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Biomedical subjects

H Matthys

Publications and source records attributed to H Matthys.

At least 19 recordsLinked to original sources

Normocapnia during nIPPV in chronic hypercapnic COPD reduces subsequent spontaneous PaCO2.

Hypercapnia has been accepted during nasal intermittent positive pressure ventilation (nIPPV) and during subsequent spontaneous breathing in patients with chronic hypercapnic respiratory failure (HRF) due to COPD. We tested the hypothesis that nIPPV aimed at normalizing PaCO2 will reduce PaCO2 during subsequent spontaneous breathing. For that purpose 14 consecutive inpatients (age 61.4 +/- 9.9 years) with chronic HRF due to COPD were established on passive pressure-controlled nIPPV in a stepwise approach. Assisted ventilation with supplemental oxygen to reach normoxemia was started followed by passive ventilation with a stepwise increment in the inspiratory pressure and finally by a stepwise increase in the respiratory rate to establish normocapnia. Baseline pulmonary function parameters were: FEV1 0.97 +/- 0.43 l, PaCO2 59.5 +/- 8.4 mmHg, PaO2 49.9 +/- 7.8 mmHg, HCO3- 35.6 +/- 5.2 mmol/l, pH 7.39 +/- 0.04. Normoxemia as well as normocapnia was thus established by decreasing PaCO2 by 19.5 +/- 7.0 mmHg during nIPPV within 8.8 +/- 3.8 days (P < 0.001) (inspiratory pressure 29.8 +/- 3.8 mmHg, respiratory rate 22.9 +/- 1.9 BPM). Spontaneous PaCO2 measured 4 h after cessation of nIPPV decreased to 46.0 +/- 5.5 mmHg (P < 0.001), and HCO3- decreased to 27.2 +/- 3.0 mmol/l (P < 0.001). At 6 months of follow-up, II patients continued nIPPV with stable blood gases and with a decrease of P0.1/Plmax from 9.4 +/- 4.3% to 5.9 +/- 2.0% (P < 0.005). In conclusion, normalization of PaCO2 by passive nIPPV in patients with HRF due to COPD is possible and leads to a significant reduction of PaCO2 during subsequent spontaneous breathing and is associated with improved parameters of respiratory muscle function.

Aged↗

[Health-related auality of life (HRQL) in patients receiving home mechanical ventilation].

Evaluation of health-related quality of life (HRQL) has become steadily more essential during the last two decades in research and health care practice in order to evaluate the human and financial costs and benefits of modern medical techniques. HRQL in its definition is based on different components of health including physical state, psychological well-being, social relations and functional capacities that are influenced by a persons experience, beliefs, expectations, and perceptions. For the purpose of assessment of HRQL several instruments have been developed. Generic instruments are not specific to any particular disease and are therefore most commonly used for general survey research on health allowing comparisons between disease states. In contrast, disease-specific questionnaires which are necessary in order to focus on domains most relevant to a particular disease are thought to be more sensitive than generic instruments following therapeutic interventions. Home mechanical ventilation (HMV) delivered noninvasively by a facial mask is a well established treatment for chronic hypercapnic respiratory failure. It is widely accepted that survival improves following institution of HMV in most patients with chest wall deformities or neuromuscular diseases while this is still controversially discussed in patients with COPD. However, patients receiving HMV usually have severe respiratory insufficiency with a past medical history of several years or decades, and suffer from end stage disease with objectively severe limitations of daily living. In addition, HMV is a time consuming and cost intensive therapy. Therefore, several studies have been conducted in the last decade to evaluate HRQL in patients receiving HMV. Recent studies using generic questionnaires have shown impairments in HRQL in patients receiving HMV compared to normals. This was primarily attributed to severe limitations in physical health, but not in mental health indicating that if severe physical limitation occurs in advanced respiratory disease this will not necessarily lead to mental limitation. In addition, limitations in HRQL in patients with HMV were not substantially higher than in patients with different chronic disease being not dependent on HMV. Improvements in HRQL following the institution of HMV were only mild or even insignificant in patients with COPD, but patients with restrictive ventilatory disorders are suspected to have more benefits. However, well validated disease-specific questionnaires which are designed to be more sensitive in the assessment of changes in HRQL than generic instruments have been introduced recently for patients with severe respiratory failure, but the influence of HMV to HRQL remains still unclear, since prospective studies using these questionnaires have yet not been finished.

Attitude to Health↗

Bone mineral density and quantitative ultrasound in adults with cystic fibrosis.

