[A complex case of miliary pulmonary tuberculosis following intravesical BCG therapy]. / Un cas complexe de miliaire pulmonaire post-BCG thérapie pour carcinome urothélial.

Bladder cancer (urothelial carcinoma in 90 % of cases) is the most common neoplasia of the urinary tract. Superficial carcinoma represents 70-80 % of bladder cancers. The treatment of these tumours includes, after transuretral resection, intravesical Bacillus Calmette-Guerin (BCG) instillation therapy. This treatment constitutes, by its immune-mediated anti-tumoral action, the first step of immunotherapy in cancer. Severe complications (granulomatosis, hypersensitivity pneumonitis or orchitis) are rare (0.5-2 %). Here we report a complex case of pulmonary granulomatosis secondary to BCG therapy. This is a 74-year-old male, treated for superficial bladder carcinoma by transuretral resection (pT1G3) and then endovesical instillations of BCG therapy for two months. Two years later, a new transuretral resection shows an infiltrating urothelial carcinoma pT2G3. The extension balance finds a persistent micro-nodular pulmonary infiltrate. A broncho-alveolar lavage is then realised but no mycobacteria was found. A surgical biopsy of a nodule is performed and revealed a histiocytic reaction without any neoplastic element. Detection of Mycobacterium tuberculosis by Polymerase Chain Reaction (PCR) was finally positive. In the absence of a secondary lesion, the patient had a cysto-prostatectomy and began a tritherapy against tuberculosis. Post-BCG therapy granulomatosis is a rare complication but should remain a differential diagnosis in front of the appearance of pulmonary nodes in patients who have received posttransuretral resection BCG instillations. Mycobacterial DNA PCR research remains the most sensitive examination.

Les carcinomes urothéliaux superficiels de vessies représentent 70 à 80 % des tumeurs de la vessie. Leur traitement comprend, après résection transurétrale, une BCG (Bacille de Calmette et Guérin) thérapie par instillations endovésicales. Les complications sévères (granulomatose, pneumopathie d'hypersensibilité ou orchite) sont rares (0,5-2 %) mais nous rapportons ici un cas complexe de granulomatose pulmonaire secondaire à une BCG thérapie. Il s'agit d'un homme de 74 ans, traité pour un carcinome urothélial superficiel de vessie par résection endo-urétrale (pT1G3) puis instillations endovésicales de BCG thérapie. Deux années après, une nouvelle résection transurétrale objective un carcinome urothélial infiltrant pT2G3. Le bilan d'extension retrouve un infiltrat pulmonaire micronodulaire persistant. Un lavage bronchoalvéolaire ne retrouve pas de bacilles acido-alcoolo-résistants. La biopsie chirurgicale d'un nodule retrouve une réaction histiocytaire sans élément néoplasique. La Polymerase Chain Reaction (PCR) à la recherche de mycobactérie du groupe tuberculosis revient finalement positive. En l'absence de lésion secondaire, le patient a bénéficié d'une cystoprostatectomie et a débuté dans les suites une trithérapie antituberculeuse. La granulomatose post-BCG thérapie est une complication rare, mais doit rester un diagnostic différentiel devant l'apparition de micronodules pulmonaires chez les patients ayant reçu des instillations de BCG post-résection transurétrale. La recherche par PCR d'ADN de mycobactéries reste l'examen le plus sensible.

Next-generation sequencing shows West Nile virus quasispecies diversification after a single passage in a carrion crow (Corvus corone) in vivo infection model.

West Nile virus (WNV) occurs as a population of genetic variants (quasispecies) infecting a single animal. Previous low-resolution viral genetic diversity estimates in sampled wild birds and mosquitoes, and in multiple-passage adaptation studies in vivo or in cell culture, suggest that WNV genetic diversification is mostly limited to the mosquito vector. This study investigated genetic diversification of WNV in avian hosts during a single passage using next-generation sequencing. Wild-captured carrion crows were subcutaneously infected using a clonal Middle-East WNV. Blood samples were collected 2 and 4 days post-infection. A reverse-transcription (RT)-PCR approach was used to amplify the WNV genome directly from serum samples prior to next-generation sequencing resulting in an average depth of at least 700 × in each sample. Appropriate controls were sequenced to discriminate biologically relevant low-frequency variants from experimentally introduced errors. The WNV populations in the wild crows showed significant diversification away from the inoculum virus quasispecies structure. By contrast, WNV populations in intracerebrally infected day-old chickens did not diversify from that of the inoculum. Where previous studies concluded that WNV genetic diversification is only experimentally demonstrated in its permissive insect vector species, we have experimentally shown significant diversification of WNV populations in a wild bird reservoir species.

