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Biomedical subjects

Marc Gewillig

Publications and source records attributed to Marc Gewillig.

47 records · Page 3Linked to original sources
PubMed2003

PTPN11 mutation in a large family with Noonan syndrome and dizygous twinning.

Noonan syndrome (NS, MIM 163950) is an autosomal dominant condition characterised by facial dysmorphy, congenital cardiac defects and short stature. Recently missense mutations in PTPN11, the gene encoding the nonreceptor protein tyrosine phosphatase SHP-2 on 12q24, were identified in 50% of analysed Noonan cases. A large four-generation Belgian family with NS and some features suggestive of cardio-facio-cutaneous syndrome (CFC) was previously used to fine map the Noonan syndrome candidate region to a 5 cM region in 12q24. We now report the identification of a mutation (Gln79Arg) in the PTPN11 gene in this large family. In D. melanogaster and C. elegans the PTPN11 gene has been implicated in oogenesis. In this family two affected females had dizygous twins. This suggests that PTPN11 might also be involved in oogenesis and twinning in humans.

Belgium↗
PubMed2003

Influence of work rate on the determinants of oxygen deficit during short-term submaximal exercise: implications for clinical research.

OBJECTIVE: The effect of increasing work rate was studied on the determinants of the oxygen deficit. METHODS: Exercise testing was performed on a treadmill and gas exchange was measured on a breath-by-breath basis. Eleven healthy subjects, aged 18-25 years, performed three square wave exercise tests of different intensity. Before exercise, gas exchange was measured at rest in the standing position for 3 min, followed by a 6-min square wave exercise test, randomly assigned at 4, 8 or 12% inclination. Immediately after exercise the recovery gas exchange was determined for 3 min. To calculate oxygen deficit, the oxygen uptake (O2) values at onset of exercise were subtracted from the steady-state value, the differences were cumulated and expressed as a percentage of the total oxygen cost for the 6-min exercise. RESULTS: The oxygen deficit increased significantly (P<0.001) with increasing work rate (6.1 +/- 1.4% for 4%, 8.4 +/- 2.1% for 8% and 9.4 +/- 1.7% at 12% inclination). This resulted from a somewhat slower increase of O2 at the onset of exercise at the highest work rate, reflected by a significantly higher time constant for O2 at 8 and 12% (24.6 +/- 7.3 s at 8% and 24.1 +/- 6.3 s at 12% versus 20.2 +/- 8.1 s at 4%). More importantly a significantly higher steady-state value for O2 was found at the highest exercise level, compared with the other exercise intensities. CONCLUSION: The higher oxygen deficit at the highest level of exercise is determined by a slower time constant and a higher asymptote value for O2.

Adult↗
PubMed2003

Mutation analysis in congenital Long QT Syndrome--a case with missense mutations in KCNQ1 and SCN5A.

Long QT Syndrome (LQTS) is a cardiac disease characterized by a prolonged QT interval on a surface electrocardiogram (ECG) and by clinical symptoms such as seizures, syncope, and cardiac sudden death. At present, causal mutations of LQTS have been identified in five cardiac ion-channel genes. Because a causal mutation is usually unique to a specific family and can be located in any region of any of these five genes, a mutation analysis effort may require screening of the complete coding regions of each of these genes. The causative nature of a detected mutation can then be determined either by family history or by functional studies, such as the electrophysiological signature of the mutation. Here we describe a mutation analysis of an LQTS patient who carries two heterozygous missense mutations in two different LQTS genes. The first mutation identified, A572D in SCN5A, was not linked with clinical LQTS features in the two other mutation carriers in the family; neither was it identified in 90 healthy controls. Therefore, this mutation most likely has either a mild effect on cardiac ion-channel function or represents a very rare polymorphism. The second mutation, V254M in KCNQ1, co-segregated with higher QT intervals and symptoms in other family members, and was previously reported in another LQTS family. Because the clinical LQTS symptoms are most pronounced in the proband, a combined effect of both mutations cannot be excluded, although no functional data are available to support such an hypothesis. We conclude that, for newly presented LQTS cases, a mutation analysis strategy should routinely screen the complete coding region of all LQTS genes, followed by an evaluation of the identified mutation(s) in conjunction with family or functional data.

Child↗
PubMed2003

Left-to-right shunting in common congenital heart defects: which patients are eligible for percutaneous interventions?

