Biomedical subjects

Michael Brehm

Publications and source records attributed to Michael Brehm.

14 recordsLinked to original sources

PubMed2006

Intracoronary autologous bone marrow cell transplantation beneficially modulates heart rate variability.

The effect of intracoronary administration of autologous bone marrow cells on autonomic modulation of heart rate has not yet been demonstrated. Therefore, we investigated different parameters of heart rate variability (HRV) in 46 patients without (n=23) or with (n=23) intracoronary stem cell therapy after transmural myocardial infarction. After three to twelve months of follow up, patients receiving stem cells showed a significant increase of HRV parameters that have been linked to cardiovascular prognosis.

Aged↗

PubMed2006

[Myocardial disease in viral infections. Myocarditis--cardiomyopathy].

Inflammation of the myocardium is a common cardiac disease. Molecular and immunhistological techniques help to assure myocarditis in terms of persistence of chronic viral infection and myocardial inflammation activity. The connection between viral myocarditis and development of dilative cardiomyopathy is of great interest. Thus, new possibilities arise for assessment of the disease prognosis and the strategy of specific immunosuppressive, immunomodulating and antiviral therapy.

Antiviral Agents↗

PubMed2006

[Myocardial infarct trial of Düsseldorf. Short- and long-term results after intracoronary stem cell transplantation in acute and chronic myocardial infarction].

Adult autologous bone marrow-derived cells contribute to the healing of myocardial infarction. At the author's institution patients after acute myocardial infarction and patients with chronic coronary heart disease and old infarction were treated. In both patient groups a significant decrease of the infarct area, an improvement of regional contractility and global left ventricular function could be demonstrated. Additional tests with SPECT and positron emission tomography could show an improved myocardial perfusion and an increased glucose uptake in the infarcted area after intracoronary bone marrow cell transplantation. Long-term controls of both patient groups could demonstrate, that the left ventricular pump function was not only increased after 3 months, but also after 12 and 24 (-36) months, respectively. These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be released in humans by bone marrow-derived cell transplantation.

Bone Marrow Cells↗

PubMed2006

[Transplantation of autologous adult bone marrow stem cells in patients with severe peripheral arterial occlusion disease].

BACKGROUND: For many patients with severe peripheral arterial occlusion disease (PAOD) an interventional or surgical treatment is not feasible. The regenerative potential of adult autologous mononuclear stem cells could contribute to neoangiogenesis. PATIENTS AND METHODS: Ten patients with severe PAOD were included. The walking distance was < 200 m and no interventional or surgical treatment was possible. After harvesting of 80 ml of bone marrow the mononuclear cell fraction was separated. Thereafter, intraarterial (10 ml into the common femoral artery) and intramuscular (5 ml into the muscles of the thigh and the lower leg) transplantation of the cell suspension was performed. RESULTS: After 2 months the walking distance was enhanced significantly in all patients. Furthermore, a significant improvement of ankle-brachial index at rest, capillary-venous oxygen saturation and parameters of venous occlusion plethysmography was seen. No complications or side effects could be monitored. CONCLUSION: These results demonstrate, that the combined intraarterial and intramuscular transplantation of autologous adult bone marrow stem cells leads to a significant improvement of perfusion indices in patients with severe PAOD.

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PubMed2006

[Effects of exercise training on mobilization of BM-CPCs and migratory capacity as well as LVEF after AMI].

