Publications by authors named "Ahmed Abid"

31 Publications

[IManagement of patients with relapsed primary naso-sinusal tuberculosis].

Pan Afr Med J 2020 12;36:84. Epub 2020 Jun 12.

Service de Pneumologie, Hôpital Militaire d'Instruction Mohamed V, Rabat, Maroc.

Primary naso-sinusal tuberculosis (TB) is a relatively rare or exceptional disorder characterized by polymorphic or non-specific clinical manifestation. Diagnosis is based on anatomo-pathological examination and mycobacteriology test of biopsy specimen. Predictor of good outcome is early conventional anti-tuberculous antibiotic therapy. However, our study reports recurrence at this rare site in an immunocompetent patient despite early suitable TB treatment and good adherence with therapy. Relapse was correlated with underdosing of rifampicin. This study highlights the diagnostic, etiological and therapeutic management of this relapse. Our experience could help clinicians to better manage this uncommon condition.
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http://dx.doi.org/10.11604/pamj.2020.36.84.13067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392870PMC
December 2020

Typical presentation of pulmonary lepidic adenocarcinoma: a rare case report.

Pan Afr Med J 2020 11;36:11. Epub 2020 May 11.

Department of Pathology, Military Hospital Mohamed V, Rabat, Morocco.

Bronchioloalveolar carcinoma (BAC) is a rare subtype of adenocarcinoma of lung with distinct features and distinctive characteristics. It accounts approximately for 4% of lung cancers. In the following study we report a rare observation of a 50 years old female with a clinical, radiological and histological presentation, which is typical of an invasive mucinous lepidic adenocarcinoma formerly named BAC.
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http://dx.doi.org/10.11604/pamj.2020.36.11.22660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7282614PMC
December 2020

Evaluation of GeneXpert MTB/RIF system performances in the diagnosis of extrapulmonary tuberculosis.

BMC Infect Dis 2019 Dec 19;19(1):1069. Epub 2019 Dec 19.

Epidemiology and bacterial resistance research team/BIO-INOVA Centre, Faculty of Medicine and Pharmacy (University Mohammed V), Rabat, Morocco.

Background: Tuberculosis represents a serious public health problem and a significant diagnostic and therapeutic challenge worldwide. Molecular diagnostic techniques are crucial in the World Health Organization's new tuberculosis control strategy. This study aims to evaluate the performance of GeneXpert MTB/RIF (Cepheid Sunnyvale, CA, United States) in diagnosis of extra-pulmonary tuberculosis then compare it's performance in detecting Rifampicin resistance to GenoType MTBDRplus (HAIN Life Sciences, Nehren, Germany).

Methods: Samples from pulmonary and/or extra-pulmonary origins were analysed in a 21 months retrospective study. Samples were sent to the bacteriology laboratory for Mycobacterium tuberculosis detection using conventional bacteriological and molecular methods (GeneXpert MTB/RIF and MTBDRplus). Sensitivity and specificity were calculated for the stained smear and GeneXpert according to culture (Gold Standard) as well as for GeneXpert MTB/RIF in both negative and positive microscopy tuberculosis cases. Data's statistical analysis was performed with SPSS13.0 software.

Results: Seven hundred fourteen patients' samples were analysed; the average age was 47.21 ± 19.98 years with a male predominance (66.4%). Out of 714 samples: 285 were from pulmonary and 429 were from extra-pulmonary origins. The positivity rates for microscopy, GeneXpert MTB/RIF and culture were 12.88, 20.59 and 15.82%, respectively. These rates were 18.9, 23.85 and 20.35% for pulmonary samples and 9.71, 18.41 and 12.82% for extra-pulmonary samples, respectively. The sensitivity and specificity of GeneXpert MTB/RIF were almost the same in both pulmonary and extra-pulmonary samples (78.2 and 90.4%) and (79,3 and 90.3%) respectively. Rifampicin resistance rate found by GeneXpert MTB/RIF was 0.84%. Comparison of Rifampicin resistance obtained by GeneXpert MTB/RIF and Genotype MTBDRplus, showed 100% agreement between the two techniques for studied samples.

Conclusions: This confirms GeneXpert MTB/RIF advantage for tuberculosis diagnosis, particularly extra-pulmonary tuberculosis with negatively stained smear. The performance of GeneXpert and Genotype MTBDRplus are similar in detection of Rifampicin resistance. However, variability of detection performance according to tuberculosis endemicity deserves more attention in the choice of screening techniques of Rifampicin resistance, hence the interest of conducting comparative studies of detection performance under low and medium endemicity on large samples of tuberculosis populations.
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http://dx.doi.org/10.1186/s12879-019-4687-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924055PMC
December 2019

Prevalence and risk factors for latent tuberculosis infection among healthcare workers in Morocco.

