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Biomedical subjects

T Rochat

Publications and source records attributed to T Rochat.

At least 19 recordsLinked to original sources

[Lake Geneva Region guidelines on management of adult asthma].

Asthma is a major cause of chronic morbidity throughout the world. In Switzerland, 6.9% of the adult population is suffering from asthma. The standards of treatment are unfortunately not met in most western countries, as well as in Switzerland. We put forward a complete guideline on management of adult asthma, inspired from GINA and BTS guidelines, and adapted to the specific needs of general practitioners working in french part of Switzerland. This guideline reflects a consensus between allergy, lung and emergency specialists, working in the 2 university hospitals of the Lake Geneva Region (HUG and CHUV).

Adult↗

[How should inhaled corticosteroids be prescribed in asthma?].

The treatment of persistent asthma is based on the concept of a maintenance therapy (inhaled corticosteroids +/- long-acting beta-2-agonists) that is associated with a reliever therapy (short-acting beta-2-agonists). A recent study has suggested a new approach: budesonide/formoterol combination as both maintenance and reliever medication. The patient is told to adjust his medication by himself according to his symptoms. The advantage and potential weakness of this approach will be discussed in the present review.

Administration, Inhalation↗

[Pneumology. Treatment of idiopathic pulmonary fibrosis: hopes and disappointment].

Idiopathic pulmonary fibrosis (IPF) is now recognized as a separate nosological entity. Despite the progresses in understanding the basic mechanisms of the disease, its prognosis remains poor. The classical treatment combines prednisone with a cytotoxic agent. Interferon gamma has the in vitro capacity of inhibiting fibroblasts proliferation. A pilot study showed positive results, but a more recent randomized double blind trial was unable to demonstrate a clear benefit to the patients. On the other hand there are many evidences for an oxydant-antioxydant imbalance in the pathogenesis of IPF. In a human controlled study N-acetylcysteine (NAC) at high doses (1800 mg per day orally) improved the pulmonary function tests when given on top of a combined therapy with prednisone and azathioprine.

Humans↗

High-level resistance to oxidative stress in Lactococcus lactis conferred by Bacillus subtilis catalase KatE.

Lactococcus lactis, a lactic acid bacterium widely used for food fermentations, is often exposed to damaging stress conditions. In particular, oxidative stress leads to DNA, protein and membrane damages that can be lethal. As L. lactis has no catalase, the impact of production of the Bacillus subtilis haem catalase KatE on its oxidative stress resistance was tested. This cytoplasmic catalase was engineered for extracellular expression in L. lactis with an optimization strategy based on fusion to the nisin-inducible promoter and a lactococcal signal peptide (SP(Usp45)). The production of KatE by L. lactis conferred an 800-fold increase in survival after 1 h exposure to 4 mM hydrogen peroxide, and a 160-fold greater survival in long-term (3 days) survival of aerated cultures in a cydA mutant, which is unable to respire. The presence of KatE protected DNA from oxidative damage and limited its degradation after long-term aeration in a cydA/recA mutant, defective in DNA repair. L. lactis is thus able to produce active catalase that can provide efficient antioxidant activity.

Bacillus subtilis↗

High hepatotoxicity of pyrazinamide and ethambutol for treatment of latent tuberculosis.

Pyrazinamide (PZA) combined with either ethambutol (EMB) or a fluoroquinolone for 6-12 months is one of the treatments recommended for latent tuberculosis infection (LTBI) in contacts exposed to multidrug-resistant tuberculosis (MDR-TB). The aim of the present study was to describe the side effects related to combined PZA and EMB treatment given for LTBI, in contacts previously exposed to MDR-TB. In total, 12 consecutive contacts, all of African origin and aged 38+/-5 yrs, were treated with daily PZA (23+/-4 mg.kg(-1)) and EMB (17+/-4 mg.kg(-1)) at Geneva University Hospital outpatient clinic (Switzerland), as a result of contact-tracing procedures for two patients with contagious MDR-TB. Clinical status and liver function tests (aspartate aminotransferase (ALAT) and alanine aminotransferase (ASAT)) were monitored monthly. In seven cases (58%) treatment was discontinued after a median of 119 days, due to hepatic toxicity in six cases (ALAT or ASAT elevation more than four times the upper normal limit), and gastrointestinal symptoms in one case. In conclusion, combined pyrazinamide and ethambutol for latent tuberculosis infection may be associated with a high risk of hepatic toxicity, and warrants close monitoring. There is clearly a need for alternative preventive treatments for contacts exposed to multidrug-resistant tuberculosis.

Adult↗

Performance vigilance task and sleepiness in patients with sleep-disordered breathing.

