Hydrogel microfluidics for the patterning of pluripotent stem cells.

Biomolecular signaling is of utmost importance in governing many biological processes such as the patterning of the developing embryo where biomolecules regulate key cell-fate decisions. In vivo, these factors are presented in a spatiotemporally tightly controlled fashion. Although state-of-the-art microfluidic technologies allow precise biomolecule delivery in time and space, long-term (stem) cell culture at the micro-scale is often far from ideal due to medium evaporation, limited space for cell growth or shear stress. To overcome these challenges, we here introduce a concept based on hydrogel microfluidics for decoupling conventional, macro-scale cell culture from precise biomolecule delivery through a gel layer. We demonstrate the spatiotemporally controlled neuronal commitment of mouse embryonic stem cells via delivery of retinoic acid gradients. This technique should be useful for testing the effect of dose and timing of biomolecules, singly or in combination, on stem cell fate.

No evidence for left ventricular diastolic dysfunction in asymptomatic normotensive type 2 diabetic patients: a case-control study with new echocardiographic techniques.

OBJECTIVE: We sought to determine whether abnormalities of left ventricular structure and function could be detected in asymptomatic type 2 diabetic patients free of cardiovascular complications. RESEARCH DESIGN AND METHODS: We compared 48 subjects with type 2 diabetes (34 men, 50+/-6 years) without hypertension, coronary artery disease and microangiopathic complications with 30 age-matched healthy controls. Left ventricular diastolic function was assessed by conventional Doppler echocardiography and new echocardiographic techniques (tissue Doppler imaging, color M-mode propagation velocity). A pseudonormal (PN) pattern of left ventricular filling was screened by several methods including Valsalva maneuver. RESULTS: Systolic function was normal in all patients. There was no significant difference in conventional and new echocardiographic Doppler indices of diastolic function between patients and control subjects. A PN diastolic function frequently suggested by the Valsalva maneuver (20 patients) was excluded using the new parameters. CONCLUSIONS: Diastolic dysfunction is not as frequent as previously described in selected patients with type 2 diabetes free of microangiopathic complications. New Doppler echocardiographic methods provide, in contrast with the Valsalva maneuver, a reliable estimate of diastolic function and should be incorporated in the non-invasive screening for diabetic cardiomyopathy.

Usefulness of B-type natriuretic peptide (BNP) as a screen for left ventricular abnormalities in diabetes mellitus.

Cardiovascular disease is the leading cause of morbidity and mortality in diabetic subjects. Diabetes, independently of the mechanism, is associated with an increased risk of left ventricular hypertrophy, left ventricular dysfunction and coronary artery disease. B-type natriuretic peptide (BNP) is a cardiac neurohormone predominantly released from the cardiac ventricles in response to left ventricular volume expansion and pressure overload. Numerous studies have shown that BNP levels are elevated in asymptomatic or symptomatic left ventricular dysfunction, hypertrophy and coronary artery disease. BNP testing plays an important role in the screening and diagnosis of left ventricular dysfunction by improving the performance of non-specialist physicians in diagnosing heart failure. In clinical practice, BNP testing is best used as a 'rule out' test targeted to patients at high risk for left-ventricular dysfunction, such as those with diabetes. Studies are needed to establish if this promising biological tool, in the next future, would assist the management of diabetic patients.

[Quantification of longitudinal myocardial velocities by Doppler tissue imaging during dobutamine echocardiography]. / Quantification des variations de vélocités myocardiques longitudinales par doppler tissulaire au cours de l'échocardiographie sous dobutamine.