[Bipolar versus monopolar transurethral resection of the prostate: a prospective randomized study]. / Résection transuréthrale de la prostate bipolaire versus monopolaire: étude prospective randomisée.

PURPOSE: To compare bipolar with standard monopolar transurethral resection of the prostate (TURP). MATERIAL AND METHODS: A prospectively randomized study was conducted between January 2010 and September 2011. Primary end points studied were efficacy (maximum flow rate [Qmax], International Prostate Symptom Score) and safety (adverse events, decline in postoperative serum sodium [Na+] and haemoglobin [Hb] levels). Secondary end points were operation time and duration of irrigation, catheterization, and hospitalization. RESULTS: Sixty consecutive patients were randomized and completed the study, with 29 patients in the monopolar TURP group and 31 in the TURIS group. At baseline, the two groups were comparable in age, prostate volume, mean prostate-specific antigen value, International Prostate Symptom Score, and they had at least 12 months of follow-up. Declines in the mean postoperative serum Na+ for bipolar and monopolar TURP groups were 1.2 and 8.7 mmol/L, respectively. However, there was no statistical difference in the decline in postoperative Hb between the two groups. The mean catheterization time was 26.6 and 52 hours in the bipolar and standard groups, respectively. This difference was statistically significant as was the difference in the time to hospital discharge. The IPSS and Qmax improvements were comparable between the two groups at 12 months of follow-up. CONCLUSION: No clinically relevant differences in short-term efficacy are existed between the two techniques, but bipolar TURP is preferable due to a more favorable safety profile and shorter catheterization duration.

[Molecular diagnosis of Gaucher disease in Tunisia]. / Diagnostic moléculaire de la maladie de Gaucher en Tunisie.

Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid ß-glucosidase. In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in 30 Tunisian patients with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing had shown that N370S was the most frequent mutation (22/50 mutant alleles, 44%), followed by L444P mutation, which is found in 16% (8/50 mutant alleles). The recombinant allele (RecNciI) represented 14%. Our findings revealed that the genotype N370S/RecNciI was mosst frequent in patients with childhood onset and it was associated with severe visceral involvement. The screening of these three mutations provided a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allowed also genetic counselling for their family members.

A novel 22bp deletion in a Tunisian phenylketonuria family.

Phenylketonuria (PKU) is an autosomal recessive metabolic disorder caused by a deficiency of phenylalanine hydroxylase. To date, more than 530 mutations in the PAH gene have been reported. In Tunisia, this disease seems to be the result of point mutations, few studies have been published about molecular defects of PKU in our country. In this study, we report a novel deletion in exon 6 of two brothers in a Tunisian family after DHPLC analysis and sequencing of the exon 6 of the PAH gene.

A rare case of ureteral tuberculosis mimicking a tumor.

Isolated ureteral involvement in urogenital tuberculosis is rare. The diagnosis can be difficult to evoke. The radiological aspect often evokes tumor involvement, hence the importance of mentioning this pathology in endemic countries. The purpose of this study is to show that it will be necessary to think of ureteral tuberculosis in the presence of ureteral thickening living in an endemic country. We reported a case of ureteric tuberculosis in a 46-years old man mimicking a tumor.

Homogénéité mutationnelle de la glycogénose de type Ia en Tunisie.

The glycogen storage disease type Ia (GSD Ia) is a rare inherited disorder, with autosomal recessive determinism. It is characterized by hepatomegaly, short stature and hypoglycemia with lactic acidemia. The confirmation of diagnosis is based on the enzymatic assay performed on liver biopsy. For Tunisians patients, this biochemical test is performed abroad. The aim of our study is the molecular characterization of GSD Ia in Tunisian patients and the development of a molecular diagnosis tool. Our study included 27 patients from 23 unrelated families, mutation analysis revealed that the R83C mutation is the most frequent (65%, 30/46 mutant alleles), followed by the R170Q mutation (30%, 14/46 mutant alleles). The homogeneity of mutation spectrum of GSD Ia in Tunisia allows the development of a cost effective and reliable tool for the confirmation of clinical diagnosis among suspected GSD Ia patients.

