Successful long-term ambulatory norepinephrine infusions in a patient with pure autonomic failure.

We present a case study of a patient with pure autonomic failure who was successfully treated with ambulatory norepinephrine (NE) infusions over a 9-year-period of time before death occurred unexpectedly. Given this patient's response to the NE infusion treatment, we discuss the option of ambulatory NE infusions as a treatment for severe orthostatic hypotension that is refractory to common treatments.

[Lacunar stroke and cerebral small vessel disease: advocacy for a recognition]. / Infarctus lacunaire et micro- angiopathie cérébrale: plaidoyer pour une reconnaissance.

Cerebral small vessel disease (cSVD) represents the sum of lesions which define a rather new clinical entity. Indeed, lacunar infarcts which are acute events of cSVD, represent 25% of all ischemic strokes. However, only few studies have dealt with acute and long term management of such stroke. Despite its rather early description around the XIXth century, the "lacune", the cardinal anatomopathological lesion of cSVD, remains only partially explained and pathogenesis is still debated. The purpose of this paper is to better define the anatomical lesions, to discuss physiopathological hypotheses and to present the most salient clinical features. Once identified cSVD should not be further overlooked.

[Thrombotic microangiopathy: when time is the key factor!]. / Microangiopathie thrombotique: quand le temps presse.

Thrombotic microangiopathy or "TMA" including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) became a public health problem following the European outbreak of E. coli (O104:H4) gastroenteritis in 2011. A rapid diagnosis and therapy in an intensive care unit provide better patient survival and lower cost for society. Supportive treatment has significantly improved the prognosis over the past decade and includes fresh frozen plasma for TTP, plasmapheresis for HUS, and recently a new therapeutic agent: anti-C5 antibodies. We will provide in this article, through the current literature and four cases encountered in our department, to establish an algorithm to manage patients with TMA.

[Geriatric patients with chronic kidney insufficiency: which antalgia?]. / Patients gériatriques insuffisants rénaux chroniques: quelle antalgie ?

Pain is a leading cause of office visits. In the geriatric population, it is known that the prevalence of renal failure increases exponentially with age, modifing the elimination of drugs and of their metabolites. What analgesia should be offered to these patients? The holy grail would be a medication without renal elimination, without toxic metabolites and without nephrotoxicity. Based on the literature we try to propose a specific approach to analgesia in older patients with kidney insufficiency, in order to help practitioners to better prescribe for this group of patients.

Normal weight obesity: relationship with lipids, glycaemic status, liver enzymes and inflammation.

BACKGROUND AND AIMS: Normal weight obesity (NWO) is defined as an excessive body fat associated with a normal body mass index (BMI) and has been associated with early inflammation, but its relationship with cardiovascular risk factors await investigation. METHODS AND RESULTS: Cross-sectional study including 3213 women and 2912 men aged 35-75 years to assess the clinical characteristics of NWO in Lausanne, Switzerland. Body fat was assessed by bioimpedance. NWO was defined as a BMI<25 kg/m(2) and a % body fat ≥66(th) gender-specific percentiles. The prevalence of NWO was 5.4% in women and less than 3% in men, so the analysis was restricted to women. NWO women had a higher % of body fat than overweight women. After adjusting for age, smoking, educational level, physical activity and alcohol consumption, NWO women had higher blood pressure and lipid levels and a higher prevalence of dyslipidaemia (odds-ratio=1.90 [1.34-2.68]) and fasting hyperglycaemia (odds-ratio=1.63 [1.10-2.42]) than lean women, whereas no differences were found between NWO and overweight women. Conversely, no differences were found between NWO and lean women regarding levels of CRP, adiponectin and liver markers (alanine aminotransferase, aspartate aminotransferase and gamma glutamyl transferase). Using other definitions of NWO led to similar conclusions, albeit some differences were no longer significant. CONCLUSION: NWO is almost nonexistent in men. Women with NWO present with higher cardiovascular risk factors than lean women, while no differences were found for liver or inflammatory markers. Specific screening of NWO might be necessary in order to implement cardiovascular prevention.

Atrial assist device, a new alternative to lifelong anticoagulation?

