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Biomedical subjects

T Rochat

Publications and source records attributed to T Rochat.

At least 37 records · Page 2Linked to original sources

[Gene therapy of cystic fibrosis].

Cystic fibrosis represents a paradigm for gene therapy of hereditary disorders. Because it is a monogenic disease, it was believed that it would be relatively simple to approach by gene therapy. In fact, it turned out that the apical side of the respiratory epithelium is resistant to transduction by various gene vectors, including recombinant adenoviruses. In addition, the relationship between the genetic defect (the mutated CFTR gene) and the pathogenesis of the disease is more complex than was thought at first. So far, the results of gene therapy trials in patients with cystic fibrosis have been disappointing in terms of efficacy. However, they have brought a fair amount of new information about the basic mechanism of this disease.

Cystic Fibrosis↗

Does the 'oxygen cost diagram' reflect changes in six minute walking distance in follow up studies?

The oxygen cost diagram (OCD) is a simple scale for quantifying a patient's evaluation of his tolerance to exercise frequently used in clinical trials; it has been shown to be well correlated with objective measures of capacity of ambulation such as the 6 min walk test (6' W). This study aimed to determine whether the OCD accurately depicts changes in capacity of ambulation either quantitatively or qualitatively. OCD ratings were analysed at baseline and after a 1 yr follow-up, in patients treated by non-invasive home mechanical ventilation, as well as objective measurements of pulmonary function [forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), arterial blood gases], physical autonomy (6' W), resting dyspnoea (Borg scale) and scores for anxiety or depressive disorders (HAD). Forty-five patients (24 male, 21 female, aged 62 +/- 16 years, mean FEV1: 38 +/- 17% of predicted) were evaluated at baseline. OCD ratings were significantly correlated with 6 min walking distance (P < 0.0001)--although with a large variability around the regression line--but not with resting dyspnoea (Borg). Patients were re-evaluated after 352 +/- 90 days. Changes in OCD ratings were not significantly correlated with changes in FFV1 FVC, PaO2, PaCO2, 6' W, HAD scores or resting dyspnoea; furthermore--albeit for Borg scores--changes in OCD did not reflect the trend of changes in these parameters. These results show that although OCD ratings are well correlated with results of a 6' W test, they cannot be used to extrapolate individual performances, because of a large variability around the regression line, furthermore, changes in the OCD over 1 yr did not depict objective changes in 6' W test results, either quantitatively or qualitatively. The use of the OCD in clinical trials should be limited to the description of the patient's perception of exercise tolerance, as a component of health-related quality of life, with the awareness of possible discrepancies between changes in objective performances and changes in OCD ratings.

Activities of Daily Living↗

Treatment of cachexia with recombinant growth hormone in a patient before lung transplantation: a case report.

OBJECTIVES: To describe the effects of recombinant human growth hormone (rhGH) in a severely malnourished patient before lung transplantation. DESIGN: Case study. SETTING: Intensive care unit. PATIENTS: A 38-yr-old severely malnourished (body mass index, 15.1 kg/m2) woman (receiving prednisone) with bronchiolitis obliterans evolving during 10 yrs presented with end-stage lung disease and required continuous noninvasive mechanical ventilation. INTERVENTIONS: Two courses of 35 days of 16 IU/day (0.42 IU/kg/day) rhGH administered subcutaneously, with an interruption of 5 wks between the two courses of rhGH. MEASUREMENTS AND MAIN RESULTS: Weight gain of 14.7% and 12.8% fat-free mass, as measured by 50-kHz bioelectrical impedance analysis, during treatment during a 3.5-month period. Nitrogen excretion decreased from 23.7 g/day before treatment to 8.0 g/day while receiving rhGH. Improvement of pulmonary function was also noted and allowed discharge of the patient from the hospital after the second course of rhGH. She underwent successful lung transplantation 2 months later and reached 48.8 kg of body weight 6 months later. CONCLUSIONS: rhGH treatment is a possible strategy that could be used with malnourished patients who are awaiting lung transplantation to improve the nutritional status and respiratory muscle function to prevent recurring respiratory infection and postoperative complications favored by malnutrition and possibly to decrease the length of hospital stay.

