Oral flurbiprofen metabolic ratio assessment using a single-point dried blood spot.

We investigated whether a single blood measurement using the minimally invasive technique of a finger prick to draw a blood sample of 5 µl (to yield a dried blood spot (DBS)) is suitable for the assessment of flurbiprofen (FLB) metabolic ratio (MR). Ten healthy volunteers who had been genotyped for CYP2C9 were recruited as subjects. They received FLB alone in session 1 and FLB with fluconazole in session 2. In session 3, the subjects were pretreated for 4 days with rifampicin and received FLB with the last dose of rifampicin on day 5. Plasma and DBS samples were obtained between 0 and 8 h after FLB administration, and urine was collected during the 8 h after administration. The pharmacokinetic profiles of the drugs were comparable in DBS and plasma. FLB's apparent clearance values decreased by 35% in plasma and DBS during session 2 and increased by 75% in plasma and by 30% in DBS during session 3. Good correlations were observed between MRs calculated from urine, plasma, and DBS samples.

The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction.

Polymorphisms of the cytochrome P450 2D6 (CYP2D6) gene affecting enzyme activity are involved in interindividual variability in drug efficiency/toxicity. Four phenotypic groups are found in the general population: ultra rapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers. The AmpliChip CYP450 test is the first genotyping array allowing simultaneous analysis of 33 CYP2D6 alleles. The main aim of this study was to evaluate the performance of this test in CYP2D6 phenotype prediction. We first verified the AmpliChip CYP450 test genotyping accuracy for five CYP2D6 alleles routinely analysed in our laboratory (alleles 3,4,5,6, x N; n=100). Results confirmed those obtained by real-time PCR. Major improvements using the array are the detection of CYP2D6 intermediate alleles and identification of the duplicated alleles. CYP2D6 phenotype was determined by assessing urinary elimination of dextromethorphan and its metabolite dextrorphan and compared to the array prediction (n=165). Although a low sensitivity of UM prediction by genotyping was observed, phenotype prediction was optimal for PM and satisfying for EM and IM.

HIV/AIDS and care provider attributions: who's to blame?

The discovery of HIV/AIDS prompted a profusion of research focusing on the disease and its causes. Though the bulk of this research emphasizes behavioural risk factors, treatment and disease progression, researcher efforts are beginning to examine the public's attitude toward individuals who are HIV-positive or have developed AIDS. Utilizing Weiner's Attribution Theory, the current study examines the beliefs of social service providers who work directly with individuals affected by HIV/AIDS. Forty-six (28 female and 18 male) HIV/AIDS social service providers from three community-based organizations were asked to read a hypothetical scenario depicting an individual at-risk for HIV/AIDS because of multiple high-risk behaviours. The gender of the target was manipulated and at the conclusion of the scenario participants completed a questionnaire designed to assess attributions. Results of the study show that social service providers who perceive individuals as more responsible for their illness report increased anger, attribute more blame and express less willingness to help those at-risk for HIV/AIDS. This research suggests that despite growing numbers of media campaigns and national distribution of information regarding the disease and its transmission, in general, people continue to stigmatize and place blame on those at-risk.

Role and activation of type III secretion system genes in Pseudomonas aeruginosa-induced Drosophila killing.

Pseudomonas aeruginosa strains PAO1 and CHA showing type III system-dependent cytotoxicity towards macrophages ex vivo are able to induce rapid death of adult fly Drosophila melanogaster accompanied by bacterial multiplication to high-titers. The role of P. aeruginosa type III secretion system in rapid fly killing was demonstrated here by using several isogenic CHA mutants, selectively affected in this system. The activation of P. aeruginosa pexsCBA, the regulatory operon of the type III system, and the activation of the Drosophila gene diptericin, showed the host-pathogen recognition during infection process.

[A rare cause of stroke in a patient with a cardiac pacemaker]. / Etiologie rare d'accident vasculaire cérébral ischémique chez un patient ayant un stimulateur cardiaque.

The authors report the case of a 78 year old woman admitted to hospital for recurrent cerebrovascular accidents, the initial investigation of which was normal. This pacemaker patient had a displacement of the definitive ventricular pacing catheter which was positioned in the left ventricle through a patent foramen ovale. The diagnosis was suspected on clinical and echocardiographic examination and confirmed by transthoracic and transoesophageal echocardiography. In view of the risk of systemic embolism, the pacing catheter was repositioned by an endovascular approach in the right ventricle.

Pore-forming activity of type III system-secreted proteins leads to oncosis of Pseudomonas aeruginosa-infected macrophages.

