The forgotten face of regular physical exercise: a 'natural' anti-atherogenic activity.

Humans are not programmed to be inactive. The combination of both accelerated sedentary lifestyle and constant food availability disturbs ancient metabolic processes leading to excessive storage of energy in tissue, dyslipidaemia and insulin resistance. As a consequence, the prevalence of Type 2 diabetes, obesity and the metabolic syndrome has increased significantly over the last 30 years. A low level of physical activity and decreased daily energy expenditure contribute to the increased risk of cardiovascular morbidity and mortality following atherosclerotic vascular damage. Physical inactivity leads to the accumulation of visceral fat and consequently the activation of the oxidative stress/inflammation cascade, which promotes the development of atherosclerosis. Considering physical activity as a 'natural' programmed state, it is assumed that it possesses atheroprotective properties. Exercise prevents plaque development and induces the regression of coronary stenosis. Furthermore, experimental studies have revealed that exercise prevents the conversion of plaques into a vulnerable phenotype, thus preventing the appearance of fatal lesions. Exercise promotes atheroprotection possibly by reducing or preventing oxidative stress and inflammation through at least two distinct pathways. Exercise, through laminar shear stress activation, down-regulates endothelial AT1R (angiotensin II type 1 receptor) expression, leading to decreases in NADPH oxidase activity and superoxide anion production, which in turn decreases ROS (reactive oxygen species) generation, and preserves endothelial NO bioavailability and its protective anti-atherogenic effects. Contracting skeletal muscle now emerges as a new organ that releases anti-inflammatory cytokines, such as IL-6 (interleukin-6). IL-6 inhibits TNF-α (tumour necrosis factor-α) production in adipose tissue and macrophages. The down-regulation of TNF-α induced by skeletal-muscle-derived IL-6 may also participate in mediating the atheroprotective effect of physical activity.

Detection of respiratory viruses by real-time polymerase chain reaction in outpatients with acute respiratory infection

Viruses are the major contributors to the morbidity and mortality of upper and lower acute respiratory infections (ARIs) for all age groups. The aim of this study was to determine the frequencies for a large range of respiratory viruses using a sensitive molecular detection technique in specimens from outpatients of all ages with ARIs. Nasopharyngeal aspirates were obtained from 162 individuals between August 2007-August 2009. Twenty-three pathogenic respiratory agents, 18 respiratory viruses and five bacteria were investigated using multiplex real-time reverse transcriptase polymerase chain reaction (RT-PCR) and indirect immunofluorescence assay (IIF). Through IIF, 33 (20.4%) specimens with respiratory virus were recognised, with influenza virus representing over half of the positive samples. Through a multiplex real-time RT-PCR assay, 88 (54.3%) positive samples were detected; the most prevalent respiratory viral pathogens were influenza, human rhinovirus and respiratory syncytial virus (RSV). Six cases of viral co-detection were observed, mainly involving RSV. The use of multiplex real-time RT-PCR increased the viral detection by 33.9% and revealed a larger number of respiratory viruses implicated in ARI cases, including the most recently described respiratory viruses [human bocavirus, human metapneumovirus, influenza A (H1N1) pdm09 virus, human coronavirus (HCoV) NL63 and HCoV HKU1].

Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

Influencia de la angina preinfarto en la semana previa en la morbimortalidad cardiovascular tardía tras el alta hospitalaria.

The occurrence of angina in the week preceding myocardial infarction is associated with a reduction in cardiovascular complications in the acute phase. However, little is known about it relationship with prognosis after hospitalization (e.g., cardiovascular death and the development of heart failure or ischemic cardiomyopathy). The study included 290 consecutive patients admitted for a first myocardial infarction: 107 (36.9%) had preceding angina while 183 did not. Those with a history of ischemic cardiomyopathy of more than 1 week or structural cardiopathy were excluded. There was no difference in baseline characteristics between the two groups. Moreover, there was no difference in the rates of cardiovascular complications after hospital discharge: cardiovascular death (7% vs. 12.6%; P=.3), heart failure (7.4% vs. 11.6%; P=.2), and myocardial ischemia, including myocardial infarction and unstable angina, requiring hospitalization (41.2% vs. 31.3%; P=.3). The occurrence of angina in the week before a first myocardial infarction did not influence cardiovascular complications after hospital discharge (odds ratio = 0.75 [0.51-1.11]; P=.15).

