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Flandre P.,French Institute of Health and Medical Research | Flandre P.,Laboratoire Of Virologie | Pugliese P.,Nice University Hospital Center | Cuzin L.,Hopital Purpan | And 9 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011

Background and objectives The main aim of this study was determining the risk factors of chronic kidney disease (CKD) in HIV-1-infected patients. Design, setting, participants, & measurements Patients were followed from seven large HIV reference centers in France that maintain prospective databases on HIV-1-infected patients. The main outcome was the time to CKD defined as two consecutive measures of estimated GFR ≤60 ml/min per 1.73 m2 over ≥3 months. A Cox's model with delayed entry was used to search predictive factors of time to CKD. Results From 1993 to 2006, 349 out of 7378 patients were found to have CKD. Of these, 166 had hypertension, 33 had diabetes, and 26 were antiretroviral therapy-naïve. Occurrence of acute kidney injury (hazard ratio [HR] = 2.40) and hypertension (HR = 2.39) were strongly associated with an increased risk of CKD. Patients with a durable level of CD4 count >200 cells/mm3 had a lower risk of CKD (HR = 0.63). Recent exposure to indinavir (HR = 2.03), totenofovir (HR = 1.55), and abacavir (HR = 1.37) were associated with an increased risk of CKD. Past exposure to tenofovir was also associated with an increased risk of CKD (HR = 2.23), and a trend toward significance was observed for past exposure to indinavir (HR = 1.28). Conclusions CKD was not rare in HIV-infected patients and occurs preferentially in HIV-infected patients exposed to certain ARVs, specifically abacavir, indinavir and tenofovir. This requires closer monitoring of renal function in patients exposed to one of these drugs. © 2011 by the American Society of Nephrology.

Merle H.,Center Hospitalier University Of Fort Of France | Olindo S.,Service de Neurologie | Jeannin S.,Service de Neurologie | Valentino R.,Center Hospitalier University Of Fort Of France | And 7 more authors.
Archives of Ophthalmology | Year: 2012

Objective: To assess the contribution of plasma exchange (PE) in association (add-on) with pulsed intravenous corticosteroids in acute optic neuritis of neuromyelitis optica (NMO) and limited forms of NMO. Methods: Thirty-six patients with optic neuritis were treated from January 1, 1995, through December 31, 2010, with pulsed intravenous corticosteroids and 16 with pulsed intravenous corticosteroids plus PE. The ophthalmologic examination was performed at least 6 months after optic neuritis treatment. Visual acuity and visual field assessed with the Snellen scale and the logarithmic scale of the Early Treatment Diabetic Retinopathy Study were measured using standard automated perimetry and frequency doubling technology perimetry. Retinal peripapillary fiber thickness was measured using optical coherence tomography. Results: Final visual acuity was 20/400 in the corticosteroid group and 20/50 in the PE group (P=.04). The gain in visual acuity was 20/200 in the corticosteroid group and 20/30 in the PE group (P=.01). A poor final visual acuity outcome (≤20/200) was found in 19 of 36 patients (53%) in the corticosteroid group and 2 of 16 patients (13%) in the PE group (P=.008). Mean (SD) thickness of peripapillary retinal nervous fibers was 63.1(20.4) μm in the corticosteroid group and 70.3(20.3) μm in the PE group (P=.16). The mean (SD) thickness in the temporal quadrant was 38.5(14.1) μm in the corticosteroid group and 44.5(12.7) μm in the PE group (P=.02). In multivariate analysis, PE treatment was the only independent factor associated with a visual acuity greater than 20/200. Conclusion: In optic neuritis associated with NMO, sequential treatment with pulsed intravenous corticosteroids and PE is more effective than standard monotherapy with corticosteroids on visual acuity outcome.

Olindo S.,Center Hospitalier University Of Fort Of France | Belrose G.,Center Hospitalier University Of Fort Of France | Gillet N.,University of Liège | Rodriguez S.,University of Liège | And 9 more authors.
Blood | Year: 2011

HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease of the central nervous system induced by human T-lymphotropic virus type 1. As a potential therapeutic approach, we previously suggested reducing the proviral load by modulating lysine deacetylase activity using valproic acid (VPA) and exposing virus-positive cells to the host immune response. We conducted a single-center, 2-year, open-label trial, with 19 HAM/TSP volunteers treated with oral VPA. Proviral load, CD38/HLA-DR expression, and CD8 + lysis efficiency were not significantly affected by VPA. Mean scores of HAM/TSP disability did not differ between baseline and final visit. Walking Time Test increased significantly (> 20%) in 3 patients and was in keeping with minor VPA side effects (drowsiness and tremor). Walking Time Test improved rapidly after VPA discontinuation. We conclude that long-term treatment with VPA is safe in HAM/TSP. © 2011 by The American Society of Hematology.