Atrial septal defects, atrio-ventricular septal defects, ventricular septal defects and the persistent arterial duct are the most common congenital heart defects which may cause, in the presence of a significant left-to-right shunt, chronic volume overload of the heart and lead to the development of pulmonary arterial hypertension. Repair is indicated to avoid these complications and evolution to right-to-left shunting (Eisenmenger syndrome). Although the long-term results of surgical interventions in uncomplicated congenital heart defects were excellent, percutaneous techniques to repair the defects became a focus of attention. The persistent arterial duct, the secundum type atrial septal defect, and, more recently, the muscular and perimembranous ventricular septal defect are currently eligible for percutaneous closure. By avoiding a sternotomy or a thoracotomy, complaints of pain become exceptional and the duration of hospitalisation is shortened. Percutaneous closure is not only better tolerated than surgery, it may also imply favourable economical aspects.

Cardiac Catheterization↗
PubMed2003

Manipulating parallel circuits: the perioperative management of patients with complex congenital cardiac disease.

In all patients undergoing cardiac surgery, the effective delivery of oxygen to the tissues is of paramount importance. In the patient with relatively normal cardiac structures, the pulmonary and systemic circulations are relatively independent of each other. In the patient with a functional single ventricle, the pulmonary and systemic circulations are dependent on the same pump. As a consequence of this interdependency, the haemodynamic changes following complex palliative procedures, such as the Norwood operation, can be difficult to understand. Comparison of the newly created surgical connections to a simple set of direct current electrical circuits may help the practitioner to successfully care for the patient. In patients undergoing complex palliations, the pulmonary and systemic circulations can be compared to two circuits in parallel. Manipulations of variables, such as resistance or flow, in one circuit, can profoundly affect the performance of the other circuit. A large pulmonary flow might result in a large increase in the saturation of haemoglobin with oxygen returning to the heart via the pulmonary veins at the expense of a decreased systemic flow. Accurate balancing of these parallel circulations requires an appreciation of all interventions that can affect individual components of both circulations.

Cardiac Surgical Procedures↗
PubMed2002

Quantification of regional right and left ventricular function by ultrasonic strain rate and strain indexes after surgical repair of tetralogy of Fallot.

The quantification of regional myocardial function in tetralogy of Fallot (TOF) by conventional M-mode and 2-dimensional echocardiography is difficult because of the complex right ventricular (RV) and altered left ventricular (LV) geometry. In 30 asymptomatic postoperative TOF patients (aged 4 to 16 years) with a low pressure in the right ventricle and with varying degrees of pulmonary regurgitation and in 30 aged-matched healthy children, the ultrasonic-derived regional deformation parameters peak systolic strain rate (SR) and systolic strain (epsilon) were acquired from ventricles and compared. In TOF RV free walls, SR, and epsilon were reduced in the basal, mid-, and apical segments and averaged -1.5 +/- 0.6 second(-1) for SR and -22 +/- 8% for epsilon, respectively (p <0.001 vs normals). Peak systolic SR of the basal RV free wall correlated significantly with the QRS duration of the electrocardiogram (r = 0.81, p <0.0001). Abnormalities in RV deformation were more marked in patients with transannular patches versus infundibular patches. In the septum there was a homogeneous reduction in SR and epsilon in the basal, mid-, and apical segments. These averaged -1.4 +/- 0.3 second(-1) for SR and -19 +/- 4% for epsilon, respectively (p <0.01 vs normals). Longitudinal SR and epsilon values of the 3 LV lateral wall segments (averaged SR = -1.6 +/- 0.4 second(-1), averaged epsilon = -20 +/- 5%; p <0.05 vs normals), and radial SR and epsilon of the LV posterior wall (SR = 3.3 +/- 0.9 second(-1); epsilon = 51 +/- 14%; p <0.05 vs normals) were significantly reduced. Thus, abnormalities in regional RV and LV systolic myocardial function in asymptomatic postoperative TOF patients were quantified by the deformation parameters SR and epsilon. RV deformation abnormalities are associated with electrical depolarization abnormalities.

Adolescent↗
PubMed2002

Progressive AV-block and anomalous venous return among cardiac anomalies associated with two novel missense mutations in the CSX/NKX2-5 gene.

