RANTES/CCL5 and risk for coronary events: results from the MONICA/KORA Augsburg case-cohort, Athero-Express and CARDIoGRAM studies.

BACKGROUND: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. METHODS AND FINDINGS: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±4.8 years). Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors and lifestyle factors revealed no significant association between RANTES and incident coronary events (HR [95% CI] for increasing RANTES tertiles 1.0, 1.03 [0.75-1.42] and 1.11 [0.81-1.54]). None of six CCL5 single nucleotide polymorphisms and no common haplotype showed significant associations with coronary events. Also in the CARDIoGRAM study (>22,000 cases, >60,000 controls), none of these CCL5 SNPs was significantly associated with coronary artery disease. In the prospective Athero-Express biobank study, RANTES plaque levels were measured in 606 atherosclerotic lesions from patients who underwent carotid endarterectomy. RANTES content in atherosclerotic plaques was positively associated with macrophage infiltration and inversely associated with plaque calcification. However, there was no significant association between RANTES content in plaques and risk for coronary events (mean follow-up 2.8±0.8 years). CONCLUSIONS: High RANTES plaque levels were associated with an unstable plaque phenotype. However, the absence of associations between (i) RANTES serum levels, (ii) CCL5 genotypes and (iii) RANTES content in carotid plaques and either coronary artery disease or incident coronary events in our cohorts suggests that RANTES may not be a novel coronary risk biomarker. However, the potential relevance of RANTES levels in platelet-poor plasma needs to be investigated in further studies.

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale <or=2) at 3 months, intracranial hemorrhage (ICH), and recurrent ischaemic stroke. RESULTS: Sixty-five (6.2%) of 1048 IVT-treated patients had SAO. Amongst SAO-patients, 1.5% (1/65) patients died, compared to 11.2% (110/983) in the non-SAO-group (P = 0.014). SAO-patients reached independence more often than non-SAO-patients (75.4% versus 58.9%; OR 2.14 (95% CI 1.20-3.81; P = 0.001). This association became insignificant after adjustment for age, gender, and stroke severity (OR 1.41 95% CI 0.713-2.788; P = 0.32). Glucose level and (to some degree) stroke severity but not age predicted 3-month-independence in IVT-treated SAO-patients. ICHs (all/symptomatic) were similar in SAO- (12.3%/4.6%) and non-SAO-patients (13.4%/5.3%; P > 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.

Contribution of major cardiovascular risk factors to familial premature coronary artery disease : the GENECARD project

Résumé Objectifs: Cette étude relève la prévalence des principaux facteurs de risque cardiovasculaire dans les coronaropathies précoces (P-CAD) familiales, survenant chez au moins deux frères et/ou soeurs d'une même fratrie. Méthodes: Nous avons recruté 213 survivants atteints de P-CAD, issus de 103 fratries, diagnostiqués avant l'âge de 50 ans chez les hommes et 55 ans chez les femmes. La présence ou non d'hypertension, d'hypercholestérolémie, d'obésité et de tabagisme a été documentée au moment de l'événement chez 163 de ces patients (145 hommes et 18 femmes). Chaque patient a été comparé à deux individus de même âge et sexe, chez qui un diagnostic de P-CAD «sporadique» (non familiale) était posé, et à trois individus choisis au hasard parmi la population générale. Résultats: En comparaison de la population générale, les patients atteints de P-CAD sporadique avaient une prévalence supérieure pour l 'hypertension (29% vs. 14%, p<0.001), le cholestérol (54% vs. 33%, p<0.001), l'obésité (20% vs. 13%, p<0.001) et le tabagisme (76% vs. 39%, p<0.001). Ces facteurs de risque étaient de prévalences similaires, voire supérieures chez les patients atteints de P-CAD familiale (43% [p0.05 vs. P-CAD sporadiques], 58% [p=0.07], 21% et 72% respectivement). Seulement 7 (4%) des 163 patients atteints de P-CAD familiale et 22 (7%) des 326 patients atteints de P-CAD sporadique, ne présentaient aucun facteur de risque cardiovasculaire, comparés à 167 (34%) des 489 patients issus de la population générale. Conclusions: Les facteurs de risque cardiovasculaire classiques et réversibles ont une haute prévalence chez les patients atteints de P-CAD familiale. Ce fait rend improbable une contribution génétique prédominante, agissant en l'absence de facteurs de risque. Summary Objectives: This study was designed to assess the prevalence of major cardiovascular risk factors in familial premature coronary artery disease (P-CAD), affecting two or more siblings within one sibship. Background: Premature CAD has a genetic component. It remains to be established whether familial P-CAD is due to genes acting independently from major cardiovascular risk factors. Methods: We recruited 213 P-CAD survivors from 103 sibships diagnosed before age ?50 (men) or ?55 (women) years old. Hypertension, hypercholesterolemia, obesity, and smoking were documented at the time of the event in 163 patients (145 men and 18 women). Each patient was compared with two individuals of the same age and gender, diagnosed with sporadic (nonfamilial) P-CAD, and three individuals randomly sampled from the general population. Result: Compared with the general population, patients with sporadic P-CAD had a higher prevalence of hypertension (29% vs. 14%, p < 0.001), hypercholesterolemia (54% vs. 33%, p < 0.001), obesity (20% vs. 13%, p < 0.01), and smoking (76% vs. 39%, p < 0.001). These risk factors were equally or even more prevalent in patients with familial P-CAD (43% [p < 0.05 vs. sporadic P-CAD], 58% [p = 0.07], 21% and 72%, respectively). Overall, only 7 (4%) of 163 of patients with familial P-CAD and 22 (7%) of 326 of patients with sporadic P-CAD had none of these conditions, as compared with 167 (34%) of 489 patients in the general population. Conclusions: Classic, remediable risk factors are highly prevalent in patients with familial P-CAD. Accordingly, a major contribution of genes acting in the absence of these risk factors is unlikely.

