Publications by authors named "Constance Michel"

5 Publications

  • Page 1 of 1

In vivo muscle function and energetics in women with sickle cell anemia or trait: a P-magnetic resonance spectroscopy study.

J Appl Physiol (1985) 2021 03 10;130(3):737-745. Epub 2020 Dec 10.

Aix-Marseille Université, CNRS, CRMBM, Marseille, France.

Sickle cell anemia (SCA) is a genetic hemoglobinopathy associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes and increase intramuscular acidosis. These alterations have been already reported in the Townes mouse model of SCA but the corresponding changes in humans have not been documented. In the present study, we used 31-phosphorus magnetic resonance spectroscopy to investigate in vivo the metabolic changes induced by a moderate-intensity exercise in twelve SCA patients, eight sickle cell trait (SCT) carriers, and twelve controls women. The rest-exercise-recovery protocol disclosed slight differences regarding phosphocreatine (PCr) consumption and lactate accumulation between SCA patients and controls but these differences did not reach a statistical significance. On that basis, the in vivo metabolic changes associated with a moderate-intensity muscle exercise were slightly altered in SCA patients and SCT carriers but within a normal range. The present results strongly support the fact that a moderate-intensity exercise is safe and could be recommended in stable SCA patients and SCT subjects. The main finding of the present study was that the metabolic changes associated with a moderate-intensity muscle exercise were slightly modified in stable sickle cell anemia patients and sickle cell trait carriers as compared to controls but still in the normal range. The present results strongly support the safety of a moderate-intensity exercise for stable sickle cell anemia patients and sickle cell trait carriers.
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http://dx.doi.org/10.1152/japplphysiol.00790.2020DOI Listing
March 2021

A novel segmentation framework dedicated to the follow-up of fat infiltration in individual muscles of patients with neuromuscular disorders.

Magn Reson Med 2020 05 2;83(5):1825-1836. Epub 2019 Nov 2.

Aix Marseille University, CNRS, CRMBM, Marseille, France.

Purpose: To propose a novel segmentation framework that is dedicated to the follow-up of fat infiltration in individual muscles of patients with neuromuscular disorders.

Methods: We designed a semi-automatic segmentation pipeline of individual leg muscles in MR images based on automatic propagation through nonlinear registrations of initial delineation in a minimal number of MR slices. This approach has been validated for the segmentation of individual muscles from MRI data sets, acquired over a 10-month period, from thighs and legs in 10 patients with muscular dystrophy. The robustness of the framework was evaluated using conventional metrics related to muscle volume and clinical metrics related to fat infiltration.

Results: High accuracy of the semi-automatic segmentation (mean Dice similarity coefficient higher than 0.89) was reported. The provided method has excellent reliability regarding the reproducibility of the fat fraction estimation, with an average intraclass correlation coefficient score of 0.99. Furthermore, the present segmentation framework was determined to be more reliable than the intra-expert performance, which had an average intraclass correlation coefficient of 0.93.

Conclusion: The proposed framework of segmentation can successfully provide an effective and reliable tool for accurate follow-up of any MRI biomarkers in neuromuscular disorders. This method could assist the quantitative assessment of muscular changes occurring in such diseases.
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http://dx.doi.org/10.1002/mrm.28030DOI Listing
May 2020

Immunothérapie dans les cancers de la prostate.

Bull Cancer 2016 Nov;103 Suppl 1:S144-S150

Service de cancérologie médicale, hôpital européen Georges-Pompidou, 20, rue Leblanc, 75015 Paris, France; CRC UMRS1138 EQ13, 15, rue de l'École-de-Médecine, 75006 Paris, France.

Immunotherapy In Uro-oncology: Immunotherapy is moving forward in prostate cancer. The autologous vaccine, Sipuleucel-T has been the first vaccine to be approved by FDA. First results with GVAX, tasquinimob or anti-PD-1 have been disappointing. Ipilimumab seen to be more active at an earlier stage of prostate disease. Identifying predictive factor or surrogate markers of activity of immunotherapy and which agents are clinically effective alone or in combination with others therapies such as hormonal or bone targeted therapies are warranted.
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http://dx.doi.org/10.1016/S0007-4551(16)30372-1DOI Listing
November 2016

Plasma and intraprostatic concentrations of ertapenem following preoperative single dose administration: a single-centre prospective experience and clinical implications-the ERTAPRO study.

Int J Antimicrob Agents 2016 Aug 2;48(2):168-74. Epub 2016 Jun 2.

