Arterial tortuosity syndrome: clinical and molecular findings in 12 newly identified families.

Arterial tortuosity syndrome (ATS) is a rare autosomal recessive connective tissue disease, characterized by widespread arterial involvement with elongation, tortuosity, and aneurysms of the large and middle-sized arteries. Recently, SLC2A10 mutations were identified in this condition. This gene encodes the glucose transporter GLUT10 and was previously suggested as a candidate gene for diabetes mellitus type 2. A total of 12 newly identified ATS families with 16 affected individuals were clinically and molecularly characterized. In addition, extensive cardiovascular imaging and glucose tolerance tests were performed in both patients and heterozygous carriers. All 16 patients harbor biallelic SLC2A10 mutations of which nine are novel (six missense, three truncating mutations, including a large deletion). Haplotype analysis suggests founder effects for all five recurrent mutations. Remarkably, patients were significantly older than those previously reported in the literature (P=0.04). Only one affected relative died, most likely of an unrelated cause. Although the natural history of ATS in this series was less severe than previously reported, it does indicate a risk for ischemic events. Two patients initially presented with stroke, respectively at age 8 months and 23 years. Tortuosity of the aorta or large arteries was invariably present. Two adult probands (aged 23 and 35 years) had aortic root dilation, seven patients had localized arterial stenoses, and five had long stenotic stretches of the aorta. Heterozygous carriers did not show any vascular anomalies. Glucose metabolism was normal in six patients and eight heterozygous individuals of five families. As such, overt diabetes is not related to SLC2A10 mutations associated with ATS.

Renal and hormonal responses to isotonic saline infusion after 3 days' head-down tilt vs. supine and seated positions.

AIM: The study aimed to determine whether prolonged exposure to simulated microgravity produces a level of thoracic volume receptor loading similar to that seen in the upright position or immediately after lying down. METHODS: We used a cross-over design to compare responses to a saline infusion in eight healthy subjects during a 4-day, -6 degree head-down tilt (HDT) and in the acute seated and acute supine positions. RESULTS: The first 24 h of HDT were associated with greater urinary excretion of water and sodium (UV, UNaV) than seated and acute supine [cumulative UV, 3035 +/- 219, 2311 +/- 156 (P < 0.05), and 2448 +/- 182 mL (P < 0.05), respectively; cumulative UNaV, 256 +/- 19, 180 +/- 11 (P < 0.05), and 189 +/- 15 mmol (P < 0.05), respectively]. Haemoglobin and haematocrit were increased after 24 h and plasma volume decreased after 48 h of HDT (P < 0.05). With prolongation of HDT, UV and UNaV returned near the baseline values, and plasma atrial natriuretic factor (ANF) and renin values returned to acute seated levels; in acute supine, ANF values were higher and renin lower than in the two other positions. After a 30-min infusion of 20 mL kg(-1) isotonic saline on the fourth HDT day or during acute seated or acute supine, sodium excretion within 4 h was similar during HDT and acute seated (83 +/- 6 and 84 +/- 9 mmol, respectively) and greater during supine (104 +/- 8 mmol, P < 0.05). The renin decrease was greater in HDT and seated than in supine. The plasma ANF increase was greater during HDT than during supine; during seated, plasma ANF was unchanged. CONCLUSION: These data suggest that, after 4 days of HDT, thoracic volume receptor loading returns to the same level as in the seated position, leading to blunted responses to volume expansion as compared with the acute supine position.

[Cardiovascular complications of Kawasaki syndrome: results of a French multicenter study]. / Complications cardiovasculaires du syndrome de Kawasaki: résultats d'une enquête cardiopédiatrique multicentrique française.

