Boisson-Dupuis S.,Rockefeller University |
Boisson-Dupuis S.,French Institute of Health and Medical Research |
Boisson-Dupuis S.,University of Paris Descartes |
Baghdadi J.E,Genetics Unit |
And 39 more authors.
PLoS ONE | Year: 2011
Background and Objectives: In the last decade, autosomal recessive IL-12Rβ1 deficiency has been diagnosed in four children with severe tuberculosis from three unrelated families from MAR, Spain, and TUR, providing proof-of-principle that tuberculosis in otherwise healthy children may result from single-gene inborn errors of immunity. We aimed to estimate the fraction of children developing severe tuberculosis due to IL-12Rβ1 deficiency in areas endemic for tuberculosis and where parental consanguinity is common. Methods and Principal Findings: We searched for IL12RB1 mutations in a series of 50 children from IRN, MAR, and TUR. All children had established severe pulmonary and/or disseminated tuberculosis requiring hospitalization and were otherwise normally resistant to weakly virulent BCG vaccines and environmental mycobacteria. In one child from IRN and another from MAR, homozygosity for loss-of-function IL12RB1 alleles was documented, resulting in complete IL-12Rβ1 deficiency. Despite the small sample studied, our findings suggest that IL-12Rβ1 deficiency is not a very rare cause of pediatric tuberculosis in these countries, where it should be considered in selected children with severe disease. Significance: This finding may have important medical implications, as recombinant IFN-γ is an effective treatment for mycobacterial infections in IL-12Rβ1-deficient patients. It also provides additional support for the view that severe tuberculosis in childhood may result from a collection of single-gene inborn errors of immunity. © 2011 Boisson-Dupuis et al. Source
Elomrani F.,National Institute of Oncology |
Zine M.,Military Hospital Mohamed V |
Afif M.,Oncology and Radiotherapy Institute |
L'annaz S.,National Institute of Oncology |
And 3 more authors.
Breast Cancer: Targets and Therapy | Year: 2015
Background: Breast cancer is a common condition. It is a leading cause of death among women, and its incidence increases with age. Aging of the population and improvement of the quality of life of elders make it a major public health issue. We reviewed the literature to try to determine the management of breast cancer in older women. Methods: We conducted a narrative review by literature searches using key words “breast cancer”, “elderly and older”, and “women” in Pubmed, Scopus, and Google Scholar. The aim of this review is to summarize the management of early breast cancer in older women by discussing the controversies of screening in older women. Then, we try to define the optimal strategy for these women, either surgery alone or primary endocrine therapy. We also discuss the indications of lymph node dissection, and we evaluate the benefit of adjuvant radiotherapy, chemotherapy, and the anti HER2 treatment for these women. Results: More than 50% of patients with breast cancer are 65 years or older, and around 30% are more than 70 years old. Most randomized trials did not include older women. Hence, the treatment of breast cancer in older patients is based on the management provided to younger women. Regardless of age, the treatment must aim for the best efficiency. Advanced age in itself should not be a limitation to treatment. There are no standard guidelines set for elderly patients. Surgical treatment for older patients evolved to avoid mastectomy, and conservative mammary surgery was proposed, similar to that used in younger patients. The proportion of elderly patients receiving adjuvant radiotherapy is increasing. The role of adjuvant radiotherapy in older patients with breast cancer was analyzed. Adjuvant chemotherapy is beneficial to women with hormone receptor-negative tumors. In those with hormone receptor-positive tumors, adjuvant chemotherapy in association to trastuzumab is beneficial for HER2-positive tumors, and for women with HER2-negative tumors adjuvant hormonal therapy is a very good option. Conclusion: Breast cancer is common in older women. This population requires particular and adapted management. It is essential for older patients to be included in new clinical trials for individualized treatment recommendation. © 2015 Elomrani et al. Source
Sinaa M.,Military Hospital Moulay Ismail |
Oukabli M.,Military Hospital Mohamed V |
Albouzidi A.,Military Hospital Mohamed V
Pan African Medical Journal | Year: 2014
Adenoid cystic carcinoma is a malignant epithelial neoplasm derived from the salivary glands. Primary adenoid cystic carcinoma of the cervix is extremely rare, accounting for less than 1% of all cervical carcinomas. Its origin is debatable. It generally presents in elderly age group, however only twenty three cases have been reported in women less than age 45 years old. In this paper we report two new cases of primary adenoid cystic carcinoma in younger women and include the cytopathology and histopathology findings. A 36, 41 year-old women were admitted with signs and symptoms suggestive of a cervical cancer. Speculum examination showed a firm mass in the uterine cervix. The diagnosis of adenoid cystic carcinoma was confirmed by the histopathology examination of the biopsy specimen in the two patients, which characteristically revealed the presence of a cribriform pattern and cylindromatous structures of the tumor cells, adhered around hyaline stoma. They were managed successfully by concurrent radiotherapy. Adenoid cystic carcinoma of the cervix is a rare disease. It usually occurs in an elderly age group. We report these two cases because of its rarity in young patients, with description of illustrative pathology and discussion on the histological diagnosis. © Mohamed Sinaa et al. Source
Grant A.V.,French Institute of Health and Medical Research |
Grant A.V.,University of Paris Descartes |
El Baghdadi J.,Genetics Unit |
Sabri A.,Genetics Unit |
And 31 more authors.
American Journal of Human Genetics | Year: 2013
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. © 2013 The American Society of Human Genetics. Source
Lezrek M.,Military Hospital Moulay Ismail |
El Harrech Y.,Military Hospital Mohamed V |
Bazine K.H.,Military Hospital Moulay Ismail |
Sossa J.,Military Hospital Mohamed V |
And 5 more authors.
Arab Journal of Urology | Year: 2013
Objectives: To report a technique of percutaneous endoscopic nephropexy, using a polyglactin suture passed through the kidney, in patients with nephroptosis. Patients and methods: Four women presenting with symptomatic right nephroptosis underwent a percutaneous endoscopic nephropexy. An upper-pole calyx was accessed percutaneously and a 24-F working sheath was placed. Another needle access was made through a lower-pole calyx and a #2 polyglactin suture was passed into the renal pelvis. It was then pulled out through the upper-pole tract using the nephroscope. A retroperitoneoscopy was performed and the tip of the nephroscope was used to cause nephrolysis. After inserting the nephrostomy tube the polyglactin suture was passed into the subcutaneous tissue and then tied without too much tension, to avoid cutting the parenchyma. Results: The operative duration was 33 min and the hospital stay after surgery was 3.5 days. The nephrostomy catheter was removed 5 days after surgery. There were no complications, especially no haemorrhagic, infectious, lithiasic or thoracic complications. The four patients were relieved of their initial symptoms, with a mean follow-up of 28 months. Ultrasonography and/or intravenous urography showed the kidney at a higher location with the patient standing. Conclusions: This technique combines the nephrostomy tract used in percutaneous techniques with the suture and nephrolysis used in laparoscopic techniques. Moreover, this procedure seems to be safe, with satisfactory anatomical and clinical results and a lower morbidity. However, a larger series will be necessary to establish its long-term morbidity and success rate. © 2012 Arab Association of Urology. Production and hosting by Elsevier B.V. All rights reserved. Source