Department of Urology, Hôpital européen Georges-Pompidou (HEGP), Assistance Publique-Hôpitaux de Paris (AP-HP), 20-40 rue Leblanc, 75015 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Faculté de médecine, 15 rue de l'École de Médecine, 75006 Paris, France. Electronic address:

The incidence of urinary tract infections caused by extended-spectrum β-lactamase (ESBL)-producing pathogens is increasing. These infections are associated with a long hospital stay in patients undergoing urological procedures. We aimed to demonstrate that significant intraprostatic diffusion of ertapenem is achieved after a single preoperative administration. A referred sample of 19 patients requiring surgery for benign prostatic hyperplasia was prospectively included. Patients received a 1 g intravenous (i.v.) dose of ertapenem 1 h (n = 10, group A) or 12 h (n = 9, group B) before blood and prostatic samples were collected. Plasma and intraprostatic concentrations of ertapenem were measured using LC-MS/MS. Intraprostatic concentrations were considered satisfactory when higher than the MIC90 value of urinary-targeted pathogens perioperatively and for 40% of the dosing interval. The Wilcoxon test and a pharmacokinetic predictive model were used. Median plasma concentrations of ertapenem were 144.3 mg/L (95% CI 126.5-157.9) in group A and 30.7 mg/L (95% CI 22.9-36.4) in group B (P < 0.001); median intraprostatic concentrations were 16.6 mg/L (95% CI 13.3-31.4 mg/L) and 4.2 mg/L (95% CI 3.1-4.9 mg/L), respectively (P < 0.001), which were above the MIC90 values of bacteria, including ESBL-producers, during surgery and for 40% of the dosing interval. The plasma-to-prostate concentration ratio was not significantly different between groups (P = 0.97). Single-dose i.v. ertapenem reached satisfactory intraprostatic concentrations, suggesting that it could be a relevant prophylactic strategy for carriers of ESBL-producing bacteria undergoing prostatic procedures, which needs to be confirmed by further prospective trials.
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http://dx.doi.org/10.1016/j.ijantimicag.2016.04.027DOI Listing
August 2016

Safety and Efficacy of Pazopanib Therapy Prior to Planned Nephrectomy in Metastatic Clear Cell Renal Cancer.

JAMA Oncol 2016 Oct;2(10):1303-1309

Cancer Sciences Unit, University of Southampton, Southampton, England.

Importance: The role of cytoreductive nephrectomy in patients with metastatic renal cancer in the era of targeted therapy is uncertain.

Objective: To establish the safety and efficacy of upfront pazopanib therapy prior to cytoreductive nephrectomy in previously untreated patients with metastatic clear cell renal cancer.

Design, Setting, And Participants: Single-arm phase 2 study of 104 previously untreated patients with metastatic clear cell renal cancer recruited between June 2008 and October 2012 at cancer treatment centers with access to nephrectomy services. The minimum follow-up was 30 months.

Interventions: Patients received 12 to 14 weeks of preoperative pazopanib therapy prior to planned cytoreductive nephrectomy and continued pazopanib therapy after surgery. Treatment was stopped at disease progression.

Main Outcomes And Measures: The primary end point was clinical benefit (using Response Evaluation Criteria in Solid Tumors, version 1.1) prior to surgery (at 12-14 weeks). Secondary end points included surgical complications, progression-free survival (PFS), overall survival (OS), and biomarker analysis.

Results: Of 104 patients recruited, 100 patients were assessable for clinical benefit prior to planned nephrectomy; 80 of 104 (76.9%) were men; median [interquartile range] age, 64 [56-71] years). Overall, 84 of 100 (84% [95% CI, 75%-91%]) gained clinical benefit before planned nephrectomy. The median reduction in the size of the primary tumor was 14.4% (interquartile range, 1.4%-21.1%). No patients were unable to undergo surgery as a result of local progression of disease. Nephrectomy was performed in 63 (61%) of patients; 14 (22%) reported surgical complications. The 2 most common reasons for not undergoing surgery were progression of disease (n = 13) and patient choice (n = 9). There was 1 postoperative surgical death. The median PFS and OS for the whole cohort were 7.1 (95% CI, 6.0-9.2) and 22.7 (95% CI, 14.3-not estimable) months, respectively. Patients with MSKCC poor-risk disease or progressive disease prior to surgery had a poor outcome (median OS, 5.7 [95% CI, 2.6-10.8] and 3.9 [95% CI, 0.5-9.1] months, respectively). Surgical complications were observed in 14 (22%) of the nephrectomies. Biomarker analysis from sequential tissue samples revealed a decrease in CD8 expression (20.00 vs 13.75; P = .05) and significant reduction in expression of von Hippel-Lindau tumor suppressor (100 vs 40; P < .001) and C-MET (300 vs 100; P < .001) and increased programmed cell death ligand 1 expression (0 vs 1.5; P < .001) in the immune component. No on-treatment biomarker correlated with response.

Conclusions And Relevance: Nephrectomy after upfront pazopanib therapy could be performed safely and was associated with good outcomes in patients with intermediate-risk metastatic clear cell renal cancer.
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http://dx.doi.org/10.1001/jamaoncol.2016.1197DOI Listing
October 2016
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