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Biomedical subjects

Gert Baumann

Publications and source records attributed to Gert Baumann.

At least 19 recordsLinked to original sources

Addition of milk prevents vascular protective effects of tea.

AIMS: Experimental and clinical studies indicate that tea exerts protection against cardiovascular diseases. However, a question of much debate is whether addition of milk modifies the biological activities of tea. We studied the vascular effects of tea, with or without milk, in humans and elucidated the impact of individual milk proteins in cell culture experiments, with isolated rat aortic rings and by HPLC analysis. METHODS AND RESULTS: A total of 16 healthy female volunteers consumed either 500 mL of freshly brewed black tea, black tea with 10% skimmed milk, or boiled water as control. Flow-mediated dilation (FMD) was measured by high-resolution vascular ultrasound before and 2 h after consumption. Black tea significantly improved FMD in humans compared with water, whereas addition of milk completely blunted the effects of tea. To support these findings, similar experiments were performed in isolated rat aortic rings and endothelial cells. Tea induced vasorelaxation in rat aortic rings and increased the activity of endothelial nitric oxide synthase by phosphorylation of the enzyme in endothelial cells. All effects were completely inhibited by the addition of milk to tea. Of the various kinds of milk proteins, the caseins accounted for these inhibiting effects of milk, probably by formation of complexes with tea catechins. CONCLUSION: Milk counteracts the favourable health effects of tea on vascular function. This finding indicates the need for particular awareness in the interpretation and design of studies comprising nutritional flavonoids.

Animals↗

Multislice computed tomography: angiographic emulation versus standard assessment for detection of coronary stenoses.

The present study investigated angiographic emulation of multislice computed tomography (MSCT) (catheter-like visualization) as an alternative approach of analyzing and visualizing findings in comparison with standard assessment. Thirty patients (120 coronary arteries) were randomly selected from 90 prospectively investigated patients with suspected coronary artery disease who underwent MSCT (16-slice scanner, 0.5 mm collimation, 400 ms rotation time) prior to conventional coronary angiography for comparison of both approaches. Sensitivity and specificity of angiographic emulation [81% (26/32) and 93% (82/88)] were not significantly different from those of standard assessment [88% (28/32) and 99% (87/88)], while the per-case analysis time was significantly shorter for angiographic emulation than for standard assessment (3.4 +/- 1.5 vs 7.0 +/- 2.5 min, P < 0.001). Both interventional and referring cardiologists preferred angiographic emulation over standard curved multiplanar reformations of MSCT coronary angiography for illustration, mainly because of improved overall lucidity and depiction of sidebranches (P < 0.001). In conclusion, angiographic emulation of MSCT reduces analysis time, yields a diagnostic accuracy comparable to that of standard assessment, and is preferred by cardiologists for visualization of results.

Aged↗

Haemodynamic effects of intravenous quinaprilat in comparison to sodium nitroprusside in patients with chronic heart failure.

We compared the haemodynamic effects of intravenous boluses of the ACE inhibitor quinaprilat with an intravenous infusion of sodium nitroprusside in 23 patients with chronic heart failure (NYHA Class III or IV). At the highest drug doses, sodium nitroprusside significantly increased stroke volume index (+6.63 ml/m(2), p=0.045), whereas quinaprilat induced only a minor increase (+1.79 ml/m(2), n.s.).

Adolescent↗

Noninvasive detection of coronary artery stenoses with multislice computed tomography or magnetic resonance imaging.

