Disseminated Mycobacterium lentiflavum responsible for hemophagocytic lymphohistocytosis in a man with a history of heart transplantation.

Mycobacterium lentiflavum is a nontuberculous, slowly growing mycobacterium usually recognized as a contaminant. Here, we report a case of disseminated M. lentiflavum infection responsible for hemophagocytic lymphohistocytosis in a heart-transplanted man.

[Amiodarone-induced optic neuropathy: A rare side effect]. / Un effet indésirable rare de l'amiodarone : la neuropathie optique.

INTRODUCTION: The diagnosis of bilateral papilledema implies emergency medical care to look for intracranial hypertension and arteritic ischemic neuropathy. However, other causes must also be mentioned, including drugs. Too often underrated because of their usual benignity, drug side ophthalmological effects can be severe and are typically bilateral. CASE REPORT: An 80-year-old woman was hospitalized for bilateral papilledema, predominantly in the left eye, with lowered visual acuity. After ruling out intracranial hypertension, arteritic ischemic optic neuropathy, non-arteritic, and inflammatory bilateral papilledema, the diagnosis was toxic optic neuropathy. CONCLUSION: Bilateral edematous optic neuropathy is a known side effect of amiodarone, uncommon but to be known because of the large number of patients benefiting from this treatment.

New concept of IEC standards for radiation protection dosemeters.

The International Electrotechnical Commission (IEC) develops new standards for radiation protection dosemeters which follow a new concept. They are much more flexible in detail, but still ensure the same measurement quality. They are, for example, no longer specific for the detector type, but rather specific for the measurement task, e.g. for individual monitoring with active direct-reading instruments. Another example is that they are flexible with respect to the ranges of influence quantities. The conceptual changes are described in this paper, together with the advantages this new concept provides for manufacturers, users and legislators.

Review of international standards for dosemeters.

International standards for radiation protection dosemeters are published by the International Electrotechnical Commission and the International Organization for Standardization. Several standards exist side by side, although they treat the same measuring task, and specify different requirements, so that dosemeters of different quality result. In this paper, the quality of dosemeters is compared by calculating the uncertainty of dose measurements for dosemeters, which just basely fulfil the respective standard. The results are related to general yardsticks on uncertainty laid down by international organisations. Furthermore, technical differences are standards and addressed and a method to make them conform is presented.

[The best of clinical pharmacology in 2006]. / L'essentiel de l'année 2006 en pharmacologie clinique cardiovasculaire.

The clinical pharmacological and therapeutic working group was particularly impressed by twelve recent publications relative to its various themes of interest. Two studies were made of the prognostic impact of non-observance of treatment which seems to be associated with an extra-mortality even when the treatment is placebo: the probable explanation is that the non-observance of drug therapy is also associated with the non observance of dietary/life style measures and with cognitive dysfunction associated with more severe cardiac disease. A recent study on n-acetyl-cysteine has rekindled the debate on this substance for preventing nephrotoxicity of radiological contrast used during angioplasty in high risk patients. The risks of AINS drug therapy has been reassessed. The increased risk of myocardial infarction is confirmed with celecoxib but not with "classical" AINS drugs if not prescribed for more than one year and without aspirin. With respect to lipid-lowering drugs, should statins be prescribed to attain a target value of LDL-cholesterol or to attain a given reduction in LDL-cholesterol? The death knell of fibrates has more or less been rung by the results of the FIELD study and the real value of OMEGA-3 drugs should be reassessed by good quality prospective studies. In the domain of hypertension, the recent arrival of aliskiren, the first of the antirenin drugs, is noteworthy although its role in the therapeutic strategy, remains to be defined. Finally, a comment is made on the results of the TROPHY study which suggest value in the possible prevention of hypertension with angiotensin II inhibitors in patients at risk of developing hypertension.