PLoS One 2019 15;14(8):e0221081. Epub 2019 Aug 15.

Genetics Unit, Military Hospital Mohamed V, Rabat, Morocco.

Increased prevalence of latent tuberculosis infection (LTBI) has been observed among high-risk populations such as healthcare workers (HCWs). The results may depend on the method of LTBI assessment, interferon-gamma release assay (IGRA) and/or tuberculin skin test (TST). Here, we investigated the prevalence and risk factors for LTBI assessed by both IGRAs and TST in HCWs living in Morocco, a country with intermediate tuberculosis (TB) endemicity and high BCG vaccination coverage. HCWs were recruited in two Moroccan hospitals, Rabat and Meknes. All the participants underwent testing for LTBI by both IGRA (QuantiFERON-TB Gold In-Tube, QFT-GIT) and TST. Different combinations of IGRA and TST results defined the LTBI status. Risk factors associated with LTBI were investigated using a mixed-effect logistic regression model. The prevalence of LTBI among 631 HCWs (age range 18-60 years) varied from 40.7% (95%CI 36.9-44.5%) with QFT-GIT to 52% (95%CI 48.2-56.0%) with TST using a 10 mm cut-off. The highest agreement between QFT-GIT and TST (κ = 0.50; 95%CI 0.43-0.56) was observed with the 10 mm cut-off for a positive TST. For a definition of LTBI status using a double positive result for both QFT-GIT and TST, significant associations were found with the following risk factors: being male (OR = 2.21; 95%CI 1.40-3.49; p = 0.0007), belonging to age groups 35-44 years (OR = 2.43; 95%CI 1.45-4.06; p = 0.0007) and even more 45-60 years (OR = 4.81; 95%CI 2.72-8.52; p = 7.10-8), having a family history of TB (OR = 6.62; 95%CI 2.59-16.94; p = 8.10-5), and working at a pulmonology unit (OR = 3.64; 95%CI 1.44-9.23; p = 0.006). Smoking was associated with LTBI status when defined by a positive QFT-GIT result (OR = 1.89; 95%CI 1.12-3.21; p = 0.02). A high prevalence of LTBI was observed among HCWs in two Moroccan hospitals. Male gender, increased age, family history of TB, and working at a pulmonology unit were consistent risk factors associated with LTBI.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0221081PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6695119PMC
March 2020

[Spinal cord compression in a patient with tuberculous spondylodiscitis].

Pan Afr Med J 2018 10;31:101. Epub 2018 Oct 10.

Service Pneumologie, Hôpital Militaire d'Instruction Mohamed V, Rabat, Maroc.

We here report the case of a 76-year old patient admitted to Pulmonology Department with tuberculous spondylodiscitis diagnosed on the basis of clinical signs including weight loss, prolonged fever and stabbing lumbar pain occurred 2 months before. The diagnosis was confirmed by lumbar CT scan and by Genexpert TB test on lumbar fluid taken from the abnormal L1 vertebral body, which showed mycobacterium tuberculosis. Three weeks after the beginning of treatment the patient had motor deficit in lower limbs followed by sensory deficit. These abnormalities were confirmed by MRI which showed abnormal L1 somatic signal with collapse of the vertebral body (A). These lesions enhanced after gadolinium injection (B) that also showed posterior cortical rupture with epiduritis. Radiological examination was performed which confirmed the diagnosis of spinal cord compression associated with TB spondylodiscitis. A few days after, the patient had severe sepsis complicated by septic shock after which he died. Spinal compression is rare in patients with spondylodiscitis. It has a high potential for irreversible complications in the absence of early treatment for spinal cord decompression. Surgery and early antibacillar treatment ensure favorable outcome in the medium and long term.
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http://dx.doi.org/10.11604/pamj.2018.31.101.17054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462379PMC
May 2019

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common missense variant.

Sci Immunol 2018 12;3(30)

St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, Rockefeller University, New York, NY, USA.

Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls ( = 8.37 × 10; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-α, IL-10, or even IL-12, which, like IL-23, induces IFN-γ via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis.
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http://dx.doi.org/10.1126/sciimmunol.aau8714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341984PMC
December 2018

A Rare Cause of Chronic Pulmonary Embolism: Hydatid Cyst.

Arch Bronconeumol 2019 02 10;55(2):101. Epub 2018 Aug 10.

Pulmonology Department, Mohammed V Military University Hospital, Rabat, Morocco, Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco.

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http://dx.doi.org/10.1016/j.arbres.2018.07.003DOI Listing
February 2019

Multi-Layer Self-Nanoemulsifying Pellets: an Innovative Drug Delivery System for the Poorly Water-Soluble Drug Cinnarizine.