BACKGROUND AND PURPOSE: Bone marrow-derived circulating progenitor cells (BM-CPCs) are mobilized in adult peripheral blood (PB) during the acute myocardial infarction (AMI) period and contribute to the regeneration of infarcted myocardium. In this study, the influence of physical training on the mobilization and the migratory activity of the BM-CPCs as well as on the left ventricular function (LVEF) after AMI was examined. PATIENTS AND METHODS: 26 patients with AMI were analyzed in two groups. The first group comprised 17 patients with standardized exercise training for 3 weeks 14 +/- 4 days after AMI, the second group nine control subjects without exercise training. PB concentrations of CD34/45+ and CD133/45+ were measured by FACS. The migratory activity of BM-CPCs was analyzed by migration assay. B-type natriuretic peptide (BNP) in PB and the functional investigations spiroergometry (VO2 and PaO2) and stress echocardiography (LVEF) were determined in both groups. RESULTS: A significant increase in both concentrations, CD34/45+ and CD133/45+, as well as in migratory capacity of BM-CPCs was found after 3 weeks of exercise training, which was significantly decreased 3 months after completion of exercise training. No significant difference was observed in the control group without exercise training. In the functional investigations a significant increase in VO2 as well as PaO2 was shown spiroergometrically after exercise training. There was no difference in stress echocardiographic LVEF at rest in both groups. On the other hand, interestingly, the findings showed that the increase of LVEF at peak stress was significantly higher after exercise training as compared to the control group. Moreover, a significant decrease in BNP values was found after exercise training as well as 3 months after AMI. No difference was found in the control group. CONCLUSION: This study demonstrates that exercise training for 3 weeks after AMI leads to a significant mobilization as well as increase of functional activation of BM-CPCs in humans. Moreover, regular exercise training might contribute to the positive effects on the regenerative potency after AMI.

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PubMed2006

Stem cell therapy in postinfarction chronic coronary heart disease.

After acute myocardial infarction, bone-marrow-derived cells (BMDCs) improve cardiac function; it is conceivable, but not yet demonstrated, that BMDC therapy might also be useful in chronic infarction. We treated 18 consecutive patients who had chronic myocardial infarction (between 5 months and 8.5 years postinfarction) using intracoronary transplantation of autologous BMDCs and compared this group with a representative control group who did not receive cell therapy. After 3 months, infarct size in the transplantation group was reduced by 30% and both global left ventricular ejection fraction and infarction wall-movement velocity were increased significantly (15% and 57%, respectively), whereas in the control group no significant changes were observed. After transplantation of BMDCs, there was an 11% improvement in maximum oxygen uptake and a 15% increase in regional (18)F-fluordeoxyglucose uptake into infarcted tissue, as determined by positron emission tomography. These results show that functional and metabolic regeneration of infarcted and chronically avital tissue can be achieved in humans using transplantation of bone-marrow-derived cells.

Bone Marrow Cells↗

PubMed2006

[Impact of attachment style, social support and the number of implantable cardioverter defibrillator (ICD) discharges on psychological strain of ICD patients].

OBJECTIVE It is well known fact, that the life of ICD patients is often affected by anxiety and depression. The number of ICD discharges is only a contributing factor explaining the variance of anxiety and depression. There have to be other factors that have more influence on the physical strain of ICD patients. In this study we examined the impact of attachment style and social support in addition to the number of ICD discharges. METHODS 119 out-patients at an out-patient ICD unit were examined consecutively with the following self report scales: (1) the State-Trait-Anxiety Inventory (STAI), (2) the Beck Depression Inventory (BDI), (3) a short form of a social support questionnaire (F-SOZU), (4) the Bielefeld Partnership Expectations Questionnaire (BFPE) and (5) a specifically designed questionnaire for the assessment of sociodemografic data. To determine the frequency and timing of the ICD discharges we analysed the ICD data. RESULTS 38 % of the ICD patients reported enhanced anxiety levels and 37 % reported enhanced depression levels. Only 38 % of the ICD patients received discharges at all. Elevated levels of anxiety and depression were found in patients who showed insecure attachment styles, low social support, long-term treatment in hospital and a higher number of ICD discharges. To explain the variance of anxiety we found social support, attachment style, and the number of ICD storms to be contributing factors. To explain the variance of depression we found social support and time spent in hospital in the previous year to be contributing factors. CONCLUSIONS Almost half of the ICD patients suffer considerably from anxiety and/or depression. These patients have to be identified and treated psychotherapeutically. Patients who show insecure attachment styles, receive low social support, undergo long-term treatment in hospital and receive a higher number of discharges, especially so called ICD storms, bear the highest risk to develop psychological strain. Attachment style and social support have even more impact on the development of anxiety and depression than the number of ICD discharges. It has to be shown in future studies whether psychotherapy can improve the quality of life of ICD patients.

Aged↗

PubMed2005

Regeneration of human infarcted heart muscle by intracoronary autologous bone marrow cell transplantation in chronic coronary artery disease: the IACT Study.

