OXY-2-15, a novel variant showing increased ceftazidime hydrolytic activity.

OBJECTIVES: Klebsiella oxytoca is a member of the family of Enterobacteriaceae and often contains the ß-lactamase blaOXY gene. Although this ß-lactamase does not naturally hydrolyse ceftazidime, this study describes possible in vivo selection of a clinical K. oxytoca isolate showing increased MICs of ceftazidime. METHODS: To reveal the molecular mechanism underlying this unusual resistance phenotype, WGS, cloning, overexpression, MIC and steady-state kinetic studies were performed. RESULTS: A patient was treated for a septic episode with ceftazidime (4 g/day). This therapy was based on earlier culture results in which, amongst others, a K. oxytoca (Velp-1) isolate was identified. After 11 days of treatment, K. oxytoca Velp-2 was isolated from a pus sample drained from the wound. The isolate showed increased resistance to ceftazidime (MIC ≥64 mg/L) compared with the original K. oxytoca isolate (Velp-1). WGS revealed the presence of a novel blaOXY-2 allele, designated blaOXY-2-15, with a two amino acid deletion at Ambler positions 168 and 169 compared with OXY-2-2. Cloning blaOXY-2-15 into Escherichia coli TOP10 resulted in increased MICs of ceftazidime, but reduced MICs of most other ß-lactams compared with OXY-2-2. Steady-state kinetics confirmed the results of the MIC data, showing clearly significant ceftazidime hydrolysis. CONCLUSIONS: This report shows the risk of in vivo selection of ceftazidime-resistant K. oxytoca isolates after prolonged ceftazidime treatment. Furthermore, it is the first known report of a K. oxytoca isolate conferring resistance to ceftazidime by a two amino acid deletion in the omega loop of OXY-2-2.

Association of TGFB1 -509C/T polymorphism gene with clinical variability in cystic fibrosis patients: A case-control study.

PURPOSE: In this work, we are interested to study the implication of -509C/T polymorphism, located in the promoter region of TGFB1 (transforming growth factor ß1), in the phenotypic variability of CF patients. PATIENTS AND METHODS: The present study enrolled 111 CF patients and 100 healthy control subjects. The study of the -509C/T polymorphism was performed using PCR-RFLP method. RESULTS: We found that patients carried non-F508del homozygous mutation with TT genotype was associated to lung symptoms (P=0.04). This association was not found in the sub-groups of patients with F508del at homozygous state P=0.145. No association was found between this polymorphism and the variability of digestive, pancreatic and ileus meconial symptoms. CONCLUSION: On the basis of our results, the -509C/T polymorphism of the TGFB1 gene seems to be a modulator factor of cystic fibrosis.

Impact of sampling origin on molecular detection of high-risk human papillomavirus and oncogene expression.

PURPOSE OF INVESTIGATION: The recognition of high-risk human papillomavirus (HR-HPV) as an etiological agent of cervical cancer has increased the importance of testing for HPV, and this might contribute to better risk stratification. METHODS: Eighty-eight randomly selected cervical cancer specimens including biopsies and their respective smears were used in this study. Control scrapings were obtained from ten healthy women. The presence of HPV16 and HPV18 was investigated using the technique of polymerase chain reaction (PCR) with the specific primers for the L1 region, while mRNA expression of HPV16 E6-E7 was evaluated by a reverse transcription PCR method (RT-PCR). RESULTS: The positivity for the viral genotype was influenced by the quantity of amplified DNA used. In tumor biopsies the higher positivity for HPV16 (54.5%) and HPV18 (15.9%) was obtained using 687.4 ng of DNA. At smears level solely 31.8% of HPV16 was detected using an average DNA quantity of about 157.2 ng. The revelation of HPV types depends on clinicopathologic data; HPV16 was detected more in advanced stages of squamous carcinoma (SC) samples (20% stage I, 62% Stage II and 80% stage III), while HPV18 and double infection were found exclusively at advanced stages of SC and in adenocarcinoma (AC), respectively (60%, 40% stage III SC and 80%, 20% Stage II A and C). The prevalence of HPV16 E6-E7 transcripts was evaluated at tumor biopsy with frequencies of 50%. CONCLUSION: Our data provide prospective evidence that HPV16/18L1 revelation at biopsy toward pathological types is efficient and correlates well with oncogenic transcript findings. Subtle changes in viral oncogene dynamics highlight the presence of other regulating proteins serving as additional biomarkers.