[Usefulness of B-type natriuretic peptide (BNP) for the diagnosis of new-onset heart failure with a preserved left ventricular systolic function in longstanding hypertensive patients with acute dyspnea]. / Apport du peptide natriurétique de type B dans le primo-diagnostic d'insuffisance cardiaque à fonction systolique preservée chez le patient hypertendu souffrant de dyspnée aiguë.

BACKGROUND: B-type natriuretic peptide (BNP) has been largely validated in the etiologic diagnosis of acute dyspnea. Nevertheless, its reliability in the setting of a preserved left ventricular systolic function (ejection fraction >50%) has not been adequately established. OBJECTIVE: the study addressed the usefulness of BNP in the diagnosis of new-onset heart failure with a preserved systolic function in hypertensive patients hospitalized for acute dyspnea. METHODS: 59 consecutive hypertensive patients without history of heart failure and coronary disease were included. BNP was measured at presentation with the Triage system. Noninvasive estimation of left ventricular filling pressures by bedside tissue Doppler echocardiography at presentation was incorporated in the diagnostic criteria. RESULTS: the 30 patients with heart failure were not significantly different from the 29 patients with noncardiac cause of acute dyspnea regarding age, gender, body mass index and ejection fraction. Median levels of BNP were significantly higher in heart failure (447 [245-644] versus 87 [43-139] pg/mL). By multivariate logistic regression analysis, BNP (odds ratio of 44, [3.6-531], p=0.003) provided independent and incremental diagnostic information over the clinical score of Boston criteria (2.25, [1.3-3.9], p=0.0037). A BNP value of >142 pg/mL (area under the ROC curve of 0.89, p<0.0001) was 93 sensitive and 79% specific for the diagnosis of heart failure in this setting. CONCLUSION: BNP is a reliable biomarker of new-onset heart failure with a preserved systolic function in hypertensive patients, in particular older, hospitalized for acute dyspnea and can be safely integrated in the diagnostic strategy.

Meta-analysis of major bleeding events on aspirin versus vitamin K antagonists in randomized trials.

BACKGROUND AND OBJECTIVES: The relative bleeding risk of aspirin versus vitamin K antagonists (VKA) is unclear. Most of previous meta-analyses included trials with target INR for VKA therapy far beyond usually recommended range (2-3). The aim of this study was to compare the bleeding risk of aspirin and VKA, as indicated by the aggregate body of clinical evidence including data from the recently published WARCEF trial. METHODS: In this meta-analysis we included randomized controlled trials that compared aspirin to VKA (1.4

Detection of Focal Longitudinal Changes in the Brain by Subtraction of MR Images.

BACKGROUND AND PURPOSE: The detection of new subtle brain pathology on MR imaging is a time-consuming and error-prone task for the radiologist. This article introduces and evaluates an image-registration and subtraction method for highlighting small changes in the brain with a view to minimizing the risk of missed pathology and reducing fatigue. MATERIALS AND METHODS: We present a fully automated algorithm for highlighting subtle changes between multiple serially acquired brain MR images with a novel approach to registration and MR imaging bias field correction. The method was evaluated for the detection of new lesions in 77 patients undergoing cardiac surgery, by using pairs of fluid-attenuated inversion recovery MR images acquired 1-2 weeks before the operation and 6-8 weeks postoperatively. Three radiologists reviewed the images. RESULTS: On the basis of qualitative comparison of pre- and postsurgery FLAIR images, radiologists identified 37 new ischemic lesions in 22 patients. When these images were accompanied by a subtraction image, 46 new ischemic lesions were identified in 26 patients. After we accounted for interpatient and interradiologist variability using a multilevel statistical model, the likelihood of detecting a lesion was 2.59 (95% CI, 1.18-5.67) times greater when aided by the subtraction algorithm (P = .017). Radiologists also reviewed the images significantly faster (P < .001) by using the subtraction image (mean, 42 seconds; 95% CI, 29-60 seconds) than through qualitative assessment alone (mean, 66 seconds; 95% CI, 46-96 seconds). CONCLUSIONS: Use of this new subtraction algorithm would result in considerable savings in the time required to review images and in improved sensitivity to subtle focal pathology.