Adult↗

[The relationship between intensive care medicine and pneumology in Switzerland. The situation in 1998].

We describe the relationships in Switzerland between two medical specialties, critical, or intensive, care and the respiratory medicine. To date, there are only few direct relationships between these medical fields, and very rarely a respirologist becomes the head of a critical, or an intensive care unit. There are two main reasons explaining this situation. First, internal medicine, or general internal medicine, is still a strong specialty in Switzerland, and the patients are frequently under the direct responsibility of an internist, whereas the pneumologists remain consultants. Second, intensive care medicine is a full specialty, distinct from anaesthesiology, with a strong structure. However, things are moving, and the general tendency now is to reduce the total number of beds in the Swiss hospitals, and to open some specialised wards under the direct supervision of specialists, including pneumologists. Nevetherless, due to the small size of the country and the important number of decentralised hospital structures, specialised intensive care units, as respiratory intensive care units, are unlikely to be open in the future.

Cardiopulmonary Resuscitation↗

[Non-invasive home ventilation (NIHV): long-term survival of 32 cases].

AIM OF THE STUDY: To analyze the course of respiratory function, compliance and tolerance to treatment, and quality of life in patients treated by NIHV, and the impact of NIHV on hospitalizations. METHODS: Prospective study of 32 patients who underwent annual evaluation of FEV1, FVC, PImax, PEmax, arterial blood gases (ABG), nocturnal pulse oxymetry, 6-minute walk test (6'W), tolerance to treatment and quality of life (scores for dyspnea, physical independence, emotional disturbances). PATIENTS: 32 patients (median age 59 y, range 20-79) including 44% who were professionally active, suffering from predominantly restrictive (n = 30) or obstructive (n = 2) syndromes, under volumetric (n = 25) or barometric (BiPAP, n = 7) NIHV, were followed for 43 months (median; range 5-54 months). RESULTS: Throughout the study period, FEV1, FVC, PImax, PEmax, and 6'W remained stable and initial benefit on ABG was maintained. Compliance rate to NIPPV was 85%, 3-year survival was 90%. A major decrease in hospitalizations after initiation of NIHV, low resting dyspnea and a low prevalence of depression and anxiety contributed to a satisfactory quality of life. CONCLUSIONS: Home NIPPV stabilizes pulmonary function tests, has a durable positive effect on PaCO2; the marked decrease in hospitalization rates after initiation of NIPPV contributes to improved quality of life while controlling medical costs.

Adult↗

[Value and limits of conventional mediastinoscopy in preoperative evaluation of primary bronchial cancer].

PURPOSE OF THE STUDY: Retrospective evaluation of conventional mediastinoscopy in the preoperative staging of primary lung cancer. METHODS: Between 1978 and March 1997, 117 consecutive patients underwent conventional mediastinoscopy in the preoperative staging of primary lung cancer, after imaging had shown mediastinal lymph nodes larger than 1.5 cm. RESULTS: In 8 instances no material was found at mediastinoscopy, in 38 the lymph nodes showed no tumorous infiltration, and in 71 the lymph nodes were metastatic. 48 patients underwent thoracotomy in the same stage, with resection achieved in 41. Contraindications for thoracotomy (in 69) were N2 (45) or N3 (11) disease adn/or small cell lung cancer (18). Mediastinal lymphadenectomy was performed in 26 of the 41 patients who underwent lung resection; half of those with negative nodes at mediastinoscopy had in fact N2 disease, with involvement of 2 areas of more in half. There were no deaths due to mediastinoscopy but 4 complications. CONCLUSIONS: A favorable mediastinoscopy is not synonymous with resectable disease, nor does it exclude N2 disease; it does however serve to avoid unnecessary thoracotomies in more than half of cases.

Adult↗

[Surgical treatment of severe emphysema: lung transplantation or volume reduction?].

