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Tours, France

Duchesne M.,University of Poitiers | Mathis S.,University of Poitiers | Corcia P.,CHU Tours | Jaccard A.,Limoges University Hospital Center | Vallat J.-M.,Limoges University Hospital Center
Medicine (United States)

Hematological malignancies include several diseases that may affect the peripheral nervous system (PNS) through various mechanisms. A common and challenging situation is represented by the occurrence of an active peripheral neuropathy in a patient with a supposed inactive hematological disorder.We report clinical, electrophysiological, biological, and pathological data of 8 patients with latent malignant hemopathies (most were considered in remission): B-cell chronic lymphocytic leukemia in 3 patients, B-cell lymphoma in 1 patient, low-grade non-Hodgkin?s lymphoma in 1 patient, Waldenström?s macroglobulinemia in 1 patient, smoldering multiple myeloma in 1 patient, and monoclonal gammopathy of undetermined significance in 1 patient.In all these cases, the nerve biopsy (NB) helped to diagnose the hematological relapse or detect a pathological mechanism linked to the hematological disorder: epineurial lymphocytic infiltration in 5 patients (including one with antimyelin-associated glycoprotein antibodies), cryoglobulin deposits in 1 patient, chronic inflammatory demyelinating polyneuropathy in 1 patient, and necrotizing vasculitis in 1 patient. In each case, pathological findings were crucial to select the adequate treatment, leading to an improvement in the neurological and biological manifestations.These observations illustrate the value of NB and the need for active collaboration between neurologists and hematologists in such cases. © 2015 Wolters Kluwer Health, Inc. Source

Pascher A.,Charite - Medical University of Berlin | De Simone P.,Azienda Ospedaliero Universitaria Pisana | Pratschke J.,Innsbruck Medical University | Salame E.,CHU Tours | And 5 more authors.
American Journal of Transplantation

Efficacy and safety of protein kinase C inhibitor sotrastaurin (STN) with tacrolimus (TAC) was assessed in a 24-month, multicenter, phase II study in de novo liver transplant recipients. A total of 204 patients were randomized (1:1:1:1) to STN 200 mg b.i.d. + standard-exposure TAC (n = 50) or reduced-exposure TAC (n = 52), STN 300 mg b.i.d. + reduced-exposure TAC (n = 50), or mycophenolate mofetil (MMF) 1 g b.i.d. + standard-exposure TAC (control, n = 52); all with steroids. Owing to premature study termination, treatment comparisons were only conducted for Month 6. At Month 6, composite efficacy failure rates (treated biopsy-proven acute rejection episodes of Banff grade ≥1, graft loss, or death) were 25.0%, 16.5%, 20.9% and 15.9% for STN 200 mg + standard TAC, STN 200 mg + reduced TAC, STN 300 mg + reduced TAC and control groups, respectively. Median estimated glomerular filtration rates were 84.0, 83.3, 81.1 and 75.3 mL/min/1.73 m2, respectively. Gastrointestinal events (constipation, diarrhea, and nausea), infection, and tachycardia were more frequent in STN groups. More patients in STN groups experienced serious adverse events compared with the control group (62.3-70.8% vs. 51.9%). STN-based regimens were associated with a higher efficacy failure rate and higher incidence of adverse events with no significant difference in renal function between the groups. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons. Source

Marie I.,CHU Rouen | Marie I.,University of Rouen | Hatron P.-Y.,Lille University Hospital Center | Cherin P.,Pitie Salpetriere Hospital | And 6 more authors.
Arthritis Research and Therapy

