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Biomedical subjects

M Dumoulin

Publications and source records attributed to M Dumoulin.

At least 19 recordsLinked to original sources
PubMed2003

In vitro stability and immunoreactivity of the native and recombinant plant food 2S albumins Ber e 1 and SFA-8.

BACKGROUND: The ability of an intact protein to reach the circulatory system may be a prerequisite to allergenicity and many allergens, particularly those from plant foods, have been found to be consistently more resistant to digestion by pepsin than other proteins. OBJECTIVE: This study assessed the pepsinolytic stability of native 2S albumins from Brazil nut and sunflower seed and their recombinant versions produced in Pichia pastoris. The physicochemical stability of native and recombinant Brazil nut 2S albumins and recombinant sunflower seed 2S albumin was also assessed. The immunoreactivity of native Brazil nut 2S albumin and recombinant 2S albumins was compared using serum from patients allergic to Brazil nuts and animals immunized with native 2S albumins. METHODS: Digestibility was measured in simulated gastric fluid followed by SDS-PAGE. Circular dichroism spectra were used to analyse unfolding, as proteins were denatured by temperature, pH and guanidinium chloride. Immunoreactivity was assessed by immunoblot, RAST and ELISA. RESULTS: Brazil nut 2S albumin was significantly more resistant to proteolytic digestion than other Brazil nut proteins. It was also resistant to thermally and chemically induced denaturation. Equally high resistance to proteolytic digestion was observed with sunflower seed 2S albumin. The recombinant albumins mirrored their native counterparts in stability and immunoreactivity. CONCLUSION: The important food allergen Brazil nut 2S albumin is as stable to digestion as is sunflower seed 2S albumin, whose allergenicity has yet to be determined. The 2S albumins and their recombinant counterparts could not be easily denatured by physicochemical treatments. The results suggest that 2S albumin is the only Brazil nut protein to reach the gut immune system intact. The production of properly folded recombinant proteins will facilitate mechanistic studies as well as diagnostic testing and antigen-based therapies.

2S Albumins, Plant↗
PubMed2002

Stability of recombinant 2 S albumin allergens in vitro.

Two well known 2 S albumins, Ber e 1 from brazil nut and sunflower 2 S albumin 8 (SFA-8), have been expressed in a eukaryotic system and purified. Analysis of recombinant versions of Ber e 1 and SFA-8 revealed them to be significantly more resistant to digestion by pepsin than BSA, and to be stable for up to 30 min in simulated gastric fluid. Unfolding monitored by CD indicated that both proteins were also very resistant to denaturation induced by heat and low pH. These results suggest that, although the ability of 2 S albumins to reach the circulatory system may be a prerequisite for the allergenicity of this group of proteins, stability is just one of a number of characteristics that provoke a selective immune response.

2S Albumins, Plant↗
PubMed2000

Homograft insertion for pulmonary regurgitation after repair of tetralogy of fallot improves cardiorespiratory exercise performance.

Surgical repair of tetralogy of Fallot (TOF) with reconstruction of the right ventricular (RV) outflow tract invariably results in pulmonary regurgitation. Chronic pulmonary regurgitation has been associated with RV dysfunction and decreased exercise performance. The present study assessed the influence of pulmonary valve replacement (PVR) for severe pulmonary regurgitation after previous TOF repair on cardiorespiratory exercise performance and RV function. Eighteen patients, between the ages of 8 and 18 years, underwent an exercise test and a cardiac magnetic resonance imaging scan at least 1 year after PVR. The exercise data were compared with those obtained from 24 age-matched normal controls and 27 age-matched patients with repaired TOF and a moderate degree of pulmonary regurgitation. A subgroup of 11 patients had an exercise test performed before and after PVR. Cardiopulmonary exercise performance was evaluated by determination of the ventilatory anaerobic threshold (VAT) and by the steepness of the slope of oxygen uptake versus exercise intensity (SVO2). After PVR there was a significant increase in VAT (86+/-11% before to 106.9+/-14% after, p = 0.03) and in SVO2 (1.71+/-0.47 to 2.3+/-0.39, p = 0.004). In patients examined after PVR, the VAT and SVO2 values were not significantly different from the values in the normal controls (104+/-15% [p>0.05] and 2.03+/-0.77 after PVR vs. 2.42+/-0.68 [p>0.25], respectively). In contrast, patients with repaired TOF and a moderate degree of pulmonary regurgitation had a significantly lower VAT (86+/-11%, p<0.05) and SVO2 (1.8+/-0.74 vs. 2.42+/-0.68, p<0.05) than normal controls. Magnetic resonance imaging studies revealed residual RV dilatation and dysfunction. However, there was no correlation between RV dilatation and RV dysfunction and aerobic exercise capacity. It is concluded that aerobic exercise capacity substantially improves after PVR for severe pulmonary regurgitation after previous TOF repair. Although the right ventricle remains significantly dilated and hypocontractile, there is no relation between RV function and exercise performance.

