Biomedical subjects

Thierry Rochat

Publications and source records attributed to Thierry Rochat.

26 records · Page 2Linked to original sources

PubMed2003

Pharmacokinetics of mycophenolic acid associated with calcineurin inhibitors: long-term monitoring in stable lung recipients with and without cystic fibrosis.

Pharmacologic interactions and absorption disturbances after transplantation may induce serologic fluctuation of immunosuppression and adversely affect outcome. We present data showing that trough levels of mycophenolic acid decreased by 50% during combined mycophenolate mofetil (MMF) and cyclosporine therapy compared with levels during combined MMF and tacrolimus therapy. In addition, cystic fibrosis patients required 30% higher doses of MMF to achieve the therapeutic levels of recipients without cystic fibrosis.

Adult↗

PubMed2003

Changing patterns in long-term noninvasive ventilation: a 7-year prospective study in the Geneva Lake area.

STUDY OBJECTIVES: To describe a 7-year follow-up (1992 to 2000) of patients who were treated by home nasal positive-pressure ventilation (NPPV) for chronic hypercapnic respiratory failure. DESIGN: Prospective descriptive study. SETTING: Two university hospitals and a pulmonary rehabilitation center. PATIENTS: Two hundred eleven patients with obstructive pulmonary disorders (58 patients) or restrictive pulmonary disorders (post-tuberculosis, 23 patients; neuromuscular diseases [NM], 28 patients; post-poliomyelitis syndrome, 12 patients; kyphoscoliosis [KYPH], 19 patients; obesity-hypoventilation syndrome [OHS], 71 patients) who were treated by long-term NPPV. INTERVENTION: Annual, elective, standardized medical evaluations. MEASUREMENTS: Pulmonary function tests, arterial blood gas levels, health status, compliance, survival and probability of pursuing NPPV, and hospitalization rates. RESULTS: Patients with OHS, NM, and KYPH had the highest probability of pursuing NPPV, while patients with COPD had the lowest values. Overall, the compliance rate was high (noncompliance rate, 15%). As of 1994, COPD and OHS became the most frequent indications for NPPV, increasing regularly, while other indications remained stable. The use of pressure-cycled ventilators progressively replaced that of volume-cycled ventilators in most indications. Hospitalization rates decreased in all groups after initiating NPPV, when compared with the year before NPPV, for up to 2 years in COPD patients, and 5 years in non-COPD patients. CONCLUSION: Major changes in patient selection for NPPV occurred during the study period with a marked increase in COPD and OHS. The shift toward less expensive pressure-cycled ventilators and the decrease in hospitalizations after initiating NPPV have had positive impacts on the cost-effectiveness of NPPV in patients with chronic respiratory failure.

Aged↗

PubMed2002

Effect of patient education on self-management skills and health status in patients with asthma: a randomized trial.

We conducted a randomized clinical trial to assess the effectiveness of a newly established education program for adults with asthma. The program was designed to improve patients' health and functional status. Hospitalized patients with asthma were randomly assigned to immediate education or a 6-month waiting list. The education program consisted of three group sessions, delivered by trained educators, and focused on improving patients' self-management skills. Of 253 eligible patients, 131 agreed to participate (66 assigned to immediate education, 65 controls) and 115 (88%) completed the follow-up assessment at 6 months. At follow-up, most indicators of self-management skills and health and functional status had improved significantly among educated patients, but similar improvements were also seen among controls. The trial arms differed significantly on only four variables: patients in the immediate-education group were more likely to develop confidence in their asthma treatment (odds ratio adjusted for baseline [OR] = 2.9; 95% confidence interval [CI]: 1.0 to 8.1), to improve their knowledge of correct inhalation technique (OR = 2.4; 95% CI: 1.0 to 5.7), and to improve knowledge of the peak flow reading that warrants calling a physician (OR = 3.1; 95% CI: 1.4 to 6.7), but they improved less on the Asthma Quality of Life Questionnaire "activity" score (difference: -0.4 on a 1 to 7 scale; 95% CI: -0.8 to 0.0). Use of health services during follow-up was similar in the two groups. The education program did not enhance patients' health and functional status, despite improving a few self-management skills. These results underscore the need for controlled evaluations of education programs.

Adult↗

PubMed2002

Personality, anxiety and mood traits in patients with sleep-related breathing disorders: effect of reduced daytime alertness.

OBJECTIVE: The etiology of depression and personality disorders in patients with sleep-disordered breathing (SDB) is not well defined and it is still unclear if they are directly related to the severity of the disease. In this study we test the hypothesis as to whether daytime sleepiness largely contributes to appearance of mood disorders. METHODS: Sixty patients diagnosed as having snoring (n=16) or OSA (n=44) were examined. Daytime sleepiness was assessed by the administration of the Epworth Sleepiness Scale (ESS) and by the Maintenance Wakefulness Test (MWT). The Hospital Anxiety (HAD-A) and Depression (HAD-D) Scale and the Temperament and Character Inventory (TCI) questionnaires were used for psychopathological evaluation. RESULTS: The mean HAD-A score was 6.9+/-0.45 and the average HAD-D score was 4.6+/-0.48, with no significant difference between snorers and OSA patients. Anxiety was present in 16% of cases and depression in 7%. The HAD-D score was related to the ESS score (R=0.37, P=0.003), the mean sleep latency at the MWT (R=-0.34, P=0.04), and the mean low SaO(2), ESS score alone explaining the 17% of variance in the HAD-D score. Compared to controls, there were no differences in almost all TCI scores, with novelty-seeking temperament score higher in patients. No relationships were found between HAD or TCI scores and apnea density. CONCLUSIONS: We conclude that among patients evaluated for SDB, higher depression scores show an association with reduced daytime alertness, which therefore may have important effects on mood.