The Pseudomonas aeruginosa cystic fibrosis isolate CHA induces type III secretion system-dependent but ExoU-independent oncosis of neutrophils and macrophages. Time-lapse microscopy of the infection process revealed the rapid accumulation of motile bacteria around infected cells undergoing the process of oncosis, a phenomenon we termed pack swarming. Characterization of the non-chemotactic CHAcheZ mutant showed that pack swarming is a bacterial chemotactic response to infected macrophages. A non-cytotoxic mutant, lacking the type III-secreted proteins PcrV, PopB and PopD, was able to pack swarm only in the presence of the parental strain CHA or when macrophages were pretreated with the pore-forming toxin streptolysin O. Interaction of P. aeruginosa with red blood cells (RBCs) showed that the contact-dependent haemolysis provoked by CHA requires secretion via the type III system and the PcrV, PopB/PopD proteins. The pore inserted into RBC membrane was estimated from osmoprotection experiments to be between 2.8 and 3.5 nm. CHA-infected macrophages could be protected from cell lysis with PEG3350, indicating that the pore introduced into RBC and macrophage membranes is of similar size. The time course uptake of the vital fluorescent dye, Yo-Pro-1, into infected macrophages confirmed that the formation of transmembrane pores by CHA precedes cellular oncosis. Therefore, CHA-induced macrophage death results from a pore-forming activity that is dependent on the intact pcrGVHpopBD operon.

Reversed bowel segments for the treatment of short bowel syndrome: assessment of their minimal length in correlation with electromyographic pattern in the rat.

Reversal of a distal intestinal loop is a surgical therapy intended to cure rapid intestinal transit in short bowel syndrome. To be active, a reversed loop must present a retrograde propagation of electromyographic patterns and must not be so long as to cause total obstruction. The aim of the current study was to propose methods to calculate the minimal length of the intestinal reversed loop taking into consideration the two previous conditions. Intestinal electromyograms were recorded in 65 rats at short-term (4 days after surgery) and ten rats at long-term (50 days after surgery). Control rats demonstrated that the preprandial regular spiking activity (RSA) of the migrating myoelectrical complex (MMC) extended simultaneously a definite part of the intestine which corresponds to the minimal length to reverse. A similar result can be obtained from a trigonometric representation. Whatever the method, the minimal lengths allowing the recording of RSA decreased along the rat intestine from 6 cm (proximal jejunum) to 4 cm (distal ileum). The experiments demonstrated that shorter loops did not present the preprandial RSA. In conclusion, the minimal reversed length depends on intestinal electromyographic parameters and, thereby, on the intestinal level.

[Comparative evaluation of hydrophilic and standard guide wires for retrograde catheterization of severe aortic stenosis]. / Evaluation comparative des guides hydrophiles versus guides standards dans le franchissement rétrograde des rétrécissements aortiques serrés.

The feasibility and safety of using hydrophilic guide wires were compared with those of standard guide wires for retrograde catheterization of aortic stenosis in a prospective randomised study. The performances of the guide wires were assessed by the time taken to catheterize the aortic valve (minutes) and the duration of radioscopy (minutes: grays). The success of the procedure was defined as presence of the guide in the left ventricle in less than 8 minutes. The two patient groups were comparable with respect to the severity of the aortic stenosis. Two failures of catheterisation were observed in the "standard guide wire" group compared with three failures with the hydrophilic guide wire. The mean catheterisation time of the "standard" group was 2.56 minutes compared with 3.12 minutes with the hydrophilic guide wire (p = 0.35 NS). This result was correlated with the duration of radioscopy and number of groups (respectively p = 0.18 NS and p = 0.5 NS). One case of tamponade and a transient ischaemic cerebral attack were observed in the "standard" group. This study does not show the hydrophilic guide wire to be superior to the standard guide wire for catheterisation of aortic stenosis. However, the hydrophilic guide wires were perfectly innocuous for this procedure.

[Acute aortic insufficiency]. / Insuffisance aortique aiguë.

Acute aortic insufficiency can now be diagnosed rapidly and accurately thanks to Doppler echocardiography. The etiologies include infectious endocarditis, aortic dissection, bioprosthesis degeneration and thoracic injury. The clinical diagnosis is substantiated by the particular etiological context, dyspnea and pulmonary edema being the main factors involved. Examination includes finding out whether there is a reduction in the first sound, S1 a generally brief apical diastolic murmur. Echocardiography detects the presence of aortic leakage, the acute character of which is confirmed by the findings of a premature closure of the mitral valve, the existence of telediastolic mitral leakage, a restriction in the transmitral flow, and finally, the absence of left ventricular dilatation. An emergency operation is recommended by most authors in the case of acute aortic leakage due to the major risk or mortality resulting from pulmonary edema, ventricular arrhythmias, electromechanical dissociation or cardiogenic shock.

