[Off label uses of tigecycline]. / Les utilisations hors-autorisation de mise sur le marché de la tigécycline.

INTRODUCTION: Tigecycline is a relatively new antibiotic that have very limited valid indications. When no other alternative is available, this drug is widely used off label with promising results. The objective of this study is to summarize the different off label uses of tigecycline so that we can decide when and how to prescribe it in the absence of guidelines. MATERIAL AND METHODS: This study a revue of the literature collecting all the articles concerning the off label uses of tigecycline. RESULTS: Tigecycline was widely prescribed, off label, to treat infections with controversial results. Randomised clinical trials were conducted to evaluate its use to treat pneumonia. The results for this indication have a respectable level of evidence. For the other indications, the data collected was insufficient to support tigecycline prescription. In fact, different protocols were used which makes it hard to evaluate the efficacy and to conclude to the best treatment regimen. A tendency to prescribe high doses of the molecule was noted in different studies. When prescribed off label, tigecycline prescriptions were associated with a higher mortality and incidence of side effects. CONCLUSION: The tigecycline remains a valid option for the treatment of infections dues to multi-resistant bacteria especially when other alternatives are scarce or in cases of renal failure.

High temperature effect on daily all-cause mortality in Tunis 2005-2007.

BACKGROUND: The relationship between thermal stress and health has been only marginally investigated in North Africa. This study aimed to estimate the short-term effect of heat on total mortality, in the city of Tunis in 2005-2007, using time series analysis. METHODS: The study period was restricted to the summer season (May-October) and heat effect was assessed using maximum temperature as exposure variable. We estimated the breakpoint above which heat-related mortality begins to increase using a segmented linear regression. A Poisson Generalized Estimating Equations (GEE) model was then used to estimate the impact of heat on daily mortality. Models were adjusted for nitrogen dioxide (NO2), trend, calendar month, day of the week, the Ramadan period, and holidays. RESULTS: The estimated breakpoint was 31.5°C (standard deviation: 0.9°C). After adjustment for potential confounders, the daily mortality increased significantly by 2.00% [95% confidence interval: 0.68-3.16] for a 1°C increase in daily maximum temperature above the breakpoint. An increase of 10mg/m3 in NO2 was associated with a significant increase in daily mortality (0.48% [0.08-0.88]). CONCLUSION: There is an important effect of heat on daily mortality in the city of Tunis. This is the first evaluation of such an association in a North African city with hot and dry summers and a lower middle economy.

Infrared study of matrix-isolated ethyl cyanide: simulation of the photochemistry in the atmosphere of Titan.

Low-temperature Ar matrix isolation has been carried out to investigate the infrared spectrum of ethyl cyanide (CH3CH2CN), a molecule present in the atmosphere of Titan. The λ > 120 nm and λ > 230 nm photolysis reactions of ethyl cyanide in an Ar matrix were also performed in order to compare the behaviour of this compound when it is submitted to high and low energetic radiations. These different wavelengths have been used with the aim to reproduce the radiation reaching the various parts of the atmosphere. Several photoproducts have been identified during photolysis such as vinyl cyanide (CH2[double bond, length as m-dash]CHCN), cyanoacetylene (HC3N), and ethylene/hydrogen cyanide (C2H4/HCN), ethylene/hydrogen isocyanide (C2H4/HNC), acetylene/hydrogen cyanide (C2H2/HCN), acetylene/hydrogen isocyanide (C2H2/HNC), and acetylene:methylenimine (C2H2:HNCH2) complexes. Ethyl isocyanide (CH3CH2NC) and a ketenimine form (CH3CH[double bond, length as m-dash]C[double bond, length as m-dash]NH) have been identified as well. Photoproduct identification and spectral assignments were done using previous studies and density functional theory (DFT) calculations with the B3LYP/cc-pVTZ basis set.

Enhanced precision of ankle torque measure with an open-unit dynamometer mounted with a 3D force-torque sensor.