OBJECTIVE: With increasing life span osteoporosis becomes a more recognized problem in patients with cystic fibrosis (CF). The aim of this cross-sectional study in 75 adult patients with CF (mean age 25.3 years) was to assess the prevalence of low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) and, for the first time, by quantitative ultrasound (QUS), and to identify predicting factors. DESIGN AND METHODS: Bone status was assessed at the lumbar spine (L2-L4) and the femoral neck by DEXA, and at the calcaneus by QUS (stiffness index). These data were correlated with a variety of clinical and anthropomorphic variables. Biochemical markers of bone turnover such as osteocalcin, bone-specific alkaline phosphatase, crosslinks in urine, 25-hydroxy vitamin D (25-OH vitamin D), parathyroid hormone, calcium and free testosterone were determined by standard assays. RESULTS: The mean BMD T score (+/-s.e.m.) was -1.4+/-0.17 at the lumbar spine, and -0.54+/-0.16 at the femoral neck. The mean T score of the calcaneal stiffness index was -0.83+/-0.19. Based on a lumbar spine T score <-2.5 by DEXA, 27% of the patients had osteoporosis. Multiple regression analysis showed that the forced expiratory volume in one second (FEV1) and the use of oral glucocorticoids were independent predictors of low lumbar spine BMD, whereas body mass index (BMI) and the use of oral glucocorticoids were independent predictors of low femoral neck BMD. The stiffness index correlated moderately with BMD (0.49-0.62, P<0.0001). QUS had a sensitivity and specificity of only 57% and 89% respectively for diagnosing 'osteoporosis' (based on a femoral neck T score <-2.5 by DEXA). Positive and negative predictive values were 36% and 95% respectively. CONCLUSIONS: Low BMD is frequent in adults with CF and is most strongly correlated with disease severity (BMI, FEV1) and the use of glucocorticoids. Calcaneal QUS might help to screen out patients with a normal BMD, but sensitivity and specificity were not sufficiently high to replace DEXA in these patients.

Absorptiometry, Photon↗

[Epidemiology and costs of bronchial asthma and chronic bronchitis in Germany].

BACKGROUND AND OBJECTIVE: Asthma bronchiale (AB) and chronic bronchitis (CB) are common chronic disorders with high rates of prevalence. We performed a cost of illness study that aimed to assess the economic burden of these disorders in Germany. PATIENTS AND METHODS: Costs were estimated in 1996. In a retrospective analysis we calculated direct and indirect costs based on secondary data from governmental institutions as well as from the pharmaceutical industry. To the best of our knowledge, this is the first study which uses data for the Federal Republic of Germany following its reunification. RESULTS: Total estimated costs were DM 5.81 billion related to AB, and DM 20.17 billion related to CB. We did not include outpatient physician services in the calculation of direct costs due to a lack of adequate data. Therefore, direct costs represented only 33% and 22% of total estimated costs, respectively. The most important cost driver of direct costs were outpatient prescribed medicines, followed by hospitalization. Outpatient prescribed medicines accounted for 55% and 63% of the direct costs, respectively. Of the indirect costs of AB 43% were associated with early retirement. The largest single cost driver of indirect costs due to CB was by far loss of work, amounting to 75%. CONCLUSIONS: The data suggest that therapeutic progress and cessation of smoking can provide distinctive savings of direct costs and even more of indirect costs of AB and CB.

Adolescent↗

Analysis of forced expired volume signals using multi-exponential functions.

Patients with pulmonary disease are often unable to complete forced expiration manoeuvres. The aim of the study is to evaluate whether forced vital capacity (FVC), the volume exhaled at the end of completed forced expiration, can be estimated by extrapolating volume-time curves obtained from uncompleted manoeuvres. The suitability of mono-, bi-, and tri-exponential functions to characterise complete volume-time curves from 50 subjects is investigated. Mono-exponential modelling is insufficient, whereas bi-exponential fitting yields an adequate description for 47 data sets. Tri-exponential models lead to overfitting in all but three cases (normalised sum of least squares: 50.2 +/- 34.5 for mono-, 2.76 +/- 4.11 for bi-, 2.74 +/- 4.19 for tri-exponential modelling; condition number of the correlation matrix: 1.0025 +/- 0.0004 for mono-, 1.08 +/- 0.08 for bi-, 34.7 +/- 100.1 for tri-exponential fitting (mean +/- SD)). Thus, FVC is estimated by the extrapolation of 27 uncompleted spirograms using bi- or tri-exponential models, depending on their accordance with measured data and on the identifiability of their parameters. This algorithm yields unbiased estimates (difference from measured inspiratory vital capacity: 0.01 +/- 0.21 L). This method can be used for investigation of the lung function of subjects who cannot complete the forced expiration manoeuvre.