In recent years, lung transplantation (LT) and volume reduction surgery (LVRS) have been proposed for selected patients with end-stage pulmonary emphysema. Retrospectively, we analyzed the perioperative time course of 30 patients with emphysema who underwent either LVRS (n = 17) or LT (n = 13). In the LVRS group, patients were significantly older, presented less severe functional disability and all but one could be extubated at the end of surgery. In contrast, patients undergoing LT required postoperative mechanical ventilation (19 +/- 11 hrs) and had a prolonged hospital stay (37 [25-60] days vs 19 [11-42] days in LVRS patients) due to reperfusion lung edema, infection, hemorrhage and acute rejection. Six months postoperatively, forced expiratory volume in 1 second was improved and was significantly larger after LT compared with LVRS (+200% vs +63%). Our preliminary results suggest that, although LT produces greater functional improvement, LVRS is associated with lower surgical risk and is an alternative therapy in selected patients with severe emphysema.

Aged↗

Non-invasive home ventilation in patients over 75 years of age: tolerance, compliance, and impact on quality of life.

The adequacy of domiciliary non-invasive positive pressure ventilation (NIHV) for hypercapnic restrictive pulmonary disease in patients aged 75 years or above has been questioned, because of a lower life expectancy, a higher risk of neuropsychological impairment and a lower potential for adapting to NIHV. This study aims to illustrate that the use of NIHV is possible and efficient in this age group. In our referral area, all patients under NIHV have been included in a database since 1994; at the end of 1996, all patients in whom NIHV had been initiated at age 75 years or above were studied. We performed a cross-sectional study of six patients (two men, four women, age: 79 +/- 3 years at time of study) who had been under NIHV for 31 +/- 17 months. Patients underwent pulmonary function testing, assessment of respiratory muscle strength, physical disability and neuropsychological performance, tolerance and compliance to NIHV, and health-related quality of life (SF-36, St. George Respiratory Questionnaire: SGRQ). Hospitalization rates were recorded for the year prior and the 2 yr following initiation of NIHV. By the time of the study, all patients showed improved arterial blood gases when compared to values before NIHV (PaCO2: 46 +/- 9 vs 66 +/- 10 mmHg, P = 0.04). Patients adapted well to NIHV, with minor side-effects and an average daily use of ventilator of 10.5 +/- 2 h. None of the patients showed signs of emotional disturbance. SF-36 scores for mental health, subjective well-being and vitality, or social functioning, did not differ from that of age-matched controls. SGRQ scores were similar to those published for younger patients under NIHV. Use of health care facilities was similar to that of younger patients under NIHV; hospitalization rates decreased significantly after initiating NIHV (40 +/- 31 days for year before NIHV, vs 13 +/- 14 days and 0.8 +/- 0.4 days for the 2 yr following NIHV, P = 0.02). Age above 75 years should not be considered per se as a contraindication to NIHV in patients with well-accepted indications for this treatment. Our results suggest that in this age group, the cost/benefit ratio of NIHV may be favourable.

Age Factors↗

Chemotactic factors in bronchial secretions of cystic fibrosis patients.

To understand chronic neutrophil attraction into cystic fibrosis airways, both global chemotactic activity and individual chemotactic factors were studied in bronchial secretions. Bronchial secretions of 8 cystic fibrosis patients, collected on the first day of admission for antibiotic treatment, showed a high chemotactic index (19.4 +/- 5.7, n = 8). Fractionation by gel filtration of bronchial secretions resulted in three chemotactic fractions. The first factor corresponded to interleukin-8, and the second activated neutrophils via the FMLP receptor. The third factor, which was of lower molecular weight, did not activate FMLP or leukotriene B4 receptors, and its nature is still under investigation. Treating patients with antibiotics reduced global chemotactic activity, mainly by reducing the activity due to stimulation of the FMLP receptor.

Adolescent↗

New bioelectrical impedance formula for patients with respiratory insufficiency: comparison to dual-energy X-ray absorptiometry.

