[Fight against tuberculosis in the world]. / La lutte antituberculeuse dans le monde.

Tuberculosis (TB) in a major health problem in the world. WHO and its partners especially, the stop TB partnership launched numerous strategies against TB especially in the 1990. Strategy DOTS (directly observed therapy short course) was launched in 1995. One main key was the direct supervision of drug intake by patients. Progress was achieved but it was insufficient. A new strategy called "Stop TB Strategy 2006-2015" was launched in 2006 in the context of Millennium Development Goals (MDG) elaborated by United Nations. The common goals were to halt and start to reverse the incidence of TB, reduce the prevalence and death rate by 50% compared to their level in 1990 by 2015 to eliminate TB as a public health problem by 2050. The end of 2010 marks the mid-point of the Global Plan and is an obvious time to update it and take into account actual progress with a focus on the 2015 to reach goals. So an updated Global Plan to stop TB 2011-2015, was launched. Expected progress and targets were defined for 2015, in diagnosis and treatment, in co-infection TB/HIV, in drug-resistant TB and achievements expected in new tests for diagnosis, new medications, new vaccines and new regimens with shorter duration of treatment. WHO and partners have started discussions to define the new post 2015 strategy to TB control and elimination. Risk factors (diabetes, malnutrition, tobacco smoke…) and socioeconomic factors, which are associated with TB, should be included in the new strategy to eliminate TB in 2050.

[Epidural emphysema complicating bronchial asthma]. / Emphysème épidural compliquant un asthme bronchique.

Epidural emphysema is an exceptional complication of bronchial asthma, revealed by an incidental finding in chest tomography. We report a case of a 21-year-old man admitted with asthma attack complicated by subcutaneous and mediastinal emphysema. Chest tomography confirmed the mediastinal emphysema and also revealed the epidural emphysema within the vertebral canal. Neurological examination was negative. The patient showed complete recovery 10days after the onset of symptoms. The epidural emphysema is a rare complication during asthma attacks. The benignity of this complication should not require a systematic chest tomography.

[Spontaneous pneumothorax associated with ankylosing spondylitis]. / Pneumothorax spontané au cours de la spondylarthrite ankylosante.

Ankylosing spondylitis (AS) is a chronic inflammatory disease that affects the axial skeleton and more frequently the sacro-iliac joints. Pleuropulmonary involvement is an uncommon event. Apical fibrosis, interstitial infiltrates, and pleural thickening are thought to be the main patterns. Rare cases of spontaneous pneumothorax were reported in the literature. A 62-year-old man, who had a diagnosis of AS since May 1994, was admitted for exertional dyspnea. The diagnosis of apical fibrosis related to AS was essentially based on radiological arguments. The patient was again hospitalized in 2011 for thoracic pain. Computed tomography of the chest revealed a right partial pneumothorax. The evolution was marked by the total regression of the pneumothorax under oxygen and strict rest.

[Choroid metastases revealing pulmonary adenocarcioma resolved with chemotherapy]. / Métastases choroïdiennes révélatrices d'un adénocarcinome bronchique et involuant sous chimiothérapie.

Lung cancer is the leading cause of choroidal metastasis in men, but choroidal metastasis is rarely inaugural. With the advent of new generations of chemotherapy molecules non-small-cell lung cancer (NSCLC) has become more chemosensitive. Choroidal metastasis may respond to chemotherapy. We report a case of a 52-year-old men who developed choroidal metastasis revealing pulmonary adenocarcinoma confirmed by the bronchial biopsy. Systemic chemotherapy using gemcitabine-cisplatin led to total involution of the choroidal metastasis with improvement of the visual acuity in one eye and stabilization in the other. Systematic search for lung cancer is required in patients presenting choroidal metastasis. If compatible with the patient's general status, histologically-adapted chemotherapy must be instituted. This approach can avoid the use of radiotherapy and therefore deterioration of visual acuity after radiation.

Alginate-diltiazem hydrochloride beads: optimization of formulation factors, in vitro and in vivo availability.

Alginate beads containing diltiazem hydrochloride (DTZ) were prepared by the ionotropic gelation method. The effects of various factors (alginate concentration, additives type, calcium chloride concentration and curing time) on the efficiency of drug loading were investigated. The formulation containing a mixture of 0.8% methylcellulose (MC) and 4% alginate cured in 2% calcium chloride for 6 h was chosen as the best formula regarding the loading efficiency. The release rate of DTZ from various beads formulations was investigated. The release of drug from alginate beads followed two mechanisms; by diffusion and relaxation of the polymer at pH 1.2, whilst diffusion and erosion are at pH 6.8. The in vitro release of DTZ from MC-alginate beads showed an extended release pattern which was compared with that from commercially available sustained-release (Dilzem SR) and fast release tablets (Dilzem). Thermal analysis revealed that the drug was molecularly dispersed in the beads matrix. Although the release characteristics of DTZ from Dilzem SR and MC-alginate beads were completely different, the bioavailability of DTZ in dogs was comparable as measured by AUC, MRT and relative bioavailability. The absolute bioavailability of MC-alginate beads and Dilzem SR was 88 and 93%, respectively.

