Serum insulin and inflammatory markers in overweight individuals with and without dyslipidemia.

CONTEXT: The worldwide epidemic of overweight and obesity is setting the scene for a new wave of premature cardiovascular disease. OBJECTIVE: The objective of this study was to define relationships between dyslipidemia and other metabolic abnormalities in overweight subjects. DESIGN: This study included comparison of overweight subjects with and without dyslipidemia. SETTING: The setting was an institutional practice. PATIENTS: Dyslipidemic subjects (n = 715) had plasma triglyceride greater than or equal to the 75th percentile in combination with high-density lipoprotein cholesterol (HDL-C) less than or equal to the 25th percentile. Unrelated, normolipidemic controls (n = 1073) had HDL-C higher than the median and triglyceride lower than the median. It was a requirement for the control subjects to have a body mass index (BMI) greater than 25 kg/m(2). MAIN OUTCOME MEASURES: The main outcome measures included BMI, inflammatory markers, adipokines, blood pressure, and fasting plasma glucose and insulin. RESULTS: The mean BMI in the subjects and controls was 28.7 and 28.2 kg/m(2), respectively. Subjects had higher levels of plasma high-sensitivity C-reactive protein (3.0 vs. 2.0 mg/liter; P < 0.001), lower levels of adiponectin (4.7 vs. 6.6 mg/liter; P < 0.001), and, after adjustment for age, BMI, gender, smoking, statin, and beta-blocker use, higher systolic (P = 0.001) and diastolic (P = 0.05) blood pressures. Fasting plasma glucose, insulin, and homeostasis model of assessment-insulin resistance were all significantly higher in subjects than controls (P < 0.0001). CONCLUSIONS: Identification of people solely on the basis of an elevated plasma triglyceride and a low HDL-C uncovers an overweight group of people who have a generalized metabolic disorder. In contrast, overweight people with normal plasma lipids have normal glucose and insulin metabolism, low levels of inflammatory markers, and normal blood pressure. Such people may thus be at relatively low risk of developing diabetes and cardiovascular disease despite being overweight.

External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study.

BACKGROUND: We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results. METHODS: For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082. FINDINGS: Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment. INTERPRETATION: In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Long-term anticoagulation treatment for acute venous thromboembolism in patients with and without cancer. The SWIss Venous ThromboEmbolism Registry (SWIVTER) II.

In patients with acute cancer-associated thrombosis, current consensus guidelines recommend anticoagulation therapy for an indefinite duration or until the cancer is resolved. Among 1,247 patients with acute venous thromboembolism (VTE) enrolled in the prospective Swiss Venous Thromboembolism Registry (SWIVTER) II from 18 hospitals, 315 (25%) had cancer of whom 179 (57%) had metastatic disease, 159 (50%) ongoing or recent chemotherapy, 83 (26%) prior cancer surgery, and 63 (20%) recurrent VTE. Long-term anticoagulation treatment for >12 months was more often planned in patients with versus without cancer (47% vs. 19%; p<0.001), with recurrent cancer-associated versus first cancer-associated VTE (70% vs. 41%; p<0.001), and with metastatic versus non-metastatic cancer (59% vs. 31%; p<0.001). In patients with cancer, recurrent VTE (OR 3.46; 95%CI 1.83-6.53), metastatic disease (OR 3.04; 95%CI 1.86-4.97), and the absence of an acute infection (OR 3.55; 95%CI 1.65-7.65) were independently associated with the intention to maintain anticoagulation for >12 months. In conclusion, long-term anticoagulation treatment for more than 12 months was planned in less than half of the cancer patients with acute VTE. The low rates of long-term anticoagulation in cancer patients with a first episode of VTE and in patients with non-metastatic cancer require particular attention.

Indications à la coronarographie en urgence. Partie II: syndromes coronariens aigus sans élévation du segment ST [Indications for urgent coronary angiography. Part II: Acute coronary syndromes without ST-segment elevation]

The optimal treatment strategy for patients presenting with an acute coronary syndrome without ST elevation is controversial and different therapeutic approaches are recognized. Currently, given the literature available, it is not possible to recommend a universal systematic invasive approach. It is essential to individually risk stratify patients in order to identify those high risk patients that have been shown to benefit from an invasive strategy. Compared to conservative medical treatment, patients at low risk have not been shown to benefit from an invasive strategy. Urgent coronary angiography remains recommended for those patients with persistent or recurrent ischemic symptoms under optimal medical treatment.