Adolescent↗
PubMed1999

Management of late complications after classic Fontan procedure by conversion to total cavopulmonary connection.

Classic Fontan procedures, such as atriopulmonary connection or atrioventricular connection, are associated with right atrial dilatation and several late complications. Seven patients with univentricular heart who presented with exercise intolerance (n = 7), severely dilated right atrium (n = 7) with pulmonary vein compression (n = 3), atrial arrhythmias resistant to medical treatment (n = 4), cyanosis (n = 4), diffuse effusions and oedema (n = 1), and protein-losing enteropathy (n = 1), underwent conversion to total cavopulmonary connection 5.8-14.4 years after a previous atriopulmonary connection (n = 6) or atrioventricular connection (n = 1). A 14-year-old boy who, preoperatively, was in ventricular failure and a very poor state died early after conversion because of low cardiac output. All survivors had either marked or partial clinical improvement with regression of cardiomegaly, absence of pulmonary vein compression or cyanosis, and recovery of sinus rhythm. Conversion to total cavopulmonary connection appears to be effective in the treatment of late complications after classic Fontan procedures. It should be considered early in symptomatic patients, before significant ventricular dysfunction and clinical deterioration ensue.

Adolescent↗
PubMed1999

Homograft valve insertion for pulmonary regurgitation late after valveless repair of right ventricular outflow tract obstruction.

OBJECTIVE: Pulmonary regurgitation after valveless repair of right ventricular outflow tract obstruction (RVOTO) results in progressive right ventricular (RV) dilatation and dysfunction in an increasing number of patients. Since 1989, we have exclusively used cryopreserved homografts to restore pulmonary valve competence in these patients. Our 9-year-experience with pulmonary valve insertion (PVI) in such cases has been reviewed to evaluate the indications for this procedure and its benefits. METHODS: From 1989 to 1998, 49 patients (original diagnosis: tetralogy of Fallot in 42 patients and pulmonary stenosis in seven) aged from 3 to 42 years (mean 18 +/- 9 years) underwent PVI with homografts late (mean 13 +/- 7 years) after valveless repair of RVOTO (transannular patch, n = 38; pulmonary valvulotomy therefore tau chi infundibular patch, n = 11). Preoperatively, all patients had severe pulmonary regurgitation, cardiomegaly, significant to severe RV dilatation and dysfunction, fatigue, reduced exercise tolerance, and were in NYHA class II (n = 43) or III (n = 6). Ten patients had ventricular arrhythmia. RESULTS: There was one early death, due to air embolism, and one late death, due to ventricular arrhythmia. All survivors but one, who subsequently underwent heart transplant, had symptomatic improvement after homograft insertion. The mean RV end-diastolic diameter decreased from 38 +/- 9 to 26 +/- 8 mm (P < 0.01), and cardiothoracic ratio decreased from 0.62 +/- 0.07 to 0.54 +/- 0.04 (P < 0.01). Good late homograft function was the rule, with all the survivors being free of reoperation for valve failure. At a mean follow-up of 42 +/- 28 months, 41 patients (87% of the survivors) were in New York Heart Association (NYHA) class I and six in class II. Within this group three patients are still in treatment for RV failure and five for ventricular arrhythmias. In these patients, the average interval between RVOTO repair and PVI was significantly longer than in the others (18 +/- 7 vs. 12 +/- 6 years, P < 0.01). CONCLUSION: Homograft PVI is safe and provides clinical improvement with a significant reduction in RV volume overload and excellent mid-term results in most patients with severe PR late after RVOTO repair. This procedure should be undertaken early in symptomatic patients, before severe RV failure and ventricular arrhythmias ensue.