[Congenital generalized lipodystrophy: a case report with neurological involvement]. / Lipodystrophie congénitale généralisée de type 1 avec atteinte neurologique.

Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by near complete absence of adipose tissue from birth. At least 2 genes located in 9q34 (AGPAT2) and 11q13 (Seipin) are implicated in type 1 and 2, respectively, and result in insulin resistance. We report here a novel case of CGL type 1 resulting from a novel homozygote mutation in the AGPAT2 gene. The clinical picture included pseudoathletic muscular hypertrophy, hypertrophic cardiomyopathy, enlarged liver, hypermetabolism rate, and hyperinsulinemia in a 1-year-old child from Libya. Peripheral hypertonia and reflex excitability revealed signal abnormalities in white matter on magnetic resonance imagery, which has not been described previously in the literature.

Glycogen storage disease type I in Tunisia: an epidemiological analysis.

OBJECTIVE: Analysis of epidemiological data concerning GSD I in Tunisia. SUBJECTS AND METHODS: All the cases diagnosed as GSD I between 1992 and 2005 in a paediatric department recruiting all the metabolic diseases referred from the North of Tunisia were reviewed. Individual data (sex, socioeconomic and educational background, geographic origins, insurance coverage) were collected and pedigrees were reconstituted. RESULTS: Twenty-two cases (9 boys and 13 girls from 20 homes) were identified. Fourteen belonged to 11 families originating from the North of Tunisia; ten of them are still alive. Both parents in 4 homes (21%) and one parent in 9 homes (47%) were illiterate. Most of the homes (60%) had a low income and 45% comprised at least 3 children. Only 7 homes (35%) had health insurance. Pedigrees indicated 44 infant deaths and at least 10 other cases fulfilling the clinical features of GSD I but not diagnosed. CONCLUSION: The paediatric prevalence of GSD I in the North of Tunisia can be estimated to 7.93 cases per one million inhabitants and its incidence to 1/100,000 births. However, it is likely to be more frequent because of underreporting or underdiagnosis leading to precocious deaths.

Phenotypic spectrum of fucosidosis in Tunisia.

Fucosidosis (OMIM 230000) is a rare autosomal recessive lysosomal disorder due to deficient α-L-fucosidase activity(EC 3.2.1.51), leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. This study contained the largest ever Tunisian survey of fucosidosis patients, diagnosed during the period 1987-2007. The clinical pictures and outcomes of these patients are compared with literature data. Ten patients (8 boys and 2 girls) from six unrelated families were diagnosed at a mean age of 29 ± 10.3 months. Six of the patients were diagnosed as having the more severe phenotype. The other four cases presented the low progressive phenotype. This distinction was determined by the presence or absence of angiokeratoma and age of death. For all of the patients in our survey, early motor development was more severely delayed than described in the literature. Six patients presented psychomotor decline during the second year of life. Clinical features consist of variable mental retardation (all patients), progressive spastic quadriplegia (6/10 cases), coarse facies (9/10 cases), growth retardation (7/9 cases), visceromegaly (3 cases), angiokeratoma corporis diffusum (4 cases), recurrent bronchopneumonias (all cases), seizures (4 cases) and variable degrees of dysostosis multiplex (all cases). Portal cavernoma, never described in the literature, was observed in one patient. The outcomes were severe in this survey, probably owing to restricted health care; death occurred in 6 of the 10 patients before age 10 years, following recurrent pulmonary infections and neurological deterioration. No intrafamilial variability was noted in the multiplex families. The clinical presentation and outcomes of some of these patients were consistent with the continuous clinical spectrum of severity in fucosidosis attested by most clinical studies.

[Atypical presentation of Wegener disease in childhood]. / Présentation atypique de la maladie de Wegener de l'enfant.