Adolescent↗

[Nebivolol (nebilet) a beta blocker of the third generation--also for patients with obstructive lung diseases?].

UNLABELLED: Twenty-four patients with bronchial hyperreactivity due to asthma (8 patients), COPD (13) and of unknown origin (3) entered and completed a randomized double-blind intraindividual cross-over study. Thirteen patients first received the highly selective vasodilatating beta 1-blocker Nebivolol (5 mg) and 11 patients first placebo with a wash-out period of at least 2 days. Before the controlled oral intake of the tablets, the patients were challenged with increasing inhalative doses of carbachol between 8 and 9 a.m. according to the recommendation of the German Society of Pneumology. At 10, 11 and 12 a.m. and 1 and 2 p.m. control measurements of airway patency (Raw, FEV1) were performed in the body box. At the same time intervals, oxygen saturation and pulse rate (pulsoximetry) including systolic and diastolic blood pressure were monitored. From 2-3 p.m. the carbachol provocation was repeated as in the morning to assess the changes in hyperreactivity due to Nebivolol. RESULTS: During the Nebivolol phase, blood pressure values and pulse rates were significantly reduced compared to the placebo phase. At the same time intervals, no significant changes of the measured body box variables to assess airway obstruction were observed during therapy with Nebivolol compared to placebo. Comparing the measured variables (maximal deviation from base-line values of Raw and FEV1) during carbachol provocation in the afternoon under Nebivolol and placebo with the values in the morning before any medication (base-line values), there were also no significant detectable differences indicating an increase of bronchial hyperreactivity under Nebivolol treatment. CONCLUSION: It seems that Nebivolol in these hyperreactive patients is as safe as placebo despite its significant effect on blood pressure and pulse rate.

Administration, Oral↗

Effect of a specific cysteinyl leukotriene-receptor 1-antagonist (montelukast) on the transmigration of eosinophils across human umbilical vein endothelial cells.

BACKGROUND: Leukotrienes have been implicated in the selective infiltration of eosinophils into the bronchial mucosa in asthma. OBJECTIVE: We studied whether eosinophil transmigration through cultured human umbilical vein endothelial cells (HUVECs) can be blocked by a specific cysteinyl LT1-receptor-antagonist. METHODS: Unstimulated and stimulated eosinophils from patients with asthma and normal controls were subjected to confluent human umbilical vein endothelial cell (HUVEC) monolayers separating the upper and lower chamber of Transwell culture plates. Unstimulated eosinophils or cells pre-incubated in the presence of the eosinophil activating cytokines GM-CSF or IL-13 were placed in the upper chambers while PAF, a potent chemoattractant factor for eosinophils, was added to the lower chamber. Migration of eosinophils was quantified by a beta-glucuronidase assay. RESULTS: The assumption that eosinophils express CysLT1 (cysteinyl-leukotriene 1)-receptors was based on our demonstration of mRNA-expression for the CysLT-1-receptor by polymerase chain reaction on purified eosinophils. The chemotactic response to PAF was significantly reduced when eosinophils were pre-incubated with montelukast for 15 min. When eosinophils were pre-incubated with GM-CSF and/or IL-13, the migratory response to PAF was also significantly reduced by montelukast. CONCLUSION: From these data we conclude that the specific cysteinyl LT1-receptor antagonist montelukast can inhibit PAF-induced eosinophil transmigration through cultured HUVEC monolayers.

Acetates↗

Interferon-gamma secretion of peripheral blood CD8+ T lymphocytes in patients with bronchial asthma: in vitro stimulus determines cytokine production.

