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Cappellini M.D.,University of Milan | Bejaoui M.,Center National Of Greffe Of Moelle Osseuse | Agaoglu L.,Istanbul University | Canatan D.,Suleyman Demirel University of Turkey | And 14 more authors.
Blood | Year: 2011

Patients with β-thalassemia require lifelong iron chelation therapy from early childhood to prevent complications associated with transfusional iron overload. To evaluate long-term efficacy and safety of once-daily oral iron chelation with deferasirox, patients aged ≥ 2 years who completed a 1-year, phase 3, randomized trial entered a 4-year extension study, either continuing on deferasirox (deferasirox cohort) or switching from deferoxamine to deferasirox (crossover cohort). Of 555 patients who received ≥ 1 deferasirox dose, 66.8% completed the study; 43 patients (7.7%) discontinued because of adverse events. In patients with ≥ 4 years' deferasirox exposure who had liver biopsy, mean liver iron concentration significantly decreased by 7.8 ± 11.2 mg Fe/g dry weight (dw; n = 103; P < .001) and 3.1 ± 7.9 mg Fe/g dw (n = 68; P < .001) in the deferasirox and crossover cohorts, respectively. Median serum ferritin significantly decreased by 706 ng/mL (n = 196; P < .001) and 371 ng/mL (n = 147; P < .001), respectively, after ≥ 4 years'exposure. Investigator-assessed, drug-related adverse events, including increased blood creatinine (11.2%), abdominal pain (9.0%), and nausea (7.4%), were generally mild to moderate, transient, and reduced in frequency over time. No adverse effect was observed on pediatric growth or adolescent sexual development. This first prospective study of long-term deferasirox use in pediatric and adult patients with β- thalassemia suggests treatment for ≤ 5 years is generally well tolerated and effectively reduces iron burden. This trial was registered at www.clinicaltrials-.gov as #NCT00171210. © 2011 by The American Society of Hematology.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.4.2-1 | Award Amount: 7.63M | Year: 2011

-thalassaemia major is one of the most severe forms of chronic congenital anaemia. The recommended treatment consists in regular blood transfusions combined with chelating therapy to remove harmful iron accumulation in the body. The use of deferoxamine, the first chelating agent only available for subcutaneous administration is limited due to toxicity and the lack of compliance, despite its satisfactory therapeutic effects. An oral iron chelating agent, deferiprone, was authorised in Europe in August 1999 and recommended for the treatment of iron overload in patients with thalassaemia major when deferoxamine is contraindicated or inadequate. Despite a wide experience of the administration of deferiprone for thalassaemic patients, limited data are available on its use in children below 10 years and the need for additional data in this age subset was clearly indicated in the 2009 priority list approved by the Paediatric Committee at the European Medicines Agency (PDCO). In addition, according to the recent scientific advancements and in consideration of the anticipated benefit of this chelator in controlling cardiac iron overload, studies evaluating the effects of the deferiprone in all the paediatric ages and in all transfusion-dependent chronic congenital anaemia (including Sickle Cell Diseases) were also considered a critical therapeutic need. The DEEP project, in line with these premises, has been funded with the specific aim to produce a new oral liquid formulation of deferiprone suitable for the paediatric use and to provide evidences for the use of this chelator as first line therapy in the whole paediatric population (from 1 month to 18 years) affected by transfusion-dependent chronic anaemia. The condition under study in the DEEP project is rare. This poses special difficulties in the conduct of the studies due to the small patient population and the need to involve a large number of recruiting centres . However, being dedicated to develop an orphan drug, DEEP has been also recognised in the context of IRDiRC, the International Rare Diseases Research Consortium devoted to repurpose/develop 200 new drugs for Rare Diseases by the end of 2020. Main features of the DEEP project are: -The innovative design of the clinical studies including pharmacokinetic modelling for the definition of the most appropriate dosage of deferiprone in younger children, the cardiac MRI T2* evaluation as primary endpoint, a three years safety study aimed at evaluating deferiprone, in monotherapy or in combination, in the real worlds setting and, for the first time, a comparative efficacy-safety trial to compare the two existing oral chelators: deferiprone and deferasirox. -The DEEP Consortium including European and non-European Countries from the Mediterranean region where the transfusion-dependent congenital anaemia, in particular -thalassemia major, is particularly widespread: the collaboration within a multinational and multicultural network makes the Project extremely challenging due to many different ethical, methodological and social approaches to be explored and positively addressed.