PURPOSE: Many studies have focused on maximum torque exerted by ankle joint muscles during plantar flexion. While strength parameters are typically measured with isokinetic or isolated ankle dynamometers, these devices often present substantial limitations for the measurement of torque because they account for force in only 1 dimension (1D), and the device often constrains the body in a position that augments torque through counter movements. The purposes of this study were to determine the contribution of body position to ankle plantar-flexion torque and to assess the use of 1D and 3D torque sensors. METHODS: A custom designed 'Booted, Open-Unit, Three dimension, Transportable, Ergometer' (B.O.T.T.E.) was used to quantify plantar flexion in two conditions: (1) when the participant was restrained within the unit (locked-unit) and (2) when the participant's position was independent of the ankle dynamometer (open-unit). Ten young males performed maximal voluntary isometric plantar-flexion contractions using the B.O.T.T.E. in open and locked-unit mechanical configurations. RESULTS: The B.O.T.T.E. was reliable with ICC higher than 0.90, and CV lower than 7 %. The plantar-flexion maximal resultant torque was significantly higher in the locked-unit compared with open-unit configuration (P < 0.001; +61 to +157 %) due to the addition of forces from the body being constrained within the testing device. A 1D compared with 3D torque sensor significantly underestimated the proper capacity of plantar-flexion torque production (P < 0.001; -37 to -60 %). CONCLUSIONS: Assessment of plantar-flexion torque should be performed with an open-unit dynamometer mounted with a 3D sensor that is exclusive of accessory muscles but inclusive of all ankle joint movements.

Photolysis of astrophysically relevant acrylonitrile: a matrix experimental study.

This report documents the photochemical study of H2C ═ C(H)CN (acrylonitrile) trapped in low-temperature argon matrices and irradiated with a microwave-discharge hydrogen-flow lamp (λ > 120 nm). We succeeded in identifying H2C ═ C(H)NC (isoacrylonitrile) as a photoproduct. HC3N (cyanoacetylene), C2H2:HCN (acetylene:hydrogen cyanide), and C2H2:HNC (acetylene:hydrogen isocyanide) complexes, which are molecules detected in molecular clouds or in the Titan atmosphere, were also identified. No imine product was observed, but other compounds coming from the HC3N photolysis have been found. Fourier transform infrared measurements and (2)H substitution experiments coupled with density functional theory calculations (B3LYP/6-31G**) were performed to confirm the spectral assignments of the photochemical products and intermediate species.

[Macrophage activation syndrome: rare complication of murine typhus]. / Syndrome d'activation macrophagique: complication rare de typhus murin.

INTRODUCTION: Typhi is one of the rickettsial species endemic in the Mediterranean countries and is associated with the zoonotic infection of murine typhus, which may have a complicated course especially in adult patients. The association with macrophage activation syndrome (MAS) has rarely been reported in the medical literature. CASE REPORT: We describe a case of murine typhus in a diabetic woman complicated with MAS, who was effectively treated with cyclin and parenteral immunoglobulin. CONCLUSION: The murine typhus can be exceptionally complicated with SAM. This infection should be suspected in front of the discovery of SAM.

[Bartonella quintana meningoencephalitis in an immunocompetent: rare case]. / Méningo-encéphalite à Bartonella quintana chez un sujet immunocompétent : une observation rare.

INTRODUCTION: Bartonella quintana (Bq) is responsible of various clinical pictures. Neuromeningeal complications are rarely reported. CASE: A 20-year-old woman was admitted for fever, headache lasting for 5 days. On admission, she was febrile at 39.3°C and had a stiff neck. Symptoms, contact with animals, biological tests and lumbar puncture (PL) rendered viral meningitis a likely diagnosis. She had received symptomatic treatment and the outcome was favorable. Three days later, the patient had headache, agitation and confusion with fever. The PL noted 130/mm(3) whites, 90% lymphocytes. The albuminorachie was 0.98 g/L, glucorachie was normal. The patient was treated with 400 mg of ofloxacine/day, seven days. Serologic tests for B. quintana were reactive. The outcome was favorable. CONCLUSION: B. quintana infection should be considered in neurological symptoms of unknown etiology.

[Visceral leishmaniasis in immunocompetent adults. About six cases]. / La leishmaniose viscérale de l'adulte immunocompétent. À propos de six cas.