Antiplatelet therapy for primary prevention in diabetes.

Aspirin is currently recommended by ADA (American Diabetes Association) for the diabetic patients over 40 years of age and without cardiovascular disease. This recommendation is at odds with drug approval for aspirin. The main explanation is the absence of appropriate trials assessing the usefulness of aspirin in such patients. Two assumptions, central to these guidelines are that diabetes is a coronary risk equivalent, and that aspirin benefit/risk ratio is similar in diabetic patients than in coronary disease patients. Unfortunately, vascular risk level is variable in diabetic patients. Patients with new onset diabetes have lower cardiovascular risk than patients with established cardiovascular disease. Smoking habits markedly increase the risk. Benefits may be lower in diabetic patients since aspirin resistance is common in these patients. Haemorrhagic risk may be higher since diabetes is a risk factor for haemorrhagic stroke. Awaiting trial evidence, aspirin therapy should be considered in diabetic patients with a very high risk, such as smokers, patients with long diabetes duration, or atherosclerotic plaques at echography.

[Prognostic value of BNP for hospital mortality in elderly subjects hospitalised for acute diastolic cardiac failure]. / Valeur pronostique du BNP pour la mortalité hospitalière chez le sujet agé hospitalisé pour insuffisance cardiaque diastolique aiguë.

The aim of this study was to evaluate the prognostic value of BNP in elderly patients hospitalised for acute diastolic cardiac failure. 108 consecutive subjects were included, aged at least 70 years old, hospitalised for isolated acute diastolic cardiac failure. All of them had a left ventricular ejection fraction > or = 50% and evidence of diastolic dysfunction on echocardiography performed shortly after admission. The plasma BNP concentration measured in the emergency department on admission was >100 pg/ml in all of the patients except five. It was positively correlated with age (R = 0.29, p = 0.002), with the plasma creatinine level (R = 0.37, p < 0.0001) and the plasma urea level (R = 0.41, p < 0.0001). On univariate analysis, compared to the patients who survived, the 20 patients who died before discharge were significantly older (88.6 versus 84.4 years, p = 0.01), and were more often residents of a care home (60 versus 31%. p = 0.02), had a lower systolic blood pressure on admission (127 +/- 33 versus 154 +/- 30 mm Hg), a higher plasma urea level (16.8 +/- 12 versus 8.9 +/- 5 mmol/l, p = 0.002) and a higher BNP (median = 1290 pg/ml, interquartile range: 721, 3026 pg/ml versus 430 pg/ml, interquartile range: 243, 886 pg/ml). On multivariate analysis, the only factors that remained significantly associated with mortality were the BNP levels (p = 0.005) and the systolic blood pressure (p = 0.01). The negative predictive value of a BNP level < 631 pg/ml (median) for death was 94% (95% confidence interval: 91 to 97%). We conclude that BNP does have an independent prognostic value for in-hospital death in elderly subjects with acute diastolic cardiac failure.

Uncertainties in workplace external dosimetry--an analytical approach.

The uncertainties associated with external dosimetry measurements at workplaces depend on the type of dosemeter used together with its performance characteristics and the information available on the measurement conditions. Performance characteristics were determined in the course of a type test and information about the measurement conditions can either be general, e.g. 'research' and 'medicine', or specific, e.g. 'X-ray testing equipment for aluminium wheel rims'. This paper explains an analytical approach to determine the measurement uncertainty. It is based on the Draft IEC Technical Report IEC 62461 Radiation Protection Instrumentation-Determination of Uncertainty in Measurement. Both this paper and the report cannot eliminate the fact that the determination of the uncertainty requires a larger effort than performing the measurement itself. As a counterbalance, the process of determining the uncertainty results not only in a numerical value of the uncertainty but also produces the best estimate of the quantity to be measured, which may differ from the indication of the instrument. Thus it also improves the result of the measurement.

