Biomedical subjects

H Wirtz

Publications and source records attributed to H Wirtz.

33 records · Page 2Linked to original sources

PubMed2001

Lipid analysis of bronchoalveolar lavage fluid (BAL) by MALDI-TOF mass spectrometry and 31P NMR spectroscopy.

Despite the high clinical relevance, only the cellular moiety of bronchoalveolar lavage (BAL) has been intensively investigated and is used for diagnosis purposes. On the other hand, the cell-free fluid is, by far, less characterized. Although this fluid represents a relatively simple mixture of only a few different phospholipids (mainly phosphatidylcholine, phosphatidylglycerol and cholesterol), methods for the routine analysis of these fluids are still lacking. In the present investigation we have applied, for the first time, MALDI-TOF mass spectrometry, as well as 31P NMR spectroscopy to the analysis of organic extracts of bronchoalveolar lavage fluids. BAL from different mammals (rat, minipig, rabbit and man) were investigated and, for means of comparison, organic extracts of lung tissue were also examined. Both applied methods provide fast and reliable information on the lipid composition of the bronchoalveolar lavage. However, despite of its comparably low sensitivity, 31P NMR spectroscopy detects all phospholipid species in a single experiment and with the same sensitivity, whereas MALDI-TOF fails in the detection of phosphatidylethanolamine in the presence of higher quantities of phosphatidylcholine. In contrast, MALDI-TOF mass spectrometry is more suitable for the detection of cholesterol and the determination of the fatty acid composition of the individual phospholipids, especially lysolipids. It will be shown that all BALs exhibit significant, species-dependent differences that mainly concern the content of phosphatidylglycerol and lyso-phosphatidylcholine. It is concluded that both methods are suitable tools in lipid research due to the (in comparison to alternative methods) simplicity of performance.

Animals↗

PubMed2001

Factors influencing breath condensate volume.

Analysis of breath condensate (BC) has received interest recently due to the need for easy and repetitive monitoring or airway and pulmonary disease. While many authors have used custom built systems, commercial systems are now available and will probably be used more widely. Early studies of markers and mediators in BC have reported concentrations following varying periods of sampling time. However, factors that influence the generation of BC have not been analysed and it is unclear whether breathing rate, tidal volume, lung function, body weight, height or age influence the amount of BC collected. We therefore studied the influence of these factors on breath condensate volume and breath condensate urea and protein concentrations in 22 healthy volunteers and 23 COPD patients. A strong correlation of total respired volume and breath condensate volume was observed for both groups (volunteers: r=0.952, p < 0.0001, COPD: r=0.883, p < 0.001) while no significant correlation existed for breath condensate volume and TLC, RV, Vc, FEV1, R(tot), height or body weight, As long as ventilation remained fairly constant, breath condensate volume increased linearly with time. The fraction of breath condensate extracted from total vapour contained in the exhalate was estimated by measuring relative atmospheric humidity before and after the collecting tube. The amount calculated by the change in temperature and saturation corresponded closely to the amount actually collected. We conclude from these results that breath condensate volume is primarily dependent on V(E), and does not seem to depend on lung function parameters. For standardisation it is suggested to report breath condensate measurements per volume respired. Both, urea and protein are present in measurable quantities in breath condensate and protein as well as BCV may be helpful denominators for comparison with e.g. cytokines in lung disease.

Asthma↗

PubMed2001

Clopidogrel and side effects.

Clopidogrel is a recently developed thrombocyte inhibitor with fewer side effects. We report 2 patients with purpura and thrombopenia, respectively, due to clopidogrel therapy. As this compound is widely used in clinical practice, the occurrence of hematological and dermal side effects should be considered.

Aged↗

PubMed2001

Breath-to-breath variability correlates with apnea-hypopnea index in obstructive sleep apnea.

BACKGROUND: Breathing in patients with obstructive sleep apnea (OSA) is frequently interrupted by periods of hypopnea and apnea. There is limited information regarding a possible disturbance of breathing outside these periods. STUDY OBJECTIVE: To analyze the degree of breathing disturbance during nonocclusion. DESIGN: Prospective determination of breathing variability during full polysomnographic sleep studies. PATIENTS: Breath-to-breath variation was monitored in 34 patients with OSA and in 9 healthy subjects. MEASUREMENTS AND RESULTS: All breath-to-breath intervals were automatically analyzed from flow signal, displayed, and manually corrected for artifacts. Distribution of all nonapneic breath intervals was analyzed for the extent of difference from a normal distribution pattern by specifying kurtosis. In untreated OSA patients, kurtosis was significantly reduced (0.0 +/- 0.5, mean +/- SD) compared to control subjects (0.8 +/- 0.5), indicating increased variability of nonoccluded breathing. This effect was present in all sleep stages, and the extent depended significantly on the degree of disease. Continuous positive airway pressure breathing was able to normalize kurtosis (1.0 +/- 0.9) immediately. CONCLUSIONS: Breathing in OSA is not only characterized by interruptions of breathing during occlusion, but by a greater variation in the pattern of normal-length breaths.

