 0.01) linked to individual energy economy capacity.In conclusion, after Roux-en-Y gastric bypass, energy economy hampers the weight loss process, probably through a low fat oxidation rate.

This study was initiated to test the hypothesis that metformin treatment leads to enhanced glucose disposal at ambient insulin concentrations.Nineteen obese patients with impaired glucose tolerance (IGT) were treated with either metformin or placebo in a randomized, double-blind, placebo-controlled, cross-over study. Insulin secretion and insulin resistance were quantified using the homeostasis model assessment (HOMA) and insulin-stimulated glucose disposal were measured by determining the steady-state plasma glucose (SSPG).The average benefit of metformin was 0.6 mmol/l for glucose (95% confidence interval (CI) 0.2-0.9 P = 0.002), 2.8 pmol/l for insulin (95% CI 0.2-5.4, P = 0.019). Insulin resistance, as quantified by HOMA, was improved by 1.1 (95% CI 0.2-2.0, P = 0.004), without any change in insulin secretion. Basal and insulin-stimulated glucose oxidation were comparable in the placebo and metformin-treated groups at the end of each treatment period, as was the SSPG concentration. However, both systolic and diastolic blood pressures fell significantly following metformin administration as compared to treatment with placebo.These results indicate that metformin administration to patients with IGT is associated with enhanced glucose disposal at baseline insulin concentrations and a fall in blood pressure. In contrast, neither glucose oxidation nor glucose disposal were increased in association with metformin treatment under conditions of physiological hyperinsulinaemia.

OBJECTIVES: To evaluate energy balance after three isocaloric oral loads of different composition and to establish possible relationships between the substrates oxidative patterns and the modifications of insulin and free fatty acids (FFA) plasma profiles. DESIGN: Each subject received, in a randomized order, three oral loads of 2658 +/- 45 kJ (636 +/- 11 Kcal) either as glucose, lipids (cream) or a mixture (glucose+cream). SETTING: The experiments were performed at the University Hospital of Geneva. SUBJECTS: Ten normal body-weight volunteers. METHODS: Energy expenditure (EE) and substrates oxidation were measured by indirect calorimetry during 8 h following each load. Plasma glucose, insulin and FFA were also measured. RESULTS: EE was 1776 +/- 107, 1818 +/- 125 and 1785 +/- 117 KJ over 8 h after glucose, mixed and lipids load, respectively. Glucose oxidation was the highest after oral glucose as compared to mixed and lipids load, while the highest value of lipids oxidation was measured after fat load. A significant relationship linked fat oxidation to plasma FFA (r = 0.54, P < 0.002) as well as to insulin (r = -0.40, P < 0.002). CONCLUSIONS: (a) The energetic cost of glucose and fat intake is the same; (2) after each load, the main source of energy corresponds to the substrate administered; (3) both plasma insulin and FFA influence the substrate oxidative patterns observed after each load; (4) alimentary fat may contribute to fat oxidation by maintaining elevated plasma FFA levels.

With obesity being recognized as an important cardiovascular risk factor, it is important to determine the optimal hypocaloric diet for decreasing that risk. The goal of this study was to compare the effects of two hypocaloric diets of similar caloric value, but differing in carbohydrate content (25% and 45%).Sixty-eight out-patients were followed for 12 w.The patients were assigned to one of two groups that received either a low (25% CHO, n = 31) or a high (45% CHO, n = 37) carbohydrate hypocaloric diet (5.0 MJ/d, 1200 Kcal/d).After 12 w, the mean weight loss was similar and did not differ significantly between the two groups: 10.2 +/- 0.7 kg (25% CHO) and 8.6 +/- 0.8 kg (45% CHO). Furthermore, loss of adipose tissue was similar, 8.1 +/- 0.5 kg (25% CHO) and 7.1 +/- 0.7 kg (45% CHO). Despite a high protein intake (1.4 g/kg/ideal body weight) there was loss of lean body mass: 2.2 +/- 0.4 kg (25% CHO) and 1.4 +/- 0.3 kg (45% CHO). The waist/hip ratio diminished significantly (P0.001) and identically in both groups. The fasting blood glucose (even though normal, along with cholesterol and triglyceride concentrations, were significantly decreased after weight loss. The fasting blood insulin which was mildly elevated before weight loss decreased more markedly with the 25% CHO diet compared to the 45% CHO diet (P0.003). The glucose/insulin ratio improved significantly (P0.05) after weight loss with both diets (0.17 +/- 0.04 mmol/mU (25% CHO) vs 0.10 +/- 0.03 mmol/mU (45% CHO).Neither diet offered a significant advantage when comparing weight loss or other, metabolic parameters over a 12 w period. However, considering the greater improvement of fasting blood insulin, the glucose/insulin ratio and blood triglyceride, the low carbohydrate diet (25%) could be more favourable in the long-term. The improvement of fasting blood insulin could be explained by the differences in monounsaturated fat composition in the low carbohydrate diet.