Estudio y prevalencia de la diabetes mellitus postrasplante; análisis en un grupo de pacientes trasplantados renales.

INTRODUCTION: The onset of post-transplant diabetes mellitus (PTDM) among kidney recipients is associated with an increased risk of graft failure and high rates of morbidity and mortality. Minimize the risk of PTDM is a priority for improving long-term survival rates. Aims. This study aims to assess the prevalence of PTDM in a renal transplant patient population, to identify risk factors and assess the graft and patient survival. METHODS: The sample consisted of 112 renal transplant patients , 69 men and 43 women , renal transplant , who attended for five years post-transplant consultation. Were analyzed as potential risk factors for PTDM : age , sex, body mass index (BMI ) , obesity , VHC , hypertension, dyslipidemia , total cholesterol (TC) , serum triglyceride and immunosuppressive therapy ( cyclosporine , tacrolimus , mycophenolate mofetil and sirolimus ), also the prevalence of acute rejection episodes was evaluated. RESULTS: The prevalence of PTDM was 24.2 %, compared with 85 patients (75.8%) with standard glucose (PGN) . PTDM patients showed a higher BMI , a higher percentage of overweight , dyslipidemia , total cholesterol levels , triglycerides and performed a greater percentage of patients with PDMPT including Mycophenolate mofetil was administered. CONCLUSIONS: There is a high incidence of PTDM in kidney recipients , the importance of weight control and strict adherence to all identified risk factors , as well as in minimizing the doses of immunosuppressive therapies to prevent the onset of PTDM.

Polyphasic characterisation of Burkholderia cepaciacomplex species isolated from children with cystic fibrosis

Cystic fibrosis (CF) patients with Burkholderia cepacia complex (Bcc) pulmonary infections have high morbidity and mortality. The aim of this study was to compare different methods for identification of Bcc species isolated from paediatric CF patients. Oropharyngeal swabs from children with CF were used to obtain isolates of Bcc samples to evaluate six different tests for strain identification. Conventional (CPT) and automatised (APT) phenotypic tests, polymerase chain reaction (PCR)-recA, restriction fragment length polymorphism-recA, recAsequencing, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) were applied. Bacterial isolates were also tested for antimicrobial susceptibility. PCR-recA analysis showed that 36 out of the 54 isolates were Bcc. Kappa index data indicated almost perfect agreement between CPT and APT, CPT and PCR-recA, and APT and PCR-recA to identify Bcc, and MALDI-TOF and recAsequencing to identify Bcc species. The recAsequencing data and the MALDI-TOF data agreed in 97.2% of the isolates. Based on recA sequencing, the most common species identified were Burkholderia cenocepacia IIIA (33.4%),Burkholderia vietnamiensis (30.6%), B. cenocepaciaIIIB (27.8%), Burkholderia multivorans (5.5%), and B. cepacia (2.7%). MALDI-TOF proved to be a useful tool for identification of Bcc species obtained from CF patients, although it was not able to identify B. cenocepacia subtypes.

Estudio de la albúmina sérica y del índice de masa corporal como marcadores nutricionales en pacientes en hemodiálisis.

Background: Protein calorie malnutrition as well as systemic inflammation and metabolic disorders are common among patients with chronic renal failure undergoing renal replacement therapy (haemodialysis), which contributes to its morbidity and mortality. Aims: The aims of this work was to evaluate the nutritional status of patients in a hemodialysis treatment through the assessment of biochemical parameters nutritional as albumin, and anthropometric parameters of body mass index during ten years of follow up. Methods: In this work has been followed 90 patients of both sexes with chronic kidney disease who were treated with hemodialysis regularly on our unit for ten years. All patients were conducted quarterly measurements of plasma albumin (Alb), and other biochemical determinations, and anthropometric measurements of height, weight and body mass index calculated by the formula weight/height², grouped n BMI < 23 kg/m2 and albumin levels <3.8 g/dl according to the consensus of the panel of experts of the International Society for renal Nutrition and metabolism. Results: During the 10 years all patients showed a significant decline in the biochemical parameters and the albumin, change in BMI does not presented significant changes in relation to malnutrition. Conclusions: Malnutrition in patients on dialysis is a fact patent, BMI does not correspond with the biochemical parameters were observed, for what nutritional impairment in these patients is mainly expressed by serum albumin.