Aspects of harmonisation of individual monitoring for external radiation in Europe: conclusions of a EURADOS action.

Following the publication of the EU Council Directive 96/29, EURADOS coordinated two working groups (WGs) for promoting the process of harmonisation on individual monitoring of occupationally exposed persons in Europe. An overview of the major findings of the second WG is presented. Information on the technical and quality standards and on the accreditation and approval procedures has been compiled. The catalogue of dosimetric services has been updated and extended. An overview of national regulations and standards for protection from radon and other natural sources in workplaces has been made, attempting to combine the results from individual monitoring for external, internal and workplace monitoring. A first status description of the active personal dosemeters, including legislative and technical information, and their implementation has been made. The importance of practical factors on the uncertainty in the dose measurement has been estimated. Even if a big progress has been made towards harmonisation, there is still work to be done.

Implications of X-ray tube parameter deviations in X-ray reference fields.

For the purpose of radiation protection, ICRU Report 57/ICRP Publication 74 provides a list of monoenergetic conversion coefficients to be used with, among others, photon reference fields generated with X-ray tubes. A comprehensive definition of these photon reference fields can be found in international standard ISO 4037; however, it lacks thorough indication of the allowed deviations of essential parameters that influence these X-ray reference fields. These parameters are the high-voltage tube potential, the thickness of the beryllium window and the purity and thickness of the filter materials used to create different radiation qualities. Small variations of these parameters can lead to significant changes in the created X-ray spectra and, hence, the spectra-dependent conversion coefficients for phantom-related radiation-protection quantities. This can lead to situations in which the conversion coefficients listed in ISO 4037 cannot be used, resulting in time-consuming spectrometry measurements. In this work, the impact on the resulting conversion coefficients is investigated using a simplified mathematical approximation model. The findings are validated with an independent X-ray spectra calculation programme. As a result, well-founded upper limit values on the allowed deviations of the essential X-ray tube parameters are proposed to be used in a future revision of ISO 4037.

EVOLUTION OF THE IEC AND EN STANDARDS FOR INDIVIDUAL MONITORING OF IONISING RADIATION.

This article presents the evolution of the International Electrotechnical Commission (IEC) and the European standards for individual monitoring of ionising radiation issued, respectively, from the committees IEC/Sub Committee 45B and European Committee for Electro-technical Standardization/Technical Committee 45B 'Radiation protection instrumentation'. Standards for passive individual photon and beta dosimetry systems as well as those for active individual monitors are discussed. A neutron ambient dose equivalent (rate) meter standard and a technical report concerning the determination of uncertainty in measurement are also covered.

Effects of folate supplementation in hyperhomocysteinemic pigs.

OBJECTIVES: The aim of this study was to evaluate the therapeutic effects of folic acid in the pig model of hyperhomocysteinemia. BACKGROUND: We have previously shown that pigs fed a methionine-rich diet develop hyperhomocysteinemia, arterial lesions and thrombotic events. Elevated homocysteine level is an independent risk factor for atherosclerosis that can be markedly lowered with daily folic acid administration. However, it is not known whether this treatment can prevent arterial lesions. METHODS: Three groups of pigs were studied: 8 control subjects received a standard diet; 8 received a methionine-rich diet for four months; 8 received a methionine-rich diet for 1 month and then the methionine-rich diet + 5 mg/day folic acid for 3 months. At month 4 after hemodynamic investigation, all the pigs were sacrificed. RESULTS: Control animals developed few usual vascular streaks. All the pigs fed a methionine-rich diet without folic acid treatment developed hyperhomocysteinemia (10.3+/-1.3 micromol/liter at basal state, 18.2+/-2.5 micromol/liter at one month and 14.6+/-3.8 micromol/liter at four months), hemodynamic abnormalities and diffuse arterial lesions with smooth muscle cell hyperplasia, endothelial alterations and elastic lamina dislocation. In this group, one pig died of venous thromboembolism and one of myocardial infarction. The pigs fed a methionine-rich diet + folic acid displayed similar arterial lesions and two had thrombotic events (one myocardial infarction and one pulmonary embolism), despite normalization of homocysteine levels (10.9+/-1.3 micromol/liter at basal state, 19.5+/-2.5 micromol/liter at one month and 11.4+/-3.8 micromol/liter at four months). CONCLUSIONS: In the pig model of hyperhomocysteinemia, 5 mg/day folic acid did not prevent arterial lesions or thrombotic events.

