Saint-Hilaire-de-Riez, France
Saint-Hilaire-de-Riez, France

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Jantzem H.,Brest University Hospital Center | Pecriaux C.,Groupe Hospitalier Cochin | Benard-Laribiere A.,Bordeaux University Hospital Center | Montastruc J.L.,French Institute of Health and Medical Research
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2015

Objective To assess the nature and conditions of the occurrence of adverse drug reactions (ADRs) of bromocriptine, which is used to inhibit lactation. Design Observational study. Setting Cases from the French pharmacovigilance database and the marketing authorisation holders. Sample Serious ADRs reported between 1994 and 2010 in association with bromocriptine used for lactation inhibition in France. Methods Each case was checked to confirm the bromocriptine indication, the seriousness of the ADR, the modalities of bromocriptine use, and to identify possible associated predisposing factors. Main outcome measures Number and description of serious ADRs, with a particular focus on misuse and associated predisposing factors. Results Among 105 serious ADRs, including two fatal cases, the most frequent were cardiovascular (70.5%), neurological (14.3%), and psychiatric (8.6%) disorders. Cardiovascular disorders primarily consisted of ischaemic manifestations (n = 47): acute ischaemic stroke (n = 18, one death), myocardial infarction (n = 11, one death), and reversible postpartum cerebral angiopathy (n = 10). Misuse was identified in 52 cases (70.3%) of cardiovascular disorders, and mostly consisted of bromocriptine continuation despite the occurrence of first symptoms suggesting an ADR or the absence of a progressive titration of bromocriptine. About half of these women had cardiovascular predisposing factors, mainly tobacco smoking, overweight or obesity, or a history of hypertension or pre-eclampsia. Conclusions This survey, together with published data, provides further evidence that serious ADRs still occur after bromocriptine use in lactation inhibition, and that most of these ADRs could have been avoided. The use of bromocriptine should therefore be limited to cases where no other options are available to inhibit lactation. © 2015 Royal College of Obstetricians and Gynaecologists.

Steib A.,University of Strasbourg | Mertes M.,Hopital Central | Morel M.H.,University of Limoges | Nathan N.,University of Limoges | And 3 more authors.
Journal of Thrombosis and Haemostasis | Year: 2010

Background: After a vitamin K antagonist (VKA) overdose, 1-2 mg of oral vitamin K can lower the International Normalized Ratio (INR) to the therapeutic range. Objective: To establish whether oral vitamin K can substitute for heparin bridging and decrease the INR to ≤ 1.5 before elective surgery. Methods: Patients on long-term VKAs were randomized either to heparin bridging after the last VKA dose on day - 5 before surgery (group H) or to VKA treatment until day - 2, followed by 1 mg of oral vitamin K on the day before surgery (group K). Blood clotting variables were assessed on days -5/-2, 1 and 0, and postoperatively. If the target INR was not achieved 2 h before incision, surgery was deferred or performed after injection of prothrombin complex concentrate (PCC). Results: In 30 of 94 included patients, baseline INR was outside the chosen range (18, INR < 2; 12, INR > 3.5), leaving 34 eligible patients in group H and 30 in group K. The groups were balanced in terms of body mass index, VKA treatment duration and indication, scheduled surgery, preoperative and postoperative hemoglobin, and blood loss. The INR was significantly higher in group K on days - 1 and 0 than in group H. An INR ≤ 1.5 was not achieved in 20 group K patients (66%). Surgery was postponed or performed after PCC injection in 12 of these 20 patients. Conclusions: Oral vitamin K (1 mg) cannot substitute for heparin bridging before surgery. In addition, one-third of patients on VKAs were exposed to a risk of bleeding (overdose) or thrombosis (underdose), thus highlighting the need for new oral anticoagulants. © 2009 International Society on Thrombosis and Haemostasis.

Dougados M.,Groupe Hospitalier Cochin | Devauchelle-Pensec V.,Brest University Hospital Center | Ferlet J.F.,RCTs | Jousse-Joulin S.,Brest University Hospital Center | And 12 more authors.
Annals of the Rheumatic Diseases | Year: 2013

Objectives To evaluate synovitis (clinical vs ultrasound (US)) to predict structural progression in rheumatoid arthritis (RA). Methods Patients with RA. Study design Prospective, 2-year follow-up. Data collected Synovitis (32 joints (2 wrists, 10 metacarpophalangeal, 10 proximal interphalangeal, 10 metatarsophalangeal)) at baseline and after 4 months of therapy by clinical, US grey scale (GS-US) and power doppler (PD-US); x-rays at baseline and at year 2. Analysis Measures of association (OR) were tested between structural deterioration and the presence of baseline synovitis, or its persistence, after 4 months of therapy using generalised estimating equation analysis. Results Structural deterioration was observed in 9% of the 1888 evaluated joints in 59 patients. Baseline synovitis increased the risk of structural progression: OR=2.01 (1.36-2.98) p<0.001 versus 1.61 (1.06-2.45) p=0.026 versus 1.75 (1.18-2.58) p=0.005 for the clinical versus US-GS versus US-PD evaluation, respectively. In the joints with normal baseline examination (clinical or US), an increased probability for structural progression in the presence of synovitis for the other modality was also observed (OR=2.16 (1.16-4.02) p=0.015 and 3.50 (1.77-6.95) p<0.001 for US-GS and US-PD and 2.79 (1.35-5.76) p=0.002) for clinical examination. Persistent (vs disappearance) synovitis after 4 months of therapy was also predictive of subsequent structural progression. Conclusions This study confi rms the validity of synovitis for predicting subsequent structural deterioration irrespective of the modality of examination of joints, but also suggests that both clinical and ultrasonographic examinations may be relevant to optimally evaluate the risk of subsequent structural deterioration.

