[Contribution of pulmonary CT angiography in assessing the severity of acute pulmonary embolism]. / Apport de l'angioscanner pulmonaire dans l'évaluation de la gravité de l'embolie pulmonaire aiguë.

Chest CT angiography has taken a major role in the management of patients with suspected pulmonary embolism. Meanwhile, it became necessary to determine the severity criteria at the time of diagnosis in order to properly assess the risk/benefit of treatment to consider. In recent years, pulmonary CT angiography has emerged as a useful tool for assessing the severity of acute lung embolism, based on morphological criteria. The two main approaches that were studied were the quantification of obstruction of pulmonary arterial bed and recognition of signs of right heart failure. The aim of our work is to define the morphological parameters in cardiovascular pulmonary CT angiography and to determine their value in the current clinical prognostic stratification of acute pulmonary embolism of, especially their correlation with the risk of developing signs of clinical severity at diagnosis and at 3 months of the occurrence of pulmonary embolism.

Disseminated histoplasmosis diagnosed in the bone marrow of an HIV-infected patient: First case imported in Tunisia.

Histoplasmosis is a fungal infection caused by a dimorphic fungus, Histoplasma capsulatum. We report a first case of disseminated histoplasmosis in a 34-year-old woman, infected with human immunodeficiency virus (HIV), originating from Ivory Coast and living in Tunisia for 4 years. She was complaining from fever, chronic diarrhoea and pancytopenia. The Histoplasma capsulatum var. capsulatum was identified by direct microscopic examination of the bone marrow. She was treated by Amphotericin B, relayed by itraconazole. Even though a regression of symptoms and normalization of blood cell count (BCC), the patient died in a respiratory distress related to CMV hypoxemic pneumonia.

[Smoking attitudes and behavior of the hospital staff Sahloul (Sousse, Tunisia)]. / Attitudes et comportements tabagiques du personnel de l'hôpital Sahloul (Sousse, Tunisie).

BACKGROUND: Smoking is a major public health problem. Legislation banning smoking in public institutions exists but is not strictly enforced, particularly in health facilities. Therefore health workers have a crucial role to play in the control of smoking on account of their contact with patients and their credibility and moral authority in health matters. They can help patients by their advice and by abstaining from smoking in the hospital themselves. The aim of our study was to determine the prevalence of smoking among medical staff at the University Hospital of Sahloul in Sousse and their attitudes and behaviour with regard to smoking. METHODS: The data came from a descriptive cross-sectional study conducted during the year 2013-2014 using a self-administered questionnaire and included the health personnel of all services and laboratories of the University Hospital of Sahloul in Sousse. RESULTS: The participation rate was 71% (768/1081). Our study population was predominantly female (51%) with a mean age of 37.8 (±11.3) years. The overall prevalence of smoking was 21%. It was significantly higher among men (38.8%) than women (4.6%). This prevalence was higher among physicians/pharmacists (29.5%). More than half the smokers (58%) started smoking between the age of 19 and 25 years. Nicotine dependence was moderate among 27.4% and strong among 18.3% of smokers. The average dependence score was 4.1±2.4 [0-9] with a median of 4.0. Two-thirds of smokers (66.5%) reported smoking in the workplace. CONCLUSION: Confronted with the problem of tobacco, health institutions should find solutions for the prevention of smoking in hospitals. It seems necessary to train and involve hospital staff in anti-tobacco measures and to help smokers to quit in order to make our hospital a tobacco smoke free space.

Asymptomatic intestinal carriage of microsporidia in HIV-positive patients in Tunisia: prevalence, species, and pathogenesis.

Asymptomatic carriage of microsporidia (ACM) has not been described in patients living with HIV (PLHIV) in Tunisia. To determine the prevalence of ACM in PLHIV followed at Tunis la Rabta hospital, describe its clinical features and course, and identify the species involved. This prospective study (2005-2009) included 71 asymptomatic PLHIV compared with 37 PLHIV with diarrhea. One stool sample per patient was examined by microscopy after Weber staining and by PCR. Species identification was confirmed by specific PCR and sequencing. In cases of ACM, a second stool sample was examined in 2010 and a clinical check-up took place in 2013. The prevalence of ACM in asymptomatic PLHIV was 11.3 % (8/71). PCR was more sensitive than microscopy (P = 0.0047). ACM was associated with stage C of HIV infection (P = 0.008) and CD4 T cells <100/µl (P = 0.033). The species involved were E. intestinalis (6 cases) and E. bieneusi (2 cases). Six PLHIV remained asymptomatic with negative stool examinations, but two developed digestive signs. ACM is common among Tunisian PLHIV and it appears to be associated with E. intestinalis.