BACKGROUND: Multislice computed tomography (CT) and magnetic resonance imaging (MRI) are the main candidates for noninvasive coronary angiography; however, multislice CT, unlike MRI, exposes patients to radiation and an iodinated intravenous contrast agent. OBJECTIVE: To compare the diagnostic accuracy of multislice CT and MRI for noninvasive detection of clinically significant coronary stenoses (> or =50%). DESIGN: Prospective intention-to-diagnose study. SETTING: Single tertiary referral center, Berlin, Germany. PATIENTS: 129 consecutive patients with suspected coronary artery disease. INTERVENTIONS: Multislice CT and MRI were both performed within a median of 1 day before conventional coronary angiography, which served as the reference standard. MEASUREMENTS: Diagnostic performance of multislice CT and MRI. RESULTS: 129 patients completed the study. Altogether, 108 patients with 430 vessels could be examined with both multislice CT and MRI and were used for analysis. In the per-patient analysis, the sensitivity of multislice CT (92% [95% CI, 82% to 96%]) was significantly higher than that of MRI (74% [CI, 61% to 83%]; P = 0.013). The sensitivity for detecting clinically significant stenoses was 82% for multislice CT and 54% for MRI (P < 0.001). Specificity and negative predictive value of multislice CT and MRI in the per-vessel analysis were 90% versus 87% (P = 0.73) and 95% versus 90% (P = 0.032), respectively. The effective radiation dose used with multislice CT (mean, 12.3 mSv [SD, 1.4]) in a consecutive subgroup of 73 patients was not significantly different from that used with diagnostic cardiac catheterization (11.4 mSv [SD, 4.8]) (P = 0.169). Most patients (74%) indicated that they would prefer multislice CT for future diagnostic imaging (P < 0.001). LIMITATIONS: This was a single-center study with 129 patients. CONCLUSIONS: In patients referred for conventional coronary angiography, multislice CT compares favorably with MRI for noninvasive detection of coronary stenoses.

Coronary Angiography↗

Head-to-head comparison of multislice computed tomography and exercise electrocardiography for diagnosis of coronary artery disease.

AIMS: To prospectively compare multislice computed tomography (MSCT) and exercise electrocardiography (ex-ECG) for diagnosis of coronary artery disease (CAD) with conventional coronary angiography as the reference standard. METHODS AND RESULTS: A consecutive cohort of 80 patients with suspected CAD was examined with MSCT using 16 x 0.5 mm detector collimation, ex-ECG, and conventional coronary angiography according to standard protocols. Results were compared using the paired McNemar's test, the chi(2) test, and 95%CIs. Both the sensitivity and specificity of MSCT [91% (40 of 44 patients, 95%CI 78-97%) and 83% (30 of 36 patients, 95%CI 67-94%)] were significantly higher (P = 0.039 and P < 0.001) than those for ex-ECG [73% (32 of 44 patients, 95%CI 57-85%) and 31% (11 of 36 patients, 95%CI 16-48%)]. The pairwise McNemar's test showed significant differences between MSCT and ex-ECG in the overall diagnosis in patients with suspected CAD (P = 0.036). The rate of non-diagnostic examinations was not significantly (P = 0.078) different between MSCT and ex-ECG [8% (6 of 80 patients, 95%CI 3-16%) vs. 19% (15 of 80 patients, 95%CI 11-29%)]. CONCLUSION: In this consecutive cohort of patients scheduled to undergo conventional coronary angiography, the performance of MSCT for diagnosis of CAD was superior to that of ex-ECG.

Aged↗

Right ventricular function assessed by two-dimensional strain and tissue Doppler echocardiography in patients with pulmonary arterial hypertension and effect of vasodilator therapy.

Two-dimensional strain echocardiography is a new method for the assessment of regional contractility. Thirty-seven patients with pulmonary arterial hypertension (mean age 56.4 +/- 11 years) and 38 normal subjects (mean age 58.3 +/- 12 years) underwent 2-dimensional echocardiography and tissue Doppler echocardiographic evaluation of right ventricular (RV) global function and regional contractility. Patients with pulmonary arterial hypertension additionally underwent 6-minute walking distance tests and right-sided cardiac catheterization before and after (8 +/- 3 months) vasodilator therapy. Moderate or severe RV dysfunction was present in all patients (2-dimensional strain of the basal segment of the RV free wall: -8.8 +/- 4.1% systolic longitudinal deformation) compared with normal subjects (-24.3 +/- 4.7% systolic longitudinal deformation, p < 0.001) and was improved with vasodilator therapy after 6 to 11 months (-13.3 +/- 6.2% systolic longitudinal deformation, p < 0.001).