Soufir J.-C.,Groupe Hospitalier Cochin | Meduri G.,Laboratoire Of Genetique Moleculaire | Ziyyat A.,Groupe Hospitalier Cochin | Ziyyat A.,University of Paris Descartes
Human Reproduction | Year: 2011

Background: We previously demonstrated in a small pilot study that oral medroxyprogesterone acetate and percutaneous testosterone (OMP/PT) induce reversible spermatogenesis suppression. The aims of this study were to determine the rate of spermatogenetic inhibition and recovery and to obtain preliminary data on efficacy for a larger population under OMP/PT. Methods: A total of 35 healthy men with normal spermiograms requesting male hormonal contraception were treated with OMP (20 mg/day) and PT (50125 mg/day) for periods up to 18 months. Couples were included in a contraceptive efficacy phase after a value of ≤1 million/ml spermatozoa was reached between 1 and 3 months of treatment. Results: Sperm counts decreased by 47 at 1 month, reaching 90 at 2 months and 98100 between 4 and 8 months. At 3 months, 80 of men had ≤1 million/ml spermatozoa. Follicle-stimulating hormone and luteinizing hormone decreased to 35 of pretreatment levels after 1 month of treatment and to 7580 at 2 and 6 months, respectively. Plasma testosterone and estradiol levels were in the eugonadal range at 3, 6, 9 and 12 months of treatment. Dihydrotestosterone concentrations were 24 times higher than pretreatment values. The rate of spermatogenetic recovery was rapid (73 ± 29.5 days). During the efficacy phase (211 months for 25 couples), one pregnancy attributable to poor compliance of the male partner was observed. Conclusions: OMP/PT efficiently inhibits spermatogenesis in 80 of men, maintains testosterone at physiological levels and avoids the need for parenteral administration, which is poorly accepted by French men. These Results: justify larger studies to define a more adequate dosage of OMP/PT and to confirm its efficacy and safety. © 2011 The Author.

Rannou F.,French Institute of Health and Medical Research | Rannou F.,University of Paris Descartes | Rannou F.,Groupe Hospitalier Cochin | Poiraudeau S.,French Institute of Health and Medical Research | And 3 more authors.
Current Opinion in Rheumatology | Year: 2010

Purpose of Review: Recommendations for nonpharmacological treatment for knee osteoarthritis are based mainly on modifying the symptomatic loading joint compartment. Braces are one of the modalities used to modify joint loading. Knee osteoarthritis braces consist of rest orthoses, knee sleeves, and unloading-knee braces. This review examines the most recent publications regarding the various bracing modalities proposed for different knee osteoarthritis compartments. Recent Findings: The effectiveness of rest orthoses for lower-limb osteoarthritis has not been studied in clinical trials. Knee sleeves are elastic nonadhesive orthoses associated with various devices aimed at patellar or femoro-tibial stabilization. They may decrease knee pain. Unloading-knee braces are functional devices composed of external stems, hinges, and straps. Several recent biomechanical studies have established the effectiveness of modifying loading with unloading-knee braces. Such braces may decrease knee pain, and improve knee function. Summary: Braces are recommended for treating knee osteoarthritis. The different bracing modalities that are available must be adapted to the symptomatic knee osteoarthritis compartment. This nonpharmacological approach must be added to the other nonpharmacological, and pharmacological modalities to decrease pain and improve function and thereby increase the quality of life of osteoarthritis patients. The structural effect of bracing has not yet been evaluated. High-quality clinical trials of the addition of various treatment modalities for knee osteoarthritis are still necessary. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Crenn P.,University of Paris Descartes | Crenn P.,University of Versailles | Cynober L.,University of Paris Descartes | Cynober L.,Groupe Hospitalier Cochin
Current Opinion in Clinical Nutrition and Metabolic Care | Year: 2010

PURPOSE OF REVIEW: The present review relates recent developments in the understanding of arginine and citrulline metabolism and complementation after intestinal resection. RECENT FINDINGS: Arginine metabolism is disturbed after significant intestinal resection, with reduced fluxes and circulating and tissue concentrations. There is also a reduction in citrulline production, a major source of endogenous arginine by enterocyte metabolism. There is evidence to suggest that arginine or citrulline supplementation may be important in this situation. SUMMARY: In experimental intestinal resection, arginine availability decreases as intestinal citrulline synthesis decreases. In this setting, there is debate over the efficiency of arginine supplementation on intestinal adaptation, perhaps due to different doses used. In contrast, citrulline, a precursor for arginine synthesis, whether provided enterally or parenterally, is more efficient at 1 g/kg/day than complementation with arginine (at the same dose) in sustaining arginine pools. In addition, citrulline is more effective than arginine in maintaining nitrogen homeostasis. Clinical studies are vital in order to establish the value of citrulline supplementation in short bowel patients. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Rannou F.,French Institute of Health and Medical Research | Rannou F.,University of Paris Descartes | Rannou F.,Groupe Hospitalier Cochin | Poiraudeau S.,French Institute of Health and Medical Research | And 2 more authors.
Best Practice and Research: Clinical Rheumatology | Year: 2010