Additive effects of levonorgestrel and ethinylestradiol on brain aromatase (cyp19a1b) in zebrafish specific in vitro and in vivo bioassays.

Estrogens and progestins are widely used in combination in human medicine and both are present in aquatic environment. Despite the joint exposure of aquatic wildlife to estrogens and progestins, very little information is available on their combined effects. In the present study we investigated the effect of ethinylestradiol (EE2) and Levonorgestrel (LNG), alone and in mixtures, on the expression of the brain specific ER-regulated cyp19a1b gene. For that purpose, recently established zebrafish-derived tools were used: (i) an in vitro transient reporter gene assay in a human glial cell line (U251-MG) co-transfected with zebrafish estrogen receptors (zfERs) and the luciferase gene under the control of the zebrafish cyp19a1b gene promoter and (ii) an in vivo bioassay using a transgenic zebrafish expressing GFP under the control of the zebrafish cyp19a1b gene promoter (cyp19a1b-GFP). Concentration-response relationships for single chemicals were modeled and used to design the mixture experiments following a ray design. The results from mixture experiments were analyzed to predict joint effects according to concentration addition and statistical approaches were used to characterize the potential interactions between the components of the mixtures (synergism/antagonism). We confirmed that some progestins could elicit estrogenic effects in fish brain. In mixtures, EE2 and LNG exerted additive estrogenic effects both in vitro and in vivo, suggesting that some environmental progestin could exert effects that will add to those of environmental (xeno-)estrogens. Moreover, our zebrafish specific assays are valuable tools that could be used in risk assessment for both single chemicals and their mixtures.

[Smoking behavior, knowledge, and attitudes towards anti-smoking regulations of nursing students in Sousse, Tunisia]. / Comportement tabagique, connaissances et attitudes relatives à la lutte anti-tabac des étudiants infirmiers de la ville de Sousse, Tunisie.

BACKGROUND: Smoking prevalence has reached high rates among health professionals. Our study aimed to assess smoking behavior, knowledge and attitudes towards anti-smoking regulations of nursing students. METHODS: In 2013, we conducted a cross-sectional study among nursing students enrolled in private and state nursing institutions of Sousse (Tunisia). RESULTS: In our study, 440 students were selected. The mean age was 22 ± 2 years. The sex ratio was 0.65. The prevalence of smoking was 20.6%. It was significantly higher in men than women (50% vs 4.5%, P < 10(-3)). Strong dependency was noted in 9%. One-third of smokers stated they wanted to quit smoking. Prohibiting the sale of cigarettes to minors and smoking in enclosed public places were the two most mentioned anti-smoking regulations. CONCLUSION: Our rate was lower than those reported in the literature. This result should encourage policymakers to continue actions and ensure sustainability.

Critical appraisal of the clinical utility of sublingual immunotherapy in allergy.

Since it was introduced by Noon in 1911, allergen-specific immunotherapy or desensitization has been widely prescribed in the management of allergic diseases. Aimed at the etiology, it represents the only effective treatment for allergy. The basic mechanisms of immunotherapy are becoming better understood and allow us to improve this technique in the future. The sublingual immunotherapy as an alternative to subcutaneous route has been widely studied. Several clinical trials confirmed that sublingual immunotherapy is efficient in reducing allergic respiratory symptoms. The sublingual immunotherapy reduces the risk of developing serious side effects due to desensitization. We performed a literature review in order to remind the mechanisms of action and to demonstrate efficacy and tolerability of the sublingual immunotherapy in the treatment of allergic rhinoconjunctivitis and asthma and its impact on the quality of life.

[Prevalence of metabolic syndrome in a population of apneic patients: a prospective study with cardiovascular risk estimation]. / Prévalence du syndrome métabolique dans une population de patients apnéiques: étude prospective avec calcul du risque cardiovasculaire.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a highly prevalent clinical condition and frequently associated with obesity. Recent literature has suggested the independent contribution of OSAS in the pathogenesis of metabolic disturbances. Metabolic syndrome (MS), a cardiovascular risk factor, was frequently associated with OSAS. METHODS: This is a prospective study without intervention. Will be included, all consecutive patients referred to the Department of Pulmonology for suspected OSAS confirmed by respiratory polygraphy. Anthropometric, clinical and biological parameters needed to define the MS will be collected. MS was defined according to the IDF 2005. Assessment of cardiovascular risk related to MS will be performed by appropriate scores. EXPECTED RESULTS: To determine the prevalence of MS in a sample of OSAS patients recruited in the Department of Pulmonology of Farhat Hached Hospital (Sousse, Tunisia). To identify risk factors independently associated with the presence of MS in patients with OSAS among the following parameters (age, gender, degree of obesity and the various parameters of OSAS severity). To assess compared cardiovascular risks according to the presence of MS by validated scales to demonstrate the impact of MS in patients with OSAS.