PATIENTS AND METHODS: Between March 1, 1995 and February 29, 1996, a multicentric prospective study was conducted in France in order to analyze the cardiovascular complications in Kawasaki syndrome, and to describe the echocardiographic features and the outcome of coronary lesions. Forty-nine cases of Kawasaki syndrome were observed. RESULTS: There were 32 boys and 17 girls (sex ratio: 1:9). The age at diagnosis was under one year in ten cases (20.4%), between one and five years in 27 cases (55.1%) and more than five years in 12 cases (24.5%). The complete diagnostic criteria were present in 42 cases (85.1%). Forty-five children (91.8%) were given intravenous immunoglobulin treatment but only 20 (40.8%) received this treatment within the seven days following the onset of the illness. Cardiovascular complications consisted of: pericardial effusion in 12 cases (24.5%), coronary dilation in seven cases (14.3%), coronary aneurysms of moderate size in seven cases (14.3%,) with hypokinetic left ventricle in two cases. No death was reported. All patients with coronary dilation and four patients with coronary aneurysms had a normal size of coronary arteries at echocardiography within the nine months of the follow-up. Among the three other patients, after a follow-up of two years, one still has a small coronary aneurysm and two have a normal size of coronary arteries. CONCLUSION: Despite a delayed administration of immunoglobulin therapy in the majority of patients in this study, outcome of coronary lesions was favorable and severe cardiac complications were rare in the acute phase of the Kawasaki syndrome.

[Pulmonary embolism in the child: diagnostic and therapeutic particularities]. / Embolie pulmonaire de l'enfant: particularités diagnostiques et thérapeutiques.

BACKGROUND: Pulmonary embolism in children is an overlooked pathology. Yet the first description dates back to the end of the 19th century and this specific pathology is not seldom observed. The main risk factors are trauma, surgery, and foreign bodies. DIAGNOSIS: Thrombophilia can be diagnosed when a thromboembolic event occurs. The initial thrombosis may be found anywhere in the venous network. Venous sonography usually gives the diagnosis. Pulmonary embolism usually has a poor clinical expression. An unexplained situation can be the first manifestation. Echocardiography guides diagnosis confirmed by ventilation-perfusion scintigraphy. TREATMENT: Prophylaxis is achieved with small doses of heparin. Treatment is based on the use of hypocoagulant doses of heparin, potentially after systemic thrombolysis and followed by oral anticoagulation.

Effects of a three-day head-down tilt on renal and hormonal responses to acute volume expansion.

To clarify whether exposure to 6 degrees head-down tilt (HDT) leads to alterations in body fluid volumes and responses to a saline load similar to those observed during space flight we investigated eight healthy subjects during a 4-day, 6 degrees HDT and during a time-control ambulatory period with cross-over. Compared with the ambulatory period, HDT was associated with greater urinary excretion of water and sodium (UV, U(Na)V) from 0 to 12 h (cumulated UV 1,781 +/- 154 vs. 1,383 +/- 170 ml, P < 0.05; cumulated U(Na)V 156 +/- 14 vs. 117 +/- 9 mmol, P < 0.05), and with higher plasma atrial natriuretic factor (ANF) at 4 h. Hemoglobin and hematocrit increased over the first 24 h, and blood and plasma volumes were decreased after 48 h of HDT (P < 0.05). Plasma renin activity (PRA) and aldosterone did not differ between the two groups. With prolongation of HDT, UV and U(Na)V returned close to baseline values. On the fourth HDT day, a 30-min infusion of 20 ml/kg isotonic saline was performed, while a large oral water load maintained a high urine output. The ambulatory period experiment was done with the subjects in the acute supine posture. Sodium excreted within 4 h of loading was 123 +/- 8 mmol during HDT vs. 168 +/- 16 mmol during the ambulatory period (P < 0.05). The increase in plasma ANF and decrease in PRA were greater during HDT than during the ambulatory period (ANF 30 +/- 5 vs. 13 +/- 4 pg/ml, P < 0.05; PRA -1.4 +/- 0.4 vs. -0.5 +/- 0.2 ng. ml(-1). h(-1), P < 0.05). Our data suggest that after a 3-day HDT period, thoracic volume receptor loading returns to the level seen in the upright position, leading to blunted responses to volume expansion, compared with acute supine control.

Effects of ANF infusion on the renal responses to lower-body negative pressure in humans.