OBJECTIVE: Studying the epidemiological variations of visceral leishmaniasis in Tunisia and proving the importance of parasitological investigations to raise the diagnosis. PATIENTS AND METHODS: Six patients hospitalised during the period between January 1998 and January 2009 at Fattouma Bourguiba Teaching Hospital in Monastir, five men and an only one woman, aged from 26 to 70 years old, originating from the central and eastern regions of the country. Epidemiological, clinical, biological and therapeutic data were obtained from the patient's medical files. RESULTS: The major clinical symptoms were fever, weakness and spleen enlargement. Biological data revealed the presence of anaemia in every case and leucopoenia associated or not associated with thrombopenia in four cases. The diagnosis of visceral leishmaniasis was confirmed by the identification of the parasite in the blood or in the bone marrow. All patients were treated with two courses of antimoniate of meglumine separated by a 6-week interval. The outcome was positive and the patients were cured. CONCLUSION: Visceral leishmaniasis is increasing among adults in Tunisia. Moreover, it is spreading outside its epidemiological area in the north to reach the central and southern regions. It should be raised when fever and spleen enlargement occur. Biological data are hardly specific. Diagnosis is based on finding the parasite in human fluids, mainly by molecular techniques. The rapid establishment of a specific treatment is vital.

[Relationship between temperature and mortality in the city of Tunis: 2005-2007]. / Relation temperature-mortalite pour la ville de Tunis: 2005-2007.

The influence of thermal stress on health is proved. In the light of the current climate change this relationship should be extensively investigated. This study aims to describe the relationship between temperature and total mortality in the city of Tunis over a period of three years, from 2005 to 2007 using time series analysis. The form of the relation (crude and adjusted) between mortality and temperatures was investigated using Poisson generalized additive models (GAM). Confounders included in the models were pollutant, trend, calendar month, day of the week, the period of Ramadan, and holidays. The adjusted relationship between mortality and temperature was "V" shaped with a steeper slope for low temperatures than for high temperatures. The impact of heat on mortality will be further analyzed to refine our findings and to contribute to the elaboration of guidelines for preventive strategies.

Toll-like-Receptor Gene Polymorphisms in Tunisian Endemic Pemphigus Foliaceus.

Pemphigus foliaceus (PF) is considered to be caused by the combined effects of susceptibility genes and environmental triggers. The polymorphisms of Toll-like receptors (TLRs) genes have been associated with the risk of various autoimmune diseases. The aim of this study was to evaluate the potential association of TLR2-3-4 and 7 gene polymorphisms with Tunisian PF. Fourteen polymorphisms were analyzed in 93 Tunisian PF patients compared to 193 matched healthy controls: rs5743703-rs5743709 and (GT)n repeat (TLR2); rs5743305, rs3775294, and rs3775291 (TLR3), rs4986790 and rs4986791 (TLR4); and rs3853839 (TLR7). Our results showed that the genetic factors varied depending on the epidemiological feature stratification. In fact, in the whole population, no association with the susceptibility to PF was found. The TLR2 GT repeat seems to be closely associated with PF risk in patients originated from the endemic localities (group 3); the GT18 allele and the heterozygous genotype GT18/GT19 seem to confer risk to endemic PF (P = 0.02; OR = 2.3 [1.1-4.9] and P = 0.0002, OR = 20 [2.5-171], respectively). In contrast, the GT23 repeat could be considered as protector allele (P = 0.02, OR = 0.2 [0.06-0.87]). Furthermore, medium GT alleles which induce high promoter activity were also significantly more frequent in patients versus short or long GT repeats (P = 0.0018 with OR = 3.26 [1.5-7]). On the other hand, the TLR3-rs574305 AA genotype and A allele were significantly more frequent in patients whose age of the onset was above 35 years (group 2) (P = 0.038, OR = 1.78 and P = 0.009, OR = 3.92, respectively). Besides, the TLR4>rs3775294 A allele was found to be protector only in patients with sporadic features (groups 2 and 4) (P = 0.03, OR = 0.57 [0.3-0.9] and P = 0.006, OR = 0.24 [0.08-0.74], respectively). No statistically significant difference was observed in the genotypic and allelic frequencies of TLR-4 and TLR-7 gene polymorphisms. The present data suggest that TLR2and TLR3 polymorphisms are significantly associated with increased susceptibility to PF in the Tunisian population.

Mediterranean spotted fever as a cause of septic shock.

Mediterranean spotted fever is a generally benign disease but with the potential of serious manifestations. We report a case of Mediterranean spotted fever in a 56-year-old woman, with pet dog exposure, who presented with a septic shock pattern. Based on clinical symptoms, history, and laboratory results, the diagnosis of Mediterranean spotted fever was suspected and the outcome was favorable with doxycycline treatment. Although rickettsiae remain an uncommon cause of the sepsis syndrome, it is important to consider it, especially as people are now traveling to endemic areas more frequently.