OBJECTIVE: Atrial fibrillation is a very common heart arrhythmia, associated with a five-fold increase in the risk of embolic strokes. Treatment strategies encompass palliative drugs or surgical procedures all of which can restore sinus rhythm. Unfortunately, atria often fail to recover their mechanical function and patients therefore require lifelong anticoagulation therapy. A motorless volume displacing device (Atripump) based on artificial muscle technology, positioned on the external surface of atrium could avoid the need of oral anticoagulation and its haemorrhagic complications. An animal study was conducted in order to assess the haemodynamic effects that such a pump could provide. METHODS: Atripump is a dome-shape siliconecoated nitinol actuator sewn on the external surface of the atrium. It is driven by a pacemaker-like control unit. Five non-anticoagulated sheep were selected for this experiment. The right atrium was surgically exposed, the device sutured and connected. Haemodynamic parameters and intracardiac ultrasound (ICUS) data were recorded in each animal and under three conditions; baseline; atrial fibrillation (AF); atripump assisted AF (aaAF). RESULTS: In two animals, after 20 min of AF, small thrombi appeared in the right atrial appendix and were washed out once the pump was turned on. Assistance also enhanced atrial ejection fraction. 31% baseline; 5% during AF; 20% under aaAF. Right atrial systolic surfaces (cm2) were; 5.2 +/- 0.3 baseline; 6.2 +/- 0.1 AF; 5.4 +/- 0.3 aaAF. CONCLUSION: This compact and reliable pump seems to restore the atrial "kick" and prevents embolic events. It could avoid long-term anticoagulation therapy and open new hopes in the care of end-stage heart failure.

A comparative study of reactive hyperemia in human forearm skin and muscle.

Reactive hyperemia (RH) in forearm muscle or skin microcirculation has been considered as a surrogate endpoint in clinical studies of cardiovascular disease. We evaluated two potential confounders that might limit such use of RH, namely laterality of measurement and intake of non-steroidal anti-inflammatory drugs (NSAIDS). Twenty-three young non-smoking healthy adults were enrolled. In Experiment 1 (n=16), the RH elicited by 3 min of ischemia was recorded in the muscle (strain gauge plethysmography, hand excluded) and skin (laser Doppler imaging) of both forearms. In Experiment 2 (n=7), RH was determined in the dominant forearm only, one hour following oral acetylsalicylic acid (1 g) or placebo. In Experiment 1, peak RH was identical in both forearms, and so were the corresponding durations of responses. RH lasted significantly less in muscle than in skin (p=0.003), a hitherto unrecognized fact. In the skin, acetylsalicylate reduced duration (43 vs. 57.4 s for placebo, p=0.03), without affecting the peak response. In muscle, duration tended to decrease with acetylsalicylate (21.4 vs. 26.0 s with placebo, p=0.06) and the peak increase in blood flow was blunted (27.2 vs. 32.4 ml/min/100 ml tissue with placebo, p=0.003). We conclude that, when using RH as a surrogate endpoint in studies of cardiovascular disease, a confounding by laterality of measurement need not be feared, but NSAIDS may have an influence, although perhaps not on the peak response in the skin.

Current treatment options of femoral pseudoaneurysms.

Femoral pseudoaneurysm (PA) is a common complication that occurs in up to 6% of diagnostic or therapeutic catheterisation. Spontaneous closure is the rule for small PA. Large and complex PA need treatment to prevent complications such as diffuse hemodynamically effective bleeding or embolisation. A manual compression repair with or without ultrasound (US) guidance remains the first line treatment. A surgical approach is indicated in selected cases and requires anaesthesia, wound healing, longer hospital stay and extensive costs. New therapies have emerged recently that are non invasive and appropriate to most patients, even in critically ill patients. We here review the non-surgical treatment options that include compression therapy, endoprosthesis placement, coil embolisation, percutaneous collagen and thrombin injection.

[Screening for atherothrombosis at the doctor's office: role of blood pressure measurement at the ankle]. / Dépistage de la maladie athéromateuse au cabinet du praticien: place de la mesure de la pression à la cheville.

Peripheral artery disease (PAD) is frequently overlooked because of its silent evolution for quite a long period and because it has not been considered as harmful as other atherothrombosis complications such as myocardial infarction or stroke. PAD is readily diagnosed by measuring the ankle brachial index (ABI). A reduced ABI is able to identify an asymptomatic PAD in a high risk patient and provides a very valuable predictor of cardiovascular events allowing to better profile the individual risk of the patient. The awareness of PAD as a mark of a generalized atherothrombosis disease holds the potential to increase the doctor's view of the true individual risk of his patient and to enforce cardiovascular risk prevention as suggested by recent studies.

Frequency of use and acceptability of clinical prediction rules for pulmonary embolism among Swiss general internal medicine residents.