To investigate the role of atrial natriuretic factor (ANF) in renal responses to a decrease in central blood volume, we examined the effects of ANF infusion on renal function and hormones during prolonged lower-body negative pressure (LBNP). Ten healthy volunteers participated in two experimental sequences, each comprising a 120-min baseline period followed by the application of -20 mm Hg LBNP for 90 min. During one of the two sequences, ANF was infused throughout LBNP application at the constant rate of 2.5 ng/kg/min. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by using inulin and p-aminohippuric acid clearance techniques. LBNP induced a significant decrease in ERPF (534 +/- 28 to 457 +/- 26 ml/min; p < 0.05), GFR (120 +/- 2.5 to 112 +/- 2.5 ml/min; p < or = 0.01), in urine excretion (12 +/- 0.9 to 5.6 +/- 0.5 ml/min; p < 0.001), in sodium excretion (0.36 +/- 0.03 to 0.30 +/- 0.02 mmol/min; p < 0.05), and in plasma ANF (19 +/- 3 to 11 +/- 2 pg/ml; p = 0.001) concomitant with an increase in plasma renin activity (PRA; 0.48 +/- 0.09 to 0.87 +/- 0.16 ng/ml/h; p = 0.01) and of forearm vascular resistance (FVR; p < 0.05). The combination of ANF infusion with LBNP led to a slight increase in plasma ANF from baseline (from 20 +/- 2 to 28 +/- 3 pg/ml; p < 0.05). Compared with values obtained during LBNP with saline vehicle infusion, values obtained during LBNP with ANF infusion were similar for ERPF (463 +/- 23 vs. 457 +/- 26 ml/min), for GFR (111 +/- 2 vs. 112 +/- 2 ml/min), and for urine excretion (7 +/- 0.6 vs. 5.6 +/- 0.5 ml/min; p = 0.07), but greater for fractional excretion of sodium (2.38 +/- 0.25% vs. 1.91 +/- 0.11%; p < 0.05) and FVR (p < 0.05), and smaller for PRA (0.49 +/- 0.1 vs. 0.87 +/- 0.16 ng/ml/h; p < 0.01). These data show that ANF infusion attenuates the antinatriuretic effect of low-level LBNP and its PRA-increasing effects without altering renal hemodynamic responses to LBNP, although there is a decrease in the LBNP-induced forearm vasoconstriction. These results were obtained with plasma ANF levels slightly higher than those in baseline. They support the hypothesis that a decrease in ANF secretion might contribute to the antinatriuretic effect of LBNP.

[Nitric oxide, from vascular physiology to therapeutics]. / Le monoxyde d'azote, de la physiologie vasculaire à la thérapeutique.

Nitric oxide (NO) synthesised by endothelial cells, plays a key role in the control of vascular tone. Its synthesis from L-arginine is assured by NO-synthase, the activity of which is dependent on intracellular calcium concentrations, which are themselves modulated by pharmacological (acetylcholine, serotonin, bradykinin...) or physical factors (shearing forces exerted by blood flow). NO acts by stimulating a soluble guanylate-cyclase of the smooth muscle cells in the vessel wall. Its vasodilator effect is therefore mediated by an increase in intracellular cyclic GMP concentration. The synthesis or liberation of NO by the endothelium may be decreased or abolished during many pathological processes (hypercholesterolaemia, atherosclerosis, systemic or pulmonary hypertension...). The significance of this abnormality of NO-mediated endothelium-dependent vasodilation in different pathological conditions has not been established. However, it is probably significant in view of the different properties of NO: vaso-relaxation, antiaggregant and inhibition of vascular smooth muscle growth. It is not yet known whether this abnormality is a cause or a consequence of the underlying disease. From the therapeutic point of view, NO is an active metabolite of nitrate derivatives, sodium nitroprussiate and molsidomine which therefore share the same mode of action as the so-called "endothelium-dependent" vasodilatoe agents. The inhalation of NO, which is increasingly used in neonatal and adult intensive care units, is an alternative therapeutic approach in many conditions associated with pulmonary hypertension.

Longitudinal study of various transport abnormalities as an index of severity in children and adolescents suffering from essential hypertension.