Bouchami O.,Center National Of Greffe Of Moelle Osseuse | Achou W.,Center National Of Greffe Of Moelle Osseuse | Ben Hassen A.,Center National Of Greffe Of Moelle Osseuse
African Journal of Microbiology Research | Year: 2011

This study was undertaken to determine the species distribution and antibiotic resistance patterns of coagulase-negative Staphylococci (CoNS) other than Staphylococcus epidermidis. A total of 142 CoNS (except S. epidermidis) strains were isolated from a variety of clinical specimens in neutropenic patients at the Bone Marrow Transplant Centre of Tunisia between 2002 and 2004. All CoNS isolates were further identified by Api ID32 STAPH and ITS-PCR and antibiotic sensitivity was performed by disc diffusion method. Staphylococcus haemolyticus was the commonest species (38%) followed by Staphylococcus hominis (36%). All isolates were sensitive to vancomycin and 8 (6%) strains showed a reduced sensitivity to teicoplanin. Resistance to penicillin G and methicillin was 84 and 60%, respectively. Methicillin-resistant CoNS strains were determined to be more resistant to antibiotics than methicillin-susceptible CoNS strains. The mecA gene was detected by PCR in 65% (92/142) CoNS isolates. Out of 92 mecA-positive isolates, 90 were phenotypically methicillin-resistant and two were methicillin-susceptible. Phylogenetic analysis, carried out to study the evolution of mecA genes between different Staphylococcal species, revealed a high homology for such genes among Staphylococci. © 2011 Academic Journals.


Mechergui A.,Center National Of Greffe Of Moelle Osseuse | Achour W.,Center National Of Greffe Of Moelle Osseuse | Ben Hassen A.,Center National Of Greffe Of Moelle Osseuse
World Journal of Microbiology and Biotechnology | Year: 2014

We aimed to compare accuracy of genus and species level identification of Neisseria spp. using biochemical testing and 16S rRNA sequence analysis. These methods were evaluated using 85 Neisseria spp. clinical isolates initially identified to the genus level by conventional biochemical tests and API NH system (Bio-Mérieux®). In 34 % (29/85), more than one possibility was given by 16S rRNA sequence analysis. In 6 % (5/85), one of the possibilities offered by 16S rRNA gene sequencing, agreed with the result given by biochemical testing. In 4 % (3/85), the same species was given by both methods. 16S rRNA gene sequencing results did not correlate well with biochemical tests. © 2014 Springer Science+Business Media Dordrecht.


Mechergui A.,Center National Of Greffe Of Moelle Osseuse | Achour W.,Center National Of Greffe Of Moelle Osseuse | Hassen A.B.,Center National Of Greffe Of Moelle Osseuse
Reviews in Medical Microbiology | Year: 2014

Although the clinically important members Neisseria gonorrhoeae and Neisseria meningitidis are relatively straightforward to identify, the differences between many of the nonpathogenic strains remain small and the speciation of these strains within a diagnostic setting is not always possible. We aim to provide an overview of laboratory identification methods used for commensal Neisseria characterization. This document focuses on a number of approaches that have been used to explore the relationships and species assignment of the genus Neisseria, including conventional biochemical methods, DNA-DNA hybridization, real-time PCR, 16S rRNA gene sequencing, analysis of the housekeeping gene fragments used in the multilocus sequence typing approach, whole genome sequencing and matrix-assisted laser desorption ionization time-of-flight. New methods exploiting next-generation sequencing genome data to classify bacterial genomes have the advantage of providing strain resolution within a given species. © 2014 Wolters Kluwer Health I Lippincott Williams & Wilkins.


Ben Ammar I.,Institute National Of Nutrition | Ksouri H.,Center National Of Greffe Of Moelle Osseuse | Trabelsi N.,Institute National Of Nutrition | Mellouli F.,Center National Of Greffe Of Moelle Osseuse | And 3 more authors.
Acta Diabetologica | Year: 2012

Allergy to insulin became a rare complication due to the introduction of recombinant human insulin preparations. Nevertheless, allergic reactions to components of such preparations can occur. We report a case of a 61-year-old man with an atopic background and affected by diabetes mellitus type 2 since 27 years, who experienced generalized allergy to insulin at the moment of switching oral anti-diabetics to insulin. Prick tests revealed an allergy specifically to zinc, and the patient was treated with zinc-free glulisine insulin. After 8 months of such treatment, patient's glucose is stable and he never experienced allergic reactions to insulin injections. Even insulin allergy due specifically to zinc is rare, such complication must be assessed especially in a patient suffering from multiple allergies. © 2010 Springer-Verlag.