Adolescent↗
PubMed1999

Contribution of the carbohydrate moiety to conformational stability of the carboxypeptidase Y high pressure study.

The process of pressure-induced denaturation of carboxypeptidase Y and the role of the carbohydrate moiety in its response to pressure and low temperature were investigated by measuring in situ the catalytic activity and, the intrinsic and 8-anilino-1-naphthalene sulfonic acid binding fluorescences. Pressure-induced denaturation of carboxypeptidase Y is a process involving at least three transitions. Low pressures (below 150 MPa) induced slight conformational changes characterized by a slight decrease in the center of the spectral mass of intrinsic fluorescence, whereas no changes in 8-anilino-1-naphthalene sulfonic acid binding fluorescence were observed and 80% of the catalytic activity remained. Higher pressure (150-500 MPa) induced further conformational changes, characterized by a large decrease in the center of the spectral mass of intrinsic fluorescence, a large increase in the 8-anilino-1-naphthalene sulfonic acid binding fluorescence and the loss of all catalytic activity. Thus, this intermediate exhibited characteristics of molten globule-like state. A further increase, in pressure (above 550 MPa) induced transition from this first molten globule-like state to a second molten globule-like state. This two-stage denaturation process can be explained by assuming the existence of two independent structural domains in the carboxypeptidase molecule. A similar three-transition process was found for unglycosylated carboxypeptidase Y, but, the first two transitions clearly occurred at lower pressures than those for glycosylated carboxypeptidase Y. These findings indicate that the carbohydrate moiety protects carboxypeptidase Y against pressure-induced denaturation. The origin of the protective effects is discussed based on the known crystallographic structure of CPY.

Carboxypeptidases↗
PubMed1999

Progeroid syndrome with facial teleangiectatic erythema, posterior subcapsular cataracts, calcification of basal ganglia and atrium septum defect type 2.

In this report we present the long-term follow-up findings in a young female born to consanguineous parents with the unique association of (1) a progeroid syndrome, (2) facial dysmorphism with relative microcephaly, triangular face, retrognathism and skin erythema, (3) bilateral posterior cataracts, (4) basal ganglia calcifications and (5) atrium septum defect type 2. Intelligence is borderline. Clinical evolution after normal puberty was positive with regression of the facial erythematous changes. Over the years differential diagnosis included progeria, hypohidrotic ectodermal dysplasia, Rothmund-Thompson syndrome, Cockayne syndrome, Bloom syndrome, but the clinical spectrum of abnormalities and the evolution with age were not compatible with one of these diagnoses. Parental consanguinity is in favour of autosomal recessive inheritance.

Abnormalities, Multiple↗
PubMed1998

Ventilatory inefficiency for carbon dioxide during exercise in patients with pulmonary hypertension.

The purpose of this study was to analyse the ventilatory efficiency for carbon dioxide (CO2) in the assessment of exercise tolerance in patients with pulmonary hypertension. Two groups of patients were studied. One group consisted of 37 patients with normal pulmonary artery pressure who underwent surgical closure of a left-to-right shunt. Another group was composed of 10 patients with pulmonary hypertension. Both patient groups were compared with the mean value of an age-matched pool of normal control subjects. Aerobic exercise performance was assessed by determination of the ventilatory threshold. The ventilatory efficiency for CO2 was assessed by calculating the slope of ventilation over carbon dioxide below the ventilatory threshold. The slope of ventilation vs. carbon dioxide output in patients with pulmonary hypertension (48 +/- 12) was steeper than the slope (31.3 +/- 7.0) in patients with normal pulmonary artery pressure (P < 0.05). Significant correlations (P < 0.05) were found between the pulmonary artery pressure and the slope of pulmonary ventilation over carbon dioxide (r = 0.92) and also with the physiological dead space-tidal volume ratio at maximal exercise (r = 0.55). This was associated with a severe reduction in exercise performance in patients with pulmonary hypertension, whereas in patients with normal pulmonary artery pressure it was only slightly below the lower limit of normal. These results demonstrate that patients with pulmonary hypertension have an inefficient ventilatory response to metabolically produced CO2 during exercise, which severely limits exercise tolerance.

Adolescent↗
PubMed1998

Percutaneous treatment of stenosed major aortopulmonary collaterals with balloon dilatation and stenting: what can be achieved?