Adult↗

PubMed2000

Potassium regulates IL-1 beta processing via calcium-independent phospholipase A2.

We report that potassium leakage from cells leads to activation of the Ca2+-independent phospholipase A2 (iPLA2), and the latter plays a pivotal role in regulating the cleavage of pro-IL-1 beta by the IL-converting enzyme caspase-1 in human monocytes. K+ efflux led to increases of cellular levels of glycerophosphocholine, an unambiguous indicator of phospholipase A2 activation. Both maturation of IL-1 beta and formation of glycerophosphocholine were blocked by bromoenol lactone, the specific iPLA2 inhibitor. Bromoenol lactone-dependent inhibition of IL-1 beta processing was not due to perturbation of the export machinery for pro-IL-1 beta and IL-1 beta or to caspase-1 suppression. Conspicuously, activation of Ca2+-dependent phospholipase A2 did not support but rather suppressed IL-1 beta processing. Thus, our findings reveal a specific role for iPLA2 activation in the sequence of events underlying IL-1 beta maturation.

Biological Transport↗

PubMed2000

Serum levels of vascular endothelial growth factor in patients with head and neck cancer.

Angiogenesis is now considered to be crucial for tumor growth and metastasis. In several tumors, microvascular density has been shown to be correlated with metastasis and aggressiveness. Vascular endothelial growth factor (VEGF) is a secreted endothelial cell-specific mitogen, which is induced by hypoxia and is angiogenic in vivo. VEGF has been identified in a wide variety of malignancies including head and neck squamous cell carcinomas (HNSCC). We investigated the circulating level of VEGF in sera from patients with various head and neck squamous cell carcinomas (n = 71) as well as from healthy normal controls (n = 47). Serum VEGF concentrations were determined as serum immunoreactivity by using a quantitative sandwich enzyme immunoassay technique. For statistical analysis, the Wilcoxon 2-sample test and Kruskal-Wallis test were performed. The majority of the patients with HNSCC were found to have high concentrations of serum VEGE The levels of VEGF in the sera of patients with cancer ranged from below the detection limit to 937.1 pg/ml (mean, 144.5 pg/ml). In contrast, the VEGF serum levels in 47 healthy individuals ranged from below the detection limit to 168.1 pg/ml (mean, 32.7 pg/ml), VEGF serum concentration being significantly higher in HNSCC patients (P = < 0.001). These findings indicate that a positive angiogenesis regulator such as VEGF might function as an endocrine growth factor, particularly for solid HNSCC tumors and may be a useful marker for clinical monitoring.

Adult↗

PubMed1998

Cyclophosphamide pulse therapy in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disorder with poor prognosis. Response to treatment is infrequent and the use of immunosuppressive agents other than corticosteroids is the subject of ongoing discussion because of uncertain efficacy and side-effects. To determine the efficacy and safety of cyclophosphamide pulse therapy in IPF, this study retrospectively analysed 18 patients with progressive IPF who were treated with intermittent i.v. cyclophosphamide (1-13 g x month(-1)) and additional oral prednisolone for 1 yr. Static lung volumes, arterial oxygen tension (Pa,O2) at rest, clinical symptoms and potential treatment-related side-effects were recorded. Cyclophosphamide had to be stopped in one patient, owing to repeated pulmonary infection; 11 patients were responders (five improving, six stabilizing) and six patients deteriorated. The change in vital capacity (VC) of responders was +6.7+/-18.0% (mean +/-SD), compared with -20.6+/-18.2% in nonresponders (p=0.008). Pa,O2 remained constant in responders (+0.13+/-0.88 kPa (+1.0+/-6.6 mmHg)), while it decreased in nonresponders (-2.08+/-1.92 kPa (-15.6+/-14.4 mmHg, p=0.008)). Additional prednisolone was reduced by 19.1+/-13.4 mg in responders, compared with 6.7+/-16.3 mg in nonresponders (p=0.02). VC at initiation of therapy was higher in responders (60.2+/-10.2 versus 40.3+/-12.9% predicted; p=0.004). No side-effects occurred, other than respiratory tract infection. These data demonstrate that intravenous cyclophosphamide pulse therapy may be a favourable regimen for certain patients with progressive idiopathic pulmonary fibrosis. Patients with a vital capacity of more than 50% predicted and a shorter duration of disease may benefit most.

