B Acad Nat Med Paris
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B Acad Nat Med Paris · Feb 2010
[Gene therapy of x-linked adrenoleukodystrophy using hematopoietic stem cells and a lentiviral vector].
X-linked adrenoleukodystrophy (ALD) is a severe demyelinating disease of the brain caused by a deficiency in ALD protein, an adenosine triphosphate--binding cassette (ABC) transporter encoded by the ABCD1 gene. ALD progression can be halted by allogeneic hematopoietic cell transplantation (HCT). We have developed a gene therapy strategy based on ABCD1 gene transfer to autologous hematopoietic stem cells (CD34+) by a lentiviral vector derived from HIV-1. ⋯ Autologous CD34+ cells were transduced ex vivo with an HIV derived vector the wild-type ABCD1 gene then re-infused after myeloablative treatment. Polyclonal reconstitution was detected up to 24 to 30 months, with between 9% and 14% of granulocytes, monocytes, and T and B lymphocytes expressing the ALD protein, strongly suggesting that the patients' hematopoietic stem cells have been successfully transduced. Cerebral demyelination halted after 14 to 16 months in two first treated patients an outcome similar to that achieved by allogeneic HCT These results suggest that lentiviral vectors are suitable for transferring therapeutic genes to hematopoietic stem cells, and provide the first example of successful gene therapy for a severe neurodegenerative disease.
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Idiopathic pulmonary fibrosis (IPF) is a severe disease with a median survival time of only 24-36 months. It is characterized by inexorably progressive respiratory failure and by acute exacerbations that are often rapidly fatal. ⋯ Many trials have recently been completed or are currently underway, but few results have been published. In the meantime, supportive treatment (oxygen therapy and rehabilitation), vaccination, and treatment of comorbidities (gastroesophageal reflux, sleep apnea) are recommended.
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B Acad Nat Med Paris · Jan 2010
[Locally advanced soft-tissue sarcomas. An innovating triad to avoid amputation: isolated limb perfusion, TNFalpha, and free microsurgical flap].
We retrospectively studied the benefits of isolated limb perfusion combined with TNFalpha administration and free flap reconstruction in locally advanced soft-tissue sarcomas of the limbs. Between 2000 and 2008, we treated 37 patients (22 women and 15 men) with locally advanced soft tissue sarcomas. The sarcomas were located in the lower and upper limbs in respectively 26 and 11 cases, and had a mean diameter of 15 cm and 12 cm, respectively. ⋯ Thirteen patients developed pulmonary metastases and seven of them died between the first and fifth years of follow-up. Isolated limb perfusion and free flap reconstruction permitted more extensive tumor excision. Amputation was avoided in 78% of our 37 patients, and early postoperative radiotherapy was possible in 25 cases.
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B Acad Nat Med Paris · Nov 2009
[Risk of importation of tropical diseases in metropolitan France: dectection, alert, response].
The French public health institute is responsible for promoting and coordinating threats the detection and assessment of health risks, and for suggesting possible responses. Transmissible diseases affecting both human and animal health are the focus of surveillance networks. Early detection of potential infectious threats is based on the screening of "alert signals" identified through routine surveillance networks and other systems. ⋯ This article examines specific cases illustrating the process of detection, risk analysis and response, with respect to infectious threats that are endemic in tropical regions and have the potential to be imported into metropolitan France. For both novel pathogens and exotic diseases--which, not being endemic in France, are less well known--the analysis and response process must regularly be adapted to the latest epidemiological, clinical and biological findings, taking interactions between the pathogen, host, and environment into consideration. The need to improve reaction times and risk assessment is also discussed.
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Among connective tissue diseases, pulmonary arterial hypertension (PAH) is frequently associated with systemic sclerosis and systemic lupus erythematosus. PAH is less common in mixed connective tissue diseases and Sjögren's syndrome, and rare in rheumatoid arthritis. ⋯ The prevalence of PAH among patients with systemic lupus erythematosus is poorly known; immunosuppressive treatment is sometimes effective by itself but most patients benefit from PAH treatment. PAH associated with connective tissue diseases has a worse prognosis than idiopathic PAH.