[Beta lactam resistance and molecular markers of 157 Haemophilus influenzae isolates from infants in Tunis]. / Etude de la résistance aux beta-lactamines et des marqueurs moléculaires chez 157 souches d'Haemophilus influenzae isolées chez l'enfant à Tunis.

The aim of this study was to precise the capsular type of Haemophilus influenzae, to determine its susceptibility to beta-lactam agents, and to search for an eventual clonality between the clinical strains of the pathogen. Polymerase chain reaction was carried out to confirm the capsular type and to determine the beta-lactamase type. Minimum inhibitory concentrations (MICs) of beta-lactam agents for H. influenzae were determined by the agar dilution method on Haemophilus test medium, and the strains were analyzed by pulsed-field gel electrophoresis after SmaI restriction. Among 157 strains of H. influenzae studied, 12.1% was of serotype b. Sixty-seven strains (42.7%) were resistant to amoxicillin, among which 51 were resistant through production of TEM-type beta-lactamase while 16 showed high MICs for amoxicillin, amoxicillin + clavulanic acid, and cefuroxim, which suggested a resistance by modification of penicillin-binding proteins. Among the latter strains, five were producing TEM-type beta-lactamase. Cefotaxim, cefixim, and cefpodoxim had low MICs in all cases. The pulsed-field gel electrophoresis revealed 110 pulsotypes. All H. influenzae strains, including noncapsulated strains and serotype-b encapsulated strains, had a high level of heterogeneity, with diversity indices of respectively 0.67 and 0.94.

[Imaging features of Takayasu's arteritis]. / Imagerie de l'artérite de Takayasu.

Takayasu's arteritis is the most frequent inflammatory arteritis in young patients. It is characterized by the presence of giant cells and typically involves specific vascular sites: aorta and its main branches and pulmonary arteries. Inflammatory arterial involvements leads to stenosis, aneurysm, occlusion and arterial wall thickening. Diagnosis relies mainly on imaging, namely Doppler US, CT, and MRI. The imaging features of this disease are reviewed based on a retrospective review of 36 patients imaged over a 13 year period.

[Nasopharyngeal angiofibroma: report of 15 cases treated by embolization]. / Le fibrome nasopharyngien: à propos de 15 cas traités par embolisation.

PURPOSE: To report a series of 15 new cases of nasopharyngeal angiofibroma treated with presurgical embolization along with a review of the literature. MATERIALS AND METHOD: Retrospective review of 15 cases of nasopharyngeal angiofibroma treated with presurgical embolization. The clinical, CT and MR features as well as postsurgical follow-up are reviewed. RESULTS: Presurgical embolization reduced surgical difficulties, especially hemorrhage, allowing complete tumor resection in most cases. Two cases of recurrent disease and 1 case of residual tumor were noted and treated by repeat embolization. CONCLUSION: Presurgical embolization reduces intraoperative hemorrhage and allows complete resection of these highly vascularized tumors.

[Implementation of antimicrobial resistance surveillance and antibiotic consumption in an intensive care burn department]. / Mise en place d'une surveillance de la résistance et de la consommation des antibiotiques dans un service de réanimation de brûlés.

BACKGROUND: The increasing consumption of antibiotics in hospitals and the economic implications of this increase lead to survey this consumption in the various hospital units. AIM: Our study proposes to measure the annual antibiotic use and antimicrobial resistance in an intensive care Burn department in order to manage the control measures. METHODS: The study was conducted during a 5 year period (1 January 2000 to 31 December 2004). The average number of admissions was 204/year and the mean number of hospitalisation was 4036/year. Antimicrobial susceptibility testing was performed by disk diffusion method. Susceptibility testing data were stored in a laboratory data base using whonet 5.3 software. The consumption of following antibiotics: imipenem, ceftazidime, ofloxacin, ciprofloxacin, piperacillin-tazobactam was measured by antimicrobial density (AD) witch takes into account the quantity of antibiotics in Grams converted to daily defined dose (DDD) and number of hospitalization days. The daily defined dose (DDD) was proposed by WHO. The calculation of the AD for each molecule was earned Out according to the following formula: AD = (Quality consumed in for the particular antimicrobial x 1000) / (DDD for that antimicrobial x number of days of hospitalizations). RESULTS: There was statistically significant relationship between increasing use of ceftazidime and ceftazidime resistant Klebsiella pneumoniae (rs = 0.93; p = 0.O2) The use of ceftazidime was not significantly associated with resistance to this molecule in P. aeruginosa (rs = 0.76 p = 0.13). Conceerning the fluoroquinolones, there was statistically significant relation ship between increasing use of ciprofloxacin and rate ciprofloxacin resistant P. aeruginosa (rs = 0.89, P = 0.043). Furthermore, the consumption of ciprofloxacin was significantly correlated to imipenem resistance in P. aeruginosa (rs = 0.87, p = 0.05). However, the consumption of imipenem was not significantly correlated to resistance of this drug in P. aeruginosa (rs = 0.45; P = 0.4). CONCLUSION: The monitoring of both antibiotic consumption and antibiotic resistance is necessary to set up targeted policies and to control their effectiveness. Nevertheless this monitoring must be integrated into global policy of good use and control of antibiotics.