Adult↗

Relaxin-a pleiotropic hormone and its emerging role for experimental and clinical therapeutics.

The insulin-related peptide hormone relaxin (Rlx) is known as pregnancy hormone for decades. In the 1980s, researchers began to recognize the highly intriguing fact that Rlx plays a role in a multitude of physiological processes far beyond pregnancy and reproduction. So, Rlx's contribution to the regulation of vasotonus, plasma osmolality, angiogenesis, collagen turnover, and renal function has been established. In addition, the peptide has been demonstrated to represent a mediator of cardiovascular pathology. The ongoing efforts to identify Rlx receptors eventually precipitated the discovery of the G protein-coupled receptors (GPCR) LGR7 and LGR8 as membrane receptors for human Rlx-2 in 2002. This review will summarize the current state of insight into this rapidly evolving field, which has further been expanded by the discovery of GPCR135 and GPCR142 as receptors for Rlx-3. In addition, Rlx has also been shown to activate the human glucocorticoid receptor (GR). There is evidence from Rlx and Rlx receptor knockouts suggesting that LGR7 is the only relevant receptor for mouse Rlx-1 (corresponding to human Rlx-2) in vivo and that insulin-like peptide (INSL)-3 represents the physiological ligand for LGR8. Regarding Rlx signal transduction, the cyclic adenosine monophosphate (cAMP) and nitric oxide (NO) pathways will be characterized as major cascades. Investigation of downstream signaling remains an important field for future research. Finally, the current state of therapeutical strategies using Rlx in animal models as well as in humans is summarized.

Animals↗

Nontoxic proteasome inhibition activates a protective antioxidant defense response in endothelial cells.

Inhibitors of the ubiquitin-proteasome system offer a new and promising approach in the therapy of proliferative and inflammatory diseases. In order to narrow the therapeutic window for cytotoxic effects on the one hand and nontoxic, anti-inflammatory effects on the other hand, we elucidated the complex cellular effects of toxic versus nontoxic proteasome inhibition in human endothelial cells by expressional profiling. Nontoxic doses of proteasome inhibitors induced a defined, dose-dependent transcriptional response that was markedly attenuated in terms of gene number and amplitude of regulation compared to toxic doses. In particular, we observed uniform upregulation of several antioxidative enzymes and differential regulation of genes involved in endothelial function. This adaptive transcriptional pattern was translated into a protective response of endothelial cells against H(2)O(2)-induced oxidative stress and into improvement of endothelial function of rat aortic rings. Our data thus suggest that nontoxic proteasome inhibition might offer a new therapeutic approach for the treatment of endothelial dysfunction in cardiovascular disorders.

Antioxidants↗

Influence of the atrio-ventricular delay optimization on the intra left ventricular delay in Cardiac Resynchronization Therapy.

BACKGROUND: Cardiac Resynchronization Therapy (CRT) leads to a reduction of left-ventricular dyssynchrony and an acute and sustained hemodynamic improvement in patients with chronic heart failure. Furthermore, an optimized AV-delay leads to an improved myocardial performance in pacemaker patients. The focus of this study is to investigate the acute effect of an optimized AV-delay on parameters of dyssynchrony in CRT patients. METHOD: 11 chronic heart failure patients with CRT who were on stable medication were included in this study. The optimal AV-delay was defined according to the method of Ismer (mitral inflow and trans-oesophageal lead). Dyssynchrony was assessed echocardiographically at three different settings: AVDOPT; AVDOPT-50 ms and AVDOPT+50 ms. Echocardiographic assessment included 2D- and M-mode echo for the assessment of volumes and hemodynamic parameters (CI, SV) and LVEF and tissue Doppler echo (strain, strain rate, Tissue Synchronisation Imaging (TSI) and myocardial velocities in the basal segments) RESULTS: The AVDOPT in the VDD mode (atrially triggered) was 105.5 +/- 38.1 ms and the AVDOPT in the DDD mode (atrially paced) was 186.9 +/- 52.9 ms. Intra-individually, the highest LVEF was measured at AVDOPT. The LVEF at AVDOPT was significantly higher than in the AVDOPT-50 setting (p = 0.03). However, none of the parameters of dyssynchrony changed significantly in the three settings. CONCLUSION: An optimized AV delay in CRT patients acutely leads to an improved systolic left ventricular ejection fraction without improving dyssynchrony.

