[Neuroendocrine carcinoma of the bladder: A single centre retrospective study]. / Carcinome neuroendocrine de la vessie: étude rétrospective monocentrique.

PURPOSE: Neuroendocrine carcinoma of the bladder is a rare tumour representing 0.5 to 1% of bladder tumours. It is a specific histological entity characterized by rapid metastatic dissemination and poor prognosis. The aim of this study was to describe the epidemiological, clinical, therapeutic modalities and the evolutive aspects of patients receiving a treatment for bladder neuroendocrine carcinoma. PATIENTS AND METHODS: Between January 2004 and January 2014, seven patients received a treatment for a neuroendocrine carcinoma of the bladder, at the department of oncology, Habib-Bourguiba Hospital, in Sfax, Tunisia. RESULTS: The median age was 58 years. All patients were male. Neuroendocrine carcinoma was pure in four cases and associated with urothelial carcinoma in the other three cases. Two patients were diagnosed at a metastatic stage. A cystectomy was performed in two cases. One patient received a chemotherapy and radiotherapy. The other four patients received chemotherapy alone. A single case of complete remission was observed. Median survival was 15 months (5-30 months). One patient is still alive 30 months after diagnosis. CONCLUSION: The management of neuroendocrine carcinoma of the bladder is not standardized and requires a multidisciplinary consultation.

Solid tumors after chronic lymphocytic leukemia patients: Report of six cases and review of the literature.

INTRODUCTION: Malignancies have been reported to occur with increased frequency in chronic lymphocytic Leukemia (CLL) patients. The aim of this study was to describe which second malignancies occur in patients with CLL, whether these malignancies are related to CLL, its treatment, or both. We also attempt to study factors predicting the development of other malignancies. PATIENTS AND METHODS: Between 1995 and 2009, six cases of CLL associated with solid tumor were diagnosed in Hematology Department of Military Hospital of Tunis. The diagnosis of CLL was made by immunophenotyping of peripheral blood circulating B cells, and the diagnosis of solid tumors was made by biopsy with anatomopathological exam and immunohistochemical study. RESULTS: The mean age of patients was 71 years. Five patients were male. The CLL was classified Stage A in one case, Stage B in three cases and Stage C in two cases. Two patients had abnormal karyotype. Three patients have not received specific treatment for their CLL. Solid tumors were represented by skin cancer in three cases, lung cancer in two cases and breast cancer in one case. The median time between diagnosis of CLL and that of solid tumor was 53 months. CONCLUSION: Patients with CLL have an increased risk of developing a second cancer. Awareness of risk factors could permit early detection.

Determining the genome-wide kinship coefficient seems unhelpful in distinguishing consanguineous couples with a high versus low risk for adverse reproductive outcome.

BACKGROUND: Offspring of consanguineous couples are at increased risk of congenital disorders. The risk increases as parents are more closely related. Individuals that have the same degree of relatedness according to their pedigree, show variable genomic kinship coefficients. To investigate whether we can differentiate between couples with high- and low risk for offspring with congenital disorders, we have compared the genomic kinship coefficient of consanguineous parents with a child affected with an autosomal recessive disorder with that of consanguineous parents with only healthy children, corrected for the degree of pedigree relatedness. METHODS: 151 consanguineous couples (73 cases and 78 controls) from 10 different ethnic backgrounds were genotyped on the Affymetrix platform and passed quality control checks. After pruning SNPs in linkage disequilibrium, 57,358 SNPs remained. Kinship coefficients were calculated using three different toolsets: PLINK, King and IBDelphi, yielding five different estimates (IBDelphi, PLINK (all), PLINK (by population), King robust (all) and King homo (by population)). We performed a one-sided Mann Whitney test to investigate whether the median relative difference regarding observed and expected kinship coefficients is bigger for cases than for controls. Furthermore, we fitted a mixed effects linear model to correct for a possible population effect. RESULTS: Although the estimated degrees of genomic relatedness with the different toolsets show substantial variability, correlation measures between the different estimators demonstrated moderate to strong correlations. Controls have higher point estimates for genomic kinship coefficients. The one-sided Mann Whitney test did not show any evidence for a higher median relative difference for cases compared to controls. Neither did the regression analysis exhibit a positive association between case-control status and genomic kinship coefficient. CONCLUSIONS: In this case-control setting, in which we compared consanguineous couples corrected for degree of pedigree relatedness, a higher degree of genomic relatedness was not significantly associated with a higher likelihood of having an affected child. Further translational research should focus on which parts of the genome and which pathogenic mutations couples are sharing. Looking at relatedness coefficients by determining genome-wide SNPs does not seem to be an effective measure for prospective risk assessment in consanguineous parents.

Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family.

The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.

Clinical and genetic characterization of Bardet-Biedl syndrome in Tunisia: defining a strategy for molecular diagnosis.

Bardet-Biedl syndrome (BBS, OMIM 209900) is a rare genetic disorder characterized by obesity, retinitis pigmentosa, post axial polydactyly, cognitive impairment, renal anomalies and hypogonadism. The aim of this study is to provide a comprehensive clinical and molecular analysis of a cohort of 11 Tunisian BBS consanguineous families in order to give insight into clinical and genetic spectrum and the genotype-phenotype correlations. Molecular analysis using combined sequence capture and high-throughput sequencing of 30 ciliopathies genes revealed 11 mutations in 11 studied families. Five mutations were novel and six were previously described. Novel mutations included c.1110G>A and c.39delA (p.G13fs*41) in BBS1, c.115+5G>A in BBS2, c.1272+1G>A in BBS6, c.1181_1182insGCATTTATACC in BBS10 (p.S396Lfs*6). Described mutations included c.436C>T (p.R146*) and c.1473+4A>G in BBS1, c.565C> (p.R189*) in BBS2, deletion of exons 4-6 in BBS4, c.149T>G (p.L50R) in BBS5, and c.459+1G>A in BBS8; most frequent mutations were described in BBS1 (4/11, 37%) and BBS2 (2/11, 18%) genes. No phenotype-genotype correlation was evidenced. This data expands the mutations profile of BBS genes in Tunisia and suggests a divergence of the genetic spectrum comparing Tunisian and other populations.

Quantum tunneling of oxygen atoms on very cold surfaces.

Any evolving system can change state via thermal mechanisms (hopping a barrier) or via quantum tunneling. Most of the time, efficient classical mechanisms dominate at high temperatures. This is why an increase of the temperature can initiate the chemistry. We present here an experimental investigation of O-atom diffusion and reactivity on water ice. We explore the 6-25 K temperature range at submonolayer surface coverages. We derive the diffusion temperature law and observe the transition from quantum to classical diffusion. Despite the high mass of O, quantum tunneling is efficient even at 6 K. As a consequence, the solid-state astrochemistry of cold regions should be reconsidered and should include the possibility of forming larger organic molecules than previously expected.

Water formation through O2 + D pathway on cold silicate and amorphous water ice surfaces of interstellar interest.

The formation of the first monolayer of water molecules on bare dust grains is of primary importance to understand the growth of the icy mantles that cover dust in the interstellar medium. In this work, we explore experimentally the formation of water molecules from O(2) + D reaction on bare silicate surfaces that simulates the grains present in the diffuse interstellar clouds at visual extinctions (A(V) < 3 mag). For comparison, we also study the formation of water molecules on surfaces covered with amorphous water ice representing the dense clouds (A(V) ≥ 3 mag). Our studies focus on the formation of water molecules in the sub-monolayer and monolayer regimes using reflection absorption infrared spectroscopy and temperature-programmed desorption techniques. We provide the fractions of the products, such as D(2)O and D(2)O(2) molecules formed on three astrophysically relevant surfaces held at 10 K (amorphous olivine-type silicate, porous amorphous water ice, and nonporous amorphous water ice). Our results showed that the formation of D(2)O molecules occurs with an efficiency of about 55%-60% on nonporous amorphous water ice and about 18% on bare silicate grains surfaces. We explain the low efficiency of D(2)O water formation on the silicate surfaces by the desorption upon formation of certain products once the reaction occurs between O(2) and D atoms on the surface. A kinetic model taking into account the chemical desorption of newly formed water supports our conclusions.

Efficient surface formation route of interstellar hydroxylamine through NO hydrogenation. I. The submonolayer regime on interstellar relevant substrates.