Doppler tissue imaging has been suggested to be a valuable method for the diagnosis of myocardial ischaemia during dobutamine echocardiography. The authors studied this mode of investigation in 49 consecutive patients (average age 60 +/- 12 years) referred for dobutamine stress echocardiography and who had undergone coronary angiography. The stress echo was carried out according to a standard protocol (5 to 40 m g/kg/min +/- atropine) with additional acquisition of 3 apical views (4, 2 and 3 chambers) with colour Doppler tissue imaging. Analysis of systolic and diastolic myocardial velocities was performed afterwards from digitised data. The different Doppler tissue parameters were measured in 12 left ventricular segments (excluding the apical segments) for each dosage of dobutamine: peak systolic velocity (S), Q-S duration, systolic velocity time integral (ITVS), peak early diastolic velocity (E), peak end diastolic velocity (A). These parameters were analysed throughout the stress for each segment without significant coronary stenosis to define normal values. ROC curves were constructed to determine threshold values of relative changes of velocity (between maximal dobutamine dosage and basal conditions) to improve detection of ischaemia in a segment with coronary stenosis (vessel diameter reduction > or = 70%). Similar diagnostic performances were observed with different systolic and diastolic parameters. The feasibility of measurement of diastolic velocities was, however, reduced (from 29% to 49%). The diagnostic accuracy of each parameter was the same for each vessel territory. A satisfactory concordance was observed between 2D echocardiography and Doppler tissue imaging for the detection of significant coronary stenosis in an analysis by vascular territory. The authors conclude that analysis of myocardial velocities during dobutamine stress echocardiography is feasible. It may be a useful complement for the detection of coronary stenosis during pharmacological stress echocardiography.

[Limits of the Valsalva manoeuvre for the detection of pseudonormal mitral flow]. / Limites de la manoeuvre de Valsalva pour la détection du flux mitral pseudonormal.

The pseudonormal mitral profile is difficult to distinguish from a normal profile with echocardiography. Ever since a study showing that the Valsalva manoeuvre could unmask the appearance of relaxation disorders of transmitral flow (E/A < 1) in subjects with cardiopathy, this method has been proposed for the analysis of diastolic function. Very few data exist on the effect of this method in healthy subjects. The aim of this study was to evaluate the changes in mitral flow with this manoeuvre in middle aged healthy subjects, in order to establish the validity of this method for identifying the pseudonormal mitral profile. In 30 subjects (aged 50 +/- 5 years) we analysed mitral flow at rest and after the Valsalva manoeuvre, pulmonary venous flow, annular tissular Doppler, propagation velocity in colour TM and the combined indices (ENp, E/Ea). An inversion of the E/A ratio was obtained in 95% of subjects with an E/A ratio >1 (n=21, E/A=1.25 +/- 0.14) while all the other Doppler indices were in favour of normal flow. In conclusion, the inversion of mitral flow is very common in healthy subjects following the Valsalva manoeuvre. This observation underlines the limit of this method for distinguishing between a normal mitral profile and a pseudonormal profile. The optimal evaluation of diastolic function must rely on the various Doppler indices currently available especially for the detection of a developing cardiomyopathy.

Left ventricular diastolic dysfunction: an early sign of diabetic cardiomyopathy?

The existence of a diabetic cardiomyopathy has been proposed as evidence has accumulated for the presence of myocardial dysfunction in diabetic patients in the absence of ischemic, valvular or hypertensive heart disease. Diastolic dysfunction has been described as an early sign of this diabetic heart muscle disease preceding the systolic damage. Abnormalities in diastolic performance have been first demonstrated by cardiac catheterisation and subsequently by mainly using echocardiography. The pathogenesis of this left ventricular dysfunction is not clearly understood. Microangiopathy, increased extracellular collagen deposition, or abnormalities in calcium transport alone or in combination are considered to be associated with this dysfunction. The relationship between diastolic dysfunction and glycemic control is still a matter of debate. Some epidemiological and clinical arguments suggest that diastolic abnormalities may contribute to the high morbidity and mortality among diabetic patients. However, the prognostic importance of subclinical diastolic dysfunction and the possibilities for intervention are not fully known. Eventually, despite numerous studies, evidence of an intrinsic diastolic dysfunction in diabetes mellitus remains questionable. Indeed, quite contradictory results have been reported. They have been obtained in small, inhomogeneous populations, with sometimes confounding factors, using various echocardiographic indices with known limitations. Also, further studies using more refined techniques for the evaluation of diastolic function are needed, as a prerequisite, to unequivocally relate diabetes mellitus to a specific cardiomyopathy.

[Left superior vena cava: a simple diagnosis by transthoracic echocardiography. A case report]. / Veine cave supérieure gauche: un diagnostic simple par échocardiographie transthoracique. A propos d'un cas.