Atrioventricular Node↗

Screening for sleep-related breathing disorders by transthoracic impedance recording integrated into a Holter ECG system.

In patients with arrhythmias, coincidence with sleep-related breathing disorders (SRBD) is high and of clinical relevance. Electrocardiogram-derived (ECG) parameters have been developed for SRBD screening, but it has proved necessary to exclude patients with frequent arrhythmias. Holter-based screening tools, easy to use, are therefore warranted. The goal of our study was to evaluate the diagnostic accuracy, with respect to SRBD detection, of transthoracic impedance recording (TTIR) integrated into a Holter System. Our investigation consisted of 2 phases. In phase 1 we compared the performance of TTIR to that of in-hospital polysomnography (PSG) in 56 patients (46 male, mean age 57). In phase 2 we compared TTIR to results from an ambulatory polygraphy (PG) system in 180 patients (143 male, mean age 56). We scored apnea and hypopnea from P(S)G, and derived a respiratory-disturbance index (P(S)G-RDI). TTIR was analyzed semi-automatically. Reduction of the impedance amplitude by more than 50% over 10 s was scored as apnea/hypopnea, with consequent calculation of TTIR-RDI. In phase 1, 20 out of 56 patients revealed a PSG-RDI > 10 h(-1). TTIR-RDI in 19 patients from this group was >10 h(-1) (sensitivity 95%, specificity 97.2%, positive predictive value 95%, negative predictive value 97.2%, interclass correlation coefficient 0.98). In phase 2, 46 of 180 patients revealed a PSG-RDI > 10 h(-1). TTIR-RDI in 37 out of this group was >10 h(-1) (sensitivity 80.4%, specificity 92.5%, positive predictive value 78.7%, negative predictive value 93.2%, interclass correlation coefficient 0.92). TTIR integrated into a Holter ECG system and tested in a large patient cohort demonstrates acceptable high accuracy in detection of SRBD. Arrhythmia analysis and screening for SRBD can be performed in a single-step approch.

Adult↗

Pacemaker-induced superior vena cava syndrome: clinical evaluation of long-term follow-up.

BACKGROUND: Pacemaker-induced superior vena cava (SVC) syndrome is a rare but serious complication of permanent pacemaker implantation. Because of its rarity, little is known about the long-term prognoses of such patients. METHODS: Five patients, mean age 62 +/- 11.4 years, with pacemaker-induced SVC syndrome for more than 10 years were investigated. The clinical evaluation included: exercise testing, thrombophilia lab tests, and a chest CT. RESULTS: Two of the patients manifested complications of SVC syndrome which included thoracoabdominal subcutaneous collaterals. One of these patients simultaneously developed an increase in the pacing threshold which required the implantation of epicardial leads. Three of the five patients had normal age-adjusted VO(2) AT und VO(2) max. Four of the patients were both heterozygous for a polymorphism of PAI-1 and were homozygous for a polymorphism of t-PA. One of these patients also was heterozygous for a polymorphism of factor V and glycoprotein IIb/IIIa. The chest CTs revealed extensive and varying collateral circulation patterns in all of the patients. CONCLUSIONS: The development of pacemaker-induced SVC syndrome is the result of various predisposing factors including thrombophilia. Many patients retain normal age-adjusted cardiopulmonary capacity and demonstrate stable clinical findings on the long-term as the result of the development of extensive collateral vessel systems. The most serious complication was the combination of SVC syndrome and the simultaneous malfunctioning of one of the leads requiring implantation of a new lead.