OBJECTIVES: Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. BACKGROUND: After acute MI, bone marrow-derived cells improve cardiac function. METHODS: We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. RESULTS: After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). CONCLUSIONS: These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation.

Adult↗

PubMed2005

[Rapid healing of a therapy-refractory diabetic foot after transplantation of autologous bone marrow stem cells].

BACKGROUND: The diabetic foot mainly depends on painless pressure lesions, which are based on diabetic polyneuropathy and microangiopathy. In these cases the regenerative potential of adult autologous mononuclear stem cells could serve as causal therapy. HISTORY AND CLINICAL FINDINGS: A 63-year-old patient with long-lasting type 2 diabetes mellitus suffers from a reduced walking distance of 200 m and a therapy-refractory ulcer at the right ball of the great toe. Therefore, the authors have decided to perform a combined intraarterial and intramuscular transplantation of stem cells into the right limb for the first time on this disease. THERAPY AND RESULTS: After harvesting of bone marrow the mononuclear cell fraction was separated (157 x 10(6) cells). Thereafter, the fractional intraarterial and intramuscular transplantation of the cell suspension was performed (10 ml each). Already 8 weeks later, the ulcer healed completely, after 6 months the walking distance increased by > 100%, on venous occlusion plethysmography the arterial blood circulation at rest increased by 23% and the reactive hyperemia by 56%. CONCLUSION: The combined intraarterial and intramuscular transplantation of autologous bone marrow stem cells could constitute a novel, clinically feasible and safe therapy for patients with diabetic foot syndrome. The success of this approach may be ascribed to microangiogenesis and to an anti-inflammatory effect of the transplanted stem cells.

Bone Marrow Transplantation↗

PubMed2003

[Stem cell therapy in acute myocardial infarction].

Remodeling of the left ventricle after myocardial infarction represents a major cause of infarct-related heart failure and death. Experimental data suggest that bone marrow-derived cells may contribute to the healing of myocardial infarction. The selective intracoronary transplantation of autologous, mononuclear bone marrow cells is safe and seems to be effective under clinical conditions concerning heart function, myocardial perfusion, and metabolism. The therapeutic effect may be attributed to bone marrow cell-associated myocardial regeneration and neovascularization.

Angioplasty, Balloon, Coronary↗

PubMed2002

Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans.

BACKGROUND: Experimental data suggest that bone marrow-derived cells may contribute to the healing of myocardial infarction (MI). For this reason, we analyzed 10 patients who were treated by intracoronary transplantation of autologous, mononuclear bone marrow cells (BMCs) in addition to standard therapy after MI. METHODS AND RESULTS: After standard therapy for acute MI, 10 patients were transplanted with autologous mononuclear BMCs via a balloon catheter placed into the infarct-related artery during balloon dilatation (percutaneous transluminal coronary angioplasty). Another 10 patients with acute MI were treated by standard therapy alone. After 3 months of follow-up, the infarct region (determined by left ventriculography) had decreased significantly within the cell therapy group (from 30+/-13 to 12+/-7%, P=0.005) and was also significantly smaller compared with the standard therapy group (P=0.04). Likewise, infarction wall movement velocity increased significantly only in the cell therapy group (from 2.0+/-1.1 to 4.0+/-2.6 cm/s, P=0.028). Further cardiac examinations (dobutamine stress echocardiography, radionuclide ventriculography, and catheterization of the right heart) were performed for the cell therapy group and showed significant improvement in stroke volume index, left ventricular end-systolic volume and contractility (ratio of systolic pressure and end-systolic volume), and myocardial perfusion of the infarct region. CONCLUSIONS: These results demonstrate for the first time that selective intracoronary transplantation of autologous, mononuclear BMCs is safe and seems to be effective under clinical conditions. The marked therapeutic effect may be attributed to BMC-associated myocardial regeneration and neovascularization.

Angioplasty, Balloon, Coronary↗

PubMed2002

Stem cells--clinical application and perspectives.