Forty-nine consecutive repeat cardiac valve replacements in 46 patients were reviewed to define in-hospital morbidity, mortality, and determinants of risk. The overall operative mortality rate was 10.2%; it was 9% for the first reoperation and 25% for the second (four patients). The mortality rate was 12% at the mitral position (25 patients), 11% at the aortic position (18 patients), and 0% for repeat double valve replacement (four patients). Univariate and multivariate stepwise logistic regression models show that age over 70 years and the use of an intraaortic balloon pump preoperatively predict operative mortality, and age over 70, preoperative care in the coronary care unit, endocarditis, and the presence of an intraaortic balloon pump are determinants of perioperative morbidity in patients undergoing repeat valve replacement. Based on these data, close follow-up of patients with initial valve replacement is encouraged so that reoperation to correct prosthetic malfunction or periprosthetic leak can be done before hemodynamic collapse occurs. Furthermore, since age was the most significant factor affecting mortality (P.01) and since most of the deaths (80%) in this study occurred in patients with torn bioprosthetic leaflets, the use of bioprostheses for initial valve replacement in patients under 70 years of age is discouraged.

Using data obtained by questionnaire in a retrospective review of patients with low-back and sciatic pain (eighty-five treated by injection of chymopapain and seventy-one, by open discectomy), the results at one and ten years after treatment were analyzed. For this analysis we used six measures of pain relief, six measures of the patients' course during the ten-year period since primary treatment, and four measures of the patients' history of employment or work since initial treatment. Validity studies demonstrated that the pain-outcome measures reflected the patients' condition adequately and that all six measures were significantly related to each other (Pearson's r, p less than 0.003). The chymopapain and discectomy groups were not distinguishable on the basis of the pain-outcome measures. However, body mass was directly related to the presence of pain ten years after discectomy but not after injection of chymopapain. Analysis of the progress measures (indicators of the course of the patients' pain during the ten-year period) showed that the rates of reoperation in the two treatment groups did not differ significantly, but the discectomy patients tended to have had a higher rate of reoperation at both one and ten years after initial treatment. These measures did not show unequivocal superiority of one treatment compared with the other. Using the work measures (assessments of the patients' history of employment since initial treatment), it was found that in both treatment groups the patients who returned to work six to twelve weeks after treatment despite persistent symptoms had significantly more pain at ten years (p less than 0.04). Also, the patients who returned to work less than six weeks after treatment, while still symptomatic, showed a similar trend. On the other hand, among the patients who were still symptomatic at twelve weeks, it made no difference in the final results whether they returned to work at twelve weeks or thereafter. These findings support the notion that after either discectomy or chemonucleolysis, patients should return to work only after complete symptomatic recovery or a minimum convalescence of twelve weeks.

Background During copulation, the major Afro-tropical malaria vector Anopheles gambiae s.s. transfers male accessory gland (MAG) proteins to females as a solid mass (i.e. the "mating plug"). These proteins are postulated to function as important modulators of female post-mating responses. To understand the role of selective forces underlying the evolution of these proteins in the A. gambiae complex, we carried out an evolutionary analysis of gene sequence and expression divergence on a pair of paralog genes called AgAcp34A-1 and AgAcp34A-2. These encode MAG-specific proteins which, based on homology with Drosophila, have been hypothesized to play a role in sperm viability and function. Results Genetic analysis of 6 species of the A. gambiae complex revealed the existence of a third paralog (68-78% of identity), that we named AgAcp34A-3. FISH assays showed that this gene maps in the same division (34A) of chromosome-3R as the other two paralogs. In particular, immuno-fluorescence assays targeting the C-terminals of AgAcp34A-2 and AgAcp34A-3 revealed that these two proteins are localized in the posterior part of the MAG and concentrated at the apical portion of the mating plug. When transferred to females, this part of the plug lies in proximity to the duct connecting the spermatheca to the uterus, suggesting a potential role for these proteins in regulating sperm motility. AgAcp34A-3 is more polymorphic than the other two paralogs, possibly because of relaxation of purifying selection. Since both unequal crossing-over and gene conversion likely homogenized the members of this gene family, the interpretation of the evolutionary patterns is not straightforward. Although several haplotypes of the three paralogs are shared by most A. gambiae s.l. species, some fixed species-specific replacements (mainly placed in the N- and C-terminal portions of the secreted peptides) were also observed, suggesting some lineage-specific adaptation. Conclusions Progress in understanding the signaling cascade in the A. gambiae reproductive pathway will elucidate the interaction of this MAG-specific protein family with their female counterparts. This knowledge will allow a better evaluation of the relative importance of genes involved in the reproductive isolation and fertility of A. gambiae species and could help the interpretation of the observed evolutionary patterns.