AAPS PharmSciTech 2018 Jul 25;19(5):2087-2102. Epub 2018 Apr 25.

Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, Egypt.

Beside their solubility limitations, some poorly water-soluble drugs undergo extensive degradation in aqueous and/or lipid-based formulations. Multi-layer self-nanoemulsifying pellets (ML-SNEP) introduce an innovative delivery system based on isolating the drug from the self-nanoemulsifying layer to enhance drug aqueous solubility and minimize degradation. In the current study, various batches of cinnarizine (CN) ML-SNEP were prepared using fluid bed coating and involved a drug-free self-nanoemulsifying layer, protective layer, drug layer, moisture-sealing layer, and/or an anti-adherent layer. Each layer was optimized based on coating outcomes such as coating recovery and mono-pellets%. The optimized ML-SNEP were characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD), in vitro dissolution, and stability studies. The optimized ML-SNEP were free-flowing, well separated with high coating recovery. SEM showed multiple well-defined coating layers. The acidic polyvinylpyrrolidone:CN (4:1) solution presented excellent drug-layering outcomes. DSC and XRD confirmed CN transformation into amorphous state within the drug layer. The isolation between CN and self-nanoemulsifying layer did not adversely affect drug dissolution. CN was able to spontaneously migrate into the micelles arising from the drug-free self-nanoemulsifying layer. ML-SNEP showed superior dissolution compared to Stugeron® tablets at pH 1.2 and 6.8. Particularly, on shifting to pH 6.8, ML-SNEP maintained > 84% CN in solution while Stugeron® tablets showed significant CN precipitation leaving only 7% CN in solution. Furthermore, ML-SNEP (comprising Kollicoat® Smartseal 30D) showed robust stability and maintained > 97% intact CN within the accelerated storage conditions. Accordingly, ML-SNEP offer a novel delivery system that combines both enhanced solubilization and stabilization of unstable poorly soluble drugs.
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http://dx.doi.org/10.1208/s12249-018-0990-7DOI Listing
July 2018

Prevalence, antibiotic resistance, and MLST typing of Helicobacter pylori in Algiers, Algeria.

Helicobacter 2017 Dec 16;22(6). Epub 2017 Oct 16.

French National Reference Center for Campylobacters and Helicobacters, Laboratoire de Bactériologie, Hôpital Pellegrin, & INSERM U 1053, Université de Bordeaux, Bordeaux, France.

Background: Helicobacter pylori infection is common in Algeria, but there are few data on the characterization of isolated strains. The aim of this study was to update data on the prevalence of H. pylori in patients submitted to endoscopy, antibiotic resistance, and phylogeography of H. pylori strains isolated in Algiers.

Materials And Methods: This is a prospective study carried out between November 2015 and August 2016. The culture of H. pylori was performed on antral and fundic gastric biopsies of adult patients from 3 hospitals. A real-time PCR using the fluorescence resonance energy transfer (FRET) principle for the detection of H. pylori followed by a melting curve analysis for the detection of mutations associated with resistance to clarithromycin was applied. Differentiation between antral and fundic isolates of the same patient was also determined by RAPD, and an MLST typing was performed for characterization of the phylogeographic group of H. pylori.

Results: By real-time PCR, the prevalence of H. pylori infection among the 147 patients included was 57%. Culture was positive in only 29% of the cases. Twenty-seven percent of patients had received H. pylori eradication treatment. The primary and secondary resistance rates to clarithromycin were 23% and 36%, respectively, and to metronidazole, 45% and 71%, respectively. Only one isolate was resistant to levofloxacin, and no resistance to amoxicillin, tetracycline, and rifampicin was detected. A double population was present in 14 patients. The MLST analysis classified the 42 H. pylori strains from 38 patients in 2 haplotypes: hpEurope (33) and hpNEAfrica (9).

Conclusion: The prevalence of H. pylori remains high in Algeria but appears to be decreasing in recent years. High resistance to clarithromycin requires increased monitoring of the evolution of antibiotic resistance and adaptation of eradication therapy.
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http://dx.doi.org/10.1111/hel.12446DOI Listing
December 2017

[Swelling of the pectoralis muscle revealing isolated muscular tuberculosis].

Pan Afr Med J 2017 18;27:44. Epub 2017 May 18.

Service de Pneumologie, Hôpital Militaire et d'Instruction Mohammed V, Rabat, Maroc.