Aged↗

Long-term therapy of interferon-alpha induced pulmonary arterial hypertension with different PDE-5 inhibitors: a case report.

BACKGROUND: Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare. CASE PRESENTATION: We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy. CONCLUSION: This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach.

3',5'-Cyclic-GMP Phosphodiesterases↗

Does contrast echocardiography induce increases in markers of myocardial necrosis, inflammation and oxidative stress suggesting myocardial injury?

BACKGROUND: Contrast echocardiography is a precise tool for the non-invasive assessment of myocardial function and perfusion. Side effects of contrast echocardiography resulting from contrast-agent induced myocardial micro-lesions have been found in animals. The goal of this study is to measure markers of myocardial necrosis, inflammation and oxidative stress in humans to evaluate potential side-effects of contrast echocardiography. METHODS: 20 patients who underwent contrast echocardiography with Optison as the contrast medium were investigated. To evaluate myocardial micro-necrosis, inflammation and oxidative stress, cardiac troponin I (cTnI), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, -8 and thiobarbituric acid reactive substances (TBARS) were measured at baseline and at 2, 4, 8 and 24 hours after contrast echocardiography. RESULTS: At baseline, 50% of the patients had cTnI and TBARS values outside the reference range. TNF-alpha, IL-6, IL-8 levels were within the reference range. Patients with cTnI above the RR clustered to significantly higher levels of TNF-alpha and IL-6. After contrast echocardiography, no statistically significant increase of cTnI, cytokines and TBARS was found. However, for nearly 50% of the patients, the intra-individual cTnI kinetics crossed the critical difference (threefold of methodical variation) which indicates a marker increase. This was neither predicted by the baseline levels of the cytokines nor the markers of oxidative stress. CONCLUSION: There are no clinically relevant increases in serum markers for micro-necrosis, inflammation and oxidative stress in humans after contrast echocardiography. Future studies have to address whether cTnI increase in some patients represent a subset with increased risk for side effects after contrast echocardiography.

Adolescent↗

Effect of statins on the proteasomal activity in mammalian endothelial and vascular smooth muscle cells.

Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, effectively prevent cardiovascular events. In addition to their lipid lowering properties, a variety of pleiotropic effects on cardiovascular cells were demonstrated in vitro and in vivo. It has been hypothized that statins deploy a part of their effects by targeting the proteasome. Statin-induced effects remarkably overlap with effects obtained by inhibition of the proteasome in endothelial and vascular smooth muscle cells (e.g., endothelial nitric oxide synthase (eNOS)-upregulation, attenuation of nuclear factor kappa B (NF-kappaB) activation, inhibition of proliferation). We therefore examined, whether statins modulate the proteasomal activity of vascular cells. We studied the effect of simvastatin, atorvastatin, and pravastatin as well as of the proteasome inhibitor clasto-lactacystin on morphology, proliferation, viability, and proteasomal activity in two mammalian endothelial cell lines (CPAE and Ea.hy962), and in primary vascular smooth muscle cells (VSMCs). Both statins and lactacystin induced comparable morphological changes and attenuated proliferation of calf pulmonary artery cell line (CPAE). Whereas the statin-induced effects were reversed by mevalonic acid, however, the lactacystin-induced alterations were not influenced by mevalonic acid. As expected, lactacystin caused a significant loss of proteasomal activity measured in the extract of treated CPAE cells, whereas the extracts of statin-treated CPAEs exhibited unchanged activities. This result was also confirmed in Ea.hy926 cells and in primary rat VSMCs. We show here, that even high doses of statins do not modulate the activities of purified human 20S proteasomes. We conclude that the similar biological effects of statins and proteasome inhibitors in vascular cells are not due to a common inhibitory mechanism of action on the proteasome.

Animals↗

Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases.