Dust grains in the interstellar medium are known to serve as the first chemical laboratory where the rich inventory of interstellar molecules are synthesized. Here we present a study of the formation of hydroxylamine--NH(2)OH--via the non-energetic route NO + H (D) on crystalline H(2)O and amorphous silicate under conditions relevant to interstellar dense clouds. Formation of nitrous oxide (N(2)O) and water (H(2)O, D(2)O) is also observed and the reaction network is discussed. Hydroxylamine and water results are detected in temperature-programmed desorption (TPD) experiments, while N(2)O is detected by both reflection-absorption IR spectroscopy and TPD techniques. The solid state NO + H reaction channel proves to be a very efficient pathway to NH(2)OH formation in space and may be a potential starting point for prebiotic species in dark interstellar clouds. The present findings are an important step forward in understanding the inclusion of interstellar nitrogen into a non-volatile aminated species since NH(2)OH provides a solid state nitrogen reservoir along the whole evolutionary process of interstellar ices from dark clouds to planetary systems.

[Eosinophilic gastroenteritis]. / Gastroentérite à éosinophiles.

PURPOSE: Eosinophilic gastroenteritis is a rare and heterogeneous disorder characterized by eosinophilic infiltration of one or more layers of the gastrointestinal tract. Although it can involve any part of the gastrointestinal tract, the stomach and the proximal small bowel are the most common sites of involvement. Clinical features depend on which layer and site are involved. We report eight cases of eosinophilic gastroenteritis. METHODS: We conducted a retrospective review of consecutive adult cases diagnosed with eosinophilic gastroenteritis from 1990 to 2010. The diagnosis was established by histologic examination of endoscopic biopsy or operative specimen or by the presence of eosinophilic ascites. RESULTS: Eight patients (three men, five women) were diagnosed with eosinophilic gastroenteritis during the study period. Three out of the eight patients had a history of allergy. All patients had gastrointestinal symptoms. The most common symptoms were abdominal pain, vomiting, weight loss and ascites. Seven patients (87.5%) had hypereosinophilia. Seven patients had involvement of the subserosa and one of the mucosa. Four patients were treated with oral prednisolone. The symptoms in all the patients subsided within one month. The remaining four patients improved spontaneously. Four of our patients were followed-up for at least 2 months (11 to 68 months). A single patient presented a relapse. CONCLUSION: Eosinophilic gastroenteritis should be suspected in patients having gastrointestinal discomfort along with peripheral eosinophilia. Definitive diagnosis requires histological demonstrations of eosinophilic infiltration of the gastrointestinal wall or high eosinophilic count in ascites fluid.

Nuclear spin conversion of molecular hydrogen on amorphous solid water in the presence of O2 traces.

Nuclear spin conversion (NSC) of ortho- to para-H(2) and para- to ortho-D(2) has been investigated on an amorphous solid water (ASW) surface at 10 K, in the presence of co-adsorbed O(2). The dynamics of the nuclear spin conversion could be revealed by combination of resonance enhanced multiphoton ionization spectroscopy (REMPI) with temperature programmed desorption (TPD) experiments. The conversion rates are consistent with a diffusion of molecular hydrogen inducing a nuclear spin conversion enhanced in the vicinity of molecular oxygen. The conversion times were found to increase with decreasing O(2) and H(2) coverage. Finally, on oxygen free ASW surface, the extremely long conversion characteristic times measured showed that such surface is not an efficient catalyst for NSC, in contradiction with hypothesis commonly made for interstellar medium.

Gas temperature dependent sticking of hydrogen on cold amorphous water ice surfaces of interstellar interest.

Using the King and Wells method, we present experimental data on the dependence of the sticking of molecular hydrogen and deuterium on the beam temperature onto nonporous amorphous solid water ice surfaces of interstellar interest. A statistical model that explains the isotopic effect and the beam temperature behavior of our data is proposed. This model gives an understanding of the discrepancy between all known experimental results on the sticking of molecular hydrogen. Moreover, it is able to fit the theoretical results of Buch et al. [Astrophys. J. 379, 647 (1991)] on atomic hydrogen and deuterium. For astrophysical applications, an analytical formula for the sticking coefficients of H, D, H(2), D(2), and HD in the case of a gas phase at thermal equilibrium is also provided at the end of the article.

[Reactivation of tuberculosis during dual therapy with pegylated interferon and ribavirin for chronic hepatitis C]. / Réactivation d'une tuberculose sous bithérapie interféron-pégylé et ribavirine pour une hépatite chronique C.