Angiographic demonstration of neoangiogenesis after intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb ischemia.

Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Suboptimal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10(6) cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement.

Assessing cardiovascular risk in hepatitis C: An unmet need.

Chronic hepatitis C virus (HCV) is associated with significant morbidity and mortality, as a result of the progression towards cirrhosis and hepatocellular carcinoma. Additionally, HCV seems to be an independent risk factor for cardiovascular diseases (CVD) due to its association with insulin resistance, diabetes and steatosis. HCV infection represents an initial step in the chronic inflammatory cascade, showing a direct role in altering glucose metabolism. After achieving sustained virological response, the incidence of insulin resistance and diabetes dramatically decrease. HCV core protein plays an essential role in promoting insulin resistance and oxidative stress. On the other hand, atherosclerosis is a common disease in which the artery wall thickens due to accumulation of fatty deposits. The main step in the formation of atherosclerotic plaques is the oxidation of low density lipoprotein particles, together with the increased production of proinflammatory markers [tumor necrosis factor-α, interleukin (IL)-6, IL-18 or C-reactive protein]. The advent of new direct acting antiviral therapy has dramatically increased the sustained virological response rates of hepatitis C infection. In this scenario, the cardiovascular risk has emerged and represents a major concern after the eradication of the virus. Consequently, the number of studies evaluating this association is growing. Data derived from these studies have demonstrated the strong link between HCV infection and the atherogenic process, showing a higher risk of coronary heart disease, carotid atherosclerosis, peripheral artery disease and, ultimately, CVD-related mortality.

Delay for admission of unstable hospitalized patients to intensive care unit: a need for a medical emergency team?

INTRODUCTION. Patients admitted in Intensive Care Unit (ICU) from general wards are more severe and have a higher mortality than those admitted from emergency department as reported [1]. The majority of them develop signs of instability (e.g. tachypnea, tachycardia, hypotension, decreased oxygen saturation and change in conscious state) several hours before ICU admission. Considering this fact and that in-hospital cardiac arrests and unexpected deaths are usually preceded by warning signs, immediate on site intervention by specialists may be effective. This gave an impulse to medical emergency team (MET) implementation, which has been shown to decrease cardiac arrest, morbidity and mortality in several hospitals. OBJECTIVES AND METHODS. In order to verify if the same was true in our hospital and to determine if there was a need for MET, we prospectively collected all non elective ICU admissions of already hospitalized patients (general wards) and of patients remaining more than 3 h in emergency department (considered hospitalized). Instability criteria leading to MET call correspond to those described in the literature. The delay between the development of one criterion and ICU admission was registered. RESULTS. During an observation period of 12 months, 321 patients with our MET criteria were admitted to ICU. 88 patients came from the emergency department, 115 from the surgical and 113 from the medical ward. 65% were male. The median age was 65 years (range 17-89). The delay fromMETcriteria development to ICU admission was higher than 8 h in 155 patients, with a median delay of 32 h and a range of 8.4 h to 10 days. For the remaining 166 patients, an early MET criterion was present up to 8 h (median delay 3 h) before ICU admission. These results are quite concordant with the data reported in the literature (ref 1-8). 122 patients presented signs of sepsis or septic shock, 70 patients a respiratory failure, 58 patients a cardiac emergency. Cardiac arrest represent 5% of our collective of patients. CONCLUSIONS.Similar to others observations, the majority of hospitalized patients admitted on emergency basis in our ICU have warning signs lasting for several hours. More than half of them were unstable for more than 8 h. This shows there is plenty of time for early acute management by dedicated and specialized team such as MET. However, further studies are required to determine if MET implementation can reduce in-hospital cardiac arrests and influence the morbidity, the length of stay and the mortality.

Prise en charge nutritionnelle préopératoire. [Preoperative nutritional support.]

