Quand les malformations pulmonaires congénitales doivent-elles être opérées ?

Both technical and anatomical features and the need for a long follow-up, usually over several years, explain the specificity of lung surgery in children. Apart from the oncological resections, the main indications for this surgery are congenital lung anomalies (cystic adenomatoid malformation, bronchopulmonary sequestration, lobar emphysema), symptomatic postinfectious lesions (bronchiectasis, atelectasis, abscess) and pneumothorax. Advances in miniaturization of the surgical equipment are used to carry the majority of these interventions by thoracoscopy, except when performed at the neonatal period. In the newborn, for which the indications for lung surgical resections are exceptional, ventilatory conditions and the tightness of the chest lead to still prefer open surgery. Pulmonary malformations can also be managed prenatally when they affect lung development or cause heart failure because of compressive complications. These interventions, performed after the 30th week of gestation, are not intended to remove the lesions, but to release the compression. But these procedures are still under evaluation and, in light of possible fetal and maternal complications, they should only be performed in tertiary centers and in the context of specific protocols.     

Delayed growth due to growth hormone deficiency (study of 16 cases)

Growth hormone deficiency is one of the scarce statural backward causes. It is difficult to make a diagnosis. The purpose of growth hormone treatment is to reach a final normal height and to avoid hypoglycemia after-effects. We give a retrospective account of 16 children (11 boys and 5 girls) who have a growth-delay due to a total growth hormone deficiency confirmed by the stimulation tests and who have also been given benefit of a biosynthetic growth hormone from 1990 to 1999. The statural backwardness varies from--2.5 DS to--4 DS, with an average of--3.5 DS. In all the cases it is a matter of a harmonious backwardness discovered at an average age of 6 years. The bone age has revealed an important backwardness of bone maturation: average bone age of 3 years for boys and 4 years for girls. The hormone balance sheet reveals, in all the cases, a total growth hormone deficiency (GH < 5 ng/ml) combined with a corticotrope deficiency (2 cases) and thyreotrope (3 cases). It is a growth hormone idiopathic deficiency among our patients. The growth hormone treatment has been administered at the average age of 8 years. The weekly doses were (0.4 to 0.8 U/kg). The evolution was favorable with an average growth speed that has gone up from 3 cm/year before the treatment to 10 cm in the first year of the treatment and to 5.5 cm during the second year of the treatment. An average statural gain of 0.8 DS and a bone maturation gain of one year over one year treatment. The authors put into relief the importance of diagnosis criteria of growth backwardness through a GH deficiency and suggest a therapeutic diagram, and a follow-up of the GH biosynthetic treatment.     

Biochemical amniotic fluid pattern for prenatal diagnosis of esophageal atresia

Prenatal diagnosis of esophageal atresia (EA) may improve the outcome of affected neonates by allowing optimization of both prenatal and postnatal care. Prenatal sonographic detection is based on polyhydramnios and/or nonvisualization of the fetal stomach bubble, two signs with a large number of etiologies. We evaluated a biochemical approach to improving diagnostic efficiency. We compared amniotic fluid biochemical markers in 44 EA cases with 88 polyhydramnios and 88 nonpolyhydramnios controls. Both matched for GA with cases. Total proteins, alpha-fetoprotein (AFP), and digestive enzyme activities were assayed, including gamma-glutamyl transpeptidase (GGTP). We defined an EA index (AFP multiplied by GGTP). A significant difference (p < 0.0001) was observed for total protein, AFP, GGTP, and EA index between the EA group and each of the two control groups. No statistical difference was observed for any marker between the two most frequent EA subgroups (type I and type III) or between the two control groups. Using a cutoff of 3 for the EA index, 98% sensitivity and 100% specificity were observed for amniotic fluid prenatal diagnosis of EA, whatever the anatomical type. A large prospective series is required to confirm these results.     

Quantitation of myocardial borderzone using reconstructive 3-D echocardiography after chronic infarction in rats: incremental value of low-dose dobutamine

Myocardial remodeling determines the degree of left ventricular dysfunction and mortality after transmural chronic myocardial infarction (CMI). Noninvasive characterization and quantitation of myocardial borderzone and collagenous scar are therefore parameters of clinical interest. The aims of this study were (i) to measure accuracy of reconstructive 3-D echocardiography (3DE) in scar and myocardial borderzone size assessment and (ii) to investigate the incremental value of low-dose dobutamine stress. 3DE was performed in 14 immunodeficient rats (rnu-rnu, 180-200 g) with anterior CMI 25 d after coronary ligation. Briefly, consecutive parallel short-axis cineloops were obtained electrocardiogram-gated starting from base to the apex. Morphology (mass, surface) and function (contractility, contractile reserve) of different compartments were assessed and correlated with 3-D histomorphometry. Histology was done using picrosirius red for collagen staining. 3DE left ventricular mass correlated closely with histomorphometry (y = 0.89x + 155, p < 0.0001, r = 0.80). Hypo- and akinetic myocardial surface correlated well with borderzone myocardium (y = 0.34x + 17, p = 0.009, r = 0.62) and collagenous scar (y = 1.9x + 4.4, p < 0.0001, r = 0.79), respectively. Extent of abnormal wall motion was closely related to borderzone and scar tissue area (y = 0.82x + 7, p < 0.0001, r = 0.77). 3DE quantitation of borderzone myocardium, but not collagenous scar, was more closely correlated to histomorphometry during inotropic stimulation. Global contractile reserve is positively associated with the size of myocardial borderzone. Regional contractile reserve of borderzone myocardium is not negatively associated with its collagen content. 3DE allows precise quantitation of myocardial borderzone and identification of transmural scar tissue noninvasively. Assessment of contractile reserve improves characterization and estimation of myocardial borderzone after CMI.     