Malnutrition in patients with severe respiratory insufficiency can lead to severe complications, justifying the use of objective nutritional assessment techniques, such as bioelectrical impedance analysis (BIA), which is an easy, noninvasive method of measuring body composition. The purpose of this study was to develop, and validate against dual-energy X-ray absorptiometry (DXA), a BIA formula to predict fat-free mass (FFM) specific for patients with chronic severe respiratory insufficiency. Seventy-five ambulatory patients (15 females and 60 males) with severe chronic respiratory insufficiency (obstructive and restrictive) aged 63.6+/-19.2 yrs (mean+/-SD), in a stable pulmonary and cardiac condition for > or = 2 months, were measured simultaneously with BIA and DXA. Patients younger than 45 yrs of age and with a body mass index > or = 32 kg x m(-2) were excluded. The best-fitting multiple regression equation to predict FFM = -6.06 +/- (height x 0.283) +/- (weight x 0.207) - (resistance x 0.024) +/- (sex (males=1, females=0) x 4.036), gave a correlation coefficient of r=0.952, slope+/-SEM 0.902+/-0.034, standard error of the estimate 1.670, and p<0.0001. The mean difference for FFM was 0.2+/-2.3 kg (mean+/-SD) and percentage fat mass was -0.7+/-3.8%. These results suggest that the bioelectrical impedance analysis formula specific to patients with severe respiratory insufficiency give a better correlation and smaller mean differences than 12 different bioelectrical impedance analysis formulae described in the medical literature. A prediction equation, validated against dual-energy X-ray absorptiometry and based on subjects with similar clinical characteristics, is more applicable to the patients with respiratory insufficiency than a formula developed for healthy subjects.

Absorptiometry, Photon↗

Transcutaneous PCO2 to monitor noninvasive mechanical ventilation in adults: assessment of a new transcutaneous PCO2 device.

UNLABELLED: The present study was designed to analyze the usability of a commercially available, transcutaneous PCO2 (TcPCO2) sensor for monitoring noninvasive positive pressure ventilation (NPPV). Twenty-six hemodynamically stable patients with intra-arterial radial catheters were assessed. After stabilization of TcPCO2, arterial blood was analyzed and results were compared with TcPCO2 at time of sampling. To evaluate the drift of the signal, samples were taken hourly in five patients for 4 h while continuously recording TcPCO2. Finally, to assess for the response of the sensor to changes in PaCO2, six patients underwent continuous TcPCO2 recording while initiating or interrupting NPPV; arterial samples were analyzed before the event, and 1, 3, 5, 7, 9, and 20 min afterwards. RESULTS: TcPCO2 and PaCO2 were tested over a range of 26 to 71 mm Hg, and were found to be closely correlated (r=0.968, p<0.0001); mean bias was 0.75 mm Hg. There was no significant drift of TcPCO2 as compared with PaCO2 over 4 h. The time of response of TcPCO2 to initiation or interruption of NPPV was <60 s. An estimation of the lag time averaged 5+/-3 min (range, 1 to 9 min). CONCLUSION: TcPCO2 in hemodynamically stable adults was in excellent agreement with arterial measurements. The time of response to a change in ventilation was compatible with the aim of clinical monitoring of patients under NPPV.

Aged↗

[Chronic obstructive pulmonary disease patients undergoing home oxygen therapy: a study of clinical parameters, nutritional status and ambulatory capacity].

