[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.

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.

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.

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.

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.

Epidemiological, clinical and laboratory features of murine typhus in central Tunisia.

OBJECTIVE: Murine typhus is an endemic zoonosis. It is difficult to diagnose because of its non-specific clinical manifestations. Our objective was to describe the epidemiological, clinical, laboratory, and treatment features of murine typhus. METHODS: We conducted a retrospective study of 73 adult patients hospitalized for murine typhus from 2006 to 2011. The diagnosis was confirmed by a single titer of IgM≥128 or by seroconversion to typhus group antigen identified by indirect fluorescent assay. RESULTS: The mean age of patients was 33.1 years (range, 13-68 years). Thirty-eight patients (52%) lived in rural or suburban areas; neither fleabites nor exposure to rats were reported. The most common clinical symptoms were: fever, headache, and myalgia. A maculopapular and non-confluent rash was observed in 47 patients (64.4%). No inoculation eschar was observed in any patient. Eight patients presented with interstitial pneumonia and two with lymphocytic meningitis. The diagnosis was confirmed by indirect fluorescence assay in every case. A single titer of IgM ≥ 128 was found in 62 (84.9%) cases. The other 11 cases were diagnosed by seroconversion. All patients were given antibiotics. Tetracyclines were prescribed in 57 cases (78%). The two patients presenting with meningitis were treated with fluoroquinolone. The outcome was favorable for all patients and no relapse was observed. CONCLUSION: The features of murine typhus are non-specific. The definitive diagnosis is based on serologic testing by indirect fluorescent assay. Cyclins were the most prescribed antibiotics.

[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.

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.

[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.

Polymorphisms of HLA microsatellite marker in Tunisian pemphigus foliaceus.

Pemphigus foliaceus (PF) is an autoimmune blistering skin disease that partly results from genetic factors, especially from human leucocyte antigen (HLA) class II genes. Several data have reported the involvement of microsatellite (STR) markers across different regions of the HLA in many auto-immune diseases. To test the hypothesis of the existence of a major HLA haplotype predisposing to PF, we analyzed six polymorphisms of microsatellite loci at 6p21.3-21.4 spanning HLA: D6S291, D6S273, TNFa, MICA, D6S265 and D6S276 in 81 PF patients compared to 123 healthy individuals recruited from the south of Tunisia. In this study, after Bonferroni's correction, 3 STR alleles from the TNFa locus were associated with the disease: the allele TNFa(∗)2 (p(c) = 4.2×10(-6)) and, at a lower level, the TNFa(∗)5 (p(c) = 0.014) as susceptibility alleles and TNFa(∗)6 (p(c) = 0.014) as protective ones. Furthermore, the expression of the TNFa(∗)2/TNFa(∗)5 genotype seem to confer susceptibility to PF (p = 0.00001, OR = 11.25). Interestingly, no significant LD was found between TNFa2/TNFa5 alleles and DRB1(∗)03/DRB1(∗)04 alleles. However, the multivariant regression analysis indicates that both the HLA class II and the TNFa alleles remained significant (p < 0.001). Although, these findings rejected our hypothesis on the existence of HLA susceptibility haplotype, they assessed the role of TNFa loci. Accordingly, TNFa seem to contribute to the aethiopathogenesis of Tunisian endemic PF may be by the induction of a high TNFα production which is known to enhance the autoimmune cascade of the disease.

Rhino-orbito-cerebral mucormycosis: five cases.

INTRODUCTION AND OBJECTIVE: Mucormycosis is an invasive fungal infection usually observed in immunocompromised patients. Mucormycosis is rapidly fatal without an early diagnosis and treatment. We report five patients of rhino-orbital-cerebral mucormycosis and a literature review. DESIGN: The medical records of five patients presenting with rhino-orbital-cerebral mucormycosis, admitted between January 1995 and December 2007, were analyzed. All patients underwent tissue biopsy. The histologic sections revealed the presence of non-septate hyphae of the order Mucorales. RESULTS: The five patients, three men and two women, between 27 and 61 years of age, were all diabetic. The main symptoms were exophthalmia (five patients), facial swelling (four patients), periorbital cellulitis (four patients), and cranial nerve palsy (four patients). Anterior rhinoscopy revealed palatine or nasal necrotic lesions in four patients. All presented with diabetic ketoacidosis and CT scan revealed rhino-orbital-cerebral involvement in every patient. All patients were given intravenous amphotericin B. Four patients underwent surgical debridement of necrotic tissue. Two patients survived. CONCLUSIONS: Mucormycosis is usually a fatal infection in diabetic patients. Early diagnosis should be based on imaging data and histology. Amphotericin B must be rapidly initiated and associated with aggressive surgical debridement to reduce mortality.