Contribution of M470V variant to cystic fibrosis: First study in CF and normal Tunisian population.

PURPOSE: Determining the frequency of M470V polymorphism in cystic fibrosis and healthy cohort in Tunisia to establish the contribution of M470V polymorphism in cystic fibrosis variable presentation and course. Additionally, studying the origin of cystic fibrosis transmembrane conductance regulator gene in Tunisian population and its evolution among populations worldwide. PATIENTS AND METHODS: The genotyping of M470V marker was realized by PCR-RFLP technique in 34 unrelated patients and 50 healthy subjects. RESULTS: Statistical difference was found in the genotype and allelic distribution between CF and control groups. Exclusive association between F508del allele and M470 allele was noted. CONCLUSION: This study has contributed to better understanding involvement of the M470V polymorphism in the CF clinical expression in the Tunisian population and has confirmed the utility of this marker in the study of the origin and evolution of the CFTR locus in the human history.

[Iatrogenic meningitis after diagnosis lumbar puncture: 3 cases reports in the paediatric Children's Hospital of Tunis]. / Méningite bactérienne iatrogène après ponction lombaire de diagnostic: à propos de trois cas observés à l'hôpital d'enfants de Tunis.

We have collected cases of iatrogenic meningitis managed in the Children's Hospital of Tunis, between January 1998 and December 2006. Clinical information about each patient were collected, all bacterial samples were investigated in the microbiology laboratory of the hospital. Bacterial isolates were identified according to conventional criteria. In the interval under study, we recorded three cases of iatrogenic meningitis after lumbar puncture. Two cases occurred in newborn admitted for suspicion of neonatal infection and one in a 2-month-old infant admitted for exploration of hyperpyretic convulsion. In all patients, the initial cerebrospinal fluid was normal. All patients developed symptoms of acute meningitis within 72 hours after lumbar puncture; the second cerebrospinal fluid was, then, typical for purulent meningitis. The causal agents isolated in the three cases were Klebsiella pneumoniae, Enterobacter cloacae, and Serratia marcescens, all resistant to beta-lactams by extended spectrum beta-lactamase production. The use of quinolones was required in all cases. Different complications were recorded: hydrocephalus and brain abscess in one case, respiratory and hemodynamic failure managed in the intensive care unit in the second, and brain hygroma in the third case. This study shows high morbidity of iatrogenic meningitis. Simple aseptic precautions undertaken before the procedure of lumbar puncture can prevent such cases. The urgent need for increasing the awareness among medical personnel in hospitals of developing countries cannot be overemphasized.

[Listeriosis in Tunis: seven cases reports]. / Les infections à Listeria monocytogenes à Tunis: à propos de sept cas.

Listeria monocytogenesis a Gram positive facultative intracellular bacterium that can be responsible for severe infections, affecting essentially pregnant women, immunocompromised patients at the early and later stages of life. In Tunisia, invasive L. monocytogenes infections are thought to be exceptional and limited data are available about listeriosis. We reported seven cases (five newborn children and two infants) of human listeriosis that occurred in Tunis from 2000 to 2008. The newborn children were hospitalized for suspicion of maternofoetal infections. The two infants were hospitalized for fever associated with digestive signs in one case and neurological signs in the other. L. monocytogenes-was isolated from culture of cerebrospinal fluid in four cases, peripheral samples in two cases and from blood culture in one case. Isolates identification was based on conventional methods. Antimicrobial susceptibility was realized according to the recommendation of the "Comité de l'antibiogramme de la Société française de microbiologie". All L. monocytogenes isolates were sensitive to amoxicillin and aminoside but resistant to 3rd generation cephalosporins. Investigations of the immune system were realized for the two infants including phenotypic analysis of peripheral blood cells by flow cytometry, lymphocyte proliferation assays, phagocytic cell functions and measurement of immunoglobulins as well as complement. All these explorations were normal for both infants. The outcome was fatal in only one case (a newborn child), and all the other patients recovered after adapted antibiotic treatment. In conclusion, our study shows that listeriosis is not exceptional in Tunis. Thus, it is necessary to know how to evoke this diagnosis, at any age, in order to establish an early and adapted antibiotic treatment and to avoid fatal outcome.

[Neisseria meningitidis invasive infections in children in Tunis: about 79 cases]. / Les infections invasives a Neisseria meningitidis chez l'enfant a Tunis : a propos de 79 cas.

