S. Quetant

Synovial fluid proteomic fingerprint: S100A8, S100A9 and S100A12 proteins discriminate rheumatoid arthritis from other inflammatory joint diseases

OBJECTIVE We investigated SF and serum proteomic fingerprints of patients suffering from RA, OA and other miscellaneous inflammatory arthritides (MIAs) in order to identify RA-specific biomarkers. METHODS SF profiles of 65 patients and serum profiles of 31 patients were studied by surface-enhanced laser desorption and ionization-time-of-flight-mass spectrometry technology. The most discriminating RA biomarkers were identified by matrix-assisted laser desorption ionization-time of flight and their overexpression was confirmed by western blotting and ELISA. RESULTS Three biomarkers of 10 839, 10 445 and 13 338 Da, characterized as S100A8, S100A12 and S100A9 proteins, were the most up-regulated proteins in RA SF. Their expression was about 10-fold higher in RA SF vs OA SF. S100A8 exhibited a sensitivity of 82% and a specificity of 69% in discriminating RA from other MIAs, whereas S100A12 displayed a sensitivity of 79% and a specificity of 64%. Three peptides of 3351, 3423 and 3465 Da, corresponding to the alpha-defensins-1, -2 and -3, were also shown to differentiate RA from other MIAs with weaker sensitivity and specificity. Levels of S100A12, S100A8 and S100A9 were statistically correlated with the neutrophil count in MIA SF but not in the SF of RA patients. S100A8, S100A9, S100A12 and alpha-defensin expression in serum was not different in the three populations. CONCLUSION The most enhanced proteins in RA SF, the S100A8, S100A9 and S00A12 proteins, distinguished RA from MIA with high accuracy. Possible implication of resident cells in this increase may play a role in RA physiopathology.

Skeletal muscle contractility and fatigability in adults with cystic fibrosis

BACKGROUND Recent discovery of cystic fibrosis transmembrane conductance regulator expression in human skeletal muscle suggests that CF patients may have intrinsic skeletal muscle abnormalities potentially leading to functional impairments. The aim of the present study was to determine whether CF patients with mild to moderate lung disease have altered skeletal muscle contractility and greater muscle fatigability compared to healthy controls. METHODS Thirty adults (15 CF and 15 controls) performed a quadriceps neuromuscular evaluation using single and paired femoral nerve magnetic stimulations. Electromyographic and mechanical parameters during voluntary and magnetically-evoked contractions were recorded at rest, during and after a fatiguing isometric task. Quadriceps cross-sectional area was determined by magnetic resonance imaging. RESULTS Some indexes of muscle contractility tended to be reduced at rest in CF compared to controls (e.g., mechanical response to doublets stimulation at 100 Hz: 74±30 Nm vs. 97±28 Nm, P=0.06) but all tendencies disappeared when expressed relative to quadriceps cross-sectional area (P>0.5 for all parameters). CF and controls had similar alterations in muscle contractility with fatigue, similar endurance and post exercise recovery. CONCLUSIONS We found similar skeletal muscle endurance and fatigability in CF adults and controls and only trends for reduced muscle strength in CF which disappeared when normalized to muscle cross-sectional area. These results indicate small quantitative (reduced muscle mass) rather than qualitative (intrinsic skeletal muscle abnormalities) muscle alterations in CF with mild to moderate lung disease.

Absence of calf muscle metabolism alterations in active cystic fibrosis adults with mild to moderate lung disease

BACKGROUND Specific alterations in skeletal muscle related to genetic defects may be present in adults with cystic fibrosis (CF). Limb muscle dysfunction may contribute to physical impairment in CF. AIMS AND OBJECTIVES We hypothesized that adults with CF would have altered calf muscle metabolism during exercise. METHODS Fifteen adults with CF and fifteen healthy controls matched for age, gender and physical activity performed a maximal cycling test and an evaluation of calf muscle energetics by 31P magnetic resonance spectroscopy before, during and after plantar flexions to exhaustion. RESULTS Maximal cycling test revealed lower exercise capacities in CF (VO2peak 2.44±0.11 vs. 3.44±0.23L·Min-1, P=0.03). At rest, calf muscle phosphorus metabolites and pHi were similar in CF and controls (P>0.05). Maximal power output during plantar flexions was significantly lower in CF compared to controls (7.8±1.2 vs. 6.6±2.4W; P=0.013). At exhaustion, PCr concentration was similarly reduced in both groups (CF -33±7%, controls -34±6%, P=0.44), while PCr degradation at identical absolute workload was greater in CF patients (P=0.04). These differences disappeared when power output was normalized for differences in calf size (maximal power output: 0.10±0.02 vs. 0.10±0.03W/cm2; P=0.87). Pi/PCr ratio and pHi during exercise as well as PCr recovery after exercise were similar between groups. CONCLUSION Similar metabolic calf muscle responses during exercise and recovery were found in CF adults and controls. Overall, muscle anabolism rather than specific metabolic dysfunction may be critical regarding muscle function in CF.