BACKGROUND: The natural history of major aortopulmonary collateral arteries (MAPCAs) in patients with pulmonary atresia and ventricular septal defect (PA-VSD) is frequently complicated by progressive stenosis, leading to pulmonary hypoperfusion and debilitating hypoxaemia. OBJECTIVE: To evaluate balloon dilatation and stenting for relief of stenoses and improvement of pulmonary flow in patients with PA-VSD. DESIGN: Retrospective analysis of all patients where dilatation of MAPCA stenoses was attempted. PATIENTS: Twelve patients with stenotic MAPCAs. INTERVENTIONS: Dilatation was attempted in 25 stenoses. Vessels were stented if elastic recoil was noticed (n = 3), in the presence of long segment stenosis (n = 4) or marked tortuosity (n = 1). MAIN OUTCOME MEASURES: Diameter of stenoses before and after dilatation as well as arterial oxygen saturation data. Patients proceeding to surgical therapy. RESULTS: Two stenosed MAPCAs could not be crossed by a catheter. Four lesions were non-dilatable despite the use of high inflation pressures (18 atm). Six stenoses could be completely dilatated using angioplasty only; in five, only partial dilatation was obtained; eight stenoses needed stenting. In the group with partial expansion the mean (SD) diameter increased from 1.7 (0.8) to 3.5 (1.7) mm (p < 0.05); where full dilatation was achieved it increased from 2.1 (0.8) to 4.8 (1.9) mm (p < 0.05); and in the stented group in increased from 2.3 (0.9) to 5.0 (2.5) mm (p < 0.01). Percutaneous arterial oxygen saturation increased from 75(8%) to 82(8)% (p < 0.001). No complications were experienced during the procedures. Repeat dilatation was attempted in six stenoses, but only two procedures were successful. There were two episodes of vasospasm and in one an aneurysm had developed after redilatation. Two patients proceeded to outflow plasty and two subsequently had a unifocalisation procedure. CONCLUSIONS: Pulmonary blood flow can be improved using balloon angioplasty or stents in patients with stenotic MAPCA; however, 17% of the lesions were not dilatable. Procedures are generally safe, but carry a small risk of vasospasm, dissection, occlusion or aneurysm formation.

Adolescent↗
PubMed1998

Self expandable stents for relief of venous baffle obstruction after the Mustard operation.

OBJECTIVE: Obstruction of the venous pathways after Mustard repair for transposition of the great arteries is associated with an increased risk of arrhythmia and sudden death. The purpose of this study was to assess the effectiveness of the largest (tracheal 22 x 40 mm) Wallstents in treating baffle obstructions. DESIGN: Retrospective analysis of patients with stented venous pathways. SUBJECTS: Eleven patients with baffle obstruction after Mustard repair for transposition of the great arteries. INTERVENTIONS: Stenoses were dilated with an 18 or 20 mm balloon. However, recoil was noticed in 11 patients: immediately (n = 7) or on repeat angiography (n = 4). Eighteen stents were implanted (mean (SD)) 18 (3.3) years postoperatively. After dilatation a tracheal Wallstent (11.5 F) was deployed. MAIN OUTCOME MEASURES: Relief of obstruction, haemodynamic improvement. RESULTS: In the inferior vena cava, 10 stents were deployed in seven baffle obstructions with an increase in diameter from 9.8 (2.4) mm to 16.5 (1.4) mm (p < 0.01) and a mean (SD) pressure gradient decrease from 5.1 (3.6) mm Hg to 1.4 (2.0) mm Hg; in the superior vena cava, eight stents were implanted increasing the diameter from 9.1 (3.7) mm to 15.6 (3.8) mm (p < 0.001) with a decrease in mean pressure gradient from 5.1 (2.7) mm Hg to 1.9 (1.5) mm Hg. No complications were experienced during implantation. No anticoagulation was prescribed. During follow up (1.7 (0.6) years; range, 0.9-2.6) no problems were noted; five patients were re-catheterised without change in measurements. There was no evidence of peal formation in any of the stents. CONCLUSION: It is concluded that Wallstents are safe, easy to use, and effective in relieving baffle obstruction. Anticoagulation does not seem necessary.

Adolescent↗
PubMed1998

Epoxyeicosatrienoic acids relax airway smooth muscles and directly activate reconstituted KCa channels.