We conducted a retrospective study of meningococcal invasive diseases (MID) contracted in children in Tunis between January 1997 and January 2006. The purpose of this study is to specify the clinical, epidemiological, therapeutic and evolutionary features of these infections and to determine antimicrobial susceptibility and the antigenic formula of N. meningitidis isolates. During the study period, we have collected 79 cases of MID arising in children aged 3 days to 11 years. The majority of children's were less than of 4 years (57.3%). We note a frequency of the MID in winter and in spring. The most frequent clinical shape was meningitis (53%). Twenty one patients (26.6%) had a fulminant meningococcal disease. In our series, the rate of lethality was equal to 17.7%. Among the 46 meningococcal isolates, the most frequent serogroup was the B (73%) followed by C and A. A high heterogeneousness of the antigenic formulae was observed The most frequent phenotype was NT: NST for the group B isolates and 4:P1.13 for the group C ones. N meningitidis with reduced susceptibility to penicillin and to amoxicillin account for 54% and 10% of all isolates respectively. The cefotaxim and the rifampin were uniformly active.

Only two mutations detected in 15 Tunisian patients with 11ß-hydroxylase deficiency: the p.Q356X and the novel p.G379V.

Steroid 11ß-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia, resulting in virilization, glucocorticoid deficiency and hypertension. The 11ß-hydroxylase enzyme is encoded by the CYP11B1 gene and mutations in this gene are responsible for this disease. The aim of this study was to characterize mutations in the CYP11B1 gene and to determine their frequencies in a cohort of Tunisian patients. The molecular genetic analysis was performed by direct nucleotide sequencing of the CYP11B1 gene in 15 unrelated Tunisian patients suffering from classical 11ß-hydroxylase deficiency. Only two mutations were detected in homozygous state in the CYP11B1 gene of all patients, the p.Q356X in exon 6 (26.6%) and the novel p.G379V in exon 7 with large prevalence (73.3%). This is the first report of screening for mutations of CYP11B1 gene in the Tunisian population and even in the Arab population.

Screening for celiac disease in idiopathic pulmonary hemosiderosis.

AIM: The aim of this report was to screen for celiac disease (CD) in patients with idiopathic pulmonary hemosiderosis (IPH). PATIENTS AND METHODS: Patients with IPH treated at the Children's Hospital of Tunis between 1976 and 2006 were reviewed and investigated for CD, using serological and histological tests. RESULTS: A total of 10 children (two boys and eight girls) had IPH. The mean age at diagnosis was 3.1 years. Three had digestive symptoms and positive CD serology, which was confirmed by histological data. Clinical and radiological findings improved markedly in all CD patients with corticosteroid treatment combined with a gluten-free diet. Symptoms of IPH and CD both returned in one patient who stopped the gluten-free diet. CONCLUSION: Three of our 10 patients with IPH also had CD. These data illustrate the close etiopathogenic link between IPH and CD, and strongly suggest that CD be looked for in IPH patients, especially in those with symptoms suggestive of CD.

[Plastic bronchitis: report of a pediatric case]. / La bronchite plastique: à propos d'une observation pédiatrique.

Plastic bronchitis (PB) is a rare disease, characterized by the formation of obstructive branching airways tracheobronchial casts. Commonly, PB often complicates the course of cardiac or respiratory disorders. The occurrence of PB before manifestation of the underlying respiratory disease is unusual. We report on the case of a boy, aged three years and eight months, free from underlying pulmonary disease, who presented with extensive atelectasis of the left lung during an acute respiratory tract infection. Bronchoscopy revealed the obstruction of the left tracheobronchial tree with large purulent casts. After bronchoscopic removal of the casts, the boy became asymptomatic. Initial aetiological investigations were negative. Two years later, the patient developed an asthma.

[Treatment of childhood cancer in Africa. Action of the Franco-African childhood cancer group]. / Le traitement des cancers de l'enfant en Afrique. Travaux du groupe franco-africain d'oncologie pédiatrique.

