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Biomedical subjects

G Baumann

Publications and source records attributed to G Baumann.

At least 91 records · Page 5Linked to original sources

Respiratory arousals in mild obstructive sleep apnea syndrome.

The objective of the study is to identify patients with mild sleep apnea by counting not only apneas and hypopneas, but also mild respiratory events, which do not fulfill apnea or hypopnea criteria, but result in an arousal (Type-R arousal). Arousals related to body movements (Type-M arousal) were separately counted. The influence of nasal continuous positive airway pressure (nCPAP) on respiratory and movement arousals was analyzed. Daytime sleepiness before and after nCPAP and its relationship to arousal types was investigated using the Multiple Sleep Latency Test (MSLT) and a standardised questionnaire. Twenty-two patients with a mean age of 43.6 +/- 9.2 years underwent polysomnographic evaluation on a baseline night, and during three nights with nCPAP. On the baseline night, subjects presented with a mean RDI of 10.5 +/- 7.2/h, an apnea index (AI) of 1.2 +/- 1.5/h, a hypopnea index (HI) of 9.3 +/- 6.6/h, a R index of 5.2 +/- 5.9/h, and a M index of 9.7 +/- 5.6/h. Use of nCPAP lowered the RDI (p < 0.001) and the R index (p < 0.01). Mean sleep latency in the MSLT increased with nCPAP (p < 0.05) and the patient's subjective well being improved (p < 0.01). Correlation analysis revealed a relationship between Type-R arousals and RDI and HI (r = 0.5, p < 0.01) as well as between questionnaire scores and mean sleep latency. The decrease of Type-R indicates the positive effect of nCPAP. Arousal analysis and detection of mild respiratory events associated with arousals are helpful in investigating the sleep structure and in objectifying clinical symptoms and treatment success in patients with mild OSAS.

Adult↗

Interaction of adenosine and prostacyclin in coronary flow regulation after myocardial ischemia.

The role of adenosine and prostacyclin in post-ischemic vasodilation was investigated using a model of sequential perfusion of two isolated hearts. Two guinea pig hearts were sequentially perfused (10 ml/min) without (control, n = 4) or with preceding 10-min ischemia (n = 6) of Heart I. Under control conditions no hemodynamic changes were observed in Heart II during sequential perfusion. After 10 min of ischemia of Heart I coronary perfusion pressure decreased by 23% in Heart II at the onset of sequential perfusion. Adenosine A1 and A2 receptor antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (2 microM) and 3,7-dimethyl-1-propargylxanthine (DMPX) (20 microM) infused simultaneously inhibited this decrease in coronary perfusion pressure by 74%, whereas indomethacin (5 microM) had no effect. DPCPX, DMPX and indomethacin in combination induced a significant increase in coronary perfusion pressure. Adenosine release (HPLC) into the coronary effluent after ischemia was significantly enhanced in the presence of indomethacin. These results suggest that after myocardial ischemia prostacyclin has an inhibitory effect on adenosine release.

Adenosine↗

A1/A2 polymorphism of glycoprotein IIIa and association with excess procedural risk for coronary catheter interventions: a case-controlled study.

BACKGROUND: A five-fold increase in risk of stent thrombosis in carriers of A1/A2 (Leu33Pro) polymorphism of glycoprotein Illa has been described. Whether this increased procedural risk applies to other coronary interventions is unknown. We investigated the role of A1/A2 polymorphism as a putative risk factor. METHODS: We genotyped 1000 consecutive patients with angiographically confirmed coronary-artery disease and 1000 controls matched for age and sex. 653 of the 1000 patients received interventions (271 coronary angioplasty, 102 directional coronary atherectomy, and 280 stenting) and were assessed for a 30-day composite endpoint of need for target-vessel revascularisation, myocardial infarction, and death. FINDINGS: The composite endpoint occurred in 41 (6.3%) patients. There was no evidence that the A2 allele was associated with excess procedural risk (relative risk 1.36 [95% CI 0.70-2.70], p=0.37). Nor, in subgroup analyses, did A2 predict events that complicated coronary angioplasty (1.17 [0.40-2.70]), directional coronary atherectomy (1.50 [0.30-8.70]), or stenting (1.45 [0.60-3.50]). Neither heterozygotes (A1/A2) nor homozygotes (A2/A2) were over-represented in any subgroup, including those with acute coronary syndromes, early disease manifestation (age <40 years), and histories of myocardial infarction. INTERPRETATION: A1/A2 polymorphism is not a major risk factor for 30-day adverse events that complicate coronary angioplasty, directional coronary atherectomy, or stenting. Furthermore, A1/A2 polymorphism has no apparent impact on more chronic processes such as atherogenesis of the coronary arteries.