[Werner's disease presenting as ischemic mitral incompetence]. / Fuite mitrale ischémique révélant une maladie de Werner.

Werner's syndrome or progeria, described for the first time in 1886, is a rare disease with autosomal recessive transmission, characterized by premature ageing of connective tissues. About 200 cases have since been reported in the literature. Most patients die young, generally from heart failure due to early coronary atherosclerosis [1]. The authors report the case of a 46-year-old woman presenting with cardiovascular abnormalities, unusual for her age, associated with a particular morphotype belonging to Werner's syndrome.

[Peripheral embolic arterial accident due to pulmonary vein thrombosis revealing bronchial carcinoma]. / Accident artériel périphérique embolique par thrombose d'une veine pulmonaire révélant un carcinome bronchique.

The authors report a case of left superior pulmonary vein thrombosis discovered on transoesophageal ultrasonography in the context of aetiological assessment of a systemic vascular accident. This unusual site of a thrombus on an anatomically perfectly normal left atrium led the authors to perform a more detailed assessment, revealing a previously undiagnosed lung cancer on thoracic CT scan.

[Transthoracic echocardiography and diagnosis of acute pulmonary embolism. Change in the diagnostic valve with respect to thresholds of classification]. / Echocardiographie transthoracique et diagnostic d'embolie pulmonaire aiguë. Variation de la valeur diagnostique en fonction des seuils de classification.

The diagnostic value of transthoracic echocardiography in acute pulmonary embolism is not well established. Although many parameters are abnormal, the thresholds used vary according to the authors, limiting the contribution of the investigation to the diagnosis. In a prospective study of 70 patients with suspected acute pulmonary embolism without previous cardio-respiratory disease, the authors tried to determine the diagnostic thresholds using discriminating linear analysis and ROC curves. Parameters easily recorded in an emergency were analysed: end diastolic ventricular dimensions, ratio of these diameters and maximal velocity of tricuspid regurgitant flow. Thirty-one patients had pulmonary embolism quantified by the Miller index (average: 16 +/- 7, range 2 to 28). Measurements of left ventricular dimension were disappointing (sensitivity: 0.52, specificity: 0.73 for a threshold value of 45 mm). The right ventricular dimension was a better predictive parameter (sensitivity: 0.70, specificity: 0.86 for a threshold value of 25 mm). However, the ratio of right to left ventricular dimension had a better diagnostic value (sensitivity: 0.85, specificity: 0.78 for a threshold value of 0.5). The best diagnostic parameter was the maximal velocity of tricuspid regurgitation (sensitivity: 0.93, specificity: 0.82 for a threshold value of 2.5 m/s). The authors conclude that the maximal velocity of tricuspid regurgitation with a threshold of 2.5 m/s and the ratio of the ventricular dimensions with a threshold value of 0.5 are valuable diagnostic indicators for acute pulmonary embolism.

[Ventricular late potentials and sleep apnea syndromes]. / Potentiels tardifs ventriculaires et syndromes d'apnées du sommeil.

This prospective study in 37 patients evaluated the prevalence of ventricular late potentials in sleep apnea syndrome, a condition associated with an increased risk of ventricular rhythm disorders and sudden death. A comparative analysis was conducted among a group of patients considered free of coronary heart disease and admitted for suspected sleep apnea syndrome based on clinical symptoms and simple blood gas measurements. The prevalence of ventricular late potentials was 56% in the subgroup with and 14% in the subgroup without polygraphy evidence of apnea (F < 0.01). The analysis of clinical, respiratory, and echocardiographic findings in the apneic subgroup failed to detect any factors associated with the presence of ventricular late potentials. Only long-term follow-up studies involving invasive heart rhythm testing could define the prognostic significance of ventricular late potentials in sleep apnea syndrome. However, our data demonstrate that there is an association between ventricular late potentials and sleep apnea syndrome.

Peripheral neurotensin participates in the modulation of pre- and postprandial intestinal motility in rats.