Echocardiography predicts embolic events in infective endocarditis.

OBJECTIVES: The aim of our study was to assess the value of transesophageal echocardiography (TEE) in predicting embolic events (EEs) in a large group of patients with definite endocarditis according to the Duke criteria, including silent embolism. BACKGROUND: The value of echocardiography in predicting embolism in patients with endocarditis remains controversial. Some studies reported an increased risk of embolism in patients with large and mobile vegetations, whereas other studies failed to demonstrate such a relationship. METHODS: Multiplane transesophageal echocardiograms of 178 consecutive patients with definite infective endocarditis (IE) were analyzed. The incidence of embolism was compared with the echocardiographic characteristics (localization, size and mobility) of the vegetations. To detect silent embolism, cerebral and thoraco-abdominal scans were performed in 95% of patients. RESULTS: Among 178 patients, 66 (37%) had one or more EEs. There was no difference between patients with and without embolism in terms of age, gender and left valve involved. On univariate analysis, Staphylococcus infection, right-side valve endocarditis and vegetation length and mobility were significantly related to EEs. A significant higher incidence of embolism was present in patients with vegetation length >10 mm (60%, p < 0.001) and in patients with mobile vegetations (62%, p < 0.001). Embolism was particularly frequent among 30 patients with both severely mobile and large vegetations (> 15 mm) (83%, p < 0.001). On multivariate analysis, the only predictors of embolism were vegetation length (p = 0.03) and mobility (p = 0.01). CONCLUSIONS: Our study shows that the presence of vegetations on TEE is predictive of embolism and that the morphologic characteristics of vegetations are helpful in predicting EEs in both mitral and aortic valve IE. It also suggests that early operation may be recommended in patients with vegetations > 15 mm and high mobility, irrespective of the degree of valve destruction, heart failure and response to antibiotic therapy.

Value and limitations of the Duke criteria for the diagnosis of infective endocarditis.

OBJECTIVES: The purpose of this study was to assess the value and limitations of Duke criteria for the diagnosis of infective endocarditis (IE). BACKGROUND: Duke criteria have been shown to be more sensitive in diagnosing IE than the von Reyn criteria, but the diagnosis of IE remains difficult in some patients. METHODS: Both classifications were applied in 93 consecutive patients with pathologically proven IE. Blood cultures, and transthoracic and transesophageal echocardiography were performed in all patients. RESULTS: Sensitivities for the diagnosis of IE were 56% and 76% for von Reyn and Duke criteria, respectively. Fifty-two patients were correctly classified as "probable IE" by von Reyn and "definite IE" by Duke criteria (group 1). However, discrepancies were observed in 41 patients. Eleven patients (group 2) were misclassified as "rejected" by von Reyn, but were "definite IE" by Duke criteria; this difference could be explained by negative blood cultures and positive echocardiogram in all patients. In eight patients (group 3), the diagnosis of IE was "possible" by von Reyn but "definite" by Duke criteria. This difference was essentially explained by the failure of the von Reyn classification to consider echocardiographic abnormalities as major criteria. Twenty-two patients (group 4) were misclassified as possible IE using Duke criteria, being false negative of this classification. Echocardiographic major criteria were present in 19 patients, but blood cultures were negative in 21 patients. The cause of negative blood cultures was prior antibiotic therapy in 11 patients and Q-fever endocarditis diagnosed by positive serology in three cases. CONCLUSIONS: Twenty-four percent of patients with proved IE remain misclassified as "possible IE" despite the use of Duke criteria, especially in cases of culture-negative and Q-fever IE. Increasing the diagnostic value of echographic criteria in patients with prior antibiotic therapy and typical echocardiographic findings and considering the serologic diagnosis of Q fever as a major criterion would further improve the clinical diagnosis of IE.