[Aeric bubbles developed on the trachea]. / Bulles aériques appendues à la trachée.

The diverticula of trachea are a frequent observation in thoracic computed tomography, in particular in patients presenting an obstructive syndrome. On the occasion of a case report of a patient presenting a dilation of bronchi, we underline the interest of the post-treatment of the computed tomography acquisition, and present a review of the literature on this entity.

BFCOD activity in fish cell lines and zebrafish embryos and its modulation by chemical ligands of human aryl hydrocarbon and nuclear receptors.

Assessment of exposure and effect of fish to pharmaceuticals that contaminate aquatic environment is a current major issue in ecotoxicology and there is a need to develop specific biological marker to achieve this goal. Benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylase (BFCOD) enzymatic activity has been commonly used to monitor CYP3A activity in fish. In this study, we assessed the capacity of a panel of toxicologically relevant chemicals to modulate BFCOD activity in fish, by using in vitro and in vivo bioassays based on fish liver cell lines (PLHC-1, ZFL, RTL-W1) and zebrafish embryos, respectively. Basal BFCOD activity was detectable in all biological models and was differently modulated by chemicals. Ligands of human androgens, glucocorticoids, or pregnanes X receptors (i.e., dexamethasone, RU486, rifampicin, SR12813, T0901317, clotrimazole, ketoconazole, testosterone, and dihydrotestosterone) moderately increased or inhibited BFCOD activity, with some variations between the models. No common feature could be drawn by regards to their capacity to bind to these receptors, which contrasts with their known effect on mammalian CYP3A. In contrast, dioxins and polycyclic aromatic hydrocarbons (PAHs) strongly induced BFCOD activity (up to 30-fold) in a time- and concentration-dependent manner, both in vitro in all cell lines and in vivo in zebrafish embryos. These effects were AhR dependent as indicated by suppression of induced BFCOD by the AhR pathway inhibitors 8-methoxypsoralen and α-naphthoflavone. Altogether our result further question the relevance of using liver BFCOD activity as a biomarker of fish exposure to CYP3A-active compounds such as pharmaceuticals.

[Smoker's clinical characteristics at a tobacco cessation consultation (Sousse university hospital, Tunisia)]. / Profil clinique des fumeurs à la consultation d'aide au sevrage tabagique (Centre hospitalier universitaire de Sousse, Tunisie).

BACKGROUND: Smoking cessation intervention is among the most vital elements of the prevention of tobacco smoking. Our study aimed to describe the clinical profile of patients attending our smoking cessation unit. METHODS: We conducted a cross-sectional study from December 2009 to June 2012. The patients were recruited in the Tobacco cessation unit of Sahloul Hospital (Sousse, Tunisia). The data were collected from the consultants' records. RESULTS: A total of 279 patients attended. They were mostly men (92.8 %). The mean age was 41.7 ± 13.4 years. Among medical conditions, a history of cardiovascular and respiratory disease was the most frequent (31 %). Anxiety was present in 46.2 % of patients. More than half of the patients (51.2 %) were heavy smokers and 50.5 % were strongly nicotine dependent (Fagerström's score>7). Seventy percent were motivated to stop smoking and 53.8 % had tried to quit at least once. CONCLUSION: The majority of our patients could be considered as heavy smokers. Therapeutic combinations and medical treatment are suggested to assist practitioners trying to help them.

Fasting insulin sensitivity indices are not better than routine clinical variables at predicting insulin sensitivity among Black Africans: a clamp study in sub-Saharan Africans.

BACKGROUND: We aimed to evaluate the predictive utility of common fasting insulin sensitivity indices, and non-laboratory surrogates [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)] in sub-Saharan Africans without diabetes. METHODS: We measured fasting glucose and insulin, and glucose uptake during 80/mU/m2/min euglycemic clamp in 87 Cameroonians (51 men) aged (SD) 34.6 (11.4) years. We derived insulin sensitivity indices including HOMA-IR, quantitative insulin sensitivity check index (QUICKI), fasting insulin resistance index (FIRI) and glucose-to-insulin ratio (GIR). Indices and clinical predictors were compared to clamp using correlation tests, robust linear regressions and agreement of classification by sex-specific thirds. RESULTS: The mean insulin sensitivity was M = 10.5 ± 3.2 mg/kg/min. Classification across thirds of insulin sensitivity by clamp matched with non-laboratory surrogates in 30-48% of participants, and with fasting indices in 27-51%, with kappa statistics ranging from -0.10 to 0.26. Fasting indices correlated significantly with clamp (/r/=0.23-0.30), with GIR performing less well than fasting insulin and HOMA-IR (both p < 0.02). BMI, WC and WHtR were equal or superior to fasting indices (/r/=0.38-0.43). Combinations of fasting indices and clinical predictors explained 25-27% of variation in clamp values. CONCLUSION: Fasting insulin sensitivity indices are modest predictors of insulin sensitivity measured by euglycemic clamp, and do not perform better than clinical surrogates in this population.