Hochedez P.,Center Hospitalier University Of Fort Of France | Hope-Rapp E.,Center Hospitalier University Of Pointe tre Abymes | Olive C.,Center Hospitalier University Of Fort Of France | Nicolas M.,Center Hospitalier University Of Pointe tre Abymes | And 2 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2010

Aeromonas species are Gram-negative bacilli of the water environment whose survival appears facilitated by warm climates. There have been no reports on Aeromonas hydrophila complex (A. hydrophila, A. caviae, A. veronii) in the Caribbean to date. Our aim was to describe clinical and bacteriological features in patients presenting with such bacteremia in Martinique and Guadeloupe. During a 14-year period, we retrospectively identified 37 patients. The mean age was 55 years and in 89% of cases underlying disease such as digestive diseases, cutaneous wounds, and malignancy were identified. One case was related to severe strongyloidiasis and one with snake bite. Polymicrobial bacteremia was identified in 38%, essentially with Enterobacteriaceae. All Aeromonas isolates were resistant to amoxicillin but extended-spectrum beta-lactam and fluoroquinolone were active against more than 95%. During hospitalization 10 patients died (27%). Older age, occurrence of multiorgan failure, and impaired renal function were associated with in-hospital mortality. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene.

Belrose G.,Center Hospitalier University Of Fort Of France | Gross A.,Montpellier University | Olindo S.,Center Hospitalier University Of Fort Of France | Lezin A.,Center Hospitalier University Of Fort Of France | And 8 more authors.
Blood | Year: 2011

A determinant of human T-lymphotropic virus-1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development is the HTLV-1-infected cell burden. Viral proteins Tax and HBZ, encoded by the sense and antisense strands of the pX region, respectively, play key roles in HTLV-1 persistence. Tax drives CD4+-T cell clonal expansion and is the immunodominant viral antigen recognized by the immune response. Valproate (2-n-propylpentanoic acid, VPA), a histone deacetylase inhibitor, was thought to trigger Tax expression, thereby exposing the latent HTLV-1 reservoir to immune destruction. We evaluated the impact of VPA on Tax, Gag, and HBZ expressions in cultured lymphocytes from HTLV-1 asymptomatic carriers and HAM/TSP patients. Approximately one-fifth of provirus-positive CD4+ T cells spontaneously became Tax-positive, but this fraction rose to two-thirds of Tax-positive-infected cells when cultured with VPA. Valproate enhanced Gag-p19 release. Tax- and Gag-mRNA levels peaked spontaneously, before declining concomitantly to HBZ-mRNA increase. VPA enhanced and prolonged Tax-mRNA expression, whereas it blocked HBZ expression. Our findings suggest that, in addition to modulating Tax expression, another mechanism involving HBZ repression might determine the outcome ofVPAtreatment on HTLV-1-infected-cell proliferation and survival. © 2011 by The American Society of Hematology.

Schrage N.F.,Klinik fur Augenheilkunde | Struck H.G.,Universitatsklinik Und Poliklinik For Augenheilkunde | Gerard M.,Center Hospitalier University Of Fort Of France
Ophthalmologe | Year: 2011

With these recommendations the authors want to improve the acute therapy of eye burns based on the literature and clinical experience. Due to the lack of studies with high evidential value we base these recommendations on the results of experimental work and reports of successfully treated eye burns. A development of this document by systematic research is necessary. Despite the limited knowledge, the collated facts are the current state of the art of treatment according to the knowledge and research of the authors. The most important clinical recommendation is to rinse a chemically or thermally burnt eye as soon and as extensively as possible. Any delay worsens the prognosis. Substances on the market for first aid have different levels of clinical evidence. Thus saline and amphoteric diphoterine ® have been evaluated in a prospective clinical study showing an advantage for the amphoter. Water, borate buffer, phosphate buffers and derivatives have never been proven to work in clinical applications. Nevertheless, they are recommended. Within experimental work in vitro we could show the value of polyvalent decontamination. Side-effects of phosphate buffers have been demonstrated in retrospective clinical and prospective experimental studies so that even in cases of beneficial effects on pH we cannot recommend these substances which propagate corneal calcification. Special types of burns, such as hydrofluoric acid need special treatment but as clinical studies are lacking only experimental data can offer suitable recommendations. © 2011 Springer-Verlag.