Aged↗

Expression of atrial myosin light chains but not alpha-myosin heavy chains is correlated in vivo with increased ventricular function in patients with hypertrophic obstructive cardiomyopathy.

The adult rodent heart adapts to increased work load by reexpression of its fetal genes, for example, beta-myosin heavy chain (MHC), in order to improve contractile function. However, the human ventricle regulates contractility by expression of atrial essential myosin light chain (ALC-1) rather than beta-MHC. We evaluated the impact of both mechanisms in patients with hypertrophic cardiomyopathy. MHC isoform expression was quantified at the mRNA and protein levels by reverse transcriptase polymerase chain reaction and immunoblotting, respectively. Although alpha-MHC mRNA was detected in control and hypertrophied human ventricular tissue, alpha-MHC protein was not observed. Similarly, we investigated the expression of ALC-1 by two-dimensional polyacrylamide gel electrophoresis and the clinical and hemodynamic parameters of the patients with hypertrophic cardiomyopathy. We found a significant positive correlation between ALC-1 protein expression and dP/dtmax in the hypertrophied human ventricle in vivo. Correlations between dP/dtmax and expression of protein for the ryanodine receptor and L-type Ca2+ channel were excluded. Our data suggest that reexpression of ALC-1 improves the contractile state of the adult human heart. We propose that two evolutionarily divergent compensatory mechanisms for increased work demand exist in the mammalian heart: MHC regulation in rodents and essential MLC regulation, of cardiac contractility, in humans.

Adult↗

Influence of polymorphonuclear leukocytes and plasma on coronary vasomotion after ischemia.

BACKGROUND: The role of plasma and neutrophils in endothelial dysfunction following myocardial ischemia was investigated. METHODS: Isolated rabbit hearts were perfused at constant pressure with a modified Krebs-Henseleit solution. After a 30-minute global ischemia the hearts were perfused at the onset of reperfusion for 10 minutes with either NaCl (group I, n = 6), autologous plasma alone (group II, n = 5), autologous polymorphonuclear leukocytes alone (PMN, group III, n = 6), or PMN and plasma in combination (group IV, n = 5). Before and after ischemia the effects of intracoronary endothelial dependent and independent vasodilation by acetylcholine (1 x 10(-7)mol/L) and glycerol trinitrate (1 x 10(-6) mol/L) were investigated. RESULTS: A similar increase in coronary flow was induced in groups I, II, and III by acetylcholine and glycerol trinitrate before and after ischemia. In contrast, in group IV the endothelial dependent vasodilation was significantly depressed (p < 0.05). In groups II and IV a moderate but significant reduction in the recovery of the left ventricular pressure was observed after ischemia and reperfusion. CONCLUSIONS: These results suggest that after myocardial ischemia, plasma is required for neutrophil-mediated endothelial dysfunction.

Animals↗

Cellular adhesion molecules on vascular smooth muscle cells.

Several studies during the last years have shown that, in addition to endothelial cells, vascular smooth muscle cells also express the cellular adhesion molecules ICAM-1 and VCAM-1 in atherosclerosis, restenosis and transplant vasculopathy. In vitro studies have characterized stimulatory and inhibitory factors that regulate the expression of ICAM-1 and VCAM-1 on cultured smooth muscle cells. There is evidence for a role of adhesion molecules on smooth muscle cells for leukocyte accumulation and activation of mononuclear cells. Some recent data suggest that the expression of adhesion molecules on smooth muscle cells are cell cycle-dependent and influence smooth muscle cell proliferation and differentiation. Therefore, ICAM-1 and VCAM-1 on smooth muscle cells may contribute to the inflammatory reaction in the vascular wall and may actively be involved in the progression and stability of atherosclerotic plaques.