Soft tissue tuberculosis is one of the rare forms of extrapulmonary tuberculosis. Furthermore, isolated muscular tuberculosis is exceptional. We here report the original case of a young immunocompetent patient with isolated muscular tuberculosis involving major pectoralis muscle. The diagnosis was mainly based on histology. The patient was successfully treated with anti bacterial therapy only. This rare case study has been combined with a literature review.
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http://dx.doi.org/10.11604/pamj.2017.27.44.12419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5516675PMC
August 2017

Micropellets coated with Kollicoat Smartseal 30D for taste masking in liquid oral dosage forms.

Drug Dev Ind Pharm 2017 Sep 16;43(9):1548-1556. Epub 2017 May 16.

a College of Pharmacy , Freie Universität Berlin , Berlin , Germany.

The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3 weeks, which exceeds the usual period of application.
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http://dx.doi.org/10.1080/03639045.2017.1323910DOI Listing
September 2017

[A rare cause of posterior mediastinal tumors: mediastinal hydatid cyst].

Pan Afr Med J 2016 27;25:122. Epub 2016 Oct 27.

Service de Pneumologie, Hôpital Militaire d'Instruction Mohammed V, Rabat, Maroc.

Mediastinal hydatid cyst is extremely rare even in endemic areas, representing 0-4% of all hydatid cyst locations. We report the case of a 50-year old patient admitted to our Department with a mass in the left dorsal paraspinal region; chest X-ray showed posterior left basal opacity. Chest CT scan showed posterior mediastinal mass located in the left costovertebral gutter extending from D9 to D11. MRI confirmed the existence of a posterior mediastinal mass with endocanalar extension and spinal cord compression, first evoking cystic schwannoma. These radioclinical data were consistent with a neoplastic origin; a transparietal biopsy was performed which showed a paucicellular specimen composed of translucent eosinophilic material with appearance just barely compatible with hydatid cyst. Hydatic serology was positive. The diagnosis of hydatid cyst was retained and the patient underwent thoracotomy which revealed mediastinal hydatid cyst, confirmed by histologic examination. The postoperative course was uneventful. Mediastinal location of hydatid cyst is very rare and poses a problem in differential diagnosis with other mediastinal tumors.
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http://dx.doi.org/10.11604/pamj.2016.25.122.9949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325506PMC
April 2017

Curing mechanism of flexible aqueous polymeric coatings.

Eur J Pharm Biopharm 2017 Jun 27;115:186-196. Epub 2017 Feb 27.

College of Pharmacy, Freie Universität Berlin, Germany. Electronic address:

The objective of this study was to explain curing phenomena for pellets coated with a flexible polymeric coating based on poly(vinyl acetate) (Kollicoat® SR 30D) with regard to the effect of starter cores, thickness of drug layer, adhesion of coating to drug-layered-cores as well as coating properties. In addition, appropriate approaches to eliminate the curing effect were identified. Sugar or MCC cores were layered with the model drugs carbamazepine, theophylline, propranolol HCl, tramadol HCl and metoprolol HCl using HPMC (5 or 25% w/w, based on drug) as a binder. Drug-layered pellets were coated with Kollicoat® SR 30D in a fluidized bed coater using TEC (10% w/w) as plasticizer and talc (35-100% w/w) as anti-tacking agent. Drug release, pellet properties (morphology, water uptake-weight loss and osmolality) and adhesion of the coating to the drug layer were investigated as a function of curing at 60°C or 60°C/75% RH for 24h. The film formation of the aqueous dispersion of Kollicoat® SR 30D was complete, and therefore, a strong curing effect (decrease in drug release) at elevated temperature and humidity (60°C/75% RH) could not be explained by the well-known hydroplasticization and the further gradual coalescence of the colloidal polymer particles. According to the provided mechanistic explanation, the observed curing effect was associated with (1) high flexibility of coating, (2) adhesion between coating and drug layer, (3) water retaining properties of the drug layer, and (4) osmotically active cores. Unwanted curing effects could be minimized/eliminated by the addition of talc or/and pore-forming water soluble polymers in the coating, increasing binder amount or applying an intermediate coating, by increasing the thickness of drug layer or using non-osmotic cores. A new insight into curing phenomena mainly associated with the adhesion between drug layer and coating was provided. Appropriate approaches to avoid unwanted curing effect were identified.
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http://dx.doi.org/10.1016/j.ejpb.2017.02.012DOI Listing
June 2017

[Severe pulmonary involvement in hypocomplementemic urticarial vasculitis (HUV)].

Pan Afr Med J 2016 28;24:285. Epub 2016 Jul 28.

Service de Pneumologie, Hôpital Militaire Mohamed V, Rabat, Maroc.