[MRI of knee tuberculous arthritis]. / IRM de l'arthrite tuberculeuse du genou.

Tuberculous arthritis is rare and the diagnosis may be confused with inflammatory arthritis. Only few cases, explored by MRI, have been reported in the literature. We report 3 cases of tuberculous arthritis of the knee revealed by insidious pain. The abnormalities revealed by MRI suggested tuberculosis. Diagnosis was confirmed by histology.

Multi-mycotoxin determination in barley and derived products from Tunisia and estimation of their dietary intake.

A study on raw barley and derived products (barley soup and beers) was carried out to determine the natural presence of twenty-four mycotoxins by both liquid chromatography and gas chromatography coupled to tandem mass spectrometry (MS/MS). The developed multi-mycotoxin procedure was based on both SLE and QuEChERS extraction steps. 66% of analyzed samples presented mycotoxin contamination and only one sample, which was soup of barley (6 ng/g), exceeded the maximum level (ML) established by EU for OTA (5 ng/g). Raw barley was the most contaminated matrix (62%), which concentrations ranged from 1.70 to 287.13 ng/g) and type of detected mycotoxins (DON, 15AcDON, NEO, NIV, HT2, FB1, OTA, ENA, ENA1, ENB and ENB1). DON was the most detected mycotoxin with an incidence of 56%, 29% and 23% in beer, soup of barley and barley, respectively. However, the highest levels detected were for ENA, in raw barley with 287 ng/g. In beer and soup of barley samples, the mycotoxins with highest level were 15AcDON (15.6 ng/g) and ENB1 (55.1 ng/g), respectively. Furthermore, 80% of positive soup of barley samples showed co-occurrence. No toxicological concern was associated to mycotoxins exposure for consumers.

[Ectopic thyroid]. / Thyroïde ectopique.

PURPOSE OF STUDY: Ectopic thyroid is defined as thyroid tissue not located anterolaterally between the second and the fourth tracheal cartilage. This anomalous localization results from abnormal embryologic development and/or migration of the gland. The purpose of this study is to demonstrate the role of imaging in the preoperative evaluation of ectopic thyroid. MATERIAL AND METHODS: A 13-year-old girl with no other significant medical history, consulted for dysphonia, fullness in the throat and breathing difficulties. Examination of the oral cavity and oropharynx showed a large mass attached to the base of the tongue, the mass was evaluated by ultrasanography, computed tomography, magnetic resonance imaging and scintigraphy. RESULTS: Ultrasound sonography showed a well-defined hypoechogenic mass in the posterior end of the tongue. Scintigraphy showed hyperfixation at the base of the tongue with no fixation in the normal thyroid site. Computed tomography scan revealed a spontaneously hyperdense spherical basilingual mass with a high enhancement after contrast injection. In MRI, the mass was isointense with the muscle in T1-weighted images and hyperintense in T2 weighted images. CONCLUSION: Ectopic thyroid must be evoked in the presence of any basilangual mass. Scintigraphy and ultrasanography are gold standard in demonstration the ectopic thyroid tissue. But computed tomography and MRI playing an increasingly important role in the diagnosis, in determination of the malignant transformation and planning the surgical approach.

[Eagle's syndrome]. / Le syndrome de Eagle.

OBJECTIVES: Elongated styloid process also known as Eagle's syndrome is an entity that may be the source of craniofacial and cervical pain. It is frequently reported but is probably more common than generally considered. The symptoms related to Eagle's syndrome can be confused with those attributed to a wide variety of oropharyngeal and maxillofacial diseases. From four observations of Eagle's syndrome, we recall the clinical and radiological findings of this affection. MATERIAL AND METHODS: Retrospective analysis of four patients examined during a 2-year period. These patients presented cervical pain associated with headache, vertigo, otalgia and dysphagia. All patients were explored by conventional radiographs and three-dimensional computer tomography reconstruction. RESULTS: Digital palpation of the fossa reproduced and exacerbated the pain. Neck radiographic examination showed a bilateral elongation of the styloid process in both cases. The cervical scanner showed a bilateral elongation of the styloid process in all cases. CONCLUSION: Eagle's syndrome is a frequent entity that remains vaguely known by physicians. Three-dimensional computer tomography is useful for the diagnosis of this entity.