Animals↗

Mutations in the growth hormone releasing hormone receptor: a new form of dwarfism in humans.

We describe a recently identified new form of dwarfism due to isolated growth hormone (GH) deficiency, secondary to inactivating mutations in the GH-releasing hormone receptor (GHRHR) gene. The identical nonsense mutations in the extracellular domain of the GHRHR (E72X or E50X, depending on whether the signal peptide is included in the numbering) has been independently described in three families residing on or originating from the Indian subcontinent (Pakistan, the Bombay region, and Delft near Sri Lanka). Another inactivating mutation, involving the donor splice site of intron 1, has been identified in a population in north-eastern Brazil. Genetic transmission is autosomal recessive; the gene is located on the short arm of chromosome 7. Affected subjects have severe isolated GH deficiency and postnatal growth failure, with a mean adult height of 130 cm for men and 114 cm for women (7-8 standard deviations below the norm). Dwarfism is proportional; a characteristic feature is relative microcephaly, which results in a 'miniaturized adult', eumorphic aspect. Bone age and puberty are delayed, but fertility appears normal. This new syndrome corresponds to the human homologue of the previously identified 'little mouse'.

Adult↗

A new bronchoscopic method to measure airway size.

Bronchoscopic evaluation of stenosis is limited due to radial distortion of bronchoscopic images and the unknown distance between the endoscope and the stenotic area. The purpose of this study was the development and validation of a method for measuring cross-sectional areas in large airways. Distance measurements were performed using a laser probe inserted into the working channel of a bronchoscope. The laser probe was positioned to the locus of interest in the airway, a ring of light (helium/neon) projected on to the luminal wall and the images acquired using an electronic bronchoscope. The images taken were distortion-corrected by means of a computer program. The method was validated by simulating airways using tubes of known diameter. Additionally, distortion-corrected bronchoscopic images were compared with distortion-free videoscopic image analysis of tracheal slices taken from pigs. In the case of the plastic tubes, Pearson's correlation coefficient (r) as well as the intraclass correlation coefficient (ICC) were slightly higher (r=0.99, p<0.01, ICC=0.97) than the correlation of cross-sectional areas between bronchoscopic and videoscopic images of tracheal slices (r=0.88, p<0.01, ICC=0.87). This concept allows accurate and reproducible determination of cross-sectional areas in large airways.

Animals↗

Cardiodepressant mediators are released after myocardial ischaemia: modulation by catecholamines and adenosine.

The interaction of recently characterized cardiodepressant mediators with catecholamines and adenosine after myocardial ischaemia was investigated using a model of sequential perfusion of two isolated guinea-pig hearts. Sequential perfusion was initiated after 10, 20, and 30 min (group I, II, and III) of global ischaemia in the first heart. At the onset of sequential perfusion LVdP/dtmax and min of Heart II decreased by 46 and 44% in group I, by 28 and 34% in group II, and increased by 60 and 24% in group III. Infusion of the beta1-receptor antagonist metoprolol (2.8 micromol L(-1)) into Heart II did not modulate contractile changes after 10 min of ischaemia in Heart I, prevented the attenuation of the cardiodepressant effect after 20 min of ischaemia, and completely reversed the positive inotropic effect after 30 min of ischaemia. The A1- and A2-receptor antagonists DPCPX (2 micromol L(-1)) and DMPX (20 micromol L(-1)) enhanced the positive inotropic and lusitropic effects in Heart II (LVdP/dtmax +154%, LVdP/dtmin +71%) during sequential perfusion after 30 min of ischaemia in Heart I. It is concluded that the effects of cardiodepressant mediators released after myocardial ischaemia are counteracted by a time-dependent release of catecholamines. Endogenous cardiac adenosine, in turn, attenuates the modulatory effects of catecholamines.