Altered vigilance performance has been documented in patients with sleep-related breathing disorders (SRBDs). Sleep fragmentation, sleepiness, respiratory disturbances and nocturnal hypoxaemia have been suggested as the pathogenesis of these deficits, yet it remains difficult to find a good correlation between performance deficits and the above factors. In the present study, which performance measure better characterised SRBD patients and the main factors implicated in these disturbances were examined. The study group consisted of 152 patients and 45 controls, all examined using a performance vigilance task and subjective sleepiness assessment. Speed and accuracy in the psychomotor vigilance task (PVT) were measured in patients and controls. Objective daytime sleepiness was assessed in the patient group using the maintenance of wakefulness test. In comparison with controls, PVT accuracy rather than speed seems to be affected in SRBD patients, with lapses and false responses significantly greater in patients with more severe objective sleepiness and higher apnoea/hypopnoea index. Although slowing and increased variability in reaction time were associated with shorter sleep latency in the maintenance of wakefulness test, subjective sleepiness, sleep fragmentation, nocturnal hypoxaemia and apnoea/hypopnoea index influenced mainly PVT accuracy. It is concluded that vigilance impairment, sleep fragmentation and severity of disease may partially and differentially contribute to the diurnal performance consequences found in sleep-related breathing disorders. Since the psychomotor vigilance task worsening is more marked in accuracy that in speed, measurement of lapses and false responses would better characterise the degree of diurnal impairment in these patients.

Adult↗

Determinants of altered quality of life in patients with sleep-related breathing disorders.

Recent reports have suggested that altered quality of life and well-being are reported by patients with sleep-related breathing disorders (SRBD). There seems to be no data available in the literature on factors underlying these behavioural consequences. In this study, health-related quality of life (HRQL) scores were examined in SRBD patients in order to establish which factors are implicated in these disturbances. The study group consisted of 130 patients: 49 snorers and 81 patients with obstructive sleep apnoea. The Medical Outcome Survey Short Form-36 questionnaire was administered the morning after the sleep study and scores for the eight dimension scores were obtained. Patient's data were compared to normative sex- and age-matched data. In comparison with normal values, scores for all HRQL dimensions were decreased in SRBD patients, with a greater impact on subscores for "vitality", "physical role", "social functioning", "mental health" and "role emotional" dimensions. While impairment in physical function was mostly influenced by sleep stage and obesity, subjective daytime sleepiness mainly affected the other dimensions. The authors conclude that the altered health-related quality of life of sleep-related breathing disorder patients is a multifactorial phenomenon depending on the interaction of sleep stages, daytime sleepiness and obesity, with no significant contribution of sleep fragmentation, hypoxaemia and apnoea recurrence.

Female↗

Nasal polyps and middle turbinates epithelial cells sensitivity to amphotericin B.

HYPOTHESIS: Intranasal application of the antimycotic agent amphotericin B (AmphoB) has been proposed as an effective treatment of chronic rhinosinusitis (CRS) with polyps. AmphoB is a sterol-binding agent known to modify cell membrane structure. The cytotoxic effects of AmphoB were studied on primary human nasal epithelial cells in vitro. METHODS: Human epithelial cells were isolated from nasal polyps and middle turbinates of patients suffering from CRS, and grown on collagen-coated polycarbonate filters with an air liquid-interface. After 15 days of culture, cells were exposed apically to 50 microM AmphoB during 4 h daily for 5 days. Some cells were treated during 4 weeks. The bioelectric properties of cells were then studied in Ussing chambers. Integrity of the cell monolayers was assessed by measurement of the transepithelial resistance (R) and immunofluorescent localization of the tight junction protein occludin. RESULTS: Disruption of the epithelial monolayer integrity was observed in all of the nasal polyps cell cultures, as demonstrated by a 60% drop in R. Immunofluorescence microscopy showed significant loss in cell number and disruption in the distribution of occludin. Turbinate cell cultures elicited no change in R and expression of occludin after AmphoB treatment. However, the transepithelial potential, the basal short-circuit current and the amiloride-sensitive current were reduced by 70%. CONCLUSIONS: AmphoB was cytotoxic for nasal polyp epithelial cells with disruption of the epithelium integrity and loss of tight junctions. In contrast, integrity of turbinate epithelial cells was conserved despite alterations in transepithelial ion transport. These observations may explain the beneficial effect of intranasal application of AmphoB on CRS observed in clinical trials.

Amphotericin B↗

Is waking electroencephalographic activity a predictor of daytime sleepiness in sleep-related breathing disorders?