Pulmonary involvement in hypocomplementemic urticarial vasculitis (HUV) or Mac Duffie syndrome is extremely rare with a poor prognosis. We report the case of a 55-year-old female patient treated for HUV over a period of 20 years. The diagnosis was confirmed on the basis of urticarial lesions, ocular inflammation, positive C1q-p test by immunodiffusion, with low rate of C1q. The patient was treated with cycles of cyclophosphamide, corticoids and rituximab as she developed class III dyspnea (NYHA classification ). The clinico-radiological and functional assessment showed thoracic distension and severe obstructive pulmonary disease which found no significant improvement with systemic treatment Aerosol therapy was started and the patient had a marked clinical improvement. Pulmonary involvement in Mac Duffie hypocomplementemic urticarial vasculitis worsens the patient short-term vital prognosis. The knowledge of the different types of pulmonary involvement opens new therapeutic prospects.
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http://dx.doi.org/10.11604/pamj.2016.24.285.8168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5267844PMC
March 2017

[Tuberculous pyopneumothorax: about 18 cases].

Pan Afr Med J 2016 9;24:26. Epub 2016 May 9.

Service de Pneumologie de l'Hôpital Militaire d'Instruction Mohammed V, Rabat, Maroc.

Tuberculous pyopneumothorax is a rare but serious complication of evolutive pulmonary tuberculosis. We report a series of 18 cases with tuberculous pyopneumothorax admitted to the Pneumo-Phthisiology Department of the Mohammed V Military Teaching Hospital in Rabat between January 2005 and December 2009. Our study included 15 men and 3 women, the average age was 35 ± 7 years. 4 patients were diabetic. Smoking was found in 9 cases. Right-sided pneumothorax was found in 13 cases. Chest radiograph showed cavitary lesions in 15 patients and extensive bilateral lesions in 8 cases. The search for Mycobacterium tuberculosis in the fluid from the gastric tube was positive in 16 cases. Chest drainage associated with antituberculosis treatment according to the 2SRHZ/7RH regimen and respiratory kinesitherapy were performed in all cases. The average duration of pleural drainage was 4 weeks. In 3 cases we noted persistent pleural suppuration requiring pleural toilet using thoracoscopy with pleurectomy and limited pulmonary resection to eliminate tuberculous parenchymal lesions and the persistence of a large pleural pocket with restrictive ventilatory defect that required surgery for pleural decortication in two cases. The outcome was favorable with minimal pachypleuritis as sequelae in the remaining cases. Tuberculous pyopneumothorax is a severe form, which is often associated with active cavitary tuberculosis. Evolution is generally progressive despite antituberculosis treatment and thoracic drainage, hence the need for early diagnosis and treatment of all forms of tuberculosis.
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http://dx.doi.org/10.11604/pamj.2016.24.26.8675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992394PMC
March 2017

A case of Kartagener syndrome with rhinolalia clausa.

Pan Afr Med J 2016 6;23:159. Epub 2016 Apr 6.

Military Hospital, Pneumology Unit, University of Rabat, Morocco.

Kartagener syndrome is an autosomal recessive genetic ciliary disorder comprising of a classic triad of sinusitis, situs inversus and bronchiectasis. It's the one of primary ciliary dyskinesia disorders with manifestations present from childhood. Most patients of PCD have situs inversus. We present a case of 18 year-old women with recurrent lower and upper respiratory tracts infections, and rhinolalia clausa.
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http://dx.doi.org/10.11604/pamj.2016.23.159.8664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4894734PMC
February 2017

[Intramedullary metastasis of lung adenocarcinoma: about a case].

Pan Afr Med J 2015 14;20:37. Epub 2015 Jan 14.

Service de Pneumo-Phtisiologie, Hôpital Militaire d'Instruction Mohammed V, CHU Rabat, Maroc.

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http://dx.doi.org/10.11604/pamj.2015.20.37.5500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441140PMC
March 2016

Rapidly fatal Askin's tumor: a case report and literature review.

Pan Afr Med J 2014 30;18:104. Epub 2014 May 30.

Department of Pneumology, Mohamed V Military Teaching Hospital, Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, Morocco.

An 18-year-old male presented with a mass in the right anterior chest wall. Chest Computed tomography revealed a heterogenous mass of 19X13 cm in the right hemithorax with areas of necrosis. There was associated pleural effusion and infiltration of the soft parts of the chest wall. Bronchoscopy showed a tumor in middle lobe bronchus. CT guided biopsy of the mass was performed. Histological examination showed small round tumor cells with scanty cytoplasm, the nuclei are large and hyperchromatic. The tumor cells were positive for CD99 and neuron specific enolase, negative for cytokeratin, leukocyte common antigen and myogenin. Based on these histologic and immunohistochemical findings, the diagnosis of askin's tumor was made. The extension assessment was negative and the patient was given chemotherapy. Two months later, our patient died. Askin's tumor is a rare, highly malignant tumor affecting children and young adults. It is classified as primitive neuroectodermal tumor of the thoracopulmonary region. Prognosis remains poor. In our case, several prognostic factors may explain the shirt 'term survival, despite no distant metastasis were found: important tumor size, impossibility of surgical treatment and pleural effusion.
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http://dx.doi.org/10.11604/pamj.2014.18.104.4549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232025PMC
August 2015

Association study of genes controlling IL-12-dependent IFN-γ immunity: STAT4 alleles increase risk of pulmonary tuberculosis in Morocco.