Ammonium chloride as nitrogen source in sugarcane harvested without burning

The great difficulty of incorporation of N fertilizers into the "green sugarcane" system causes concern and since urea is the most commonly used source, there is the risk of loosing NH3 through volatilization. For this reason, a field experiment was undertaken (in a Hapludox Typic) with the objective of evaluating the agronomic efficiency of ammonium chloride on stubble of the second ratoon (SP89 1115), as well as its residual effect on the subsequent cycle (third ratoon). The experimental design was randomized blocks with four replications. Treatments consisted of three N rates (60, 120 and 180 kg ha-1 N) in the form of NH4Cl, in addition to a control treatment without the addition of N fertilizer. The ratoon cane of the second cutting was harvested in November 2006 and the treatments were applied in December 2006. The second ratoon was harvested mechanically in November 2007 and in December 2007, 450 kg ha-1 of the NPK mixture 20-05-19 was applied, providing 90, 22 and 86 kg ha-1 N, P2O5 and K2O, respectively, for the purpose of evaluating the effect of residual-N from the treatments implanted in December 2006. An increase in the rates of N-NH4Cl had a positive effect on the leaf concentrations of P, Mg and S. Stalk yield (MSS - Mg ha-1 of sugarcane stalks) and sugar (MSH - Mg ha-1 of sucrose) in the November 2006 harvest responded linearly to the increase of N doses in the form of NH4Cl. In relation to the effect of residual-N in the 2007/2008 harvest, it was observed, in general, that the concentrations of macronutrients in the sugarcane leaf +1 were within the range considered adequate in the state of São Paulo, Brazil. The residual-N of the NH4Cl doses resulted in a significant reduction in stalk (MSS) and sugar (MSH) production. It may be concluded that the NH4Cl source at a dose of 120 kg ha-1 N in ratoon fertilization of the second cutting was agronomically efficient, presenting, however, less efficiency of residual-N in the subsequent cycle.

Morphostructural characterization of soil conventionally tilled with mechanized and animal traction with and without cover crop

The structural stability and restructuring ability of a soil are related to the methods of crop management and soil preparation. A recommended strategy to reduce the effects of soil preparation is to use crop rotation and cover crops that help conserve and restore the soil structure. The aim of this study was to evaluate and quantify the homogeneous morphological units in soil under conventional mechanized tillage and animal traction, as well as to assess the effect on the soil structure of intercropping with jack bean (Canavalia ensiformis L.). Profiles were analyzed in April of 2006, in five counties in the Southern-Central region of Paraná State (Brazil), on family farms producing maize (Zea mays L.), sometimes intercropped with jack bean. The current structures in the crop profile were analyzed using Geographic Information Systems (GIS) and subsequently principal component analysis (PCA) to generate statistics. Morphostructural soil analysis showed a predominance of compact units in areas of high-intensity cultivation under mechanized traction. The cover crop did not improve the structure of the soil with low porosity and compact units that hamper the root system growth. In areas exposed to animal traction, a predominance of cracked units was observed, where roots grew around the clods and along the gaps between them.

Etudes Coût-efficacité: ce que devraient retenir les médecins [Cost-effectiveness analyses: what doctors should know]

The resources of our heath care system are limited. Choices in the attribution of resources are necessary to ensure its stability. A cost-effectiveness analysis compares the effects of one health intervention to another, taking into account the costs (including the saved costs) and the saved life years, adjusted for the quality of life (cost-utility). Cost-effectiveness analyses should take the societal perspective and the studied intervention should be compared to a relevant intervention actually in use. Physicians, at the interface between patients and payers, are in an ideal position to interpret, or even perform cost-effectiveness analysis, and to promote the interventions that are most effective and that have a reasonable cost.

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.

Preserved capillary density of dorsal finger skin in treated hypertensive patients with or without type 2 diabetes.