Assessment of EGFR mutation status in Tunisian patients with pulmonary adenocarcinoma.

BACKGROUND: Despite recent advances, non-small cell lung cancer carries a grim prognosis. For appropriate treatment selection, the updated guidelines recommend broad molecular profiling for all patients with pulmonary adenocarcinoma. Precise histological subtyping and targeted epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) testing are mandatory. METHODS: Herein, we assessed the EGFR mutation status of 26 formalin fixed-paraffin embedded (FFPE) samples of lung adenocarcinoma. Mutational analysis concerned exons 18-21 of EGFR by real-time polymerase chain reaction (Real time-PCR) using the Therascreen EGFR RGQ PCR mutation kit. ALK status was established on 22 among 26 patients using D5F3 antibody with a fully automated Ventana CDx technique. RESULTS: Activating EGFR mutations were found in 3 men among 26 patients (11.5%). Positive ALK expression was found in 2 cases among 22 patients (9.09%). CONCLUSION: Frequency of EGFR mutations in pulmonary adenocarcinomas of our series is similar to that found in the European ones with some particularities. The mutations detected are uncommon. Whereas, we found a high frequency of positive ALK expression in our series compared to frequency reported in literature. Further studies with larger Tunisian series are required to obtain more conclusive results.

[Demographic, clinical and therapeutic features of adult visceral leishmaniasis at the Rabta hospital in Tunis (tunisia) from 1983 to 2002]. / Aspects épidémiologiques, cliniques et thérapeutiques de la leishmaniose viscérale de l'adulte à l'hôpital de la Rabta à Tunis (tunisie) entre 1983 et 2002.

The purpose of this study was to evaluate in a retrospective analysis, cases of Mediterranean visceral leishmaniasis (VL) diagnosed in adults during a 20-year period in a department of infectious diseases. Demographic data, clinical and laboratory features and therapeutic findings were considered. During the study period, 22 cases of VL were diagnosed, and 6 (27%) were associated with HIV infection. Fever and splenomegaly were observed in all cases. Anaemia was constant. The anti-leishmanial IF titer was positive among 21 patients (95%). Smears from bone marrow aspiration were positive at microscopy in 95% of cases. Zymodeme analysis was carried out in nine isolates. L. infantum zymodeme MON-1 was characterized in all cases. Seventeen patients (77%) received meglumine antimoniate (MA) (20 mg SbV/kg per day) and 5 (23%) patients amphotericin B (AB) (0.5-1 mg/kg per day) for an average period of 25 days (10-49 days). Adverse events occurred in 7 patients (32%), among them 4 received AB. Clinical cure was achieved with success in 21 patients (95%). After a successful MA treatment of the initial episode, VL relapse was observed in one HIV-positive patient. Only one HIV-positive patient died from neurological disorders. VL is rare in adults. However, its incidence is increasing everywhere in the world, because of HIV-related cases. Its prognosis depends on the precocity of diagnosis and treatment.

[Meningitis revealing Rickettsia typhi infection]. / Méningite révélant une infection à Rickettsia typhi.

INTRODUCTION: Neurological manifestations are rarely observed in murine typhus. We present a case of meningitis caused by Rickettsia typhi. EXEGESIS: We report a case of Tunisian 57-year-old woman admitted for suspicion of meningitis. Clinical examination revealed fever at 39,5 degrees C and nuchal rigidity. There were no focal neurologic signs, cutaneous rash or eschar. Lumbar puncture showed clear cerebrospinal fluid containing normal glucose, 0,48 g/l protein and 30 WBC (78% lymphocyte). Gram-stained smear and culture were negative. Serology confirmed the diagnosis. The patient was initially treated by ampicillin 12 g daily but remained febrile. Retinal lesions were detected on ophthalmic examination, suggesting rickettsial infection. Clinical outcome was good after 7-day treatment with oral ciprofloxacin 1,5 g daily. The mean follow-up was six months. CONCLUSION: Murine typhus is an endemic zoonosis. Neurological manifestations were uncommon. An ophthalmic examination is recommended if rickettsiosis was suspected.

