Biomedical subjects

Jean-Christophe Fournet

Publications and source records attributed to Jean-Christophe Fournet.

24 records · Page 2Linked to original sources

PubMed2002

Bronchoalveolar cells in children < 3 years old with severe recurrent wheezing.

STUDY OBJECTIVE: To determine the cell profile of BAL from infants with severe recurrent wheezing who were not acutely ill at the time of investigation, suggesting an ongoing inflammation. DESIGN AND PATIENTS: In a retrospective study, we determined BAL cell profiles for 83 children with wheezing aged 4 to 32 months (mean +/- SD, 11.3 +/- 5.5 months). Fiberoptic bronchoscopy was performed in children with severe recurrent wheezy bronchitis unresponsive to inhaled steroids. These children were compared with 17 children aged 6 to 36 months (mean, 15.1 +/- 7.5 months) with various nonwheezing pulmonary diseases. Children were included as control subjects if they had no endobronchial inflammation and no atopy. RESULTS: The BAL cell profile of young children with wheezing typically includes a significantly higher cell count (mean, 644.4 +/- 956.8 x 10(3)/mL vs 313 +/- 203.2 x 10(3)/mL, p = 0.008), a significantly higher percentage of neutrophils (mean, 9 +/- 12.1% vs 2.1 +/- 2.2%, p = 0.003), and a higher neutrophil count (mean, 43.2 +/- 81.6 x 10(3)/mL vs 7.9 +/- 11.8 x 10(3)/mL, p = 0.003), as compared with control subjects. The larger number of neutrophils in children with wheezing was not correlated with bacterial or viral infection, or with age, sex, or atopic status. In contrast to the situation in asthmatic adults, eosinophil levels were not higher in children with wheezing than in control subjects (mean, 0.09 +/- 0.27% vs 0.08 +/- 0.25%). CONCLUSION: Neutrophil-mediated inflammation in the airways appears to better characterize severe recurrent wheezing in children < 3 years old.

Adult↗

PubMed2002

Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother.

A child with X-linked osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency (OL-EDA-ID) was recently reported. We report the clinical features of a second boy with this novel syndrome and his mother, who presented with signs of incontinentia pigmenti (IP). The child had mild osteopetrosis without neurosensory complications, unilateral lymphedema of the left leg, and characteristic features of anhidrotic ectodermal dysplasia with sparse hair, facial dysmorphy, delayed eruption of teeth, and sweat gland abnormalities. He died at 18 months of severe immunodeficiency with multiple infections caused by Gram-negative (Salmonella enteritidis) and Gram-positive (Streptococcus pneumoniae) bacteria, nontuberculous mycobacteria (Mycobacterium kansasii), and fungi (Pneumocystis carinii). His 30-year-old mother's medical history, together with residual cutaneous lesions, was highly suggestive of IP without neurologic impairment. In this patient with OL-EDA-ID, we detected the same NF-kappaB essential modulator stop codon hypomorphic mutation identified in the previous patient. The occurrence of the same clinical features in 2 unrelated patients with the same genotype demonstrates that OL-EDA-ID is a genuine clinical syndrome. The clinical and biological descriptions of the proband and his mother further corroborate the relationship between IP and EDA. Both syndromes are allelic and are associated with mutations in NF-kappaB essential modulator, with a genotype-phenotype correlation in hemizygous males. In contrast, loss-of-function mutations and hypomorphic mutations may cause IP in females.

Abnormalities, Multiple↗

PubMed2002

Severe cardiac involvement in children with systemic sclerosis and myositis.

OBJECTIVE: To assess the outcome of children with systemic sclerosis (SSc) and features of polymyositis. METHODS: The charts of 4 children who met the American College of Rheumatology criteria for SSc and had features of polymyositis, as defined by the presence of proximal muscle weakness and elevated serum creatine phosphokinase or aldolase level, were retrospectively reviewed. RESULTS: All children had multivisceral involvement including (1) myocardial perfusion defects in all cases, with mild to severe dilated cardiomyopathy in 3; (2) lung restrictive syndrome in 3; (3) mild to severe esophageal involvement in all cases; and (4) severe intestinal dysfunction in one child. Combination therapy of corticosteroids, methotrexate (MTX), and cyclosporine resulted in improved skin thickness and muscle strength scores in all cases, as well as in lung restrictive syndrome in 2, but was not effective regarding the progression of intestinal malabsorption in one patient, esophageal dysmotility in 3 patients, and dilated cardiomyopathy in 3. Endstage cardiac failure caused 2 deaths. In one child, heart transplantation was performed for the first time in this indication. CONCLUSION: Children with diffuse cutaneous SSc and features of polymyositis are prone to develop severe cardiomyopathy. Combination therapy of corticosteroids, MTX, and cyclosporine seems to be active on muscle, skin, and lung involvement but does not impair progression of esophageal or myocardial dysfunction. Heart transplantation might be considered, as an experimental treatment, in young patients with severe cardiomyopathy and no other irreversible organ damage.