It has been postulated that T lymphocytes orchestrate the chronic inflammation in bronchial asthma. In animal models, infiltration of CD8+ T lymphocytes into the bronchial mucosa prevented bronchial hyperresponsiveness and decreased early and late phase reaction. IFN-gamma antagonizes IL-4-dependent IgE production as well as IL-5-induced proliferation and activation of eosinophils. We therefore investigated the secretion of IFN-gamma of isolated CD8+ T lymphocytes from peripheral blood of patients with allergic asthma (n = 6) and from healthy controls (n = 7) in vitro. In this setting we compared the effect of stimulation with anti-CD3 antibodies with that of phorbol myristate acetate (PMA) and calcium-ionophore. As expected, CD8+ T lymphocytes from peripheral blood of healthy volunteers produced significantly more IFN-gamma in the presence of PMA and calcium-ionophore than after stimulation with anti-CD3 antibodies. However, in subjects with allergic asthma, IFN-gamma secretion of CD8+ T cells was significantly higher when incubated with anti-CD3 antibodies than after activation with PMA and calcium-ionophore. While IFN-gamma secretion of CD8+ T lymphocytes of patients with allergic asthma was lower than that of healthy controls in the presence of PMA/calcium-ionophore, it was significantly elevated when compared with normal controls after stimulation with anti-CD3 antibodies. Thus, potent activators of cytokine secretion, such as PMA and calcium-ionophore, induce a cytokine profile different from that induced by weaker stimulants, such as anti-CD3 antibodies. These findings have implications for further studies investigating cytokine production of inflammatory cells in vitro.

Adult↗

[Epidemiology and costs of lung cancer in Germany].

OBJECTIVE: Lung cancer shows the leading incidence of all cancers among men in the developed world and an increasing incidence among women. We performed a cost of illness study that aimed to assess the economic burden of lung cancer in Germany and to identify the main cost drivers. METHODS: Costs were estimated for the year 1996. In a retrospective analysis we calculated direct and indirect costs based on secondary data from governmental institutions as well as from the pharmaceutical industry. We chose the cost perspective of sickness funds to estimate direct costs. The human capital approach was applied for the calculation of indirect costs. RESULTS: Total estimated costs were DM 8.31 billion per year. The indirect costs of DM 7.40 billion accounted for 89 % of total estimated costs. The most important cost driver of the indirect costs, early death, represented on its own DM 4.85 billion, according to 58 % of total estimated costs. Of the direct costs, 93 % were due to hospitalization, amounting to DM 0.85 billion. CONCLUSIONS: This cost of illness study concerning lung cancer illustrates the outstanding importance of the indirect costs, mostly due to early death, for total costs. Based on these findings and on the leading role of smoking in the etiology of lung cancer, we suggest that studies dealing with the net costs of smoking to society should include indirect costs.

Adult↗

Is there a need for another inhalative beta(2)-agonist besides formoterol in patients with asthma?

Formoterol can substitute the rapid- and short-acting beta(2)-agonists as well as the slow- and long-acting salmeterol. Therefore formoterol in a fixed combination with an inhalant steroid reduces the aerosol devices necessary for asthma control to only one, to be used for regular "controller" and, as needed, "rescue therapy". The side effect profile of formoterol is comparable to the short-acting beta(2)-agonists which makes the combination with a topically active glucocorticoid applicable in patients of any asthma severity as long as they are able to perform an inspiratory vital capacity maneuver

Administration, Topical↗

Change in perforin-positive peripheral blood lymphocyte (PBL) subpopulations following exercise.

Perforin, one of the cytotoxic proteins of the immune system, plays a prominent role in protection against viral and bacterial infections. We investigated its expression in PBL and their CD3+, CD4+, CD8+ and CD16+ and/or CD56+ subpopulations in endurance athletes before and after a triathlon. Lymphocyte subpopulations were analysed by flow cytometry following separation of peripheral blood mononuclear cells and staining with antibodies against specific membrane antigens and intracellular perforin. The number of total lymphocytes decreased from 2.1 x 10(3)/microl before the triathlon to 1.0 x 10(3)/microl 1 h after the triathlon (P < 0.01). Interestingly, there was already a significant spontaneous decline in the percentage of CD3+/perforin+, and in CD8+/perforin+ cells, in the week proceeding the triathlon, when subjects were instructed to refrain from strenuous exercise training. The percentage of CD3+/perforin+, CD8+/perforin+ and CD16+ and/or CD56+/perforin+ cells in each lymphocyte subpopulation decreased 1 h after exercise even further from 14.3% to 5.8% (P < 0.05), 18.5% to 6.5% (P < 0.05) and 77.3% to 67.3%, respectively. However, at 18 h and 48 h after exercise the percentage of perforin-expressing CD3+, CD8+ and CD16+/56+ cells increased again towards baseline levels. Compared with normal controls, baseline perforin co-expression in CD3+ and CD8+ lymphocytes was significantly higher in trained athletes. From our data we conclude that trained athletes have an increased percentage of perforin+ PBL and that following exercise the percentage of perforin+ and therefore potentially cytotoxic lymphocytes transiently decreases in peripheral blood.

Adult↗