Undernutrition is an independent factor of postoperative morbidity and mortality The aim of a preoperative nutritional support is to enhance immune muscular and cognitive functions, and to support wound healing This nutritional support (e g dietary management enteral or parenteral nutrition) should be limited to high risk situations with a beneficial effect of nutrition for the patient undernutrition major surgery and elderly Preoperative nutritional support should be scheduled for atleast 7 to 10 days before the surgery During the preoperative period the type and route of an eventual postoperative nutritional assistance should be anticipated In the case of emergency surgery nutritional assessment of the patient should be done as soon as possible before surgery or in the 48 h postoperative period Finally, in elective surgery, preoperative fasting should be limited to 2-3 hours for clear liquids and 6 hours for solids (C) 2010 Published by Elsevier Masson SAS

Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence

Methadone is widely used for the treatment of opioid dependence. Although in most countries the drug is administered as a racemic mixture of (R)- and (S)- methadone, (R)-methadone accounts for most, if not all, of the opioid effects. Methadone can be detected in the blood 15-45 minutes after oral administration, with peak plasma concentration at 2.5-4 hours. Methadone has a mean bioavailability of around 75% (range 36-100%). Methadone is highly bound to plasma proteins, in particular to alpha(1)-acid glycoprotein. Its mean free fraction is around 13%, with a 4-fold interindividual variation. Its volume of distribution is about 4 L/kg (range 2-13 L/kg). The elimination of methadone is mediated by biotransformation, followed by renal and faecal excretion. Total body clearance is about 0.095 L/min, with wide interindividual variation (range 0.02-2 L/min). Plasma concentrations of methadone decrease in a biexponential manner, with a mean value of around 22 hours (range 5-130 hours) for elimination half-life. For the active (R)-enantiomer, mean values of around 40 hours have been determined. Cytochrome P450 (CYP) 3A4 and to a lesser extent 2D6 are probably the main isoforms involved in methadone metabolism. Rifampicin (rifampin), phenobarbital, phenytoin, carbamazepine, nevirapine, and efavirenz decrease methadone blood concentrations, probably by induction of CYP3A4 activity, which can result in severe withdrawal symptoms. Inhibitors of CYP3A4, such as fluconazole, and of CYP2D6, such as paroxetine, increase methadone blood concentrations. There is an up to 17-fold interindividual variation of methadone blood concentration for a given dosage, and interindividual variability of CYP enzymes accounts for a large part of this variation. Since methadone probably also displays large interindividual variability in its pharmacodynamics, methadone treatment must be individually adapted to each patient. Because of the high morbidity and mortality associated with opioid dependence, it is of major importance that methadone is used at an effective dosage in maintenance treatment: at least 60 mg/day, but typically 80-100 mg/day. Recent studies also show that a subset of patients might benefit from methadone dosages larger than 100 mg/day, many of them because of high clearance. In clinical management, medical evaluation of objective signs and subjective symptoms is sufficient for dosage titration in most patients. However, therapeutic drug monitoring can be useful in particular situations. In the case of non-response trough plasma concentrations of 400 microg/L for (R,S)-methadone or 250 microg/L for (R)-methadone might be used as target values.

L'état de santé des Lausannois: premiers résultats de l'étude CoLaus. [Health examination survey of the Lausanne population: first results of the CoLaus study].

Cardiovascular diseases (CVD) remain the main cause of morbidity and mortality in our society. CoLaus is a population-based health examination survey started in 2003 in Lausanne in order to assess: 1. Prevalence of cardiovascular risk factors, 2. New genetic determinants of cardiovascular risk factors such as hypertension, 3. Association of mood disorders with incidence of cardiovascular events and 4. Trends in prevalence of cardiovascular risk factors. In order to do so, over 6000 subjects (ages 35-75 years) provided data on CVD risk factors. Herein we provide preliminary results of this study, in particular on classical risk factors such as hypertension, obesity and diabetes. Implications and perspectives of this population based-study for public health and genetic studies are also discussed.

Use of trochanteric nail for proximal femoral extracapsular fractures.

Proximal femoral extracapsular fractures have shown a significantly high morbidity and mortality rate at 1 year in cases of nonoperative treatment. The standard gamma nail was originally designed to provide stable fixation and allow early mobilization and weight bearing for elderly patients. The design of the standard gamma nail, however, appears to be associated with intraoperative or postoperative femoral shaft fractures in < or = 17% of patients, compromising the outcome. The trochanteric nail was developed to overcome the problems encountered with the use of the standard gamma nail. Between July 2000 and January 2001, 88 consecutive proximal femoral extracapsular fractures were treated with a trochanteric nail, Seventy-five patients (76 fractures) were observed clinically and radiographically for 2 years.