The pediatric forms of Wegener granulomatosis (WG) are rare. The clinical picture and the profile have specificities compared to those of adults. We report a case of a girl aged of four years and a half who presented initially with a clinical picture of Henoch Schönlein purpura. Physical examination revealed additionally to purpura, scabby lesions on the buttocks. The histopathological examination of a skin biopsy disclosed histiocyte infiltration. There were no Ig A deposits on direct immunofluorescence study. One year later, the diagnosis of WG was suspected, when the patient developed a respiratory problem related to left pulmonary infarction. Screening for thromboembolic factors was positive for antiphosphilipid antibodies. Diagnosis of WG was confirmed by the histopathological study lung tissue and a significant titre of serum ANCA. Blood tests failed to provide evidence of renal involvement. Cyclophosphamide and prednisolone therapy was administrated. A relapse occurred one year later on the controlateral lung; but no biological marker of disease activity could be detected.

Mutation spectrum of glycogen storage disease type Ia in Tunisia: implication for molecular diagnosis.

Glycogen storage disease type Ia (GSD Ia; OMIM 232200) is an autosomal recessive disorder of glycogen metabolism caused by a deficiency of the microsomal glucose-6-phosphatase (G6Pase). It is characterized by short stature, hepatomegaly, hypoglycaemia, hyperuricaemia, and lactic acidaemia. Various mutations have been reported in the G6Pase gene (G6PC). In order to determine the mutation spectrum in Tunisia, we performed mutation analysis in 22 Tunisian type I glycogen storage disease (GSD I) patients belonging to 18 unrelated families. All patients were clinically classified as GSD Ia. The R83C mutation was found to be the major cause of GSD Ia, accounting for 24 of 36 mutant alleles (66.6%), The R170Q mutation was the second most frequent mutation; it accounts for 10 of 36 mutant alleles (27.7%). The R83C and R170Q mutations could be rapidly detected by PCR/RFLP. Since the majority of Tunisian patients carried R83C and/or R170Q mutations, we propose direct screening of these mutations as a rapid, valuable and noninvasive tool for diagnosis of GSD Ia in Tunisian as well as in Northern African populations.

[Myalgia in familial Mediterranean fever]. / Myalgies au cours d'une fièvre méditerranéenne familiale.

INTRODUCTION: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterized by recurrent attacks of fever and painful episodes of sterile peritonitis, pleuritis and arthritis. Among rare symptoms of the disease, muscular manifestations, first described in 1945, sometimes as one of the main clinical manifestations or as its sole feature should be recognized. We present a patient with FMF in whom severe myalgia were predominant. CASE REPORT: An 18 year-old Tunisian boy treated with corticosteroids for an "inflammatory myopathy" in another institution was admitted for abdominal pain. FMF was suspected because of a history of paroxysmal abdominal pain with fever from the age of 5 leading two times to laparotomy and one attack of left knee arthritis at the age of 14. FMF diagnosis was confirmed genetically, corticosteroids were tapered and a treatment with colchicine was started. Two years and a half later, he was admitted for severe and incapacitating myalgia of the upper and lower limbs without fever nor abdominal pain that responded well to rest and colchicine. Myalgia was then definitively attached to FMF. CONCLUSION: Three clinical patterns of myalgia are now well identified in FMF: the spontaneous pattern as observed in our patient, the exercise-induced pattern and the protracted febrile myalgia syndrome. The three patterns differ in the severity of pain, grade of fever and duration of the episode.

[A case of papillitis revealing primary syphilis]. / Papillite révélant une syphilis primaire.

OBJECTIVE: Syphilitic ocular manifestations are polymorphous and usually occur during the secondary or tertiary stage of syphilis. We report a case of primary syphilis revealed by papillitis. DESIGN: A 22 year old man presented with blurred vision in the left eye and decreased visual acuity. Fundus examination and fluorescein angiography revealed a papilledema in the left eye and chorioretinitis in the right one. Clinical examination revealed a painless ulceration of the chin. Blood tests were positive for syphilis (positive reaction to the VDRL test and TPHA titer at 1/640) but negative for HIV. After penicillin therapy, the ocular manifestations resolved. RESULTS: Papillitis is a relatively rare ocular manifestation of syphilis. Our case is original because papillitis was the presenting manifestation of the disease and that it was concomitant with the primary chancre. CONCLUSION: Systematic screening for syphilis should be performed in unexplained ocular inflammation.

[Mutation spectrum of Gaucher disease in Tunisia: high frequency of N370S/Rec NciI compound heterozygous]. / Spectre mutationnel de la maladie de Gaucher en Tunisie: forte fréquence des hétérozygotes composites N370S/Rec NciI.