Merle H.,Center Hospitalier University Of Fort Of France | Olindo S.,Center Hospitalier University Of Fort Of France | Donnio A.,Center Hospitalier University Of Fort Of France | Beral L.,Center Hospitalier University Of Fort Of France | And 3 more authors.
European Journal of Ophthalmology | Year: 2010

PURPOSE. To measure peripapillary retinal nerve fiber layer (RNFL) thickness and spatial and temporal contrast sensitivity in multiple sclerosis (MS) taking into account previous history of optic neuropathy (ON). METHODS. Thirty patients (60 eyes) with relapsing-remitting MS were selected (MS group). The MS ON group was composed of 31 eyes with previous history of optic neuropathy and the MS non-ON group of 29 eyes was without previous history of optic neuropathy. Thickness of the RNFL was measured with optical coherence tomography (OCT) with the Stratus OCT. As for sensitivity to spatial contrast, we used Pelli-Robson and Sloan charts. Sensitivity to temporal contrast was explored using frequency doubling technology perimetry (FDTP). RESULTS. The average thickness of RNFL in the MS, MS ON, MS non-ON, and control groups were 88.2±18.9 μm, 80.81±18.4 μm, 96.7±15.8 μm, and 106±12.2 μm, respectively. The spatial contrast vision and FDTP results were less in the MS non-ON group than in the control group. The average thickness of RNFL correlated to the scores of spatial and temporal contrast vision. CONCLUSIONS. MS is accompanied by visual function alteration even in the absence of acute optic neuropathy. The important correlation between functional and anatomic aspect confirms the value of OCT to appreciate the subclinical involvement of the optic nerve. Associated with tests exploring visual function, the OCT could reveal itself pertinent in evaluation of the different therapeutics used in MS ON. © 2010 Wichtig Editore.

Beral L.,Center Hospitalier University Of Fort Of France | Richer R.,Center Hospitalier University Of Fort Of France | Donnio A.,Center Hospitalier University Of Fort Of France | Merle H.,Center Hospitalier University Of Fort Of France
Canadian Journal of Ophthalmology | Year: 2010

Objective: The purpose of this study is to suggest an alternative surgery to mutilating exenteration and enucleation surgeries in the management of nonfunctional, unattractive, and painless eyes. The suggested alternative is lamellar keratectomy with conjunctiva recovery. Design: Retrospective study. Participants: Four patient cases in a unit with the benefit of this technique. Methods: The surgical processes and results of the four cases were reviewed. Results: Postoperative results were most satisfactory with good esthetic results and, above all, a better psychological experience of surgery. Conclusions: For a nonfunctional, unattractive, and painless eye, lamellar keratectomy with conjunctiva recovery appears to be an appealing alternative to nonconservative eyeball surgeries.

Wingerchuk D.M.,Mayo Medical School | Banwell B.,Childrens Hospital of PhiladelphiaPA | Bennett J.L.,University of Colorado at Denver | Cabre P.,Center Hospitalier University Of Fort Of France | And 15 more authors.
Neurology | Year: 2015

Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) that is associated with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). Prior NMO diagnostic criteria required optic nerve and spinal cord involvement but more restricted or more extensive CNS involvement may occur. The International Panel for NMO Diagnosis (IPND) was convened to develop revised diagnostic criteria using systematic literature reviews and electronic surveys to facilitate consensus. The new nomenclature defines the unifying term NMO spectrum disorders (NMOSD), which is stratified further by serologic testing (NMOSD with or without AQP4-IgG). The core clinical characteristics required for patients with NMOSD with AQP4-IgG include clinical syndromes or MRI findings related to optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral presentations. More stringent clinical criteria, with additional neuroimaging findings, are required for diagnosis of NMOSD without AQP4-IgG or when serologic testing is unavailable. The IPND also proposed validation strategies and achieved consensus on pediatric NMOSD diagnosis and the concepts of monophasic NMOSD and opticospinal MS. © 2015 American Academy of Neurology.

Afonso P.V.,Institute Pasteur Paris | Mekaouche M.,French National Center for Scientific Research | Mortreux F.,French National Center for Scientific Research | Toulza F.,Imperial College London | And 10 more authors.
Blood | Year: 2010

Approximately 3% of all human T-lymphotropic virus type 1 (HTLV-1)-infected persons will develop a disabling inflammatory disease of the central nervous system known as HTLV-1-associated myelopathy/tropical spastic paraparesis, against which there is currently no efficient treatment. As correlation exists between the proviral load (PVL) and the clinical status of the carrier, it is thought that diminishing the PVL could prevent later occurrence of the disease. We have conducted a study combining valproate, an inhibitor of histone deacetylases, and azidothymidine, an inhibitor of reverse transcriptase, in a series of baboons naturally infected with simian T-lymphotropic virus type 1 (STLV-1), whose PVL was equivalent to that of HTLV-1 asymptomatic carriers. We show that the combination of drugs caused a strong decrease in the PVL and prevented the transient rise in PVL that is seen after treatment with histone deacetylases alone. We then demonstrate that the PVL decline was associated with an increase in the STLV-1-specific cytotoxic T-cell population. We conclude that combined treatment with valproate to induce viral expression and azidothymidine to prevent viral propagation is a safe and effective means to decrease PVL in vivo. Such treatments may be useful to reduce the risk of HAM/TSP in asymptomatic carriers with a high PVL. © 2010 by The American Society of Hematology.

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