J Infect Dis 2014 Aug 8;210(4):611-8. Epub 2014 Mar 8.

Genetics Unit, Military Hospital Mohamed V, Hay Riad, Rabat, Morocco.

Background: Only a minority of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis. Genetic epidemiological evidence suggests that pulmonary tuberculosis has a strong human genetic component. Previous genetic findings in Mendelian predisposition to more severe mycobacterial infections, including by M. tuberculosis, underlined the importance of the interleukin 12 (IL-12)/interferon γ (IFN-γ) circuit in antimycobacterial immunity.

Methods: We conducted an association study in Morocco between pulmonary tuberculosis and a panel of single-nucleotide polymorphisms (SNPs) covering 14 core IL-12/IFN-γ circuit genes. The analyses were performed in a discovery family-based sample followed by replication in a case-control population.

Results: Out of 228 SNPs tested in the family-based sample, 6 STAT4 SNPs were associated with pulmonary tuberculosis (P = .0013-.01). We replicated the same direction of association for 1 cluster of 3 SNPs encompassing the promoter region of STAT4. In the combined sample, the association was stronger among younger subjects (pulmonary tuberculosis onset <25 years) with an odds ratio of developing pulmonary tuberculosis at rs897200 for GG vs AG/AA subjects of 1.47 (1.06-2.04). Previous functional experiments showed that the G allele of rs897200 was associated with lower STAT4 expression.

Conclusions: Our present findings in a Moroccan population support an association of pulmonary tuberculosis with STAT4 promoter-region polymorphisms that may impact STAT4 expression.
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http://dx.doi.org/10.1093/infdis/jiu140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4111910PMC
August 2014

[Do smokers know the harmful effects of tobacco?].

Pan Afr Med J 2014 3;19:127. Epub 2014 Oct 3.

Service de Pneumologie, Hôpital Militaire d'Instruction Mohammed V, Rabat, Maroc.

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http://dx.doi.org/10.11604/pamj.2014.19.127.5163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341264PMC
October 2015

Age-dependent association between pulmonary tuberculosis and common TOX variants in the 8q12-13 linkage region.

Am J Hum Genet 2013 Mar 14;92(3):407-14. Epub 2013 Feb 14.

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U980, Paris, France.

Only a small fraction of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB) in their lifetime. Genetic epidemiological evidence suggests a genetic determinism of pulmonary TB (PTB), but the molecular basis of genetic predisposition to PTB remains largely unknown. We used a positional-cloning approach to carry out ultrafine linkage-disequilibrium mapping of a previously identified susceptibility locus in chromosomal region 8q12-13 by genotyping 3,216 SNPs in a family-based Moroccan sample including 286 offspring with PTB. We observed 44 PTB-associated SNPs (p < 0.01), which were genotyped in an independent set of 317 cases and 650 controls from Morocco. A single signal, consisting of two correlated SNPs close to TOX, rs1568952 and rs2726600 (combined p = 1.1 × 10(-5) and 9.2 × 10(-5), respectively), was replicated. Stronger evidence of association was found in individuals who developed PTB before the age of 25 years (combined p for rs1568952 = 4.4 × 10(-8); odds ratio of PTB for AA versus AG/GG = 3.09 [1.99-4.78]). The association with rs2726600 (p = 0.04) was subsequently replicated in PTB-affected subjects under 25 years in a study of 243 nuclear families from Madagascar. Stronger evidence of replication in Madagascar was obtained for additional SNPs in strong linkage disequilibrium with the two initial SNPs (p = 0.003 for rs2726597), further confirming the signal. We thus identified around rs1568952 and rs2726600 a cluster of SNPs strongly associated with early-onset PTB in Morocco and Madagascar. SNP rs2726600 is located in a transcription-factor binding site in the 3' region of TOX, and further functional explorations will focus on CD4 T lymphocytes.
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http://dx.doi.org/10.1016/j.ajhg.2013.01.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591857PMC
March 2013

Encapsulation of water-soluble drugs by an o/o/o-solvent extraction microencapsulation method.

Int J Pharm 2011 May 26;409(1-2):89-95. Epub 2011 Feb 26.

College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.