Adenosine↗

Successful streptokinase lysis of a right-atrial thrombus in a heart-transplant recipient.

This report describes a mobile right-atrial thrombus formation diagnosed by transthoracic echocardiography in a 22-year-old patient seven months after orthotopic heart transplantation. To prevent embolic complication, systemic streptokinase lysis was performed over 48 hours. Echocardiographic control examinations have shown that this therapy completely removed the thrombus.

Adult↗

Phase-related changes in right ventricular cardiac output under volume-controlled mechanical ventilation with positive end-expiratory pressure.

OBJECTIVE: To examine determinants of right ventricular function throughout the ventilatory cycle under volume-controlled mechanical ventilation with various positive end-expiratory pressure (PEEP) stages. DESIGN: Prospective observational animal pilot study. SETTING: Animal research laboratory at a university hospital. SUBJECTS: Eight healthy swine under volume- controlled mechanical ventilation. INTERVENTIONS: Flow probes were implanted in eight swine in order to continuously measure blood flow in the pulmonary artery and inferior vena cava. After a recovery phase of 14 days, the swine were subjected to various PEEP stages (0, 5, 10 cm H2O) during volume-controlled positive pressure ventilation. MEASUREMENTS AND MAIN RESULTS: Continuous flow measurement took place in the pulmonary artery and inferior vena cava. Data on standard hemodynamic parameters were additionally acquired. Respiration-phase-specific analysis of right ventricular cardiac output and of additional hemodynamic function parameters followed, after calculation of mean values throughout five respiration cycles. PEEP at 5 cm H2O led to significant decreases in inferior vena cava flow (4.1%), and in right ventricular cardiac output (5.2%); the respective decreases at PEEP 10 cm H2O were 13.9% and 18.3%. In the inspiration phase at PEEP 10 cm H2O, results revealed an overproportionally pronounced decrease in comparison with the expiration phase in inferior vena cava flow (-24.6% vs. -10%) and right ventricular cardiac output (-35% vs. -13.5%). This phenomenon is presumably caused by a PEEP-related increase in mean airway pressure by the amount of 10.7 cm H2O in inspiration. CONCLUSIONS: Increases in PEEP during volume-controlled mechanical ventilation leads to respiration-phase-specific reduction of right ventricular cardiac output, with a significantly pronounced decrease during the inspiration phase. This decrease in cardiac output should be taken into particular consideration for patients with already critically reduced cardiac output.

Airway Resistance↗

Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease.

Oxidative damage is a major cause of atherosclerosis. Since human paraoxonase has been postulated as a factor which plays a role in protection from low density lipoprotein oxidation, recent studies have dealt with the impact of hereditary PON1 gene polymorphisms as risk factors for coronary artery disease (CAD). The results from these studies are conflicting. In a case-control study, 1000 Caucasian patients with angiographically confirmed CAD were recruited and matched by age and gender to 1000 control individuals. PON1 mutations in codons 55 and 192 were evaluated by polymerase chain reaction-restriction fragment length polymorphism and allocated to defined haplotypes *1 (55L/192Q), *2 (55L/192R), and *3 (55M/192Q). Frequency of PON1 genotypes without any mutation (PON1*1/*1, wild-type) in CAD cases was 16.9% versus 17.1% in control individuals. PON1*2/*2 showed a frequency of 6.6% versus 7.3% (P = 0.68 compared to wild-type), and PON1*3/3 occurred in 11.8% in CAD cases versus 10.3% among control individuals (P = 0.40). There was also no difference in the distribution of carriers heterozygous for *2 or *3 among cases and control individuals. A haplotype containing both mutations 55M and 192R was not observed. None of the investigated genotypes demonstrated association with early manifestation, severity of disease, acute coronary syndromes, or myocardial infarction. Logistic regression analysis with adjustment for age, gender, diabetes, hypertension, hypercholesterolemia and smoking revealed no evidence of increased coronary risk associated with PON1 genotypes. These results suggest that PON1 polymorphisms are not major genetic determinants of CAD.

Alleles↗

Automatic and efficient R wave discrimination in the right atrium using a two-state hidden Markov model.