Management of voriconazole hepatotoxicity in a lung transplant patient.

S. Belaiche, M. Roustit, P. Bedouch, S. Quetant, C. Saint‐Raymond, C. Pison. Management of voriconazole hepatotoxicity in a lung transplant patient.
Transpl Infect Dis 2011: 13: 309–311. All rights reserved

Glucose trajectories in cystic fibrosis and their association with pulmonary function

BACKGROUND The prevalence of cystic fibrosis-related diabetes is increasing. This condition is potentially responsible for respiratory decline. METHODS At inclusion, then yearly (over three years), 111 children and 117 adults with cystic fibrosis had oral glucose tolerance and insulin tests at one (G1) and 2h (G2). KmL analysis identified homogeneous G1 and G2 glucose trajectories. A linear mixed model quantified the relationships between trajectories and FEV1 changes. RESULTS In children, there were three G1 and four G2 trajectories and FEV1 decrease was not significantly different between G1 or G2 trajectories. In adults, two G1 and four G2 trajectories were identified and FEV1 change was estimated at -0.85/year (95% CI: [-1.54; -0.17], p=0.01) whatever the G1 trajectory and found significantly faster in the high and increasing G2 trajectory (-2.1/year, [-3.9; -0.2], p=0.03). CONCLUSIONS In case of persistent G2 abnormality, physicians should be alert for clinical deterioration and intensify patient surveillance.

Comment je traite une hypertension pulmonaire

L’hypertension arterielle pulmonaire (HTAP) necessite une prise en charge par des centres experts. Le traitement repose sur des mesures generales et des traitements symptomatiques en premiere intention. A ces mesures, peuvent s’ajouter selon le type et la gravite de la maladie des traitements dits « specifiques » developpes depuis le debut des annees 2000 et actuellement au nombre de dix. Il existe quatre familles de medicaments specifiquement indiques dans l’HTAP : les analogues de la prostacycline, les antagonistes des recepteurs de l’endotheline (ET-1), les inhibiteurs de la PDE-5 et les stimulateurs de la guanylate cyclase soluble (sGC). Pour le cas particulier de l’hypertension pulmonaire thromboembolique chronique (HTP-TEC), la chirurgie de thromboendarteriectomie est indiquee pour les formes operables et plus recemment l’angioplastie lors des contre-indications de la chirurgie. Enfin, la transplantation pulmonaire constitue le seul traitement curatif.

262 Glucose tolerance in cystic fibrosis patients: The DIAMUCO study

Objective: CFRD is the most common comorbidity in CF. The recommended treatment of CFRD is Insulin, but other options are also in use. Only few data exist related to other treatment options. Therefore we analyzed the German CFregister for the documented therapy of CFRD. Methods: Data from the German CF-register were used from patients with CFRD in 2010 in a retrospective observational study. Delta FEV1% and delta BMI-Zscore from 2 year before diagnosis of CFRD to year of diagnosis and from year of diagnosis to 2 years after were calculated for each treatment group (Insulin, oral anti-diabetic drugs, no therapy with drugs) and compared using ANOVA-analysis. Results: 798 patients with CFRD were documented in 2010. 51.9%.were female; age (mean±SD) at diagnosis 23.8±9.3 years; CFRD duration 5.8±4.5 years. Treatment: 57.6% Insulin, 9.8% oral anti-diabetic drugs, 2.1% with both and 30.2% without any drug treatment. The mean (±SD) CFRD duration in the non-treated patients was 4.5±4.0 years. ANOVA tests showed no differences between treatment groups regarding changes in FEV1% and BMI-Z-score from 2 years before to the year of diagnosis and delta FEV1 and delta BMI-Z-score and from year of diagnosis to 2 years later. Conclusions: The percentage of patients treated with oral anti-diabetic drugs is in the international published range. We know the weakness of retrospective studies. Nevertheless the numbers are high and the observation time is long. Our data point to the question if insulin is the only successful initial treatment of CFRD in all CF patients. At least a part of patients with CFRD seems to be well treated with other regimes. Supported by German CF Foundation.