Association of the insertion/deletion gene polymorphism of the apolipoprotein B signal peptide with myocardial infarction in Tunisian patients

BACKGROUND: Numerous polymorphisms of the apolipoprotein B (APOB) gene have been described. Particularly, the insertion/deletion (Ins/Del) polymorphism located in the coding part of the signal peptide of apoB, associated with modification of lipid concentrations and the risk of coronary artery disease and/or myocardial infarction (MI), has been reported in the general population. Moreover, conflicting results emerge from the literature and suggest that the effect is context-dependent. In the present study, the first investigation of the Ins/Del polymorphism of the APOB gene in Tunisian patients with MI, we examined a possible association between this polymorphism and MI in a subgroup of the Tunisian population. METHODS: A total of 318 Tunisian patients with MI and 368 healthy controls were included in the study. Genomic DNA was extracted from white blood cells, and the Ins/Del polymorphism was determined by electrophoresis in polyacrylamide gels after PCR amplification. A binary logistic regression analysis was performed to test how the association between MI and Ins/Del polymorphism is independent from confounding factors. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with MI had a frequency of 7.2% for the Del/Del genotype, 39.6% for the Ins/Del genotype, and 53.1% for the Ins/Ins genotype. Controls had a frequency of 3.0% for the Del/Del, 32.1% for the Ins/Del and 64.9% for the Ins/Ins genotype (chi2=12.93, p=0.002). The MI patient group showed a significantly higher frequency of the Del allele compared to controls (27.1% vs. 19.1%; chi2=12.50, p=0.0004). In comparison to the Ins/Ins homozygotes, the odds ratio (95% confidence interval) for MI was 1.51 (1.09-2.07) for Ins/Del heterozygotes and 2.95 (1.40-6.22) for Del/Del homozygotes. In multivariate analysis, age (p=0.001), smoking (p<0.001), hypertension (p=0.001), diabetes mellitus (p<0.001), and dyslipidemia (p=0.01) were independent correlates of the presence of MI, whereas the Ins/Del polymorphism (p=0.330) was not an independent predictor of MI. CONCLUSIONS: The present study shows a significant but not independent association between the Ins/Del polymorphism of the APOB gene and MI in the Tunisian population.     

Functional and electrophysiological characterization of four non-truncating mutations responsible for creatine transporter (SLC6A8) deficiency syndrome

Intellectual disability coupled with epilepsy are clinical hallmarks of the creatine (Cr) transporter deficiency syndrome resulting from mutations in the SLC6A8 gene. So far characterization of pathogenic mutations of SLC6A8 has been limited to Cr uptake. The aim of our study was to characterize the electrogenic and pharmacological properties of non truncating SLC6A8 mutations identified in patients presenting variable clinical severity. Electrophysiological and pharmacological properties of four mutants (including two novel ones) were studied in X. laevis oocyte expression system. Creatine uptake was assessed with [¹⁴C]-Cr in X. laevis and patients’ fibroblasts. Subcellular localization was determined by immunofluorescence and western blot. All mutants were properly targeted to the plasma membrane in both systems. Mutations led to the complete loss of both electrogenic and transport activities in X. laevis and Cr uptake in patients’ fibroblasts. Among the Cr analogs tested, guanidinopropionate induced an electrogenic activity with the normal SLC6A8 transporter similar to creatine whereas a phosphocreatine derivative, PCr-Mg-CPLX, resulted in partial activity. SLC6A8 mutants displayed no electrogenic activity with all Cr analogs tested in X. laevis oocytes. Although the mutations altered various domains of SLC6A8 Cr uptake and electrogenic properties were completely inhibited and could not be dissociated. Besides the metabolic functions of Cr, the loss of SLC6A8 electrogenic activity, demonstrated here for the first time, may also play a role in the altered brain functions of the patients.     

Endometrial atypical complex hyperplasia with extensive squamous metaplasia: two cases

We report two cases of endometrial atypical complex hyperplasia with an extensive squamous hyperplasia occurring in two women aged 48 and 31 years old. The histological study showed an increase in the gland to stroma ratio with a false crowding aspect due to an extensive area of squamous metaplasia; some metaplastic areas were centered by necrosis. There was glandular cytologic atypia. Histologic examination is necessary to confirm the diagnosis and to definitively rule out adenocarcinoma.     

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of myocardial infarction among Tunisian male patients

ObjectivesThe aim of the present study was to investigate the association between CCR2-Val64Ile and CCR5-Δ32 variants and the estimation of haplotypes with MI in a sample of the Tunisian population.Design and methodsA total of 290 unrelated MI patients and 282 healthy controls were studied. The CCR2-Val64Ile and CCR5-Δ32 variants were analyzed by PCR-RFLP.ResultsSubjects carrying at least one copy of the CCR5-deletion allele were significantly more common in the control group, suggesting an atheroprotective effect (adjusted OR = 0.44, 95% CI = 0.28–0.72, p = 0.001). Haplotype analysis showed that MI patients had significantly less 64Val-Del haplotype (9.9% vs. 21.3%, OR = 0.30, 95% CI = 0.21–0.43, p < 0.001) and 64Ile-Ins haplotype (12.3% vs. 16.7%, OR = 0.58, 95% CI = 0.42–0.80, p < 0.001).ConclusionA protective effect of the CCR5-Δ32 polymorphism against MI in the Tunisian population was found.