L'année 2012 de la perspective de l'interniste hospitalier [What is new in 2012 for the specialist in hospital internal medicine?].

The knowledge in internal medicine is constantly and so rapidly evolving that practices have to be updated and adjusted to recent scientific rules, in order to improve quality and efficiency in the day to day activities. Residents in the Service of internal medicine of the Lausanne University present several relevant papers published in 2012, whose results are susceptible to change the daily hospital practices. From modest impacts to real revolution, a variety of subjects are discussed in the perspective of evidence based medicine.

Improved coronary artery definition with T2-weighted, free-breathing, three-dimensional coronary MRA.

BACKGROUND: Three-dimensional (3D) navigator-gated and prospectively corrected free-breathing coronary magnetic resonance angiography (MRA) allows for submillimeter image resolution but suffers from poor contrast between coronary blood and myocardium. Data collected over >100 ms/heart beat are also susceptible to bulk cardiac and respiratory motion. To address these problems, we examined the effect of a T2 preparation prepulse (T2prep) for myocardial suppression and a shortened acquisition window on coronary definition. METHODS AND RESULTS: Eight healthy adult subjects and 5 patients with confirmed coronary artery disease (CAD) underwent free-breathing 3D MRA with and without T2prep and with 120- and 60-ms data-acquisition windows. The T2prep resulted in a 123% (P<0. 001) increase in contrast-to-noise ratio (CNR). Coronary edge definition was improved by 33% (P<0.001). Acquisition window shortening from 120 to 60 ms resulted in better vessel definition (11%; P<0.001). Among patients with CAD, there was a good correspondence with disease. CONCLUSIONS: Free-breathing, T2prep, 3D coronary MRA with a shorter acquisition window resulted in improved CNR and better coronary artery definition, allowing the assessment of coronary disease. This approach offers the potential for free-breathing, noninvasive assessment of the major coronary arteries.

Interaction between widening of diameter of abdominal aorta and cardiovascular risk factors and atherosclerosis burden.

The aim of this study was to investigate influence of traditional cardiovascular risk factors (CVRF) and subclinical atherosclerosis (ATS) burden on early stages of abdominal aortic diameter (AAD) widening among adults. 2,052 consecutive patients (P) (39 % women), mean age 52 ± 13 years, were prospectively screened for CVRF, ATS, and AAD. B-mode ultrasound was used to evaluate the largest AAD and to detect carotid and femoral atherosclerotic plaques. Mean AAD was 15.2 ± 2.8 mm. Atherosclerotic plaques were detected in 71 % of patients. Significant univariate correlation between AAD, traditional CVRF, and ABS was found. However, multiple regression analysis showed that only seven of them were significantly and weakly correlated with AAD (R² = 0.27, p < 0.001). On the other hand, a multivariate logistic analysis was used to evaluate CVRF impact on enlarged AAD ≥25 mm (EAAD) as compared to those with AAD <25 mm. These factors did not account for more than 30 % of interaction (R² = 0.30, p = 0.001). Furthermore, despite a large proportion of patients with high number of CVRF, and subclinical ATS, rate of patients with AAD ≥25 mm was low (1 %) and scattered regardless their CHD risk score or ATS burden. In conclusion, these results suggest that although some traditional CVRF and presence of ATS are associated with early stages of EAAD, other determinants still need to be identified for a better understanding of abdominal aortic aneurysm pathogenesis.

La médecine interne generate: un terrain propice à l'exercice de l'éthique au quotidien [Everyday bioethics in general internal medicine]

The knowledge of the national legislation and the key concepts of bioethics are necessary for medical practice. The four principles of bioethics are autonomy, beneficence, non-maleficence, and justice. General internal medicine is the speciality of comprehensive care for often elderly patients with multiple chronic illnesses. This care is related to many ethically difficult decisions. In our article, we discuss common ethical problems in general internal medicine, including ethical aspects of the patient-physician relationship and medical decision making, the ethical significance of time management, research in bioethics and medical education.