Erythrocyte cation fluxes were measured in fresh cells, on two different occasions, in 90 children and adolescents suffering from essential hypertension who were followed for a prolonged period. The purpose of the present study was to track the stability of erythrocyte cation fluxes with time, and to determine whether a known sodium transport abnormality can predict the severity of essential hypertension. The patients with an increased Na-Li countertransport were the most severely hypertensive in three different ways. Clinically, they presented a stable rather than a labile form of hypertension. Hemodynamically, the mean arterial pressure was higher than that of the other subgroups. Finally, in those children followed for more than 2 years, this subgroup remained hypertensive with time. The patients with a decreased Na,K cotransport activity were second in severity; however, blood pressure was often labile, mean arterial pressure was slightly lower than that of the previous subgroup and all patients remained hypertensive with time but in four out of six patients the hypertension was labile. The patients with increased passive sodium permeability presented a mild form of hypertension. The patients with normal erythrocyte cation fluxes seemed to form a heterogeneous group. A few were severely hypertensive, but in most the hypertension was borderline and transient. We conclude that determination of erythrocyte cation fluxes may be reproducible, and may be a useful index of the severity of essential hypertension in children and adolescents.

Evaluation of vein of Galen arteriovenous malformation in newborns by two dimensional ultrasound, pulsed and colour Doppler method.

Two babies with severe cardiac failure caused by a large arteriovenous malformation of the vein of Galen were evaluated with 2-dimensional ultrasound, pulsed and colour Doppler techniques. In both cases similar findings were recorded: dilated right cardiac chambers with high cardiac output in superior vena cava and ascending aorta; retrograde diastolic flow in descending aorta and continuous forward flow in arch arteries reflecting low resistance to flow in cerebral arteries; recirculation of microbubbles through the superior vena cava after passage unchanged through the cerebral malformation following contrast injection of saline into a peripheral vein or an arterial umbilical line. In addition, colour Doppler study of the brain clearly showed the malformation and the dilated straight sinus. Arteriovenous malformation of the vein of Galen can be noninvasively and easily detected by ultrasound studies of the heart and the brain.

[Obstructions to pulmonary ejection and restrictive interventricular septal defects]. / Obstacles à l'éjection pulmonaire et communications interventriculaires restrictives.

The association of a restrictive ventricular septal defect with a pulmonary tract obstruction is rare and may cause diagnostic and therapeutic problems. The authors report their experience of such an association in 10 children. 3 had a tetralogy of Fallot (1 death), 4 a double-outlet right ventricle (2 deaths), and 3 a coarctation of the aorta with ventricular septal defect and pulmonary artery banding (no death). Prognosis depends on the type of malformation. It has improved with years because of sooner recognition of these malformations and better surgical technics and post-operative care.

[Subvalvular aortic stenosis discovered after surgical repair of an atrioventricular canal in the adult. Apropos of a case]. / Rétrécissement aortique sous-valvulaire découvert après correction d'un canal atrio-ventriculaire chez l'adulte. A propos d'une observation.

The case of an adult female patient in whom subaortic stenosis was discovered 9 months after surgical correction of a partial atrioventricular canal is reported. The authors describe the difficulties encountered in the pre-operative diagnosis of this uncommon association and the paraclinical methods now available, notably echocardiography, that may help overcome these difficulties.

Value of respiratory variations of right ventricular dimension in the identification of small atrial septal defects (secundum type) not requiring surgery: an echocardiographic study.

In search of reliable criteria that could help differentiate insignificant atrial septal defects (ASDs) from those with a large shunt, M-mode echocardiograms of three groups of patients were studied retrospectively: group I = 10 normal children (mean age 5.7 years); group II = 10 patients (mean age 7 years) with small ASD in whom the decision was taken not to proceed to surgical closure, based on hemodynamic and angiographic criteria; and group III = 15 patients (mean age 7 years) with an "operable" shunt, who underwent corrective surgery. The results showed that right ventricular end-diastolic dimensions during expiration (RVDDE) were increased in all patients in group III but were normal in only 3 of the 10 patients in group II. A normal septal movement was found in all patients in groups I and II but also in five patients in group III. The variation in right ventricular diastolic dimension with respiration (RVDVR) was always normal in group II. However, in group III all patients but one had a small RVDVR (less than 6%). It was concluded that a normal RVDDE is very specific (100%) but not sensitive (30%), a normal septal movement is very sensitive (100%) and moderately specific (70.6%), and a normal RVDVR is both very sensitive (100%) and specific (94.4%) as a criterion for identification of small ASDs not requiring surgery.

[Endocardial fibroelastosis: prenatal manifestation of aortic valve stenosis]. / Fibroélastose de l'endocarde: manifestation anténatale du rétrécissement aortique orificiel. Diagnostic échographique.