[Effect and bioaccumulation of heavy metals (Zn, Cd) on Micractinium pusillum ALGA]. / Effet et bioaccumulation des metaux lourds (Zn, Cd) chez l'algue Micractinium pusillum.

Heavy metals (Zn and Cd) effect and their bioaccumulation by a microalga Micractinium pusillum were investigated. Results showed that Cd was more toxic than Zn on Micractinium pusillum. Indeed, inhibitory concentrations of 50% of alga population in 72h (IC(50,72h)) were 0.28 and 0.34 mg l(-1) respectively for Cd and Zn. On the other hand, metal extracted rates from medium solution were more important for Zn than for Cd, essentially for the two first concentrations tested (0.06 and 0.12 mg l(-1)). Furthermore, Zn and Cd extracted proportions were more important for the low concentrations tested and decreased progressively with increasing concentrations applied. This mechanism of extraction corresponds principally to their biosorption by Micractinium pusillum.

[Prevalence of diabetes-related autoantibodies in celiac disease]. / Prévalence des marqueurs sérologiques du diabète de type 1 chez les enfants atteints de maladie coeliaque.

THE AIM: of this study is to investigate the prevalence of diabetes-related autoantibodies in a group of children with celiac disease and to compare it with a control group. MATERIAL AND METHODS: We recruited 31 celiac children at diagnosis (on gluten containing diet) and 31 age and sex matched healthy children. Anti-islet cell antibodies (ICA) were detected by indirect immunofluorescence on monkey pancreas. Anti-glutamate decarboxylase (anti-GAD) and anti-tyrosine phosphatase (anti-IA2) antibodies were assessed by a radio-immuno- precipitation method. RESULTS: Three out of 31 celiac patients (9.7%) had one or more diabetes-related autoantibodies. ICA, anti-GAD and anti-IA2 were found in respectively 3.2%; 3.2% and 9.7% of patients. Only one control (3.2%) had anti-GAD. There was no statistically significant difference between the 2 groups. CONCLUSION: The risk to develop diabetes seems to be the same in celiac patients and in healthy subjects thus screening of diabetes-related autoantibodies is not justified in celiac patients.

[Pyogenic splenic abscesses. A review of 8 cases]. / Les abcès de la rate à pyogènes. A propos de 8 cas.

PURPOSE: Pyogenic splenic abscess is un uncommon and potentially life-threatening disease. Due to inconspicuous and nonspecific clinical picture, it remains a diagnostic challenge. Medical imaging progresses are helpful for diagnosis and treatment. METHODS: We tried to establish epidemiologic and clinical features and therapeutic possibilities of 8 cases of splenic abscesses occurred between 1993 and 2002. RESULTS: There were 5 male patients and 3 female patients. Aged ranged from 17 to 53 years, with a median of 34 years. One patient was immunocompromised (colonic carcinoma). Common clinical presentations included fever (n=8) and left upper quadrant abdominal pain (n=7). Positive blood cultures were found in only four patients (50%) : Staphylococcus aureus (3) and coagulase negative Staphylococcus (1). Staphylococcus aureus and Bacteroïdes fragilis were isolated in one abscess pus respectively. The diagnosis was obtained by ultrasonography in all 8 cases. Antibiotics were prescribed in all cases for a mean length of 60 days (30 - 110 days). Splenectomy and percutaneous CT-guided drainage were performed in one case respectively. Evolution was good in all cases. CONCLUSION: Splenic abscesses are increasingly recognized. The combination of clinical features and imaging findings, early diagnosis and treatment can be made.

[Phalengeal actinomycosis: a rare disease]. / Actinomycose des os du pied: un diagnostic à ne pas méconnaître.

INTRODUCTION: Bone involvement in actinomycosis is rare. EXEGESIS: We report a case of a 38 year-old woman with foot bone actinomycosis. The clinical symptoms were non-specific and the diagnosis was difficult. An X-ray revealed an osteolysis and a sclerosis of the proximal phalanx of the big toe. A phalengiectomy was carried out after the failure of antistaphylococcic antibiotherapy. The diagnosis of actinomycosis was substantiated by a histological examination. The clinical outcome was good after six-month treatment by penicillin G substitutes for cotrimoxazol. The patient completely recovered and was feeling well. The mean follow up was fifteen months. CONCLUSION: Clinical and therapeutic aspects of this rare localization are reviewed.