Médecine interne générale ambulatoire: quelques enseignements de la littérature en 2005 [Primary care in general internal medicine: relevant information in 2005]

During the year 2005, the chief residents of the University Medical Outpatient Clinic of Lausanne have done a database of useful articles for daily practice, scientifically validated and with excellent didactic quality, from 10 electronic journals. They have used those selected articles in personal meetings between the chief residents on a regular basis and the possibility to access the database by the junior physicians. Six of these articles concerning different topics (depression, tuberculosis detection, anticoagulation at home, cholinesterase inhibitors, insomnia and therapies, transdermal nitroglycerin and tendinopathies) are presented.

Phosphate forms in plant and their internal buffering in five soybean cultivars

Differences among plants in their ability to support nutritional stress periods may be caused by a differential vacuole capacity of ion storage and release and may also depend on the intensity of nutrient re-translocation under such conditions. In five soybean cultivars, submitted to eight days of P deprivation, the dry matter production and the contents of three phosphorus (P) forms - inorganic (Pi), organic (Po), and acid-soluble total (Pts) of different plant organs were determined. Pi release velocity (RSPi) was estimated as the tangent to the equations obtained for Pi f(t) at the point t = 2 days (the mean point in the period of greatest Pi decrease), considering that -deltaPi/deltat expresses the rate of Pi release. The internal Pi buffering capacity (IBCPi) was calculated as the inverse of the RSPi. Cultivars' differences in size of the non-metabolic Pi pool, RSPi, and the ability to transport Pi from less to more actively metabolizing regions were evaluated. The preferential Pi source and sink compartments under limited P absorption conditions were also evaluated. The cultivar Santa Rosa showed the highest Pi storage ability when the external supply was high, and a more intensive release under low P supply conditions than IAC8 and UFV1. The cultivar Uberaba was superior to Doko in its ability to store and use Pi. In all cultivars, upper leaves and roots were the main sink of Pi stored in the middle and lower leaves. Roots and upper leaves showed larger RSPi and lower IBCPi values than middle and lower leaves.

Fonction ventriculaire gauche après revascularisation pour occlusion d'une coronaire d'une durée de 1-2 heures [Left ventricular function following revascularization for occlusion of a coronary artery lasting 1 to 2 hours].

The time-lag between coronary occlusion and irreversible damage to the myocardium is ill-defined in man. In 10 patients the changes in left ventricular function have been studied after coronary occlusion during diagnostic or therapeutic cardiac catheterization of 1-2 hours' duration. Revascularization was achieved either surgically or through intracoronary streptokinase infusion. The interval between occlusion and onset of extracorporal circulation or reopening was 61 to 119 minutes. Despite enzyme elevation (CPK, CK-MB, SGOT) and appearance of Q-waves in 5 patients, no significant alteration of left ventricular function was noted on repeat cardiac catheterization 10 to 230 days after the accident. These observations, suggest that coronary occlusion of 1-2 hours' duration fails to produce significant irreversible damage to the myocardium despite electrocardiographic and enzymatic signs of myocardial infarction.

Acetaminophen increases blood pressure in patients with coronary artery disease.

BACKGROUND: Because traditional nonsteroidal antiinflammatory drugs are associated with increased risk for acute cardiovascular events, current guidelines recommend acetaminophen as the first-line analgesic of choice on the assumption of its greater cardiovascular safety. Data from randomized clinical trials prospectively addressing cardiovascular safety of acetaminophen, however, are still lacking, particularly in patients at increased cardiovascular risk. Hence, the aim of this study was to evaluate the safety of acetaminophen in patients with coronary artery disease. METHODS AND RESULTS: The 33 patients with coronary artery disease included in this randomized, double-blind, placebo-controlled, crossover study received acetaminophen (1 g TID) on top of standard cardiovascular therapy for 2 weeks. Ambulatory blood pressure, heart rate, endothelium-dependent and -independent vasodilatation, platelet function, endothelial progenitor cells, markers of the renin-angiotensin system, inflammation, and oxidative stress were determined at baseline and after each treatment period. Treatment with acetaminophen resulted in a significant increase in mean systolic (from 122.4±11.9 to 125.3±12.0 mm Hg P=0.02 versus placebo) and diastolic (from 73.2±6.9 to 75.4±7.9 mm Hg P=0.02 versus placebo) ambulatory blood pressures. On the other hand, heart rate, endothelial function, early endothelial progenitor cells, and platelet function did not change. CONCLUSIONS: This study demonstrates for the first time that acetaminophen induces a significant increase in ambulatory blood pressure in patients with coronary artery disease. Thus, the use of acetaminophen should be evaluated as rigorously as traditional nonsteroidal antiinflammatory drugs and cyclooxygenase-2 inhibitors, particularly in patients at increased cardiovascular risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00534651.

Report on a review of selected general and application controls over the Iowa Department of Transportation’s Internal Billing System for the period April 6, 2009 through July 31, 2009

Report on a review of selected general and application controls over the Iowa Department of Transportation’s Internal Billing System for the period April 6, 2009 through July 31, 2009