[Vertebral and spinal cord hydatidosis: contribution of imaging]. / Hydatidose vertébromédullaire: intérêt de l'imagerie.

The authors report the case of a vertebromedullary hydatidosis revealed by medullar compression in a 40-year-old male patient. Magnetic resonance imaging showed lesions of the seventh and eighth dorsal vertebras, cystic lesions in the epidural space and in the perivertebral soft tissues. Surgical excision lead to clinical cure. Vertebromedullary hydatidosis is rare and severe. Modern techniques of imaging are very helpful for the diagnosis and the follow-up of patients after treatment.

[Imaging of rhinocerebral mucormycosis]. / L'imagerie dans la mucormycose rhinocérébrale.

PURPOSE: Rhinocerebal mucormycosis is a rare life threatening fungal infection observed in immunocompromised patients. We report six cases of patients with rhinocerebral mucormycosis confirmed histologically. Our study confirms the necessity of early diagnosis when clinical and CT findings are suggestive. MATERIALS AND METHODS: This is a retrospective study including 6 diabetic patients (3 women and 3 men) aged from 28 and 63 years. Five patients had ethmoiditis evolving for a few days (3 to 5 days), and one patient was in an ketoacidotic coma and had a severe infectious syndrome with purulent rhinorrhea evolving for 4 days. All of our patients underwent computed tomography (CT) scan of the paranasal sinuses. MRI was performed in two patients with neurological findings. RESULTS: Unilateral ethmoido-maxillary sinusitis was noted in 5 cases. Only one case of pansinusitis was found. All patients presented orbital involvement. Cerebral involvement was noted in 4 cases (cerebral venous thrombosis: 2 cases; abscess: 2 cases; cerebral ischemia: 2 cases). The diagnosis of mucormycosis was based on endonasal biopsy. When available, MRI allowed a more precise evaluation of the orbital and cerebral extension. CONCLUSION: Mucormycosis is an opportunist mycosis due to mucoralis fungus. It is very invasive with a highly aggressive potential in diabetic or immunocompromised patients. Imaging study particularly CT scan, plays an important role in diagnosis especially to evaluate cerebral extension.

Preliminary study of haplotypes linked to the rare cystic fibrosis E1104X mutation.

The analysis of some extra- and intragenic markers within or closely linked to the cystic fibrosis transmembrane regulator (CFTR) gene is useful as a molecular method in clinical linkage analysis. Indeed, knowing that the molecular basis of cystic fibrosis (CF) is highly heterogeneous in our population, the study of haplotype association with normal and CF chromosomes could be very helpful in cases where one or both mutations remain unidentified. In this study, we analysed with PCR-RFLP and capillary electrophoresis some extra (pJ3.11, KM19 and XV2C) and intragenic (IVS8CA, IVS17bTA and IVS17bCA) polymorphic markers in 50 normal and 10 Tunisian patients carrying the rare E1104X mutation in order to determine the haplotype associated with this mutation. For the extragenic markers, 8 haplotypes were identified. The most frequent of them are the 221 and 112 accounting for 80% of total haplotypes. For the intragenic markers, five haplotypes were present on the E1104X chromosomes. One of them 16-31-13 accounted for 50%. To our knowledge, this is the first work to be interested to the haplotypes linked to the E1104X mutation. This preliminary study of haplotypes could be a helpful method to determine the molecular lesions responsible of this pathology.

[Clinical and electrophysiological study of 2 familial cases of Marcus Gunn phenomenon]. / Etude clinique et électrophysiologique de 2 cas familiaux de phénomène de Marcus Gunn.

Two cases of jaw-winking synkinesia or Marcus Gunn (MG) phenomenon are reported, with electromyographic and genetic studies. In the first patient a right eyelid ptosis which had been occurring since birth was associated with a bilateral MG phenomenon confirmed by electromyography. An examination of other family members revealed 3 other cases in the mother's family. The second patient had a congenital left eyelid ptosis associated with an MG phenomenon. His maternal uncle and his mother also had this "jaw-winking" synkinesia. The authors discuss the physiopathology of this complex phenomenon up to now without known neurological lesions. Concerning the genetic aspect of the MG phenomenon, they conclude that in their patients the hereditary pattern was that of an incomplete autosomal dominant trait with varied expressivity in the two families.