Epoxyeicosatrienoic acids (EETs) relax various smooth muscles by increasing outward K+ movement, but the molecular mode of action of EET regioisomers remains to be clarified. The effects of EETs were investigated on bovine airway smooth muscle tone and on reconstituted Ca2+-activated K+ (KCa) channels. 5,6-EET and 11, 12-EET induced dose-dependent relaxations of precontracted bronchial spirals. These effects were partly abolished by 10 nM iberiotoxin. Bilayer experiments have shown that 0.1-10 microM 11,12-EET produced up to fourfold increases in the open probability of KCa channels from the cis (extracellular) side by enhancing the mean open time constant and reducing the long closed time constant, without affecting the unitary conductance. EET-induced activations were blocked by 10 nM iberiotoxin. Addition of vehicles or other lipids as well as of GTP and guanosine 5'-O-(3-thiotriphosphate) in the absence of EET had no effect on channel activity. Thus EETs directly activate KCa channels from airway smooth muscle through an interaction with the extracellular face of the channel. We propose that EETs could represent candidate molecules as epithelium-derived hyperpolarizing factors.

8,11,14-Eicosatrienoic Acid↗
PubMed1998

Direct modulation of tracheal Cl--channel activity by 5,6- and 11,12-EET.

Using microelectrode potential measurements, we tested the involvement of Cl- conductances in the hyperpolarization induced by 5,6- and 11,12-epoxyeicosatrienoic acid (EET) in airway smooth muscle (ASM) cells. 5,6-EET and 11,12-EET (0.75 microM) caused -5.4 +/- 1.1- and -3.34 +/- 0.95-mV hyperpolarizations, respectively, of rabbit tracheal cells (from a resting membrane potential of -53.25 +/- 0.44 mV), with significant residual repolarizations remaining after the Ca2+-activated K+ channels had been blocked by 10 nM iberiotoxin. In bilayer reconstitution experiments, we demonstrated that the EETs directly inhibit a Ca2+-insensitive Cl- channel from bovine ASM; 1 microM 5,6-EET and 1.5 microM 11,12-EET lowered the unitary current amplitude by 40 (n = 6 experiments) and 44.7% (n = 4 experiments), respectively. Concentration-dependent decreases in channel open probability were observed, with estimated IC50 values of 0.26 microM for 5,6- and 1.15 microM for 11,12-EET. Furthermore, pharmacomechanical tension measurements showed that both regioisomers induced significant bronchorelaxations in epithelium-denuded ASM strips. These results suggest that 5,6- and 11,12-EET can act in ASM as epithelium-derived hyperpolarizing factors.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1998

Direct activation of K(Ca) channel in airway smooth muscle by nitric oxide: involvement of a nitrothiosylation mechanism?

Clinically, nitric oxide (NO*) is widely used as a pulmonary vaso- and bronchodilator agent. However, the precise molecular mechanisms by which NO. induces smooth muscle relaxation are not well established. It has been suggested that NO. relaxes airway smooth muscle (ASM) via a 3',5'-cyclic guanosine monophosphate (cGMP)-dependent pathway, and our previous work has shown that Ca2+-activated K+ (KCa) channels are susceptible to cGMP-dependent protein kinase (PKG)-dependent phosphorylation (A. Alioua, J. P. Huggins, and E. Rousseau. Am. J. Physiol. 1995;268:L1057-L1063). To assess whether KCa channels are also directly activated by NO. or one of its derivatives such as peroxynitrite, the activity of these channels was measured upon fusion of sarcolemmal vesicles derived from bovine tracheal smooth muscle cells into planar lipid bilayers (PLB). It was found that in the absence of adenosine triphosphate (ATP), cGMP, and cGMP-dependent protein kinase, NO* donors such as 1-propanamine-3-(2-hydroxy-2-nitroso-1-propylhydrazine) (PAPA NONOate) or 3-morpholinosydnonimine hydrochloride (SIN-1) in the presence of superoxide dismutase (SOD), added on either side of the bilayer, caused a concentration- dependent increase in the open probability (Po) of KCa channels without altering their unitary conductance. Release of NO*, which was measured by chemiluminescence analysis in parallel experiments, affected the gating behavior of KCa channels in the presence of SOD and ethyleneglycol-bis-(beta-aminoethyl ether)- N,N'-tetraacetic acid (EGTA) by reducing the mean closed times and increasing the number and duration of short open events. PAPA NONOate, a true NO. donor, had similar effects in the presence of ethylenediaminetetraacetic acid (EDTA), a heavy-metal chelator, and K-urate, a peroxynitrite scavenger. Addition of either 5 mM dithiothreitol (DTT) or 5 mM reduced glutathione (GSH), as well as 5 mM N-ethylmaleimide (NEM)-an alkylating agent-to the trans (intracellular) side of an experimental chamber slightly increased channel Po but prevented further channel activation by NO* donors. However, neither DTT nor GSH was able to reverse the effect of NO*. In contrast to SIN-1, DTT had no effect when added to the cis (extracellular) side of the chamber. This suggests that the effect of NO* is most likely due to a chemical modification (nitrothiosylation) of intracellular sulfhydryl group(s). Neither PAPA NONOate (NO*), nor SIN-1 had any effect on sarcolemmal Cl- channels reconstituted from the same membrane preparations. Pharmacomechanical measurements made on epithelium-denuded rat bronchus showed that 100 nM charybdotoxin decreased the sensitivity of bronchial smooth muscle to SIN-1-induced relaxations. Altogether, our data suggest that NO-induced bronchorelaxation occurs partly via a direct activation of KCa channels, possibly through a covalent interaction with the cytoplasmic side of their alpha subunit.