Differences in pharmacokinetics, pharmacodynamics, and physiology contribute to the phenomenon that women and men frequently respond differently to cardiovascular drugs. Hormonal influences, in addition, can play an important role: for example, the menstrual cycle, menopause, and pregnancy--as a result of fluctuations in concentrations of sexual steroids, and of changes in total body water--can be associated with gender-specific differences in the plasma levels of cardiovascular drugs. Clinical relevance accordingly results, especially for substances with a narrow therapeutic margin. This review treats the most important pharmacodynamic gender-relevant differences in this context, and surveys available evidence on the benefits of therapy of chronic cardiovascular diseases in women. On the whole, the study situation for women is appreciably less favourable than for men: owing to the fact that women are under-represented in most studies, and that few gender-specific analyses have been conducted.

Adrenergic beta-Antagonists↗

Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke.

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established treatment in acute stroke. To prevent rethrombosis after rtPA therapy, secondary anticoagulation with heparin is commonly performed. However, the recommended time-point and extent of heparin treatment vary and are not well investigated. CASE PRESENTATION: We report a 61-year-old man who developed an acute global aphasia and right-sided hemiparesis. Cranial CT was normal and systemic thrombolytic therapy with tPA was started 120 minutes after symptom onset. Low-dose subcutaneous heparin treatment was initiated 24 hours later. Transthoracic echocardiography (TTE) 12 hours after admission showed slightly reduced left ventricular ejection fraction (LVEF) but was otherwise normal. 48 hours later the patient suddenly deteriorated with clinical signs of dyspnea and tachycardia. TTE revelead a large left ventricular apical thrombus as well as a reduction of LVEF to 20 %. Serial further TTE investigations demonstrated a complete resolution of the thrombus and normalisation of LVEF within two days. CONCLUSION: Our case demonstrates an intracardiac thrombus formation following rtPA treatment of acute stroke, probably caused by secondary hypercoagulability. Rethrombosis or new thrombus formation might be an underestimated complication of rtPA therapy and potentially explain cases of secondary stroke progression.

Acute Disease↗

Role of immunoglobulin G3 subclass in dilated cardiomyopathy: results from protein A immunoadsorption.

BACKGROUND: Immunoadsorption (IA) by anti-immunoglobulin G (anti-IgG) columns that effectively eliminates total IgG, including IgG3 subclass, represents an additional therapeutic approach in dilated cardiomyopathy (DCM). A recent study revealed that IA with protein A columns does not effectively remove IgG3 and does not induce hemodynamic improvement in DCM. METHODS: Eighteen patients with DCM (left ventricular ejection fraction < or =30%) were included in this case-control study. In all patients, IA with protein A was performed in 4 courses, at 1-month intervals until month 3. Nine patients underwent protein A IA with an improved treatment regimen for IgG3 elimination. Data of these patients were compared retrospectively to existing findings for 9 comparable patients treated by protein A IA with ineffective IgG3 reduction. RESULTS: In both groups, IA induced a comparable reduction of the total IgG level. However, reduction of the IgG3 level was different in the 2 groups (P < .001). Hemodynamics did not significantly change throughout the 3 months in the group with ineffective IgG3 reduction. In contrast, the group with improved IgG3 reduction demonstrated during the first IA course an increase in cardiac index from 2.2 +/- 0.1 to 2.8 +/- 0.2 L min(-1) m(-2) (P < .05). After 3 months before the last IA course, cardiac index was 2.2 +/- 0.1 L min(-1) m(-2) in the group with ineffective IgG3 elimination and 2.8 +/- 0.2 L min(-1) m(-2) in the group with improved IgG3 reduction (P < .01). In the group with ineffective IgG3 reduction, left ventricular ejection fraction increased after 3 months from 21.6 +/- 2% to 24.4 +/- 2% (NS), and from 24.3 +/- 2 to 34.7 +/- 4% in the group with improved IgG3 reduction (P < .05). CONCLUSIONS: Autoantibodies belonging to IgG3 may play an important role in cardiac dysfunction of patients with DCM. Protein A IA in conjunction with an improved treatment regimen for IgG3 elimination induces hemodynamic benefit in patients suffering from DCM.

Adsorption↗