The childhood cancer survival rate is currently 75% in industrialized countries. Rates in developing countries are much lower. The Franco-African Childhood Cancer Group (French acronym, GFAOP) was founded in 2000 with aim of reducing this unfavorable situation in Africa. The GFAOP has developed two forms of action. The main form consists of organizing two- to twelve-month training sessions for physicians and nurses in France and Morocco. The other form involves assessing the feasibility of modern treatment protocols for various cancers in Africa. The first feasibility trials were carried out on nephroblastoma and Burkitt's lymphoma in 12 pilot units in North Africa, West Africa, and Madagascar. In the first study from 2001 to 2005 we treated 306 cases of Burkitt's lymphoma using French LMB protocols adapted to the African setting and achieved a survival rate of 61%. A second study started in 2005 using Endoxan alone achieved a highly satisfactory survival rate of 73% for neuroblastoma in all stages except bilateral. Altogether from 2001 to 2007 more than 1000 cases of nephroblastoma and Burkitt's lymphoma were treated in African hospitals by African doctors and nurses. No patients were transferred to Europe. The GFAOP supplied drugs when necessary and took care of most travel expenses. African and French doctors worked together on protocol design, trial management, and data analysis. These promising results show that the latest therapeutic techniques can be used to treat childhood cancer in Africa by adapting the protocol to conditions in developing countries. Sanofi-Aventis Laboratories in association with the International Union against Cancer has launched a major campaign to improve Pediatric Oncology in developing countries. Projects in four GFAOP units are being financed through this campaign. In 2006 the GFAOP began assessment of two new treatment protocols, i.e., one for acute lymphoblastic leukemia and the other for Hodgkin's disease. Two other projects are being planned, i.e., one for treatment of retinoblastoma and the other for treatment of some types of brain tumors.

[A new case of acute transverse myelitis following hepatitis A virus infection]. / Myélite aiguë secondaire à une hépatite A: à propos d'une nouvelle observation.

Transverse myelitis is a rare manifestation of hepatitis A virus infection. We report the case of an eleven-year-old girl who presented a progressive flabby paraplegia with sphincter incontinence, superficial hypoesthesia, without deep involvement. Medullar MRI was suggestive of myelitis. Despite the absence of jaundice and hepatic cytolysis, the serology yielded a high rate of anti-hepatitis A immunoglobulin M. Neurological disorders disappeared within 15 days, after treating with a high dose of corticosteroids and physical rehabilitation. 24 months later she was asymptomatic. Screening for hepatitis A virus infection in patients with acute transverse myelitis should be indicated specially in endemic countries were vaccinal prophylaxis is not common practice.

[Severe corrosive oesophagitis : are high doses of methyl prednisolone efficient to prevent oesophageal caustic stricture in children?]. / Les oesophagites caustiques severes. Les doses elevees de solumedrol sont-elles efficaces pour prevenir les stenoses caustiques ?

BACKGROUND: Corrosive oesophagitis stricture is the long term complication of severe corrosive oesophagitis. The aim of our study was to evaluate the effect of a high doses of steroids on incidence and quality of oesophageal stricture. PATIENTS AND METHODS: We reviewed the case histories of 28 children seen at children hospital from 31 December 1991 to 31 december 2001. These children has second and third degree oesophageal burns and they were treated by systemic Methylprednisolone (1000mg/1,73/m2 SC). RESULTS: the frequency of stricture was 12/26 (46%). Ten children required A mean of 6,7 (5,74) dilatation range (1 - 17). One patient required an oesocoloplasty. The frequency of stricture in the group treated early before the 24th hour and after the 24th hours was (9/21) (47,4%) versus (3/7) (42,9%). This difference was not significant (P = 1). The frequency of stricture in the group treated less than 21 days and more than 21 days was 6/17 (40%) versus 6/9 (66,7%). This difference was not significant (P = 0,400). High doses of methyl prednisolone seems to decrease the risk of oesophageal stricture. We found no difference between the children treated before the 24th hours and those treated after the 24 hours and those treated less than 21 days and those more than 21 days.

Burkitt lymphoma in a child with Bloom syndrome.

BACKGROUND: Bloom syndrome is a rare disease characterized by chromosomal instability and increased risk of developing lymphoma. OBSERVATION: We report on a case of Bloom syndrome in a 5-year-old boy with Burkitt lymphoma. The diagnosis was suspected by growth retardation, repeated respiratory infections, facial telangiectasia, and a low immunoglobulin level, then confirmed cytogenetically by sister chromatid exchanges. Chemotherapy was poorly tolerated, which required reducing the doses. Unfortunately, it was not sufficient to control the neoplasm and the patient died 14 months after diagnosis. CONCLUSIONS: Cancers in Bloom syndrome are a challenge since the potentially life-threatening side effects of the chemotherapy may require modifications in standard treatment such as dose reduction, which can compromise the tumor prognosis.

[Secondary TFE3-associated renal cell carcinoma in a child treated for Ewing sarcoma]. / Carcinome à cellules claires du rein et sarcome d'Ewing pelvien : une association rare chez l'enfant en rapport avec la translocation TFE3 Xp11.2.