INTRODUCTION: Discrimination of far-field R waves from atrial events in atrial electrograms (EGMs) is problematic in present implantable pacing systems. Adjustments of atrial refractory periods and sensitivity settings are the only options, and they will not provide optimal performance in many patients. The reliable detection or rejection of R waves in atrial EGMs would avoid problems of atrial undersensing or oversensing, thus benefiting DDD patients by providing more reliable and specific atrial arrhythmia detection. In addition, detection of far-field R waves could allow a measurement of AV conduction time in AAI and aid in discrimination of supraventricular tachyarrhythmia from ventricular tachyarrhythmia. METHODS AND RESULTS: Both atrial and ventricular unipolar EGMs were collected from 25 patients undergoing pacemaker implant or replacement. An average of 141 seconds of intrinsic or VVI paced EGMs was recorded and post analyzed. A new two-state hidden Markov model (HMM) was developed specifically for far-field R wave and P wave discrimination in the atrium. The recorded patients' EGMs were analyzed using this model, and the sensitivity and positive predictivity of far-field R wave detection were evaluated. The collected atrial EGMs were visually examined and marked as the control for verification of the detection analysis. Far-field R wave detection using this model had an overall sensitivity of 94% +/- 9.4% and a positive predictivity of 98.3% +/- 4.4%; and the far-field R wave rejection using the same model had a sensitivity and a positive predictivity of 98.8% +/- 3.8% and 99.1% +/- 1.7%, respectively. CONCLUSION: Far-field R wave detection in the right atrium by the two-state HMM is reliable and accurate, and can significantly improve atrial arrhythmia management for patients.

Adolescent↗

Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis.

OBJECTIVE: The clinical course of fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) may vary considerably from stable condition for years to continuous fatal progression. This prospective study aimed at identifying the prognostic value of bronchoalveolar lavage fluid (BALF) analysis in FASSc. METHODS: Seventy three consecutive patients with SSc and clinical signs of pulmonary involvement were enrolled. Every patient underwent clinical examination, lung function tests, computed tomography (CT), gallium scan, echocardiography, and bronchoalveolar lavage (BAL). Forty nine patients, 26 with pathological and 23 with normal BALF findings were prospectively followed up for two years and re-evaluated annually. RESULTS: At baseline, 51 subjects (70%) showed radiological signs of lung fibrosis and/or alveolitis by CT and diffusion capacity for carbon monoxide (DLco) was decreased in 47 patients (64%). Thirty five patients (48%) had pathological BALF findings. BALF differential counts included BALF granulocytosis in 18, BALF lymphocytosis in 12, and a mixed increase of both granulocytes and lymphocytes in five patients. On follow up, a progression of FA with a significant decrease of DLco was only observed in patients with BALF granulocytosis. In contrast, patients with BALF lymphocytosis or normal BALF cell count had stable lung function parameters during the study period. In none of our patients echocardiography showed evidence of pulmonary hypertension. CONCLUSION: BALF granulocytosis predicts progression of FA with deterioration of lung function, which is most sensitively monitored by DLco. Immunosuppressive treatment is recommended in patients with granulocytic FASSc.

Bronchoalveolar Lavage Fluid↗

Growth hormone heterogeneity in human pituitary and plasma.

Several isoforms of growth hormone (GH) have been identified in humans. There are many reasons for this heterogeneity. At the genetic level, two genes encode GH: GH-N, expressed in the pituitary, and GH-V, expressed in the placenta. At the mRNA level, GH-N undergoes alternative splicing into 20K and 22K isoforms. Post-translationally, 22K GH undergoes modifications, such as acetylation at its amino terminus, deamidation, and oligomerization. The picture is complicated further in the circulation, where GH binds to two GH-binding proteins, each with different affinities for the GH isoforms. In addition, a highly heterogeneous mixture of GH fragments has been demonstrated. The implications of this heterogeneity relate to differences between GH immunoassays, such that assay results cannot be compared between laboratories. The reasons for GH heterogeneity and its practical and clinical implications are considered here.

Alternative Splicing↗