[Smoking behavior among nursing students in Sousse, Tunisia: a preliminary study]. / Comportements tabagiques chez les étudiants infirmiers de Sousse, Tunisie: étude préliminaire.

INTRODUCTION: Smoking is an entirely preventable, man-made, epidemic. It is a major, worldwide, public health problem whose social costs are very high. Health care workers have an important role to play in tobacco control. We conducted a study among nursing students to examine their smoking behavior, their attitudes towards smoking, and their participation in prevention. METHODS: This descriptive, transverse study was conducted in March 2011 during which an anonymous self-completion questionnaire was administered to nursing students. RESULTS: The study included 150 students aged between 18 and 25 years with a sex ratio of 1:3. The prevalence of smoking was 32.6%. Male students began smoking at an earlier age (16.5±2.3 years vs 18.9±1.1 years). The main initiating factors were stress (55%), pleasure (46.9%) and peer influence (36.5%). The Fagerstrom score showed a high level of dependency in 26.5% of smokers. More than 75% of student smokers have tried to quit. Most of the students surveyed (93%) think that health care workers should set a good example by not smoking and 91% of them think they should help others quit smoking. CONCLUSION: Health care workers should be well informed about the harmful effects of tobacco. They should be convinced of the need for their participation in smoking prevention and the fight against this medico-social scourge. It is essential that their training prepares them for this task and that their environment helps them fulfill their responsibility.

[Syndrome coronarien aigu sous traitement antirétroviral]. / Acute coronary syndrome during antiretroviral treatment.

AIM: The aim of this study is to determine epidemiological, clinical, therapeutic and outcome characteristics of acute coronary syndrome in AIDS patients under HAART. Results- The charts of 5 patients were reviewed. The mean age, at the time of the discovery of HIV infection, was 35 years. Three patients were smokers and one had a family history of diabetes and acute coronary syndrome (ACS). Three patients received 2 nucleoside reverse transcriptase inhibitors (NRTIs) with indinavir. The 2 others received 2 NRTIs with efavirenz with good immunovirologic response. Four patients developed mixed dyslipidemia after an average period of 26 months. Tow patients developed diabetes and one a hypertension. A specific treatment was initiated in all cases. These five patients developed an ACS after respectively 51, 95, 96,103 and 145 months of ART (median=98 months). ACS occurred in 3 patients receiving 2 NRTIs and PI and two others 2 NRTIs with efavirenz. The mean age at the onset of ACS was 46 years. One patient underwent a triple bypass surgery, tow a stenting of the stenotic coronary and the last 2 patients received medical treatment with a good clinical outcome. The PI was replaced by efavirenz in two patients. Four patients had a recurrence of ACS respectively after 2months, 3 months, 12 months, and 62 months after the first episode. The five patients are still followed with good clinical and biological outcome.

WITHDRAWN: Allergen specific immunotherapy induced multi-organ failure.

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Passive samplers for chemical substance monitoring and associated toxicity assessment in water.

The European legislation, and in particular the Water Framework Directive requires the development of cost efficient monitoring tools that can provide the required information for the assessment of water contamination. Passive sampling methods represent one of the novel tools that have a potential to be used in various regulatory monitoring programmes aimed at assessing the levels of chemical pollutants. These methods are particularly interesting for sampling polar organic pollutants in water because they provide representative information of the water quality over extended time periods (days to weeks) in environments with fluctuating contaminant concentrations. This is achieved by integrative sampling of pollutants over the whole sampler deployment period. These tools can be coupled to toxicity testing using bioassays that give information on toxic and ecotoxic hazards associated to substances that are present, these substances being identified or not. In this study the polar organic chemical integrative sampler (POCIS) was used in surface water to evaluate the water contamination by polar organic compounds and their potential toxicity.

Androgen receptor binding affinity: a QSAR evaluation.