OBJECTIVES: Capillary rarefaction is a hallmark of untreated hypertension. Recent data indicate that rarefaction may be reversed by antihypertensive treatment in nondiabetic hypertensive patients. Despite the frequent association of diabetes with hypertension, nothing is known on the capillary density of treated diabetic patients with hypertension. METHODS: We enrolled 21 normotensive healthy, 25 hypertensive only, and 21 diabetic (type 2) hypertensive subjects. All hypertensive patients were treated with a blocker of the renin-angiotensin system, and a majority had a home blood pressure ≤135/85 mmHg. Capillary density was assessed with videomicroscopy on dorsal finger skin and with laser Doppler imaging on forearm skin (maximal vasodilation elicited by local heating). RESULTS: There was no difference between any of the study groups in either dorsal finger skin capillary density (controls 101 ± 11 capillaries/mm(2) , nondiabetic hypertensive 99 ± 16, diabetic hypertensive 96 ± 18, p > 0.5) or maximal blood flow in forearm skin (controls 666 ± 114 perfusion units, nondiabetic hypertensive 612 ± 126, diabetic hypertensive 620 ± 103, p > 0.5). CONCLUSIONS: Irrespective of the presence or not of type 2 diabetes, capillary density is normal in hypertensive patients with reasonable control of blood pressure achieved with a blocker of the renin-angiotensin system.

Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease.

BACKGROUND: Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9 micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5 +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by approximately 2.5% (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients without OVD there was a significant reduction of approximately 34% (from 32.7+/-14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were reduced by > 15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P = 0.001). CONCLUSIONS: These results indicate that the homocysteine-lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.

Computational problems in perfect phylogeny haplotyping: typing without calling the allele.

A haplotype is an m-long binary vector. The XOR-genotype of two haplotypes is the m-vector of their coordinate-wise XOR. We study the following problem: Given a set of XOR-genotypes, reconstruct their haplotypes so that the set of resulting haplotypes can be mapped onto a perfect phylogeny (PP) tree. The question is motivated by studying population evolution in human genetics, and is a variant of the perfect phylogeny haplotyping problem that has received intensive attention recently. Unlike the latter problem, in which the input is "full" genotypes, here we assume less informative input, and so may be more economical to obtain experimentally. Building on ideas of Gusfield, we show how to solve the problem in polynomial time, by a reduction to the graph realization problem. The actual haplotypes are not uniquely determined by that tree they map onto, and the tree itself may or may not be unique. We show that tree uniqueness implies uniquely determined haplotypes, up to inherent degrees of freedom, and give a sufficient condition for the uniqueness. To actually determine the haplotypes given the tree, additional information is necessary. We show that two or three full genotypes suffice to reconstruct all the haplotypes, and present a linear algorithm for identifying those genotypes.

Poison without antidote for the historical Socrates and french classical tragedy in El verí del teatre (The Poison of the Theatre) by Rodolf Sirera. (An extreme dose of sadism to put a stop to the excesses of theatrical fiction).

Socrates' serene attitude before his death -although this is questioned-, as described by Xenophon in his Apologia Socratis becomes for the playwright Rodolf Sirera a useful reference in an effort to reflect boldly on the limits of theatrical fiction in another clear example of the Classical Tradition, including that derived from Baroque Tragedy. However, in this case, it is judged severely to make us more conscious of the risk of turning life into a mere theatrical performance and human beings into actors and actresses in a play they did not write.

Daytime sleepiness with and without cataplexy in Chinese-Taiwanese patients.

BACKGROUND AND PURPOSE: Investigation of Chinese-Taiwanese patients with excessive sleepiness, but no association with other sleep disorders, and with the presence or absence of cataplexy. PATIENTS AND METHODS: Thirty-five patients, successively referred between 2002 and 2004, underwent polysomnography (PSG), repeat multiple sleep latency test (MSLT), and human leukocyte antigen (HLA) typing. Three patients without cataplexy also had cerebrospinal fluid (CSF) hypocretin measurements. RESULTS: DQB1*0602 was associated with cataplexy in over 90% of Chinese-Taiwanese cases. Absence of cataplexy and <2 sleep-onset REM periods (SOREMPs) was seen in only two subjects, but presence of two SOREMPs did not dissociate DQB1*0602 positive and negative or cataplexy positive and negative subjects. As a group, narcoleptics with cataplexy had a higher number of SOREMPs, and the mean sleep latency was much shorter in narcoleptics with cataplexy than in the non-cataplectic patients, independent of the number of SOREMPs. CONCLUSIONS: Chinese-Taiwanese patients with cataplexy present with similar HLA findings as Black and Caucasian patients, but the presence of two or more SOREMPs in Chinese-Taiwanese patients is not a sufficient diagnostic tool to identify narcolepsy. When cataplexy is not present, description of PSG nd HLA findings may be a better approach than using a label with little scientific significance, allowing for better collection of patients' phenotype.