Journal Article↗

PubMed2002

Gene therapy for cystic fibrosis by means of aerosol.

Gene therapy by aerosol is an attractive approach for the treatment of cystic fibrosis (CF). Clinical trials with aerosols in CF patients have been conducted by five different groups, three using adenoviral vectors and two using cationic liposomes carrying the coding sequence for the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). These trials revealed that gene transfer from the lumen to the respiratory epithelium can currently be achieved in vivo, but only with low efficiency and for limited duration. Some of the many hurdles on the way to successful gene therapy for this disease will be discussed in this review. Innovative strategies need to be developed to reach this tantalizing goal.

Adenoviridae↗

PubMedDate not supplied

Discrimination between cystic fibrosis and CFTR-corrected epithelial cells by a membrane potential-sensitive probe.

Methods to detect functional cystic fibrosis transmembrane conductance regulator (CFTR) are needed for the assessment of new therapies in cystic fibrosis (CF). We have combined patch-clamp and fluorimetric techniques to investigate whether the fluorescent voltage-sensitive probe bis-(1,3-diethylthiobarbituic anid) trimethine oxonol (Di5BAC2(3)) discriminates between changes of membrane potential (Vm evoked by cAMP in CF and CYFT-corrected epithelial cells. About 60% of the (FTR-correrced cells increased their membrane conductance and depolarized in response to cAMP, as compared to about 20% of CF cells. CFTR was found to contribute only to a fraction of the cAMP-induced responses, as indicated by the differential effects of Cl- channel blockers. Simultaneous reocording of fluorescence (AF) and membrane potential revealed that AF detected Vm changes as small as 10 mV . The relationship between deltaF and deltaVm however, was not proportional. When a large number of cells were analyzed by digital imaging, an increase in deltaF in response to cAMP was detected in the majority of CFTR-corrected cells, but only in a small proportion of CF cells. The results indicate that the DiSBAC2(3) approach is a valid tool to compare cell populations with different proportions of cells responding to CFTR arcivation by cAMP. It cannot be used, however, for quantitative assessment of functional CFTR in individual CF cells.

Cyclic AMP↗

PubMedDate not supplied

Src signaling links mediators of inflammation to Cx43 gap junction channels in primary and transformed CFTR-expressing airway cells.

Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is associated with recurrent pulmonary infections and inflammation. We previously reported that tumor necrosis factor (TNF)-alpha decreases gap junction connectivity in cell lines derived from the airway epithelium of non-cystic fibrosis (non-CF) subjects, a mechanism that was defective in cells derived from CF patients, and identified the tyrosine kinase c-Src as a possible bridge between TNF-alpha and Cx43. To examine whether this modulation also takes place in primary epithelial cells, the functional expression of Cx43 was studied in non-CF and CF airway cells, obtained from surgical polypectomies and turbinectomies, which were grown either on culture dishes or permeable filters. Expression of Cx43 was detected by immunofluorescence on cells grown under both culture conditions. Non-CF and CF airway cells also showed intercellular diffusion of Lucifer Yellow. Dye coupling was rapidly abolished in non-CF cells in the presence of TNF-alpha, lipopolysaccharide and lysophosphatidic acid, and could be prevented by tyrphostin47, an inhibitor of Src tyrosine kinases. This down-regulation, however, was not detected in CF airway cells. These data indicate that CFTR dysfunction is associated with altered Src signaling, resulting in the persistence of gap junction connectivity in primary and transformed CF airway cells.

Caveolin 1↗

PubMedDate not supplied

Validity and reliability of a French version of the MRF-28 health-related quality of life questionnaire.

BACKGROUND: Evaluation of health-related quality of life (HRQL) in chronic respiratory failure (CRF) is an important issue for evaluating the impact of treatment. OBJECTIVES: To elaborate a French version of the Maugeri Foundation Respiratory Failure Questionnaire (MRF-28) disease-specific HRQL questionnaire and determine its validity and reliability in patients with CRF treated by home mechanical ventilation (HMV). METHODS: Forward- and back-translation of the MRF-28 questionnaire; the final version was submitted to 81 patients treated with HMV for CRF, simultaneously with the St. George's Respiratory Questionnaire (SGRQ), the Short Form 36 (SF-36), and the Hospital Anxiety and Depression scale (HAD). Validity was determined by correlation with previously validated HRQL scores and recorded physiological parameters. Reliability was evaluated by assessing internal consistency and test-retest stability of the MRF-28 scores. RESULTS: The French version of the MRF-28 and its subscores ('daily activity', 'cognitive function', and 'invalidity') were highly significantly correlated with subscores of the SGRQ, the SF-36 and the HAD. Both the MRF-28 and the SGRQ were correlated only with age and the 6-min walk test. The MRF-28 showed high test-retest reliability after 2 weeks (r2 = 0.80, p < 0.0001) and high internal consistency (Crohnbachs' alpha coefficient: 0.91). CONCLUSION: The French version of the MRF-28 is a valid and reliable disease-specific questionnaire for assessing HRQL in patients with CRF.

Adult↗