Gaucher disease is the most common lysosomal storage disorder, it results from the inherited deficiency of the enzyme glucocerebrosidase, the accumulation of its substrate causes many clinical manifestations. Since the discovery of GBA gene, more than 200 different mutations have been identified, but only handful mutations are recurrent (N370S, L444P and c.84insG). In order to determine the mutation spectrum in Tunisia, we performed recurrent mutation screening in ten unrelated Tunisian children with Gaucher disease. Screening of recurrent mutation by PCR/RFLP and direct sequencing, has shown that N370S is the most frequent mutation (6/20 mutant alleles, 30%), followed by recombinant allele (RecNciI) which is found in five patients (5/20 mutant alleles, 25%), the L444P mutation represent 20% (4/20 mutant alleles). Our findings revealed that five among ten studied patients, were compound heterozygous N370S/RecNciI (50%). The screening of these mutations provides a simple tool for molecular diagnosis of Gaucher disease in Tunisian patients and allows also genetic counselling for their family members.

Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy.

PURPOSE: To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features. METHODS: We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups. RESULTS: Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1-2] year-interval by 10.1% and [3-4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1-2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1-4, in colon cancer and in stage III but without impact in rectal cancer and stage II. CONCLUSION: Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.

[Takayasu's arteritis associated with acute myeloblastic leukemia]. / Association artérite de Takayasu et leucémie aiguë myéloblastique.

INTRODUCTION: We present one patient with acute myeloblastic leukemia diagnosed two months after the onset of Takayasu's arteritis. EXEGESIS: A 21-year old woman with a previous history of erythema nodosum and episcleritis was admitted for a left cervical mass. Diagnostic imaging showed an aneurism of the left extracranial internal carotid and a stenosis of the left subclavian artery. Histological findings of the carotid aneurism revealed a granulomatous giant cell arteritis consistent with Takayasu's arteritis. Two weeks after, she was discharged, elevated white cell count (440.000/mm3 ) was disclosed. A bone marrow aspirate documented an acute myeloid leukemia. The patient died of intracerebral hemorrhage. CONCLUSION: Leucocytoclastic vasculitis and polyarteritis nodosa occur in acute myeloid leukemia, but the association with Takayasu's arteritis is new. In our knowledge, only two documented cases of Takayasu's arteritis in association with acute myeloblastic leukemia have been published.

[Behçet's disease in Tunisia. Clinical study of 519 cases]. / La maladie de Behçet en Tunisie. Etude clinique de 519 cas.

PURPOSE: To describe clinical characteristics of Behçet's disease in Tunisia. METHODS: It's a retrospective and multicentric study conducted by the Tunisian society of internal medicine. Inclusion criteria were those of the international study group. Were also included patients without international study group criteria but with at least one manifestation among arthritis, venous thrombosis or neurological manifestation with oral and genital ulceration or oral ulceration and skin lesions. RESULTS: Five hundred and nineteen patients were included. 87.5% of them fulfilled the international criteria. The male to female ratio was 2,7. The mean age was 28.7+/-9.3 years at onset and 32.7+/-9.2 years at diagnosis. The incidence of each manifestations was as follows: oral ulcers: 100%, genital ulcers: 87.5%, pseudo-folliculitis: 67.6%, erythema nodosum: 17.5%, positive pathergy test: 51%, joint involvement: 55%, uveitis: 32.2%, vein thrombosis: 24.9%, arterial aneurysms: 3.9%, neurological involvement: 11.6%. The frequency of HLA B51 antigen was 35% among the 187 patients tested. There was no difference in the manifestations of the disease between patients having B51 and those lacking it. Venous thrombosis (29.8 vs 11.4%), arterial involvement (4.4 vs 1.4%) and uveitis (37.5 vs 17,9%) were significantly more frequent in men whereas erythema nodosum (22.9% vs 15.6%) and joint involvement (70,7 vs 49.9%) more frequent in women. The mean follow up was 6,1+/-5.7 years. Mortality rate was 2.3% in our series. CONCLUSION: Our study confirms the androtropism of the disease in Mediterranean and Middle east countries. Positive pathergy test and venous thrombosis were more frequent in our study, like those from Mediterranean region. Whereas, ocular and neurological involvement were quite less frequent in our series.