Administration, Oral↗

PubMed1995

Exogenous surfactant application in respiratory failure due to chronic obstructive pulmonary disease.

Recent results of basic research on regulation of surfactant secretion and surfactant physiology not only in the alveolus but also in peripheral small airways allow the conclusion that disorders in surfactant homeostasis may contribute to the pathophysiology of airway obstruction and hyperinflation. We therefore hypothesized that patients with respiratory failure due to obstructive lung disease may benefit from exogenous surfactant. Here we report a case that indicates the clinical situation to be considered for treatment with exogenous surfactant. The benefit for the patient was successful weaning from the ventilator. Improvements in effective compliance, resistance and blood gas parameters were observed following surfactant application.

Aged↗

PubMed1995

[Sarcoidosis of the lung: clinical course and inflammatory activity].

On the whole, sarcoidosis of the lung has a good prognosis with the exception of a few cases where it takes a progressive course. In such instances it would be useful to enable a prognosis already at the time of diagnosis by means of clinical parameters or inflammation markers. We examined a number of cell-biological inflammation parameters in the serum and bronchoalveolar lavage fluid of 72 patients in the x-ray stages I and II with and without Löfgren's syndrome (phenotyping of lymphocytes, interleukin-1 alpha, soluble interleukin-2 receptors [sIL-2R], interleukin-6, interleukin-8, platelet-derived growth factor, procollagen-3 peptide) and followed up these patients for one year by clinical parameters. It was found that markers of the active lymphocytic inflammation were mostly associated with spontaneous remission during the follow-up period. Hence, acute lymphocytic inflammation is a favourable prognostic sign and should not prompt premature treatment with cortisone.

Adult↗

PubMed1992

Ventilation and secretion of pulmonary surfactant.

Various factors are involved in the regulation of surfactant secretion: chemical agonist; local environmental factors such as mediators, locally produced hormones, and possibly pH; and finally, mechanical stress occurring during lung inflation. Here we suggest a model of regulation which is grouped into three levels: a basal autoregulatory mechanism with local factors being superimposed and a systemic level acting through hormones reaching the lung via the bloodstream. Depending on the situation, the different levels may vary in their importance. For the normal situation, in the absence of stress factors, we suggest the autoregulation of stretch-induced secretion and SP-A inhibition as indicated by in vitro experiments to be the prominent regulatory mechanism for surfactant secretion. From this model, mechanisms can be derived which indicate involvement of the surfactant system in, for example, obstructive lung disease. Support from the literature for this hypothesis is reviewed. Because quantitative measurement of the amount of surfactant-associated phospholipids cannot be done adequately at this time, we suggest testing the relatively risk-free application of exogenous surfactant in a pilot phase based on indications for its involvement and usefulness derived from animal and in vitro experiments.

Animals↗

PubMed1992

Stretch-dependent regulation of atrial peptide synthesis and secretion in cultured atrial cardiocytes.

We have developed a novel system to study stretch-dependent secretion of atrial natriuretic peptide (ANP) using cultured neonatal rat atriocytes in vitro. Application of tension (i.e., 2 sequential stretches) to cells grown on a flexible culture surface effected a dose-dependent increase in immunoreactive (ir) ANP release into the medium. Analysis of atriocyte cytoplasmic RNA 24 h poststretch revealed an increase in ANP mRNA levels of about ninefold relative to the unstretched controls. Medium ATP levels, measured as an index of cellular damage, were similar in control and stretched cells. Furthermore, cooling the cultures to 0 degrees C suppressed both basal as well as stretch-stimulated release. These findings argue against cellular damage and nonspecific release of irANP as an explanation for the increase in medium immunoreactivity. Stretch was incapable of amplifying the secretory response to prostaglandin F2 alpha, suggesting possible overlap in the pathways whereby these stimuli effect release of the peptide. The calcium channel blocker verapamil had no effect on stretch-dependent irANP release, whereas calmidzolium, a calmodulin inhibitor, suppressed basal as well as stretch-dependent secretion, implying a potentially important relationship between intracellular calcium metabolism and irANP release.

1-Methyl-3-isobutylxanthine↗

PubMed1975