[The best of clinical pharmacology in 2004]. / L'essentiel de 2004 en pharmacologie clinique cardiovasculaire.

The year 2004 was not marked by major pharmacological advances, but by confirmation of previous "evidence". Several innovative drugs for stable angina (ranolazine, ivabradine), some interesting results in acute coronary syndrome (PROVE IT study), some classic concepts (cannabinoid receptors and their antagonists such as rimonabant) applied to novel indications (treatment of obesity), hopes for the "sartans" revived in the light of new evidence (VALUE study), advances in the management of diabetes and hypertension (ASCOT and CARDS studies), nebivolol which is not just a betablocker but also produces the NO radical (is this why it decreased the mortality of heart failure in the elderly in the SENIOR study?). In contrast, although Chronadalate did not live up to expectations for coronary insufficiency, the year was marked above all by the much heralded withdrawal of Vioxx for increasing cardiovascular risk. The old adage: primum non nocere springs to mind.

Association of mild hyperhomocysteinemia with cardiac graft vascular disease.

In non-transplant patients mild hyperhomocysteinemia is an independent risk factor for vascular disease. The aim of this study was to determine whether hyperhomocysteinemia is associated with graft vascular disease. Fasting total plasma homocysteine was assessed in 18 patients with graft vasculopathy and 18 transplanted patients without graft vasculopathy matched for age, sex and the time since transplant. All were on cyclosporin. Graft vasculopathy was defined at coronary angiography as stenoses > or = 25%, or aneurysms. We found that hyperhomocysteinemia ( > or = 15 micromol/l) is common among transplanted heart recipients and significantly more frequent in the patients with graft vasculopathy (17/18 versus 11/18). Accordingly, the mean homocysteinemia was significantly higher in the group with graft vasculopathy (23.6+/-7.8 versus 16.9+/-7.1 micromol/l, P=0.01). The elevation of homocysteine plasma levels in the heart transplant recipients has probably multiple causes. The main cause seems to be renal failure. Additional causes could be azathioprine treatment or genetic polymorphisms. These results suggest that besides the immunological factors, homocysteine can play an additional role in the pathogenesis of graft vascular disease.

Cytofluorometric detection of human endothelial cells in whole blood using S-Endo 1 monoclonal antibody.

It has long been debated whether endothelial cells are present at very low frequency in peripheral blood. Elevated concentrations of such circulating cells may represent a good marker of vascular injury. We have therefore designed an immunocytometric assay for the detection of rare endothelial cells in whole blood. This assay is based on a new monoclonal antibody (MAb) S-Endo 1, made against human umbilical vein endothelial cells (HUVEC) and specific for endothelial cells of various origins without detectable reactivity with blood cells. First, the sensitivity of the assay was established by using normal blood samples with admixed HUVEC as an in vitro model. A good correlation was obtained between added and counted endothelial cells; the recovery was greater than 90% and the minimum detectable concentration of HUVEC was about 0.2 cells/microliters whole blood. Using this rapid counting technique, no detectable levels of endothelial cells were found in the blood of normal individuals (CE less than or equal to 0.1 cells/microliters) while elevated concentrations (up to 8 cells/microliters) were detected in a human model of vascular injury corresponding to a traumatic venepuncture. Thus, this new whole blood immunocytometric assay using S-Endo 1 MAb may be useful in determining the levels of circulating endothelial cells in vascular disorders.