Persistent left superior vena cava is an anomaly of the systemic venous return occurring in 0.5% of the general population. We report the case of a patient with an incidental diagnosis made during a dyspnea while he had chronic pulmonary disease. The diagnosis was suspected by the presence of a markedly dilated coronary sinus and confirmed by a simple contrast injection into the left antecubital vein. Transesophageal echocardiography and magnetic resonance imaging confirmed the existence of 2 superior vena cava with the left superior vena cava draining into the coronary sinus. This congenital anomaly is of minimal hemodynamic significance when isolated. The diagnosis can be useful for placement of central catheters from left superior approach.

[Characteristic electrocardiographic procedures of isthmic-dependent atrial flutter; influence of clinical and echocardiographic procedures]. / Caractéristiques électrocardiographiques des flutters auriculaires isthmiques-dépendants: influence des paramètres cliniques et échocardiographiques.

The appearance of the F waves on the ECG is considered to be related to the type of circuit of the anti-clockwise flutters and the clockwise isthmic-dependant flutters. In the authors' experience, the usual ECG description of these two types of flutter is not always observed. This study was undertaken to analyse the different appearances of anti-clockwise and clockwise flutters and to try and explain the reasons for these differences. Over a 4 year period, 139 patients with an ECG of atrial flutter required electro-physiological studies and echocardiography of the 156 flutters analysed: 130 were anti-clockwise and 26 clockwise. Three types of anti-clockwise flutter were observed: type 1 with exclusively negative F waves in the inferior leads: type 2 and 3 with negative F waves in the inferior leads and a small (type 2) or large (type 3) positive terminal components. The types 2 and 3 were associated with a higher incidence of left atrial dilatation, cardiac disease and atrial fibrillation than type 1. Two types of clockwise flutter were observed: type 1 with positive notched F waves in the inferior leads with a return to the iso-electric line and type 2 with wide F waves in the inferior leads with two components, predominantly positive and negative, without return to the iso-electric line. There are different ECG appearances of anti-clockwise and clockwise flutter which seem to be correlated with structural cardiac abnormalities. The anti-clockwise flutters with a positive terminal component of the F waves in the inferior leads corresponds to a subgroup with a high probability of cardiac disease and left atrial dilatation.

[Myocardial infarction due to spontaneous coronary dissection during the postpartum period]. / Infarctus du myocarde par dissection coronaire spontanée lors du post-partum.

The authors report the case of a 34 year old woman, admitted to hospital because of myocardial infarction two months after delivery of her fifth child. The infarction was caused by spontaneous dissection of the left main coronary and left anterior descending arteries. Twenty-three months later, the patient was well with medical therapy. This case is an example of spontaneous post-partum coronary dissection which is the commonest cause of infarction occurring in that period. The physiopathology of this complication is not fully understood. The prognosis is poor, lethal in two thirds of cases. However, it must be emphasised that coronary dissection may regress spontaneously. Patients were previously referred systematically for surgery, but now it is usually reserved for cases with persistent myocardial ischaemia despite medical therapy. Angioplasty may be preferred despite the risks and may be successful in some cases.

[Complete atrioventricular block disclosing Fabry's disease]. / Bloc auriculo-ventriculaire complet révélateur de maladie de Fabry.

Fabry's disease is a hereditary sex-linked sphinglopidosis characterised by abnormal cellular lipid overload in most organs due to deficiencies in enzymes implicated in the catabolism of certain neutral glycolipids. There are two main clinical forms; cardiovascular manifestations usually congestive cardiac failure, and renal manifestations progressing to renal failure and death due to uraemic coma. The authors report a case presenting with juvenile, symptomatic complete infrahisian atrioventricular block. They describe the different cardiovascular complications of Fabry's disease from a review of the medical literature.

[Unilateral lesions of basal ganglia nuclei in children during myxovirus para-influenzae infection]. / Lésions unilatérales des noyaux gris centraux de l'enfant au cours d'une infection à myxovirus para-influenzae.

Unilateral disorders of the basal ganglia in childhood have received little attention. Infections are a rare cause where as infarction is the most common one. We report the case of a 11 year-old boy who presented an acute hemiplegia with hypodense areas limited to the left lenticular, caudate nuclei and internal capsule. Virologic investigations showed a recent infection due to myxovirus para influenzae. Angiography demonstrated no focal vascular disease. The course was favorable with full recovery.