In vitro and in vivo evaluation of Pluronic F127-based ocular delivery system for timolol maleate.

The purpose of this study was to develop Pluronic F127 (PF127) based formulations of timolol maleate (TM) aimed at enhancing its ocular bioavailability. The effect of isotonicity agents and PF127 concentrations on the rheological properties of the prepared formulations was examined. In an attempt to reduce the concentration of PF127 without compromising the in situ gelling capabilities, various viscosity enhancing agents were added to PF127 solution containing 0.5% TM. The viscosity and the ability of PF127 gels to deliver TM, in vitro, in absence and presence of various viscosity enhancing agents were also evaluated. At the used concentration, some of the examined isotonicity agents had effect on the viscosity of TM gel. However, the viscosity of gel increased as the PF127 concentrations increased. The viscosity of formulations containing thickening agents was in the order of PF-MC 3%>PF-HPMC 2%>PF-CMC 2.5%>PF127 15%. The slowest drug release was obtained from 15% PF127 formulations containing 3% methylcellulose. In vivo study showed that the ocular bioavailability of TM, measured in albino rabbits, increased by 2.5 and 2.4 fold for 25% PF127 gel formulation and 15% PF127 containing 3% methylcellulose, respectively, compared with 0.5% TM aqueous solution.

Preparation and evaluation of ketoprofen floating oral delivery system.

A sustained release system for ketoprofen designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microparticles by the emulsion-solvent diffusion technique. Four different ratios of Eudragit S100 (ES) with Eudragit RL (ERL) were used to form the floating microparticles. The drug retained in the floating microparticles decreased with increase in ERL content. All floating microparticle formulations showed good flow properties and packability. Scanning electron microscopy and particle size analysis revealed differences between the formulations as to their appearance and size distribution. X-ray and DSC examination showed the amorphous nature of the drug. Release rates were generally low in 0.1 N HCl especially in presence of high content of ES while in phosphate buffer pH 6.8, high amounts of ES tended to give a higher release rate. Floating ability in 0.1 N HCl, 0.1 N HCl containing 0.02% Tween 20 and simulated gastric fluid without pepsin was also tested. The formulation containing ES:ERL1:1 (FIII) exhibited high percentage of floating particles in all examined media.

A repeat polymorphism in interleukin-4 gene is highly associated with specific clinical phenotypes of asthma.

BACKGROUND: IL-4 is a determining factor in immunologic mechanisms to allergy and inflammation. The authors designed a case-controlled study to investigate the potential association of a repeat polymorphism in IL-4 gene with specific clinical phenotypes of asthma. METHODS: The authors used the polymerase chain reaction to characterize the variation of the IL-4 intron 2 region in 145 unrelated Tunisian patients with asthma and 160 healthy control subjects. In order to strengthen the case-controlled study, analysis of IL-4 polymorphism was performed in families of several asthmatic patients. Asthma scores were determined and correlated with this polymorphism. RESULTS: Analysis of IL-4 polymorphism in patients with allergic asthma and in control subjects demonstrated a significant association between the IL-4 A1 allele and asthma. Further evidence of the strong association found between IL-4 intron 2 polymorphism and asthma was provided by the finding that asthma is transmitted in association with the inheritance of the IL-4 A1 marker. When patients were stratified into two groups according to the degree of the severity of asthma, the IL-4 A1 allele was specifically not associated with mild asthma, but highly associated with the moderate and severe forms of the disease. The relative risk (RR) of severe asthma is especially high in patients carrying the A1/A3 genotype (RR = 3.94, p = 0.0001). Conversely, a major decrease in the frequency of the IL-4 A3/A3 genotype was observed in patients with severe asthma, resulting in a significantly negative RR of this clinical phenotype of asthma (RR = 0.165, p = 0.0001). CONCLUSIONS: Tunisian persons carrying the IL-4 A1/A3 genotype may have an increased risk of severe asthma.

Manipulation of powder characteristics by interactions at the solid-liquid interface: 1-sulphadiazine.