BACKGROUND: Augmentation of myocardial performance in experimental models of therapeutic infarction and heart failure has been achieved by transplantation of exogenous cells into damaged myocardium. The quest for suitable donor cells has prompted research into the use of both embryonic stem cells and adult somatic stem cells. MULTIPOTENT SOMATIC STEM CELLS: Recently, there has been a growing body of evidence that multipotent somatic stem cells in adult bone marrow exhibit tremendous functional plasticity and can reprogram in a new environmental tissue niche to give rise to cell lineages specific for new organ site. This phenomenon has made huge impact on myocardial biology, while multipotent adult bone marrow hematopoeitic stem cells and mesechymal stem cells can repopulate infarcted rodent myocardium and differentiate into both cardiomyocytes and new blood vessels. CONCLUSION: These data, coupled with the identification of a putative primitive cardiac stem cell population in the adult human heart, may open the way for novel therapeutic modalities for enhancing myocardial performance and treating heart failure.

Adult↗

PubMed2002

Elevated serum markers of collagen degradation in patients with mild to moderate dilated cardiomyopathy.

BACKGROUND AND AIMS: Left ventricular (LV) dilation and myocardial remodelling are hallmarks of heart failure in idiopathic dilated cardiomyopathy (DCM). Interstitial collagen is essential for LV integrity and function while degradation of collagen by collagenases, especially matrix-metalloproteinases (MMPs), are suggested to contribute to ventricular dilation. In the present study, serological markers of collagen metabolism were investigated. METHODS AND RESULTS: Serum levels of MMP-1 and its inhibitor (TIMP-1), the markers for collagen degradation type I (collagen carboxyterminal telopeptide (ICTP)) and synthesis (carboxyterminal propeptide of type I procollagen (PICP)) were quantified by ELISA and RIA of 43 patients with DCM and 47 age-matched control subjects. Free MMP-1 serum concentration was significantly increased in the DCM group (5.29+/-0.83 vs. 2.22+/-0.29 ng/ml; P=0.01) as well as the free TIMP-1 concentration (206.54+/-12.65 vs. 181.44+/-8.55 ng/ml; P=0.05). The free MMP-1/TIMP-1-ratio was higher in DCM than in the control group (0.030+/-0.005 vs. 0.012+/-0.001; P=0.01). ICTP was significantly increased (7.60+/-1.21 vs. 3.44+/-0.19 microg/l; P<0.001). PICP was not significantly increased (125.29+/-8.93 microg/l vs. 113.11+/-5.47 microg/l; P=n.s.). Free MMP-1 and MMP-1/TIMP-1-ratio correlated with LV end diastolic diameter [cm/m(2) body surface area (BSA)] (r=0.28; P=0.03 and r=0.34; P=0.01, respectively) as well as with cardiac index (CI) (r=-0.32; P=0.04 and r=-0.33; P=0.04, respectively) in patients with DCM. CONCLUSION: Serum markers of collagen degradation are elevated and might be valuable markers for progression of LV dilation in patients with DCM.

Adult↗

PubMed2002

Detection of enteroviral RNA (poliovirus types 1 and 3) in endomyocardial biopsies from patients with ventricular tachycardia and survivors of sudden cardiac death.

The purpose of this study was to determine the prevalence of enteroviral infection in the myocardium of consecutive patients with serious ventricular arrhythmias by using a reverse transcription nested PCR followed by direct DNA sequencing. After exclusion of coronary heart disease, right ventricular endomyocardial biopsies were obtained from 32 consecutive patients with a history of ventricular tachycardia or sudden cardiac death. Control biopsies were obtained from 36 subjects with no history of viral myocarditis, dilated cardiomyopathy, ventricular tachycardia or recent infection. Enteroviral genome was found in endomyocardial biopsies from 4/32 patients (12.5%), 2 with a history of ventricular tachycardia and 2 with a history of ventricular fibrillation. Three of these 4 enteroviral RNA-positive patients had dilated cardiomyopathy and the other had normal cardiac geometry and ventricular function. In the latter and in 1 patient with enteroviral-positive dilated cardiomyopathy, an active inflammatory process in the myocardium was found by means of immunohistology. Enteroviral RNA in the myocardium of 3 patients had the highest homology to poliovirus type 1 (strain CHAT 10A-11) and in the other was similar to poliovirus type 3 (strain P3/119). All control samples were negative for enteroviral RNA. In summary, these findings raise the possibility that enteroviruses, such as poliovirus types 1 and 3, may be involved in the pathogenesis of ventricular tachycardia and sudden cardiac death.

Base Sequence↗