AIM OF THE STUDY: The aim of the study was to document the nutritional status and the calorie demands of patients suffering from severe chronic airflow obstruction (BPCO) who were on continuous domiciliary oxygen therapy (OCD) and to correlate this information with the clinical picture, the severity of the respiratory disease and the daily distance walked, this to be measured in a prospective manner. PATIENTS AND METHODS: Fifty clinically stable patients with chronic airflow obstruction on continuous oxygen therapy for 33 months (range 4-106) in whom the following measures were made at home: pulmonary function, maximal static inspiratory and expiratory pressure (PIMAX and PEMAX), strength of hand, grip, the mean distance walked daily (wearing a pedometer for one week), body mass index (IMC), and the body composition by electrical bio-impedence and calorie requirements. RESULTS: Thirty four per cent of patients presented with an excessive body mass (IMC > 27 kg/m2), 42 per cent had normal nutrition (IMC 20-27 kg/m2) and 24 per cent were malnourished (IMC < 20 kg/m2). Malnourished patients had, in a statistically significant manner, airflow obstruction of greater severity and a lower oxygen saturation and a PEMAX as well as a lower daily distance compared to over weight subjects. However, their net calorie requirements were markedly higher (39 +/- 5 Kcal/kg/j) compared to patients having normal weight (29 +/- 11 kcal/kg/j) or excess weight (25 +/- 8 kcal/kg/j). From the clinical standpoint no malnourished patient fulfilled the clinical criteria of chronic bronchitis. By contrast 61 per cent of subjects with normal nutrition and 94 per cent of subjects with excessive weight were chronic bronchitics. CONCLUSION: In the group of patients with severe airflow obstruction on domiciliary oxygen, 25 per cent were malnourished and this was in spite of netly increased calorie consumption which is superior to their theoretical need. This suggests that the solution of increasing supplements to their dietary requirements would be a difficult to realise. These subjects presented also with a more marked ventilatory handicap and a clinical picture characterised by the absence of the classical signs of chronic bronchitis.

Adult↗

Management 1997 of chronic obstructive pulmonary disease. Working Group of the Swiss Society of Pneumology.

COPD is a disorder characterized by expiratory flow limitation that does not change markedly over periods of several months' observation. When the diagnosis is suspected, COPD patients should be submitted to full assessment and initiation of therapy. Initial assessment includes a complete history, a detailed physical examination, pulmonary function tests, a chest X-ray, and blood tests. Therapy of COPD aims at reducing symptoms, preventing exacerbations and preserving optimal lung function. Many COPD patients have a bronchospastic component and usually show some response to bronchodilator therapy. Anticholinergics, beta 2-agonists or theophylline are used as monotherapy or in combination. A subgroup of patients with COPD may benefit from oral long-term corticosteroid therapy. At prime diagnosis of COPD, a trial of oral steroid under optimal bronchodilator therapy is warranted in order to identify steroid responders early in the course of the disease. Stopping smoking is the most effective preventive measure and should be combined with complementary approaches such as eviction of environmental irritants, vaccines and prescription of antioxidants. Long-term oxygen therapy is beneficial in chronically hypoxemic patients. Respiratory rehabilitation uses a multidisciplinary approach aiming at decreasing dyspnea, increasing exercise tolerance and improving quality of life. Nocturnal home noninvasive mechanical ventilatory assistance can improve arterial blood gas tensions in patients with respiratory failure, but the long-term effect on survival is still under investigation. In selected patients, surgery (bullectomy, lung volume reduction, lung transplantation) may greatly improve pulmonary function.

Adrenal Cortex Hormones↗

[Somatic gene therapy of mucoviscidosis using recombinant adenovirus: the start of a long course].

The identification of the gene on which mutations cause cystic fibrosis has opened the way to the concept of gene therapy of this disease. Somatic gene therapy for cystic fibrosis should be directed to the epithelial cells of the bronchi where the biological defect is the most deleterious. In order to have the normal DNA coding sequence penetrate the bronchial epithelial cells of a patient, a gene vector is necessary, and recombinant adenoviruses have been the subject of extensive studies in this regard. Data are available from many laboratories as well as from several phase I clinical trials. Successes and limits of this approach are reviewed here. The advantage of non-viral vectors, in particular cationic liposomes, as an alternative to recombinant adenoviruses is briefly discussed. Significant advances still need to be made before gene therapy becomes a reality in cystic fibrosis. These future improvements should include the construction of more efficient gene vectors, and also the development of better tools for the evaluation of a biological effect of gene therapy in individual patients.

Adenoviridae↗

Parvovirus [correction of Parovirus] B19-induced red cell aplasia in solid-organ transplant recipients. Two case reports and review of the literature.