The present study was undertaken to determine whether neurotensin is involved in the regulation of the intestinal postprandial motor response and, if so, whether the regulatory pathway depends upon peripheral or central neurotensin secretion. Neurotensin, injected by the i.v. route (5 micrograms/kg) during the fasting state, induced firstly an increased irregular spiking activity during 30-40 min. This effect was followed by an increase of frequency of the myoelectrical complexes during 60 min. When injected by the i.c.v. route, neurotensin (0.5 microgram/kg) reinforced the fasting motility pattern of the small intestine after a latency of 70 min. Neurotensin was ineffective on the colon. The neurotensin receptor antagonist SR 48692 (200 micrograms/kg i.v.) reduced the duration of the postprandial motor response of the small intestine and blocked the late postprandial phase on the proximal colon while it suppressed the early postprandial phase on the distal colon. When administered i.c.v. (20 micrograms/kg), SR 48692 had no effect. It is concluded that neurotensin modulates intestinal postprandial motility essentially by a peripheral regulatory pathway. Endogenous neurotensin is involved in the maintenance of the postprandial motility pattern on the small intestine and the proximal colon while it is involved in the initiation of this response on the distal colon. This suggests that endogenous neurotensin acts via both endocrine and nervous mechanisms.

The hupTUV operon is involved in negative control of hydrogenase synthesis in Rhodobacter capsulatus.

The hupT, hupU, and hupV genes, which are located upstream from the hupSLC and hypF genes in the chromosome of Rhodobacter capsulatus, form the hupTUV operon expressed from the hupT promoter. The hupU and hupV genes, previously thought to belong to a single open reading frame, encode HupU, of 34.5 kDa (332 amino acids), and HupV, of 50.4 kDa (476 amino acids), which are >/= 50% identical to the homologous Bradyrhizobium japonicum HupU and HupV proteins and Rhodobacter sphaeroides HupU1 and HupU2 proteins, respectively; they also have 20 and 29% similarity with the small subunit (HupS) and the large subunit (HupL), respectively, of R. capsulatus [NiFe]hydrogenase. HupU lacks the signal peptide of HupS and HupV lacks the C-terminal sequence of HupL, which are cleaved during hydrogenase processing. Inactivation of hupV by insertional mutagenesis or of hupUV by in-frame deletion led to HupV- and Hup(UV)- mutants derepressed for hydrogenase synthesis, particularly in the presence of oxygen. These mutants were complemented in trans by plasmid-borne hupTUV but not by hupT or by hupUV, except when expressed from the inducible fru promoter. Complementation of the HupV- and Hup(UV)- mutants brought about a decrease in hydrogenase activity up to 10-fold, to the level of the wild-type strain B10, indicating that HupU and HupV participate in negative regulation of hydrogenase expression in concert with HupT, a sensor histidine kinase involved in the repression process. Plasmid-borne gene fusions used to monitor hupTUV expression indicated that the operon is expressed at a low level (50- to 100-fold lower than hupS).

[Estimation of left ventricular volumes and ejection fraction with acoustic quantification in myocardial infarction. Comparison with echocardiographic, angiographic and scintigraphic data]. / Estimation des volumes et de la fraction d'éjection ventriculaires gauches par quantification acoustique dans l'infarctus du myocarde. Comparaison aux données échographiques, angiographiques et scintigraphiques.

The object of this study was to assess the reliability of measurements of left ventricular volumes and ejection fraction by acoustic quantification by the method of summation of discs in acute myocardial infarction. Thirty-two patients with an average age of 55.9 +/- 12 years were studied prospectively on average 6 +/- 2 days after the onset of myocardial infarction. Within 48 hours, the patients underwent TM echocardiography (Teichholz's method) two-dimensional echocardiography (Simpson's method on freeze frames and acoustic quantification) before left ventricular angiography and isotopic ventriculography, considered as the reference methods for comparing left ventricular volumes and ejection fractions. The data displayed in real time by acoustic quantification correlated well with the results of left ventricular angiography (r = 0.77; p = 0.0001) and moderately underestimated (+4.1 +/- 11.9%) the ejection fraction, but were relatively disappointing for estimating volumes. When compared with isotopic ejection fraction, the correlation coefficient was r = 0.71 (p = 0.0004) and the values were overestimated. In this study, acoustic quantification was the most reliable echocardiographic method of assessing the left ventricular ejection fraction with reference to contrast angiography (Teichholz: r = 0.56; p = 0.0014; Simpson: r = 0.76; p = 0.001). The authors conclude that assessing the left ventricular ejection fraction with acoustic quantification is reliable in acute myocardial infarction. However, the method is not very accurate in measuring end systolic and end diastolic volumes.