[Clinical and genetic analysis of 188 families with spinocerebellar degeneration. Friedreich's disease and P. Marie's hereditary ataxias]. / Analyse clinique et génétique de 188 familles d'hérédo-dégénérescence spino-cérébelleuse. Maladies de Friedreich et hérédo-ataxies de P. Marie.

Based on the hereditary ataxias concepts and a large field survey, the authors analyzed 392 cases of spino-cerebellar degeneration belonging to 188 families. Two main clinical groups were identified: 227 cases of Friedreich ataxia and 74 cases of cerebellar hereditary ataxia of P. Marie type. The association in the same patient of peroneal atrophy of Charcot Marie type with Friedreich ataxia (17 cases) or P. Marie cerebellar hereditary ataxia (13 definite cases and 13 probable) was the most striking finding. "Forme fruste", incomplete form or complex form of Friedreich ataxia were present in some families while in some others there was spastic paraplegia or pure Charcot Marie Tooth disease. This clinical heterogeneity in families of spino-cerebellar degeneration is discussed.

[Subacute brainstem hematoma. A surgically treated case]. / Hématome du tronc cérébral d'installation subaigue. Un cas opéré.

We report a case of pontine haemorrhage in which symptoms and signs developed over a 2-months period. Surgery was successful but the patient subsequently died. The pathophysiology of subacute and chronic symptoms and signs is discussed.

[Intradural extramedullary neuro-enteric cysts without associated malformation. 3 cases with magnetic resonance imaging]. / Kystes neurentériques intraduraux extramédullaires sans malformation associée. Trois cas avec imagerie en résonance magnétique.

We report 3 cases of extramedullary neurenteric cyst without associated dysraphic lesions. One of the cases had an ultrastructural study. Magnetic resonance imaging provided a preoperative diagnosis. The embryogenesis of neurenteric cysts, their main clinical aspects and their surgical treatment are reviewed.

[MRI of cerebral cortical dysgenesis]. / IRM des dysgénésies corticales.

PURPOSE: Cortical cerebral dysgenesis is a heterogeneous disorder of cortical development and organization. It is well known by neuropathologists and is becoming more important in the clinical setting, mainly due to MRI. Our purpose is to report the MRI features of cortical dysplasia in 30 patients and to propose a simple classification with review of the literature. PATIENTS AND METHODS: It is a retrospective study of the MRI features of 30 cases of cortical dysgenesis. All patients were evaluated by electroencephalography and brain MRI using T1 and T2 weighted, inversion recovery T1 weighted, FLAIR and MPR 3D sequences with multiplanar reformations. RESULTS: Twenty-nine patients were referred to the neurology department because of refractory epilepsy and one patient for mental retardation. Our patients were distributed in 4 groups: diffuse forms represented by agyria-pachygyria (4 cases), polymicrogyria (one case), and nodular heterotopias (5 cases), local bilateral forms represented by bilateral polymicrogyria (11 cases), unilateral forms represented by hemi-megalencephaly (one case), and focal cortical forms found in eight cases. CONCLUSION: Neuroblast migration disorders are better known, mainly due to high resolution MRI techniques that by the quality of multiplanar study and a better differentiation between gray and white matter, allow a more precise diagnosis.

[MRI in the diagnosis of Rathke's cleft cyst]. / IRM dans le diagnostic des kystes de la poche de Rathke.

PURPOSE: Rathke's cleft cysts are non neoplastic lesions of the sellar area that seldom are symptomatic. Their incidence has been underestimated before magnetic resonance imaging (MRI). The aim of this work was to assess the value of MRI in the diagnosis and differential diagnosis of Rathke's cleft cyst based on a retrospective review of 12 cases and a review of the literature. PATIENTS AND METHODS: We retrospectively reviewed the MRI features of 12 patients with Rathke's cleft cyst collected over 4.5 years. Patients included ten females and two males (mean age: 39 years). The most common presentation was the association of dysmenorrhea and pituitary dysfunction. MRI examinations were performed using a 1.5 Tesla system, T1 and T2 weighted sequences performed before and after Gd- DTPA injection. Signal intensity, shape, size and location of the lesion were analyzed. RESULTS: In all cases, MRI examination showed a cystic lesion of variable size and signal intensity. The cyst was purely intrasellar in nine cases and a suprasellar extension was noted in three cases. Five patients underwent surgery providing pathological confirmation, four underwent routine follow-up and three were lost of follow-up. CONCLUSION: We conclude that MRI is an efficient tool for diagnosis, allowing appropriate medical decision making.