Two solid-organ transplant recipients (one heart and one lung) developed severe anemia with reticulocytopenia. Both were heavily immunosuppressed. Bone marrow aspiration revealed almost complete absence of erythroid precursors. A few giant megaloblastic proerythroblasts with cytoplasmic vacuolisation and intranuclear inclusions were seen. Human parvovirus B19 (B19V)-DNA genome was found by nested-PCR assays in blood and bone marrow samples in both cases. Twelve similar cases are described in the literature. When looked for, B19V DNA was positive either in serum or bone marrow or both. Twelve of the fourteen patients were successfully treated by high dose i.v. immunoglobulin (IVIG). One patient recovered spontaneously and another after treatment with recombinant human erythropoietin (rHu-EPO) only. Transplant patients should be considered at risk for severe erythroblastopenic anemia due to B19V infection. Diagnosis is based on bone marrow examination and detection of B19V DNA by PCR in serum and/or marrow. IVIG is an effective and safe treatment. The role of erythropoietin in this indication needs further study.

Adult↗

Health-related quality of life in patients under long-term oxygen therapy: a home-based descriptive study.

Long-term home oxygen therapy (LTOT) improves survival of hypoxic patients with chronic respiratory insufficiency. However, the health-related quality of life (HRQL) of these patients, when LTOT is initiated, is severely impaired. The present study aims to describe the health-related quality of life (HRQL) of patients under LTOT, assessed at home, to identify parameters relevant to HRQL, and to describe changes over a 1-yr period. Seventy-nine patients (aged 68 +/- 11 years, under LTOT for 34 +/- 24 months) underwent pulmonary function testing, measurement of average daily distance walked, SaO2, dyspnoea scores (Borg scale and oxygen-cost diagram), and Hospital Anxiety and Depression scores. After 1 yr, measurements were repeated, and HRQL was measured with the St George Respiratory Questionnaire (SGRQ). Forced expiratory volume in 1 s (FEV1% of predicted) was 36 +/- 19; SaO2 (room air) was 87 +/- 5%, daily distance walked was 1202 +/- 1140 m; 21% suffered from anxiety and 27% from depression. After 1 yr, pulmonary function tests, dyspnoea or prevalence of anxiety or depression were unchanged. Mortality was high (31% 1-yr mortality). Daily distance walked (rho = -0.55, P = 0.01 vs. SGRQ) and number of days spent in hospital (rho = 0.5, P = 0.01 vs. SGRQ) were the parameters with the highest correlation with HRQL scores. Quality of life was poor in these patients, with high rates of emotional disorders. Restoring and maintaining sufficient exercise capacity for everyday life activities through outpatient rehabilitation programmes and support for emotional disturbances should be major goals in the care of these patients.

Adolescent↗

A new device for in vivo measurement of nasal transepithelial potential difference in cystic fibrosis patients and normal subjects.

Measurement of transepithelial potential difference (PD) on the nasal mucosa has been proposed to test for defective ion transport in cystic fibrosis (CF), and its possible correction after gene therapy or other treatments. The "classical" method records nasal PD under the inferior turbinate, with the disadvantage that the tip of the electrode is not seen by the operator. We have developed a purpose-designed perfusion electrode for PD recording on the visible, medial/posterior aspect of the turbinate. We wanted to determine whether such PD recordings adequately discriminate between CF patients and normal subjects. Measurements of baseline PD and response to a standardized perfusion protocol were performed in 20 normal subjects and 12 CF patients. Solutions of amiloride, with or without low chloride buffer were applied for 3 min. Increased baseline PD and depolarization after amiloride discriminated CF patients from normal subjects. Only one CF patient overlapped with the normal range. Superfusion of low chloride buffer with amiloride and terbutaline caused repolarization in 18 out of 20 normal subjects (90%), consistent with physiological Cl- secretion process, but in none of the CF patients. We conclude that measurements of potential difference on the medial/posterior aspect of the turbinate can discriminate between cystic fibrosis patients and normal subjects. At this site, visual control of the measurement is possible, and the mucosa is easily accessible for subsequent cytological sampling or biopsy.

Adult↗