Renal cell carcinoma is a rare pediatric malignant tumor of the kidney. Unlike Wilms tumor, the efficacy of chemotherapy and radiation therapy in pediatric renal cell carcinoma remains uncertain. Surgery is the best treatment and prognosis is favorable when the tumor is localized and completely eradicated. We report an exceptional observation in a 7-year-old girl with renal cell carcinoma who had been treated 20 months previously for Ewing sarcoma with chemotherapy and radiotherapy. The renal tumor was revealed by abdominal pain without hematuria. She underwent a radical nephrectomy, and histopathology concluded in renal carcinoma associated with translocation Xp 11.2 grade 3 of Furhrman pT3a N1. No adjuvant therapy was given. After 3 years of follow-up, there is no evidence of local or metastatic recurrence. This observation is significant given the very young age of this patient, the occurrence after Ewing sarcoma with a short disease-free interval. It seems that translocation renal cell carcinoma is associated with previous exposure to chemotherapy, particularly topoisomerase II inhibitors or alkylating agents.

Infantile status epilepticus in Tunisia. Clinical, etiological and prognostic aspects.

This retrospective study includes 139 infants (74 girls and 65 boys) treated for status epilepticus at two University hospitals in Tunisia between 1990 and 1997. Their mean age was 11 months. The majority of seizures were generalized (74%) and lasted between 30 minutes and 1 hour (70%). The cause of status epilepticus was classified as acute symptomatic in 56, febrile in 57, remote symptomatic in nine, progressive neurologic in 10 and idiopathic in seven. Overall mortality was 15.8% and neurological sequelae were identified in 36% of the cases during the mean follow-up time of 3.5 years. The incidence of significant sequelae was a function of aetiology (especially acute symptomatic causes) and age (under 1 year of age). We conclude that the most frequent causes of infantile status epilepticus in Tunisia were fever and acute symptomatic causes. Status epilepticus among infants is an important public health problem, with significant associated mortality and morbidity. Management of status epilepticus can be improved by more rapid access to appropriate medical care.

[High doses of steroids in the management of caustic esophageal burns in children]. / Corticothérapie à forte dose dans le traitement des oesophagites caustiques sévères chez l'enfant.

UNLABELLED: Esophageal burns are frequent in some countries. Esophageal stricture is a severe complication after caustic ingestion. Its frequency is estimated to 5% and reaches 47% in severe esophagitis. AIM OF THE STUDY: To study the influence of management of severe esophageal burns with high doses of steroids in the occurrence of esophageal stricture through the experience of an endoscopic unit. PATIENTS AND METHODS: Twenty-six children with a mean age of 3.5 years (15 months-8 years) with a second b- (N =22) or a third-degree (N =4) esophageal burns due to accidental ingestion of a caustic substance were included between 1993 and 1999. Corrosive substances ingested were sodium hydroxide (N =17), bleach (N =4), alkali (N =3), others (N =2). Upper GI endoscopy was performed in 17 children within the 24 hours of caustic ingestion and within the first 48 hours in all cases. All patients received methylprednisolone (1 g/1.73 m2/day) plus cimetidine and ampicillin plus early oral feeding resumption. RESULTS: Three children (2 grade II et one grade I) were not controlled on day 30 of the protocol and have then been excluded. The remaining 23 children were divided in two groups depending on the upper GI endoscopic results: group I of 12 patients completely or partially healed and group II of 11 patients who developed an esophageal stricture. No difference was observed between the two groups with regard to the delay between caustic ingestion and the start of treatment and the number of shots of methylprednisolone. Second b- degree esophagitis complicated with an esophageal stricture underwent a median of five esophageal dilations (1-12). After a median follow-up of three years, four of them have a normal esophagus. All children with a third-degree esophagitis developed an esophageal stricture. One had a surgical replacement of the esophagus with a segment of colon with good outcome. The three others underwent a median of seven esophageal dilations (5-10). One of them has a normal esophagus after a follow-up of five years while the two others were lost to follow-up. CONCLUSION: High dose of corticosteroids seems to improve second b-degree esophagitis prognosis and may prevent from esophageal stricture.

[Heterotopic gray matter. Report of four pediatric cases]. / Hétérotopies de la substance grise. A propos de quatre observations pédiatriques.