INTRODUCTION: Whether clinical prediction rules for pulmonary embolism are accepted and used among general internal medicine residents remains uncertain. We therefore evaluated the frequency of use and acceptability of the Revised Geneva Score (RGS) and the Pulmonary Embolism Severity Index (PESI), and explored which factors were associated with rule use. MATERIALS/METHODS: In an online survey among general internal medicine residents from 10 Swiss hospitals, we assessed rule acceptability using the Ottawa Acceptability of Decision Rules Instrument (OADRI) and explored the association between physician and training-related factors and rule use using mixed logistic regression models. RESULTS: The response rate was 50.4% (433/859). Overall, 61% and 36% of the residents reported that they always or regularly use the RGS and the PESI, respectively. The mean overall OADRI score was 4.3 (scale 0-6) for the RGS and 4.1 for the PESI, indicating a good acceptability. Rule acceptability (odds ratio [OR] 6.19 per point, 95% confidence interval [CI] 3.64-10.51), prior training in emergency medicine (OR 5.14, CI 2.20-12.01), and availability of internal guidelines recommending RGS use (OR 4.25, CI 2.15-8.43) were associated with RGS use. Rule acceptability (OR 6.43 per point, CI 4.17-9.92) and rule taught at medical school (OR 2.06, CI 1.24-3.43) were associated with PESI use. CONCLUSIONS: The RGS was more frequently used than the PESI. Both rules were considered acceptable. Rule acceptability, prior training in emergency medicine, availability of internal guidelines, and rule taught at medical school were associated with rule use and represent potential targets for quality improvement interventions.

[Drug addicts as cardiovascular patients]. / Le toxicomane, un patient "polyvasculaire".

Drug addicts very often present with vascular complications. A great number of these lesions require medical care. Vascular problems are diverse and multiple affecting both veins and arteries, the latter being often the most dramatic. This article attempt to describe the most frequent lesions observed in drug addicts considering two different mechanisms; traumatic versus drug induced complications.

[Early detection of atherosclerosis]. / Détection précoce de la maladie athéroscléreuse.

According to the guidelines, the global assessment of cardiovascular risk is based on traditional risk factors. The emergence of new cardiovascular risk factors may be helpful. However, at every level of risk factor exposure, there is a substantial variation of atherosclerosis. Thus, subclinical disease measurements, representing the end result of risk exposure may be useful for improving cardiovascular risk prediction. In comparison to the ankle-brachial index, the high resolution B-mode ultrasound is a more promising tool to detect early atherosclerosis both on carotid and femoral arterial wall in asymptomatic patients. It appears as a new approach to predict the risk of cardiovascular disease and to monitor the cardiovascular therapy.

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

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.

Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment.

BACKGROUND: Local pulse pressure (PP) is an independent determinant of carotid artery wall thickness, stronger than mean blood pressure (BP). The present study was designed to assess whether a beta-adrenoceptor antagonist-based or an ACE inhibitor-based treatment was able to reduce carotid artery wall hypertrophy through a reduction in carotid PP rather than by lowering mean BP and whether the influence of local PP reduction could also be detected at the site of a muscular artery, the radial artery. METHODS AND RESULTS: Ninety-eight essential hypertensive patients were randomized to 9 months of double-blind treatment with either celiprolol or enalapril. Arterial parameters were determined with high-resolution echo-tracking systems. PP was measured locally with applanation tonometry and independently of mean BP. After 9 months of treatment, mean BP, carotid PP, and intimal-medial thickness (IMT) decreased significantly, with no difference between the 2 groups. The reduction in carotid PP but not in mean BP was a major independent determinant of the reduction in carotid IMT. Radial artery IMT and PP decreased significantly with both treatments. However, the reduction in radial artery IMT was not related to the changes in radial artery PP. CONCLUSIONS: The regression of carotid artery wall hypertrophy during long-term antihypertensive treatment was dependent on the reduction in local PP rather than on the lowering of mean BP. The effect of PP lowering on IMT reduction was observed at the site of an elastic artery but not at the site of a muscular artery.

Pitting edema of the four extremities of rapid appearance.

We report the case of a 70 year old white man with rapid onset edema of the four extremities without any other systemic symptoms. Cardiac failure, nephrotic syndrome and hepatic dysfunction were ruled out. Rheumatoid factor was slightly elevated at 33 UI/ml and sedimentation rate was within normal range. Ultrasound examination of the upper limb revealed increased blood flow (400 ml/min) at the level of the brachial artery and edema of the tenosynovial sheaths. A diagnosis of remitting seronegative symmetrical synovitis and pitting edema (RS3PE) was made and prednisone 15 mg/day was prescribed with rapid disappearance of the edema and reduction of the forearm blood flow.

A novel interferon-gamma regulated human melanoma-associated antigen, gp33-38, defined by monoclonal antibody Me14-D12. II. Molecular cloning of a genomic probe.