A solvent-treatment technique aiming at manipulating the properties of powdered materials is reported. Potentials of the technique were assessed using sulphadiazine (SD). A suspension of the drug in a preselected solvent (5% aqueous ammonia solution) was stirred under controlled conditions. The solvent was subsequently removed and the material dried. The effect of experimental variables such as stirring speed and time, powder/solvent ratio and inclusion of additives (Tween 80, sodium chloride and PVP) on the properties of solvent treated SD was assessed. Data obtained were compared with those for SD recrystallized under identical conditions. Solvent treatment of SD in the absence of additives resulted in a limited change in crystal morphology as indicated by SEM. This was associated with improved flowability and a limited reduction in dissolution rate relative to untreated SD. On the other hand, recrystallized SD exhibited superior flowability but a considerably low dissolution rate. Solvent treatment of SD in the presence of 2% PVP produced a microgranular directly compressible material.

[Diffuse interstitial pulmonary fibrosis and bronchial cancer]. / Fibrose pulmonaire interstitielle diffuse et cancer bronchique.

Mortality due to lung cancer was 25% (7/28) in this study of patients with diffuse interstitial pulmonary fibrosis. Opacities on the chest x-ray suggestive of lung cancer were observed in 5 of the 7 cases. All 7 had squamous cell carcinoma. The percentage of smokers was significantly higher in patients with pulmonary fibrosis who developed lung cancer than in those with fibrosis who did not develop lung cancer (p = 0.016). These 7 cases of lung cancer with pulmonary fibrosis were compared with 174 cases of lung cancer without associated fibrosis. Peripheral localizations and lower lobe involvement were higher in cases of lung cancer with pulmonary fibrosis.

Polymorphism in transporter antigen peptides gene (TAP1) associated with atopy in Tunisians.

BACKGROUND: Transporter antigen peptide 1 (TAP1) and TAP2 gene products from a transporter molecule involved in antigen presentation. Polymorphic residues have been described in both genes and could have functional consequences in the immune response. OBJECTIVE: We designed a case-control study to investigate the potential association of polymorphism of the TAP1 gene with atopy. METHODS: We used the amplification refractory mutation system polymerase chain reaction to characterize TAP1 gene polymorphism in 84 unrelated Tunisian patients with atopy and 81 healthy control subjects. RESULTS: Analysis of TAP1 polymorphism in Tunisian patients with atopy and in unaffected control subjects demonstrates a high relative risk (RR) of atopy in carriers of a codon (d) corresponding to a glycine at position 637 of the TAP1-B and TAP1-D alleles. The relative risk of allergic asthma is markedly higher in homozygotes (d/d) (RR = 22; p < or = 0.0001). The TAP1-D allele, not observed in European populations, has a frequency of 5% in the Tunisian control subject group. 4 major increase of the frequency (f) of the D allele is observed in patients with allergic asthma (f = 35%) and in those with allergic rhinitis (f = 22%), indicating a high relative risk of allergic asthma (RR = 10.2; p < 0.0001) and of allergic rhinitis (RR = 5.4; p < or = 0.005) in individuals carrying this allele. DD homozygotes were found only among patients with allergic asthma (23% of patients with asthma). Further evidence of the strong association between TAP1 polymorphism and atopy was provided by the finding that atopy is transmitted by inheritance of the glycine-637 marker. CONCLUSIONS: Tunisian persons carrying the glycine-637 of the TAP1 protein may have an increased risk of atopy. Specific association was found between the homozygous TAP1 D/D genotype and allergic asthma.

Pulmonary eosinophilia due to Trichomonas tenax.

A 39 year old woman was admitted with fever and an exacerbation of asthma. The chest radiograph showed extensive bilateral lung infiltrates, but transtracheal needle aspiration did not reveal any infectious organisms. The bronchoalveolar fluid lavage contained a large number of Trichomonas tenax and an increased percentage of eosinophils. Corticosteroids provided a dramatic response. Because of the relatively high frequency of colonisation of the human mouth by T tenax (about 20%), this organism should be considered in all cases of pulmonary eosinophilia.

[Functional contribution of inhalation spacers in the treatment of asthma]. / Apport fonctionnel des chambres d'inhalation dans le traitement de l'asthme.

The aim of this study is to evaluate the ventilatory gain obtained by using metered dose inhaler (MDI) plus spacer versus MDI alone in 30 asthmatic patients (19 men and 11 women); aged 30 to 70 years old. Initial spirometry showed air flow obstruction. A reversibility test was performed with beta 2 agonists: first with MDI and then, later, with MDI plus spacer. In 27 cases (90%) the improvement of FEVI, referring to its initial value, was significantly better with spacer. This improvement was equal or superior to 20% in 19 patients with spacer versus only 9 patients with MDI. The improvement of FEVI was always better with spacer which ever the ways of expressing the bronchodilating response (referring to initial, predicted or absolute value). in conclusion, since the treatment of asthma is now based on local administration of medications, it is recommended to use spacers not only for children and patients who have coordination problems but more widely specially in severe asthma.