Introduction: The aims of this present study were firstly to assess the outcome, including functional course, in anti-Jo1 positive patients with antisynthetase syndrome (ASS), and secondly to determine predictive parameters of poor outcome in these patients.Methods: The medical records of 86 consecutive anti-Jo1 patients with ASS were reviewed in 4 academic centers.Results: 13 patients (15.1%) achieved remission of ASS, whereas 55 (63.9%) improved and 18 (20.9%) deteriorated in their clinical status. Both steroid and cytotoxic drugs could be discontinued in only 4.7% of patients. ASS was associated with decreased quality of life at long-term follow-up: only 69.2% of patients considered to be in remission experienced a return to previous normal activities; and 24.7% of other patients with non-remitting ASS still had a marked reduction of activities (as shown by the disability scale of the Health Assessment Questionnaire). Decreased quality of life was further due to calcinosis cutis (8.1%) and adverse effects of steroid therapy (36%). Factors associated with ASS deterioration were older age, pulmonary and esophageal involvement, calcinosis cutis and cancer. Higher anti-Jo1 levels were further associated with disease severity in ASS patients.Conclusions: The present study shows high morbidity related to ASS. Furthermore, we suggest that patients with predictive factors of ASS deterioration may require more aggressive therapy. Our findings also suggest that in anti-Jo1 patients with severe esophageal manifestations, combined high dose steroids and intravenous immunoglobulins might be proposed as the first line therapy. Finally, as cancer occurred in 14% of anti-Jo1 patients, our findings underscore that the search for cancer should be performed in these patients. © 2013 Marie et al.; licensee BioMed Central Ltd. Source

Picard N.,French Institute of Health and Medical Research | Picard N.,Limoges University Hospital Center | Picard N.,University of Limoges | Yee S.W.,University of California at San Francisco | And 9 more authors.
Clinical Pharmacology and Therapeutics

The goal of this study was to determine the roles of the organic anion-transporting polypeptides (OATPs) OATP1A2, OATP1B1, and OATP1B3 and their genetic variants in the pharmacokinetics of the immunosuppressive drug mycophenolate mofetil (MMF). Using OATP-transfected human embryonic kidney (HEK) cells, we measured the uptake of mycophenolic acid (MPA) and its glucuronide (MPAG). MPAG, but not MPA, significantly accumulated in cells expressing OATP1B3 or OATP1B1 (P 0.05). The pharmacokinetics of both MPA and MPAG were significantly influenced by the OATP1B3 polymorphism 334TG/699GA in 70 renal transplant patients receiving combination treatment of MMF with either tacrolimus or sirolimus, but not in 115 patients receiving MMF and cyclosporine. The decrease in dose-normalized (dn) MPA exposure and the concomitant increase in the MPAG/MPA metabolic ratio are consistent with reduced enterohepatic cycling in patients carrying the OATP1B3 334G-699A haplotype. Further studies demonstrated that this variant of OATP1B3 exhibited a reduced maximal velocity (V max) in transfected HEK cells, thereby providing functional evidence to support our clinical findings. © 2009 American Society for Clinical Pharmacology and Therapeutics. Source

There is a continuous relationship between arterial pressure and the risk of chronic kidney disease (CKD), although the risk of CKD is much greater in African Americans than in other patients. The cause of the greater risk of CKD in this population is presently unknown; however, many hypotheses have been made, including the lower number of nephrons and the higher frequency of apolipoprotein-1 polymorphism associated with protection against trypanosomiasis, with greater risk of renal lesions, especially within the podocytes. Regardless of the cause of the elevation of arterial pressure, the greater the arterial pressure, the faster the evolution toward terminal renal failure. Current guidelines indicate that arterial pressure should be lowered to 130/80mmHg in patients with renal dysfunction and diabetes mellitus (British and Canadian guidelines kept this cut-off value for arterial pressure). Results of randomized clinical trials are less convincing. Lowering systolic arterial pressure toward 134mmHg was associated with less renal lesions in patients with type 2 diabetes mellitus; however, lowering of arterial pressure had no protective renal effect in African-American patients with CKD and probable nephrosclerosis (AASK study) when proteinuria was<0.22 g/g urine creatinine), thus confirming previous meta-analyses. Finally, lowering arterial pressure toward 130mmHg or lower should be reserved to patients with CKD and proteinuria (and in those with diabetes); in CKD patients without proteinuria, arterial pressure lowering< 130/80mmHg affords no nephroprotection (the real effect of renin-angiotensin blockade is not even fully demonstrated): the cut-off value of 140/90mmHg can be kept in these patients. Source

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