A diagnosis of fibroelastosis was made in a 33-week-old fetus, based on the echocardiographic features of a marked impairment of left ventricular contractility and hyperechogenicity of the endocardium. Fibroelastosis was associated with an aortic stenosis. There was no evidence of hydrops fetalis. Prenatal detection of this severe congenital heart disease allowed its early management in an intensive care unit. Heart failure due to closure of the ductus required the use of prostaglandin, then a surgical aortic valvulotomy was performed. There was no postoperative problem, and one year after surgery the infant is doing well. His left ventricular contractility is normal, and echocardiographic features of fibroelastosis are no more present. Prenatal diagnosis, use of prostaglandin and increasing safety of neonatal cardiac surgery have improved the prognosis of this serious association.

Wall thickness, cavity dimensions, and myocardial contractility of the left ventricle in patients with simple transposition of the great arteries. A multicenter study of patients from 10 to 20 years of age.

Fifty-one patients with uncomplicated transposition of the great arteries (TGA) and normal pulmonary pressure who were 10 to 20 years old and 69 normal subjects matched for age were studied by M mode echocardiography. Left ventricular internal dimensions and posterior wall thickness showed positive correlation with the body surface area in the TGA as well as in the control groups. Values for these parameters in the TGA group were generally smaller than those in the normal population. Septal thickness of patients with TGA (5.9 +/- 1 mm) was also smaller than that in the control group (6.6 +/- 1 mm) (p less than .01). Septal motion was normal in 11 patients with TGA and paradoxical in 19 patients in this group. In the other 21 patients the septum was flat. The following systolic time intervals of the left ventricle were found for patients with TGA: preejection period (PEP) 64 +/- 11 msec, ejection time (ET) 310 +/- 37 msec, and PEP/ET 0.21 +/- 0.04. These values were significantly different from those of the right ventricle for the normal population: PEP 77 +/- 12 (p less than .01), ET 327 +/- 25 (p less than .05), and PEP/ET 0.24 +/- 0.03 (p less than .01). Shortening fraction and mean velocity of circumferential fiber shortening (49 +/- 7% and 1.6 +/- 0.3 circ/sec, respectively) were also significantly higher (p less than .01) in patients with TGA than in the control group (33 +/- 4% and 1.1 +/- 0.2 circ/sec). These data should help achieve reliable quantitative and qualitative interpretations of echocardiograms of patients with TGA.

[Respiratory variations in the right ventricular diameter: an echocardiographic element in the diagnosis of partial isolated pulmonary venous return anomaly]. / Variations respiratoires du diamètre ventriculaire droit: un élément échocardiographique du diagnostic de l'anomalie partielle du retour veineux pulmonaire isolée.

Isolated partial anomalous pulmonary venous drainage (PAPVD), in contrast to atrial septal defect (ASD), does not cancel out the effects of respiration on blood flow in the right ventricle. The aim of this study was to see whether this difference could contribute to the diagnosis of PAPVD without ASD on M mode echocardiography. The diastolic dimensions of the right ventricle on expiration and inspiration were compared in 4 groups of patients aged 2 to 17 years. Group 1 comprised 6 children with PAPVD without ASD; Group 2: 10 children with PAPVD and ASD; Group 3: 11 children with isolated non-restrictive ASD, and Group 4: 10 normal children. Groups 1 and 4 were comparable with a respiratory variation of RV dimension of 10 to 29%. On the other hand, in Groups 2 and 3 the percentage variation was less than 6%. The finding of isolated RV dilatation with normal respiratory variation of its internal dimension should therefore alert the operator to the possible diagnosis of PAPVD without ASD.

[Fetal torsades de pointe and the long QT syndrome]. / Torsades de pointe foetales et syndrome du QT long.

The authors report a case of pregnancy interrupted by caesarian section at 38 weeks' gestation for attacks of fetal ventricular tachycardia. The recording of a long QT interval at birth indicated a diagnosis of fetal torsades de pointe. These attacks recurred 2 hours after birth leading to cardiac arrest. The arrhythmia was immediately controlled by betablockers therapy. The diagnostic, epidemiological and physiopathological features of the long QT syndrome are reviewed. The links with maturation of the sympathetic nervous system are recalled. Finally, a diagnostic and therapeutic strategy is proposed, based on the results of fetal echocardiography.