The human Me14-D12 antigen is a cell surface glycoprotein regulated by interferon-gamma (IFN-gamma) on tumor cell lines of neuroectodermal origin. It consists of two non-convalently linked subunits with apparent mol. wt sizes of 33,000 and 38,000. Here we describe the molecular cloning of a genomic probe for the Me14-D12 gene using the gene transfer approach. Mouse Ltk- cells were stably cotransfected with human genomic DNA and the Herpes Simplex virus thymidine kinase (TK) gene. Primary and secondary transfectants expressing the Me14-D12 antigen were isolated after selection in HAT medium by repeated sorting on a fluorescence activated cell sorter (FACS). A recombinant phage harboring a 14.3 kb insert of human DNA was isolated from a genomic library made from a positive secondary transfectant cell line. A specific probe derived from the phage DNA insert allowed the identification of two mRNAs of 3.5 kb and 2.2 kb in primary and secondary L cell transfectants, as well as in human melanoma cell lines expressing the Me14-D12 antigen. The regulation of Me14-D12 antigen by INF-gamma was retained in the L cell transfectants and could be detected both at the level of protein and mRNA expression.

[Atherosclerosis: which are the tools available for the practionner?]. / Athérosctérose: quels sont les marqueurs à disposition du praticien?

Identification of atherosclerotic lesions in asymptomatic subjects improves the stratification of their absolute cardiovascular risk. Several methods allowing detection of atherosclerosis rely on sophisticated and expensive apparatus. Only simple and inexpensive methods can be used in general practice. The ankle-brachial index (ABI) is a very simple, cheap and easy to learn method to identify peripheral artery disease, one of several clinical manifestations of atherosclerosis. ABI is not only a marker of atherosclerosis but a strong predictor of cardiovascular mortality. Pulse wave velocity a marker of large artery stiffness is another strong predictor of cardiovascular morbidity and mortality. It is presently used only for clinical studies but may soon be part of the vascular assessment performed in general practice.

Contributions of vascular tone and structure to elastic properties of a medium-sized artery.

Isobaric compliance and distensibility of the radial artery were recently reported to be normal or slightly increased in untreated hypertensive patients. However, these findings provide no information on the intrinsic mechanical properties of the wall material. To address this question, we determined intima-media wall thickness, wall-to-lumen ratio, and incremental elastic modulus in the radial artery of 25 untreated hypertensive patients with blood pressure of 150 +/- 14/103 +/- 6 mm Hg (mean +/- SD) and 25 matched control subjects with blood pressure of 118 +/- 9/79 +/- 6 mm Hg. High-resolution echotracking for assessment of internal diameter and intima-media wall thickness was combined with measurements of blood flow velocity by Doppler and blood pressure by photoplethysmography. In addition, isobaric compliance and distensibility and incremental elastic modulus were measured at peak diameter during reactive hyperemia after a 5-minute brachial occlusion. No significant difference was found between the two groups for isobaric compliance or distensibility at baseline or during hyperemia. However, incremental elastic modulus at 100 mg Hg tended to be lower in hypertensive patients than control subjects (1.9 +/- 1.1 versus 2.5 +/- 1.2 mm Hg x 10(4), P = .1) in resting conditions. Hypertensive patients and control subjects had similar internal diameters (2.47 +/- 0.32 versus 2.41 +/- 0.35 microm), but intima-media wall thickness and wall-to-lumen ratio were significantly increased in hypertensive patients compared with control subjects (0.268 +/- 0.032 versus 0.236 +/- 0.025 mm -P < or = .01- and 0.220 +/- 0.038 versus 0.195 +/- 0.028 -P < or = .05-, respectively). Peak hyperemic blood flow response (hypertensive patients versus control subjects: 349% versus 360% increase from baseline) and reactive hyperemic dilation (7.2% versus 7.9%) were similar in amplitude and duration in the two groups. These results suggest that wall thickening is an adaptive process that reduces wall tension in hypertensive patients while preserving a normal mechanical behavior of the radial artery. This is most likely accomplished by modification of the incremental elastic modulus of wall components rather than by a change in vascular tone.

Differences in the mechanical properties of the rat carotid artery in vivo, in situ, and in vitro.

The elastic properties of carotid arteries of spontaneously hypertensive rats (SHR) and normotensive controls (Wistar-Kyoto rats [WKY]) were examined in vivo, in situ, and in vitro. The changes of internal diameter were measured with a high-resolution A-mode echo-tracking device simultaneously with the intra-arterial pressure at the carotid. The internal diameter at mean arterial blood pressure (MBP) was substantially smaller in vitro than in vivo in SHR (-33.8%) and WKY (-48.3%). The arterial distensibility was lower in vitro in all arteries compared with in vivo conditions (SHR, -30.1%; WKY, -60.4%; at MBP) despite a reduced incremental elastic modulus in vitro (SHR, -56.9%; WKY, -45.1%; at MBP). However, the in vitro and in vivo measurements show consistent elastic behavior of the carotid arteries between both strains of rats. Carotid arteries from WKY were also examined in situ. Although no significant reduction in internal diameter could be observed in situ, distensibility was dramatically decreased (-87% at MBP). These results emphasize the importance of considering the original vascular geometry when determining elastic properties of arteries. We conclude that experimental conditions are likely to be a critical determinant for the assessment of the mechanical properties of conduit vessels.