Bejaoui M.,Center National Of Greffe Of Moelle Osseuse | Guirat N.,Center National Of Greffe Of Moelle Osseuse
Mediterranean Journal of Hematology and Infectious Diseases | Year: 2013

Beta-thalassemia major (TM) remains to be one of the major health problems particularly in developing countries. Tunisia is a part of the Mediterranean countries mostly affected by this disease which is highly concentrated in small towns in families with low-income earners. The main objectives of this study are to provide a description of the demographic, clinical features and transfusion-related complications in patients with TM living in Tunisia. A standardized questionnaire was sent to clinicians throughout 33 different medical institutions caring for thalassemic patients. 391 transfusion dependant thalassemic patients with a median age of 10.7 years (range 3 months-31 years) were included in the study. The majority originated from the north west of the country.A moderate iron overload between 1501 and 2500 ng/ml was found in 61patients, while 81 patients (26.9%) had a ferritin level more than 2500 ng/ml and greater than 5000ng/ml in 21 patients (6.9%). 51 patients died from complications related to their disease. Heart failure was the main cause of death. The incidence of cardiac, endocrine, and infectious complications will be reviewed. Preventive measures such as health education, carrier screening and premarital screening remain the best ways for lowering the incidence of these diseases, which might be reflected in financial saving, social s and health benefits.


Mechergui A.,Center National Of Greffe Of Moelle Osseuse | Achour W.,Center National Of Greffe Of Moelle Osseuse | Giorgini D.,Institute Pasteur Paris | Baaboura R.,Center National Of Greffe Of Moelle Osseuse | And 2 more authors.
APMIS | Year: 2013

Multilocus sequence typing and pulsed-field gel electrophoresis were used to type 22 commensal isolates of Neisseria perflava collected by swabbing from neutropenic patients. High genetic diversity was found among our N. perflava clinical isolates. © 2012 APMIS. Published by John Wiley & Sons Ltd.


Touati A.,Center National Of Greffe Of Moelle Osseuse | Pereyre S.,Bordeaux University Hospital Center | Bouziri A.,Service de Reanimation Polyvalente | Achour W.,Center National Of Greffe Of Moelle Osseuse | And 4 more authors.
Diagnostic Microbiology and Infectious Disease | Year: 2010

Specific microbiologic, molecular, and serologic assays are hardly available in Tunis to confirm a suspected infection of Mycoplasma pneumoniae (MP). These diagnosis methods were used for the first time in a Tunisian prospective study to estimate the prevalence of MP infection in children and to evaluate their usefulness for diagnosis. A total of 540 children hospitalized in Tunis for lower respiratory tract infections (LRTIs) between 2005 and 2009 and 580 clinical specimens were investigated for the presence of MP by culture and by end-point polymerase chain reaction (PCR) targeting the P1 and the 16S rRNA genes. Real-time PCR was also used for MP detection on 158 respiratory samples. A total of 525 serum samples were tested for detection of MP-specific IgM and IgG. The P1 adhesin type and the antibiotic susceptibility testing were determined for the 9 clinical strains isolated during the study period. MP was detected in 33 (5.7%) clinical samples. Specific MP seropositivity was confirmed in 54 serum samples (10.3%), among which 19 (3.6%) were indicative of acute MP infection. MP infection was confirmed in 39 (7.2%) patients: 24 positive by PCR and/or culture, 10 serologically positive only, and 5 confirmed positive by both methods. MP infections occurred throughout the year with a slight decrease in autumn. The 9 MP isolates were susceptible to erythromycin, tetracycline, and ciprofloxacin, and all belonged to type I. The prevalence of MP infection in children with LRTI was 7.2% between 2005 and 2009, in Tunisia. Combination of direct detection and serology was required to enhance the clinical sensitivity of MP detection in clinical specimens. © 2010 Elsevier Inc.


PubMed | Tunis el Manar University and Center National Of Greffe Of Moelle Osseuse
Type: Journal Article | Journal: Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion | Year: 2016

Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. We evaluated the effects of polymorphic markers within the -globin gene cluster to identify the genetic mechanics that influence HbF on Tunisian sickling patients (n=242). Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the framework polymorphism was established by PCR-sequencing, four independent regions of interest were identified: the 5 region of -LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal (G and A) genes and the 5 region of -globin gene. The correlation of these various Haplotypes and SNPs with HbF expression and clinical data was studied. Our data showed that among the various polymorphic markers analyzed, only the sequence (AT)xN12(AT)y in LCR HS2 region was significantly associated (p<0.05) with increased HbF levels, suggesting that the -globin gene cluster exerts a significant effect on HbF in sickle cell patients. This study can improve understanding of the physiopathology of the disease and aid to increase our ability to predict clinical severity.

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