[Value of transesophageal echocardiography in post-infarction septal ruptures]. / Intérêt de l'échographie transoesophagienne dans les ruptures septales postinfarctus.

The role of transoesophageal echocardiography in the diagnosis of ventricular septal defect in the acute stage of myocardial infarction, was evaluated in 15 consecutive patients (10 men and 5 women) with a mean age of 72 years in the period between June 1991 and April 1995. The patients had 11 anterior infarcts and 4 inferior infarcts with extension to the right ventricle. One patient was in Killips class I,7 patients in class II, 2 in class III and 5 in class IV. Only 8 of the 15 septal ruptures could be visualised directly by conventional transthoracic echocardiography, though all 15 were suspected from continuous Doppler and colour Doppler analysis. Transoesophageal echocardiography was successfully performed in 14 of the 15 patients with a monoplane probe in 11 cases and a multiplane probe in 3 cases. The average duration of the procedure was 12 minutes and clinical and haemodynamic tolerance was good. Ventricular septal defect was directly visualised in all cases in the short axis transgastric view and in 7 cases in transoesophageal views. Transoesophageal echocardiography was concordant with peroperative findings with regards to the site of ventricular septal defect (8 apical, 5 postero-basal and 1 median), their type (6 punched-out defects, 5 fissures, and 3 perforated aneurysms), their size (average 9.3 mm), their number with 5 multiple defects, and associated lesions (4 right ventricular extensions, 4 hemopericardiums and 1 free wall fissure). Transoesophageal echocardiography completes traditional transthoracic echocardiographic examination in the diagnosis of post-infarction ventricular septal defect. It is well tolerated and, in the authors' experience, allows limitation of invasive procedures to coronary angiography alone.

Use of transthoracic Doppler echocardiography combined with clinical and electrocardiographic data to predict acute pulmonary embolism.

Transthoracic echocardiography and continuous wave Doppler were prospectively performed in 132 out-patients with suspicion of pulmonary embolism, and who had no previous history of severe cardiac or pulmonary disease. Bedside echocardiography determined diagnosis other than pulmonary embolism in 55 patients. Further study was completed in 70 patients; pulmonary embolism was found in 31 and excluded in 39. Significant differences were found as regards right ventricular diameter (27 +/- 8 vs 22 +/- 5 mm, P < 0.001), left ventricular diameter (41 +/- 9 vs 49 +/- 7 mm, P < 0.001), right over left ventricular diameter ratio (0.67 +/- 0.23 vs 0.43 +/- 0.15, P < 0.0001), tricuspid regurgitant flow peak velocity (2.9 +/- 0.4 vs 2.4 +/- 0.7 m.s-1, P < 0.0001), and abnormal septum motion (12 vs 4, P < 0.01). Multivariate analysis of echocardiographic data included a tricuspid regurgitant flow peak velocity greater than 2.5 m.s-1 and a right over left ventricular diameter ratio greater than 0.5 in a logistic model (sensitivity 93%, specificity 81%). The combination of echocardiographic and non-echocardiographic data included the two previous echocardiographic variables, together with signs of deep vein thrombosis, a deep S wave in lead D1, and a Q wave in lead D3 on the electrocardiogram in a logistic model (sensitivity 96%, specificity 83%). It can be concluded that emergency echocardiography, alone or combined with clinical examination and electrocardiogram, satisfactorily predicts acute pulmonary embolism.

[Deformation of the tricuspid annulus by pericardial adhesions: a rare cause of early tricuspid regurgitation after mitral valve replacement]. / Déformation de l'anneau tricuspide par des adhérences péricardiques: une cause rare d'insuffisance tricuspid précoce après replacement valvulaire mitral.

The authors report the case of major tricuspid regurgitation occurring early after mitral valve replacement. The mechanism was demonstrated at reoperation: the heart was deformed by a posterior pericardial effusion and cardiodiaphragmatic pericardial adhesions.

[Transesophageal echocardiographic diagnosis of left ventricular parietal rupture, a complication of myocardial infarction]. / Diagnostic par échographie transoesophagienne d'une rupture pariétale du ventricule gauche sur infarctus du myocarde.

The authors report the case of postero-lateral myocardial infarction complicated by free wall rupture at the 48th hour. The diagnosis was suspected clinically and transoesophageal echocardiography showed the appearance of pericardial effusion in a patient difficult to examine by conventional echocardiography. Transoesophageal echocardiography was performed and well tolerated. The transgastric view showed a thrombus adjacent to a thinned and lacerated postero-lateral wall. The clinical outcome was favourable after surgical repair.