Non-syndromic cardiac septation defects are common, yet the causative factors remain largely uncharacterised. Septation defects are an integral part of many syndromes, some of which are associated with chromosomal alterations. For the majority, the physiopathogenesis is believed to be multi-factorial, hindering the identification of causative factors. Ten mutations in the gene encoding the transcription factor CSX/NKX2-5 have been described in individuals with ASD and/or atrioventricular conduction defects. In addition, several other cardiac abnormalities were observed, yet the mildest forms are reminiscent of non-syndromic septation defects. The CSX/NKX2-5 gene is thus a good candidate for various cardiopathies. We have collected two families with inherited predisposition to cardiac abnormalities. Some members of the families presented ASD and AV block. In both families a novel CSX/NKX2-5 mutation was identified in the homeodomain. Variable expressivity in the phenotype was observed in both families. Importantly, mutation carriers did not present any symptoms at young age. In addition, anomalous venous return, a phenotype not previously associated to CSX/NKX2-5 mutations, was observed in one of the families. We also screened the CSX/NKX2-5 gene in sporadic and familial cases of other cardiopathies. As additional mutations were not found, substitutions in CSX/NKX2-5 gene seem to be a rare cause of cardiopathies without conduction defect.

Amino Acid Sequence↗
PubMed2002

Creation with a stent of an unrestrictive lasting atrial communication.

A new technique is presented to create percutaneously an unrestrictive and lasting atrial communication in small children. In 2 infants, a stent was deployed in a restrictive atrial communication and first inflated with an 8 mm balloon. The stent was then further expanded up to 10 or 12 mm. The gradient and turbulent flow between the two atriums disappeared completely. The stent retained a very stable position without embolisation. Other complications, such as formation of thrombus or arrhythmia, were not observed until elective explantation after 2 and 11 months. We conclude that, in infants, dilation of the atrial septum with a stent can provide a safe, lasting, and unrestrictive atrial communication.

Catheterization↗
PubMed2002

Quantification of regional left and right ventricular radial and longitudinal function in healthy children using ultrasound-based strain rate and strain imaging.

BACKGROUND: Noninvasive assessment of left (LV) and right (RV) ventricular function in children could benefit from a technique that would characterize local myocardial deformation. Color Doppler myocardial imaging (CDMI) allows the calculation of either local longitudinal or radial Strain Rate (SR) and Strain (epsilon). To determine the clinical feasibility and reproducibility of longitudinal and radial SR and epsilon, the following study was carried out. METHODS: CDMI data were obtained from 33 healthy children (4-16 years). To quantify regional longitudinal and radial function SR and epsilon data were obtained from apical and parasternal views respectively. From the extracted SR curves, peak values for systole, early diastole, and late diastole were calculated. From the extracted epsilon curves the systolic, early and late diastolic epsilon values were calculated. RESULTS: LV longitudinal deformation were homogeneous for LV basal, mid and apical segments (peak systolic SR: -1.9 +/- 0.7 s(-1), systolic epsilon -25% +/- 7%). Longitudinal SR and epsilon values were significantly higher and heterogeneous in the RV (compared with LV walls) and were maximal in the mid part of the RV free wall (peak systolic SR: -2.8 +/- 0.7 s(-1), systolic epsilon -45% +/- 13%). The RV inferior wall showed homogeneous but lower longitudinal SR and epsilon values. The LV systolic and diastolic SR and epsilon values were higher for deformation in the radial direction compared with the longitudinal direction (radial peak systolic SR: 3.7 +/- 0.9 s(-1), radial systolic epsilon 57% +/- 11%; P <.0001). The interobserver variability for radial systolic epsilon and SR was 10.3% and 13.1%, respectively. CONCLUSION: Ultrasound-based Strain SR/epsilon imaging is a practical, reproducible clinical technique, which allows the calculation of regional longitudinal and radial deformation from both LV and RV segments. The combination of regional SR/epsilon indices and the timing of specific systolic or diastolic regional events may offer a new noninvasive approach to quantifying regional myocardial function in congenital and acquired heart disease in children.

Adolescent↗
PubMedDate not supplied

Fontan procedure for univentricular hearts: have changes in design improved outcome?

The Fontan operation has undergone numerous design changes in the last 30 years, which have resulted in an improved morbidity and mortality of patients with a univentricular heart. However, good patient selection and a staged approach to the Fontan operation have also contributed greatly to a better outcome in these patients.

Arrhythmias, Cardiac↗