Hepatitis C viral infection can be associated with other infectious diseases including viral and bacterial infections such as tuberculosis. Mycobacterium tuberculosis infection may be latent for many years and revealed during an immunodeficiency state. The responsibility of antiviral treatment in the reactivation of tuberculosis is controversial. We report two cases of tuberculous reactivation during bitherapy with pegylated interferon and ribavirin for chronic hepatitis C. A rapid viral response was obtained in both cases. Tuberculous reactivation occurred at 12 and 13 weeks of antiviral treatment, respectively. Tuberculosis involved urinary tract in one patient and lymph nodes in the other. Antituberculous treatment was given and antiviral treatment maintained. The outcome of tuberculosis was favourable and a sustained viral response was obtained for both patients.

[Peritoneal tuberculosis--report of 43 cases]. / La tuberculose péritonéale--a propos de 43 observations.

BACKGROUND: Peritoneal tuberculosis represents 0, 1 to 4% of all forms of tuberculosis. AIM: The aim of our study is to describe clinical, therapeutic characteristics and the outcome of peritoneal tuberculosis. METHODS: Retrospective study of all cases of peritoneal tuberculosis diagnosed in gastroenterology B department - Rabta Hospital during a 12 years period (1996 to 2007). RESULTS: Forty three cases of peritoneal tuberculosis were included: 15 male and 28 female with mean age of 38years (extremes: 16 to 85years). Five patients were cirrhotic. Clinical manifestations were dominated by ascitis (83%). Ascitic fluid were exsudative in 97% of cases and lymphocytic in all cases. The diagnostic was based on coelioscopy with peritoneal biopsy in 26 cases demonstrating caseating granulomatous lesions in 64% of cases. Extra peritoneal tuberculosis was noted in 60, 4% dominated by pleuro-pulmonary localisations. Patients were given antituberculous therapy for a mean duration of 9, 8 months and the outcome was favourable in 93%. CONCLUSION: Peritoneal tuberculosis is still a medical problem in Tunisia. It is more common in young female. Diagnosis is based on the results of peritoneal biopsies during celioscopy. The outcome is good in most cases after antituberculous treatment.

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.

[Budd-Chiari syndrome associated with celiac disease]. / Syndrome de Budd-Chiari associé à une maladie coeliaque.

The association of Budd-Chiari syndrome and celiac disease is rare and has been reported in only 13 cases. We report a 23-year-old man with celiac disease, treated with gluten-free diet since the age of 16 years. He presented with epigastric pain that was secondary to a Budd-Chiari syndrome. No other cause than celiac disease could be identified.

A novel UBE3A truncating mutation in large Tunisian Angelman syndrome pedigree.

We identified in a large Tunisian pedigree a novel UBE3A frameshift mutation in exon 16 coding region, and we expect that the resulting UBE3A truncated protein in our patients is non-functional since the mutation implies the catalytic region of the enzyme. The family includes 14 affected patients born from four sisters. This mutation was found in all surviving affected individuals and their mothers pointing out the importance of genetic counseling possibility in Angelman syndrome (AS). All patients had severe mental retardation with epilepsy and microcephaly. Minor clinical expression variation was observed among the investigated patients. The severity of clinical expression is related to the detected molecular variation: deletion of 15 bp and insertion of 7 bp. These results are concordant with the gene expression observed in previously reported individuals with AS and truncated UBE3A protein.

[Late revelation of homocysteinuria: clinical, biological and progressive aspects]. / Homocystéinurie à révélation tardive : aspect clinique, biologique et évolutif.

UNLABELLED: Homocysteinuria is a metabolic disorder with defect in genes encoding for methionine metabolism enzymes. The clinical features consist in: ophthalmic, neurological, orthopedic and vascular manifestations. It is generally diagnosed in childhood. Vascular involvements characterize adult's forms. We report one case. OBSERVATION: A 26-year-old man, who has lentis ectopia and a recent epilepsy, was hospitalized for deep vein thrombosis. Regarding the marfanoid phenotype and the high level homocysteinemia (231 micromol/L), homocysteinuria was suspected. Amino acid chromatography and reduced CBS activity were used to confirm the diagnosis. Vitamin enriched diet with vitamin B6 and folates has reduced slightly the homocysteine level. CONCLUSION: Homocysteinuria must be diagnosed early since a simple vitamin supply could ameliorate prognosis and decrease complications.