The multiparameter formulation of the COmmon REactivity PAttern (COREPA) approach has been used to describe the structural requirements for eliciting rat androgen receptor (AR) binding affinity, accounting for molecular flexibility. Chemical affinity for AR binding was related to the distances between nucleophilic sites and structural features describing electronic and hydrophobic interactions between the receptor and ligands. Categorical models were derived for each binding affinity range in terms of specific distances, local (maximal donor delocalizability associated with the oxygen atom of the A ring), global nucleophilicity (partial positive surface areas and energy of the highest occupied molecular orbital) and hydrophobicity (log Kow) of the molecules. An integral screening tool for predicting binding affinity to AR was constructed as a battery of models, each associated with different activity bins. The quality of the screening battery of models was assessed using a high value (0.9) of the Pearson contingency coefficient. The predictability of the model was assessed by testing the model performance on external validation sets. A recently developed technique for selection of potential androgenically active chemicals was used to test the performance of the model in its applicability domain. Some of the selected chemicals were tested for AR transcriptional activation. The experimental results confirmed the theoretical predictions.

Anti-androgenic activities of environmental pesticides in the MDA-kb2 reporter cell line.

Pesticides have been suspected to act as endocrine disruptive compounds (EDCs) through several mechanisms of action, however data are still needed for a number of currently used pesticides. In the present study, 30 environmental pesticides selected from different chemical classes (azole, carbamate, dicarboximide, organochlorine, organophosphorus, oxadiazole, phenylureas, pyrazole, pyrimidine, pyrethroid and sulfonylureas) were tested for their ability to alter in vitro the transcriptional activity of the androgen receptor in the MDA-kb2 reporter cell line. The responsiveness of the system was checked by using a panel of reference ligands of androgen and glucocorticoid receptors. When tested alone at concentrations up to 10 µM, none of the studied pesticides were able to induce the reporter gene after a 18 h exposure. Conversely, co-exposure experiments with 0.1 nM dihydrotestosterone (DHT) allowed identifying 15 active pesticides with IC(50) ranging from 0.2 µM for vinclozolin to 12 µM for fenarimol. Fipronil and bupirimate were here newly described for their AR antagonistic activity.

Impact of urban wastewater discharges on the sediments of a small Mediterranean river and associated coastal environment: assessment of estrogenic and dioxin-like activities.

The Mediterranean region includes many small coastal rivers about which little is known concerning organic contaminant loads in their sediment. This study was designed to assess organic contamination in one of these small coastal rivers (Lez River) and associated coastal sediments. Levels of alkylphenols (APs), polycylic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) were measured in sediments of the Lez River and two coastal lagoons impacted by wastewater discharges. In parallel, sediment surrounding a recently built submarine outfall that discharges treated wastewater, from an area encompassing some 450,000 inhabitants, into the sea was monitored a year after the beginning of emission via the outfall. Finally, these sediments were characterized by screening estrogenic, PAH-like and dioxin-like activities using in vitro bioassays. Both chemical analyses and bioassays revealed that wastewater inputs were a source of organic contamination of sediments from the Lez and lagoons, which still persisted 2 years after the discharges were stopped. APs could explain a small proportion of the overall estrogenic activities (up to 31%), suggesting that other estrogenic compounds were also present in the sediments. PAHs explained a great share (83% on average) of the EROD induction potency of the extracts. This survey should be the first step in the long-term monitoring of these sites.

A stable fish reporter cell line to study estrogen receptor transactivation by environmental (xeno)estrogens.

Cross-species differences between human and fish estrogen receptor (ER) binding by environmental chemicals have been reported. To study ER transactivation in a fish cellular context, we stably co-transfected the PLHC-1 fish hepatoma cell line with a rainbow trout estrogen receptor (rtER) and the luciferase reporter gene driven by an estrogen response element (ERE). This new cell model, called PELN-rtER (for PLHC-1-ERE-Luciferase-Neomycin), responded to 17beta-estradiol (E2) in a both concentration- and temperature-dependent manner, as well as to environmental ER ligands from different chemical classes: natural and synthetic estrogens, zearalenone metabolites, genistein, alkyphenoles and benzophenone derivatives. The comparison with other in vitro models, i.e. human reporter cell lines (HELN-rtER, MELN) and vitellogenin induction in primary cultures of rainbow trout hepatocytes, showed an overall higher sensitivity of the human cells for a majority of ligands, except for benzophenone derivatives which were active at similar or lower concentrations in fish cells, suggesting species-specificity for these substances. Correlation analyses suggest that the fish cell line is closer to the trout hepatocyte than to the human cell context, and could serve as a relevant mechanistic tool to study ER activation in fish hepatic cellular context.