For the most part, non-pharmacological approaches are recommended for osteoarthritis treatment. This recommendation is based mainly on biomechanical observations leading to a modulation of the symptomatic loading joint. Approaches include orthoses, insoles, exercise, diet and patient education. The approach used for each osteoarthritis site must be adapted for the individual patient. Here, we use an evidence-based approach, including the European League Against Rheumatism (EULAR) and Osteoarthritis Research Society International (OARSI) recommendations, to summarise the non-pharmacological treatments available for knee, hip and hand osteoarthritis and to help the physician in daily clinical practice. © 2009 Elsevier Ltd. All rights reserved.

Terris B.,University of Paris Descartes | Terris B.,French Institute of Health and Medical Research | Terris B.,Groupe Hospitalier Cochin | Cavard C.,University of Paris Descartes | And 3 more authors.
Journal of Hepatology | Year: 2010

Background & Aims: Cancer progression/metastases and embryonic development share many properties including cellular plasticity, dynamic cell motility, and integral interaction with the microenvironment. We hypothesized that the heterogeneous nature of hepatocellular carcinoma (HCC), in part, may be owing to the presence of hepatic cancer cells with stem/progenitor features. Methods: Gene expression profiling and immunohistochemistry analyses were used to analyze 235 tumor specimens derived from 2 recently identified HCC subtypes (EpCAM(+) alpha-fetoprotein [AFP(+)] HCC and EpCAM(-) AFP(-) HCC). These subtypes differed in their expression of AFP, a molecule produced in the developing embryo, and EpCAM, a cell surface hepatic stem cell marker. Fluorescence-activated cell sorting was used to isolate EpCAM(+) HCC cells, which were tested for hepatic stem/progenitor cell properties. Results: Gene expression and pathway analyses revealed that the EpCAM(+) AFP(+) HCC subtype had features of hepatic stem/progenitor cells. Indeed, the fluorescence-activated cell sorting-isolated EpCAM(+) HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate. Moreover, these cells were capable of initiating highly invasive HCC in nonobese diabetic, severe combined immunodeficient mice. Activation of Wnt/beta-catenin signaling enriched the EpCAM(+) cell population, whereas RNA interference-based blockage of EpCAM, a Wnt/beta-catenin signaling target, attenuated the activities of these cells. Conclusions: Taken together, our results suggest that HCC growth and invasiveness is dictated by a subset of EpCAM(+) cells, opening a new avenue for HCC cancer cell eradication by targeting Wnt/beta-catenin signaling components such as EpCAM. © 2009 European Association for the Study of the Liver.

Rozenberg F.,Groupe Hospitalier Cochin | Deback C.,Groupe Hospitalier Cochin | Agut H.,Groupe Hospitalier Cochin
Infectious Disorders - Drug Targets | Year: 2011

Herpes simplex virus (HSV) is the cause of herpes simplex encephalitis (HSE), a devastating human disease which occurs in 2-4 cases per million/year. HSE results either from a primary infection or virus reactivation, in accordance with the common pattern of HSV infection which is a chronic lifelong process. However its pathophysiology remains largely unknown and its poor prognosis is in contrast with the usually good tolerance of most clinical herpetic manifestations. HSE is due to HSV type 1 (HSV-1) in most cases but HSV type 2 (HSV-2) may be also implicated, especially in infants in the context of neonatal herpes. Polymerase chain reaction detection of HSV DNA in cerebrospinal fluid is the diagnosis of choice for HSE. Acyclovir, a nucleoside analogue which inhibits viral DNA polymerase activity, is the reference treatment of HSE while foscarnet constitutes an alternative therapy and the efficacy of cidofovir is currently uncertain in that context. The emergence of HSV resistance to acyclovir, a phenomenon which is mainly observed among immunocompromised patients, is a current concern although no case of HSE due to an acyclovir-resistant HSV strain has been reported to date. Nevertheless the identification and development of novel therapeutic strategies against HSV appears to be a non dispensable objective for future research in virology. © 2011 Bentham Science Publishers Ltd.

There is in France a demand for male contraception. It is possible to respond it using steroids (androgens, progestins). Studies in several countries, including France, have confirmed the contraceptive efficacy of these treatments - equivalent to female contraception. Androgens may be indicated, in defined conditions, to couples for which traditional methods of contraception are not suitable. Two obstacles limit widespread use of androgens: risk of a prolonged state of hyperandrogenism and mode of administration by injection. The combination of progestins to low doses of androgens should reduce these drawbacks. © 2012 SALF et Springer-Verlag France.

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