A new o/o/o-solvent extraction microencapsulation method based on less toxic solvents is presented in this study. The drug is dissolved/dispersed into a poly(D,L-lactide)/or poly (D,L-lactide-co-glycolide) (PLGA) solution in a water-miscible organic solvent (e.g., dimethylsulfoxide or 2-pyrrolidone) (o(1)), followed by emulsification into an oil phase (o(2)) (e.g., peanut oil). This emulsion is added to the external phase (o(3)) to solidify the drug-containing polymer droplets. The polymer solvent and the oil are extracted in an external phase (o(3)) (e.g., ethanol), which is a nonsolvent for the polymer and miscible with both the polymer solvent and the oil. One major advantage of this method is the reduced amount of solvent/nonsolvent volumes. In addition, very high encapsulation efficiencies were achieved at polymer concentration of 20%, w/w for all investigated polymers and o(1)/o(2) phase ratios with ethanol as the external (o(3)) phase. The encapsulation efficiency was very low (<20%) with water as external phase. The particle size of the microparticles increased with increasing polymer concentration and o(1)/o(2) phase ratio and larger microparticles were obtained with 2-pyrrolidone compared to dimethylsulfoxide as polymer solvent (o(1)). After an initial burst, in vitro drug release from the microparticles increased for the investigated polymer as follows: Resomer(®) RG 506>RG 756>R 206. A third more rapid release phase was observed after 6 weeks with Resomer(®) RG 506 due to polymer degradation. Similar drug release patterns were obtained with the o/o/o and w/o/w multiple emulsion methods because of similar porous structures. This new method has the advantages of less toxic solvents, much lower preparation volume and solvent consumption and high encapsulation efficiencies when compared to the classical w/o/w method.
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http://dx.doi.org/10.1016/j.ijpharm.2011.02.029DOI Listing
May 2011

Reduction in burst release after coating poly(D,L-lactide-co-glycolide) (PLGA) microparticles with a drug-free PLGA layer.

Pharm Dev Technol 2012 Jan-Feb;17(1):66-72. Epub 2010 Sep 20.

College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169 Berlin, Germany.

The high initial burst release of a highly water-soluble drug from poly (D,L-lactide-co-glycolide) (PLGA) microparticles prepared by the multiple emulsion (w/o/w) solvent extraction/evaporation method was reduced by coating with an additional polymeric PLGA layer. Coating with high encapsulation efficiency was performed by dispersing the core microparticles in peanut oil and subsequently in an organic polymer solution, followed by emulsification in the aqueous solution. Hardening of an additional polymeric layer occurred by oil/solvent extraction. Peanut oil was used to cover the surface of core microparticles and, therefore, reduced or prevented the rapid erosion of core microparticles surface. A low initial burst was obtained, accompanied by high encapsulation efficiency and continuous sustained release over several weeks. Reduction in burst release after coating was independent of the amount of oil. Either freshly prepared (wet) or dried (dry) core microparticles were used. A significant initial burst was reduced when ethyl acetate was used as a solvent instead of methylene chloride for polymer coating. Multiparticle encapsulation within the polymeric layer increased as the size of the core microparticles decreased (< 50 µm), resulting in lowest the initial burst. The initial burst could be controlled well by the coating level, which could be varied by varying the amount of polymer solution, used for coating.
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http://dx.doi.org/10.3109/10837450.2010.513989DOI Listing
April 2012

Drug release from and sterilization of in situ cubic phase forming monoglyceride drug delivery systems.

Eur J Pharm Biopharm 2010 Aug 18;75(3):375-80. Epub 2010 Apr 18.

College of Pharmacy, Freie Universität Berlin, Berlin, Germany.

Since a monoglyceride-based cubic phase is too viscous to be injected parenterally, mixtures of monoglyceride, water and water-miscible cosolvents were investigated as low viscosity injectable in situ cubic phase-forming formulations. Upon contact with the release medium, a highly viscous cubic phase formed rapidly and served as an extended release matrix for the oligonucleotide drug. Extended drug release was obtained with all formulations. The drug release followed the square root of time relationship indicating a diffusion-controlled release mechanism. The release depended on the type of cosolvent and followed the order of ethanol>PEG 300>2-pyrrolidone>DMSO. Higher water or monoglycerides contents decreased the drug release because of an increased viscosity and increased swollen matrix thickness. The bioburden of different commercially available monoglycerides and of the prepared in situ cubic phase-forming formulations met USP XXIII requirements. Monoglycerides can be successfully sterilized by gamma irradiation or by autoclaving and the in situ cubic phase-forming formulations by autoclaving and aseptic filtration. The monoglycerides and in situ cubic phase-forming formulations retained their phase behaviour and release properties after sterilization.
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http://dx.doi.org/10.1016/j.ejpb.2010.04.004DOI Listing
August 2010

Effect of water-soluble polymers on the physical stability of aqueous polymeric dispersions and their implications on the drug release from coated pellets.