Adolescent↗

PubMedDate not supplied

Obstetric US: watch the fetal hands.

Hand anomalies are difficult to diagnose and are often overlooked during prenatal ultrasonography (US). The spectrum of malformations varies from subtle finger deformities to the complete amputation of limbs. Malformations of the hand can be classified, according to the predominant anomaly, among the following categories: alignment abnormalities (clenched hand, camptodactyly, clinodactyly, hypokinesia, clubhand, phocomelia), thumb anomalies, abnormal size (macrodactyly, trident hand), abnormal echogenicity (abnormal calcifications), abnormal number (polydactyly, syndactyly, ectrodactyly), and constriction band sequence. A fetal hand anomaly has important diagnostic and prognostic implications as well as functional consequences. Malformation may be isolated but often is associated with a syndrome or karyotype anomaly. Classification and characterization of the anomaly help to narrow the differential diagnosis: Some malformations (clenched hand, hitchhiker thumb) are highly suggestive of a specific diagnosis. The detection of a fetal hand malformation warrants a complete work-up, including complete fetal and cardiac US examinations, as well as genetic counseling to determine whether familial inquiry and karyotype analysis are necessary.

Hand Deformities, Congenital↗

PubMedDate not supplied

ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyperinsulinemic hypoglycemia of infancy and evaluation of different therapeutic measures.

Persistent hyperinsulinemic hypoglycemia of infancy (PHHI) can occur as a result of mutations in the subunits that form the ATP-sensitive potassium channel (K+ATP) in pancreatic beta-cells which play a major role in modulating insulin secretion from the beta-cells. Mutations have been shown in the genes for these subunits, namely for the plasma membrane sulfonylurea receptor (SUR1), ABCC8, and its associated inwardly rectifying potassium channel (KIR6.2) KCNJ11. Drugs which act on K+ATP channels, such as diazoxide, seem to need intact ABCC8 to be able to show their effects. Thus, it would be desirable to know the exact locus of the abnormality in the beta-cell to be able to choose the right therapeutic agent or to perform early pancreatectomy. The aim of this study was to search for the correlation between the mutations of the K+ATP channel and the outcome of therapeutic measures in patients with PHHI followed for a duration of 4 months to 7.3 years. Thirteen patients (5 F, 8 M) with PHHI with a median age of 2.5 months (8 days-12.1 years) were included in the study. Therapy for PHHI was initiated either with diazoxide (n = 9) or with calcium channel blocker (n = 4) as the agent of first choice. Three patients unresponsive to drugs underwent 95% pancreatectomy. Mutation analysis was performed by polymerase chain reaction (PCR) and single strand conformation polymorphism (SSCP) in DNA samples extracted from patients' peripheral leukocytes. The PCR products were directly sequenced. Screening of ABCC8 and KCNJ11 for mutations revealed abnormalities in the ABCC8 gene in three patients out of 13: homozygosity for the 155del1 mutation, compound heterozygosity for T267-->G/A4612-2-->G, and compound heterozygosity for G4310-->A/ R1494Q. No mutations in the KCNJ11 gene were identified. Of the three patients who underwent pancreatectomy, two had identified mutations and one did not have any known mutation. In two patients in whom hyperinsulinism recurred after surgery and in the rest of the children, therapy with either diazoxide or calcium channel blocker proved to be effective in controlling hypoglycemia over the follow-up period. Thus it may be concluded that mutations in the ABCC8 gene were not predictive of the response to drugs. Unidentified mutations in the K+ATP channels other than those screened or other functional abnormalities in these channels may account for the different therapeutic responses.

ATP-Binding Cassette Transporters↗

PubMedDate not supplied

Cadherins in Wilms' tumor: E-cadherin expression despite absence of WT1.

Loss of heterozygosity of chromosome 16q occurs in 17-25% of Wilms' tumors. Two cadherin genes mapping to 16q22 were chosen as candidate gens: E-CAD, encoding epithelial cadherin, because it is involved in kidney development and it was recently reported to be a WT1 target; and KSP-CAD because it encodes a kidney-specific cadherin. By RT-PCR analysis in a series of 39 Wilms' tumors, we identified a very low expression of E-CAD and KSP-CAD in 72% and 95% of the tumors, respectively. To ascertain whether down-expression of these genes could be related to WT1 alterations in tumors, we looked for a relationship between WT1 and CAD expression. Our data suggest (i) the existence of alternative mechanisms for regulating E-CAD expression, and (ii) that E-CAD does not belong to the WT1 pathway that is altered in Wilms' tumorigenesis.

Cadherins↗