No data are available in the literature assessing the potential use of waking electroencephalographic (EEG) activity in the detection of excessive daytime sleepiness (EDS) in patients with sleep-related breathing disorders (SRBD). The aim of this study was to evaluate whether waking EEG spectral power reflects the level of EDS in SRBD patients. The study was performed in 48 patients in whom quantitative EEG analysis, including the alpha attenuation coefficient (AAC), was performed. Sleepiness was assessed by the Epworth Sleepiness Scale, the Stanford Sleepiness Scale, the Visual Analogue Scale and the maintenance of wakefulness test. Although AAC and EEG spectral power tended to vary throughout the day, none of these variations correlated with EDS measures. Waking EEG measures were not different between snorers and apnoeic patients. Compared to nonsleepy patients, sleepy patients had greater theta and slow alpha powers, but the differences did not reach statistical significance. The EEG slowing was independent of hypoxaemia, severity of SRBD, or degree of sleep disruption. The authors conclude that waking electroencephalographic measures are not sensitive enough to predict variation in alertness or to differentiate sleepy from nonsleepy sleep-related breathing disorders patients. The degree of electroencephalographic slowing was related neither to sleep disruption nor to severity of sleep-related breathing disorders.

Electroencephalography↗

Effects of first generation E1E3-deleted and second generation E1E3E4-deleted/modified adenovirus vectors on human endothelial cell death.

Adenoviral vectors are promising tools for pulmonary vascular gene transfer. In first generation vectors, the viral E4 region is preserved (E4+ Ad), but E4 is deleted in second generation vectors (E4- Ad). These vectors were compared for their toxicity in human endothelial cells in terms of apoptosis and necrosis. Infection with E4+ Ad vectors reduced whereas E4- Ad vectors enhanced apoptosis under normal culture conditions. Furthermore, E4+ Ad protected against apoptosis induced by growth factor deprivation, while E4- Ad enhanced apoptosis triggered by ceramide. Ad vectors containing different E4 open reading frames, alone or in different combinations, showed similar effects to E4- Ad, leaving the viral genes that might be responsible for reducing apoptosis unidentified at the present time. As previously observed with E4+ Ad devoid of transgene, E4+ Ad carrying beta-galactosidase or green fluorescent protein under the control of either the RSV or CMV promoter also reduced apoptosis triggered by growth factor deprivation. In contrast, E4+ Ad containing a CFTR expression cassette did not reduce apoptosis, and E4- Ad with CFFR showed increased toxicity. We conclude that Ad vectors may have important effects on the control of apoptosis in transfected cells, depending on the residual expression of viral genes. This effect can be complicated by the action of transgene expression on cell survival.

Adenoviridae↗

Ticlopidine-induced interstitial pulmonary disease: a case report.

We report a case of interstitial pulmonary disease that occurred together with lymphocytic colitis during treatment with ticlopidine. The drug was prescribed for transient ischemic cerebrovascular accidents. Ticlopidine treatment was stopped, and a prolonged course of prednisone was necessary to treat the pulmonary and intestinal symptoms. So far, few cases of pulmonary side effects caused by ticlopidine have been reported. This case is unique in that interstitial lung disease evolved in parallel with colitis and caused severe hypoxemia. Special care should be taken when pulmonary symptoms appear in association with ticlopidine treatment.

Aged↗

Predictors of participation and attendance in a new asthma patient self-management education program.

BACKGROUND: Low participation limits the effectiveness of patient education interventions. In this study, the characteristics of patients who agreed to participate in a clinical trial of disease self-management education for asthma were compared to the characteristics of those who declined, and among the former group patients who actually attended were compared to those who did not. METHODS: The education program, implemented at the Geneva University Hospitals between 1996 and 1998, consisted of three interactive sessions spread over 3 weeks. Only 131 of 253 eligible patients (52%) agreed to participate in the trial, and only 83 patients (63%) attended two to three educational sessions. All eligible patients filled out baseline questionnaires and were interviewed by a trained physiotherapist. RESULTS: Lower confidence in the patient's own current treatment regimen and a more severe baseline asthma attack were independently associated with participation in the trial. Among those who agreed to participate in the study, a university education, longer asthma duration, older age, and a higher level of asthma management knowledge were associated with higher attendance. Quality-of-life scores were not associated with higher course attendance. Among all eligible participants, persons with lower knowledge of asthma management (which was assessed by what to do during an asthma attack and knowledge of the correct use of a peak expiratory flowmeter and inhalers) were less likely to enroll in the trial and to attend the educational training sessions. CONCLUSIONS: Strategies need to be developed to motivate patients with lower disease self-management knowledge to participate in asthma education programs.

Asthma↗