Drug Dev Ind Pharm 2010 Feb;36(2):152-60

Freie Universität Berlin, Berlin, Germany.

Purpose: To investigate the physical stability and drug release-related properties of the aqueous polymer dispersions Kollicoat((R)) SR 30 D and Aquacoat((R)) ECD (an ethylcellulose-based dispersion) in the presence water-soluble polymers (pore formers) with special attention to the potential flocculation of the polymer dispersions.

Methods: A precise characterization of the flocculation phenomena in undiluted samples was monitored with turbidimetric measurements using the Turbiscan Lab-Expert. Theophylline or propranolol HCl drug-layered pellets were coated with Kollicoat((R)) SR 30 D and Aquacoat((R)) ECD by the addition of water-soluble polymers polyvinyl pyrrolidone (Kollidon((R)) 30 and 90 F), polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat((R)) IR), and hydroxypropyl methylcellulose (Pharmacoat((R)) 603 or 606) in a fluidized bed coater Glatt GPCG-1 and drug release was performed according to UPS paddle method.

Results: Stable dispersions were obtained with both Kollicoat((R)) SR 30 D (a polyvinyl acetate-based dispersion) and Aquacoat((R)) ECD with up to 50% hydrophilic pore formers polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat((R)) IR) and polyvinyl pyrrolidone (Kollidon((R)) 30). In general, Kollicoat((R)) SR 30 D was more stable against flocculation than Aquacoat((R)) ECD. Stable dispersions were also obtained with higher amounts of water-soluble polymer or by reducing the concentration of the polymer dispersion. Flocculated dispersions resulted in porous films and, thus, in a sharp increase in drug release.

Conclusions: Kollicoat((R)) SR 30 D was more resistant to flocculation upon addition of water-soluble polymers than Aquacoat((R)) ECD. The continuous adjustment of drug release from Kollicoat((R)) SR 30-coated pellets was possible with Kollicoat((R)) IR amounts over a broad range.
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http://dx.doi.org/10.3109/03639040903410334DOI Listing
February 2010

Preparation of preformed porous PLGA microparticles and antisense oligonucleotides loading.

Eur J Pharm Biopharm 2009 Feb 25;71(2):264-70. Epub 2008 Sep 25.

College of Pharmacy, Freie Universität Berlin, Berlin, Germany.

The objective of this study was to load preformed highly porous microparticles with drug. The microparticles were prepared by a modified multiple emulsion (w/o/w) solvent evaporation method with the addition of pore formers (NaCl into the internal aqueous phase or of glycerol monooleate to the poly(lactide-co-glycolide) (PLGA) polymer phase). The drug-free solidified microparticles were then washed with either water (for NaCl) or hexane (for glycerol monooleate) to extract the pore formers. The drug was then loaded into the preformed porous microparticles by incubation in aqueous drug solutions followed by air- or freeze-drying. The drug was strongly bound to the polymeric surface with air-dried microparticles. A biphasic drug release with an initial rapid release phase (burst effect) was followed by a slower release up to several weeks. The initial burst was dependent on the drug loading and could be significantly reduced by wet (non-aqueous) temperature curing.
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http://dx.doi.org/10.1016/j.ejpb.2008.09.007DOI Listing
February 2009

Reduction in burst release of PLGA microparticles by incorporation into cubic phase-forming systems.

Eur J Pharm Biopharm 2008 Nov 23;70(3):765-9. Epub 2008 Jul 23.

College of Pharmacy, Freie Universität Berlin, Berlin, Germany.

A high initial burst release of an phosphorothioate oligonucleotide drug from poly(lactide-co-glycolide) (PLGA) microparticles prepared by the w/o/w solvent extraction/evaporation was reduced by incorporating the microparticles into the following glycerol monooleate (GMO) formulations: 1) pure molten GMO, 2) preformed cubic phase (GMO+water) or 3) low viscosity in situ cubic phase-forming formulations (GMO+water+cosolvent). The in situ cubic phase-forming formulations had a low viscosity in contrast to the first two formulations resulting in good dispersability of the microparticles and good syringability/injectability. Upon contact with an aqueous phase, a highly viscous cubic phase formed immediately entrapping the microparticles. A low initial burst and a continuous extended release over several weeks was obtained with all investigated formulations. The drug release profile could be well controlled by the cosolvent composition with the in situ systems.
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http://dx.doi.org/10.1016/j.ejpb.2008.07.008DOI Listing
November 2008