Animals↗
PubMed1998

Risk factors for maternal condition at admission to an intensive care unit: does health care organisation play a role? Study Group of the Maternal Morbidity.

The objective of this study was to analyse the relation between severity of maternal condition at the time of intensive care unit (ICU) admission and various individual and institutional factors. This study analysed data from a retrospective population-based study in three French regions during 1991. The population study included 355 patients who were admitted to an ICU during pregnancy, delivery or within 42 days after delivery, for an obstetrical cause. The main outcome measure was the severity of maternal condition at ICU admission estimated from the level of consciousness and from the Simplified Acute Physiology Score (SAPS). The most severe maternal condition was associated with a change in hospital category (from the initially chosen hospital to the hospital referring for ICU) (OR 3.8, 95% CI 1.5-9.6) and with treatment in a private hospital at ICU referral (OR 3.3, 95% CI 1.3-8.3). Foreign nationality was the only individual factor related to very severe maternal condition. These results suggest that health care organisation during pregnancy affects the prognosis of severe maternal condition. The factors involved appear to include the management of unpredictable disorders, the conditions of maternal transfers before ICU admission, and antenatal care of foreigners.

Adult↗
PubMed1998

Polyhydramnios as a prenatal symptom of the digeorge/velo-cardio-facial syndrome.

Prenatal diagnosis of the DiGeorge/velo-cardio-facial syndrome has become possible since it was recognized that this syndrome is caused by a submicroscopic deletion in chromosome 22q11. In a sporadic patient presenting a conotruncal heart defect and polyhydramnios, the del 22q11 was made prenatally by fluorescence in situ hybridization (FISH) after amniocentesis. Seven additional patients with a del 22q11 were identified, who presented during pregnancy with polyhydramnios. In one of them, unilateral hydronephrosis was present. These findings further add to a growing list of clinical presentations of a del 22q11 and suggest that in patients with polyhydramnios and a conotruncal heart defect or uropathy, fetal karyotyping should be complemented by FISH for a del 22q11.

Amniocentesis↗
PubMed1997

Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS.

We report data on a group of 37 VCFS patients with specific reference to their intelligence, behaviour, and social competence. Fifty five percent of the children had a borderline to normal IQ. Mental retardation (defined as IQ < 70 or > -2 SD below the mean) was found in 45%. In the majority, the mental retardation was mild (38%) and only two patients had moderate mental retardation. Severe mental retardation seems to be rare in VCFS. The present study shows also that the incidence of mental retardation is much higher in the familial than the de novo group. Intelligence is not correlated with the presence or absence of a heart defect. Significantly higher verbal IQs than performance IQs (probably related to deficits in visuospatial-perceptual functioning) were found. Problems in social-emotional functioning and attention were also found. Further longitudinal studies are necessary to provide an accurate prognosis and appropriate intervention for VCFS children.

Abnormalities, Multiple↗