Severe infant epilepsy is included within difficult etiologic diagnosis. Gray matter heterotopias are an uncommon cause. The authors report four observations of gray matter heteropias concerning three-, six-, seven- and nine-year-old girls, presenting no particular antecedents. No consanguinity was noted. The first occurrence of epilepsy ranged from the age of nine months to the age of four years. A mild mental retardation was found in three cases, and mental regression in one case. A status epilepticus was noted in three children. Magnetic resonance imaging scans showed subependymal heterotopias in one case and diffuse cortical heterotopias in three cases associated to a partial agenesis of corpus calloseum in one case and pachygyria in two cases.

[Cardiac manifestations of sickle cell disease]. / Les manifestations cardiaques de la drépanocytose.

In this study the authors report the cardiac complications seen in the course of sickle-cell disease. Among 41 homozygot patients the complications reported were as follow. Effort dyspnea in 15/32 (46% cases); systolic souffle in 36 patients (87.8% of cases); cardiomegaly in 30 patients (17% of cases) and electric abnormalities in 70% of cases. The echotomography practised in 27 cases was normal in 12 cases and showed a hyperkinetic aspect in 10 cases, a cardiomyopathy in four cases.

[Clinical aspects and etiology of lower respiratory tract infections in hospitalized children]. / Aspect clinique et etiologique des infections respiratoires basses de l'enfant en milieu hospitalier.

The authors report a prospective study conducted in one of the general pediatrics unit. One hundred one children, aged 20 days to 12 years, admitted with acute lower respiratory tract infections have been studied on clinical paraclinicals and etiology grounds. All children had a chest Ray roentgenogram, a total blood cell count and C-reactive protein. The detection of a viral agent in nasopharyngeal aspirate by immunofluorescent technic were performed. 85% of patients have bronchiolitis, the chest--Rays showed an abnormal pictures in 84.2% of cases, an anaemia was present in 54.7%. Viral agent as identified in 58 patients, the RSV indicated in 56 cases. Bacterial infection as present in 57 of the 101 children. A mixed viral-bacterial infection as documented in 28 cases. Among bacterial causes the predominant agent as Haemophilus influenzae 24, Branhamella Catarrhalis 17, streptococcus pneumoniae in 16 cases. Early empiric antibiotic as performed. All patients recovered uneventfully.

[Chronic septic granulomatosis in a young girl manifesting as invasive pulmonary aspergillosis and flaccid paraplegia]. / Granulomatose septique chronique chez une fillette revelee par une aspergilose pulmonaire invasive et une paraplegie flasque.

UNLABELLED: The invasive Pulmonary Aspergillosis (IPA) is the principal cause of death in patients with chronic granulomatosis disease (CGD). It can happen before age of one and can reveal the (CGD). Usually, the transmission of GSD is linked to x in 65% of cases. We report, the case of a girl aged 3 years issued from consanguine marriage referred to hospital for hemoptysia. We note that at 40 days she presents an suppurate adenitis. She is hypotrophic at--3DS without respiratory problem, she have a splenomegaly. The radiography chest note an alveolar and interstitial opacity bilateral, apical right and basal left. There is a biological inflammatory syndrome. During the evolution, the child presents a paraplegia secondary to compression myelitis. A D5 laminectomy in urgency was done. The vertebral Biopsia, the serology and the culture isolate fumigatus aspergillus the GCD is evoqued confirmed by the NBT test who was negative. IN CONCLUSION: --We have to look for GCD in front of pulmonary aspergillus.--The vertebra lesion is secondary to pulmonary lesion.--Our observation is noticeable by the recessive autosomal transmission who was seen in 35% of cases, and by the neurologic complication rarely reported.

[Role of enteroviruses in aseptic meningitis in Tunisia]. / Place des entérovirus dans les méningites aseptiques en Tunisie.

Despite the favourable clinical outcome in most cases, viral meningitis can cause a serious public health problem especially when several cases occur during outbreaks. The first part of this work is a retrospective study conducted in three hospitals in Tunisia and covering a period of three years. It showed an incidence of viral meningitis 2.4. The second part of the study is a prospective one, it included 94 cases of aseptic meningitis notified during a period of 12 months. Virus isolation in cell culture was performed on CSF and stool samples, using cell lines sensitive to enteroviruses. A PCR to detect enteroviruses was also used in parallel. This study represents a first approach to viral meningitis in Tunisia. It highlights the importance of a regular surveillance of the disease and the contribution of molecular methods to a more sensitive diagnostic. However, cell culture remained necessary for viral isolation and serotyping.