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Biomedical subjects

Friedhelm Sayk

Publications and source records attributed to Friedhelm Sayk.

9 recordsLinked to original sources
PubMed2005

Histopathologic findings in a novel decellularized pulmonary homograft: an autopsy study.

Innovative valved conduits for reconstruction of the right ventricular outflow tract are desirable to overcome the risk of valve deterioration of conventional homografts. This study describes the histopathology of a novel decellularized pulmonary homograft (SynerGraft) implanted in the right ventricular outflow tract of a 60-year-old man 5 weeks before death. The histomorphology of this decellularized homograft showed integrity of its extracellular matrix and a gradual cellular infiltrate consisting predominantly of macrophages, resembling an early nonspecific inflammatory phase of recellularization without any signs of a specific immunologic interference 5 weeks after implantation. Whether this morphologic appearance precedes the desired repopulation with autologous fibroblasts remains to be established.

Autopsy↗
PubMed2004

Effect of facial cooling and cold air inhalation on sympathetic nerve activity in men.

In nine healthy subjects, cold stimuli were administered to the forehead and hand, to the oral and nasal cavities via ice cubes and to the bronchial system via inhalation of cold air (-25 degrees C). Blood pressure, heart rate and muscle sympathetic nerve activity (MSNA) from the peroneal nerve were recorded. MSNA expressed as total activity increased during cold air inhalation, cooling of the forehead (P < 0.001, ANOVA), hand and mouth (P < or = 0.05), paralleled by a rise in blood pressure during cold air inhalation and cooling of the forehead and hand (P < 0.01). Cooling of the forehead provoked a faster increase of MSNA expressed as total activity (P < 0.05) and higher levels of diastolic blood pressure (P = 0.05) compared with cooling of the hand. Bradycardia was observed only during cooling of the nasal cavity (P < 0.001) and the forehead (P < 0.05). It is concluded that cooling of the skin and mucous membranes of the tracheobronchial tract elicits sympathetically mediated hemodynamic adaptations, probably via stimulation of cold-sensitive afferents.

Action Potentials↗
PubMed2004

Significant damage of the conduction system during cardioplegic arrest is due to necrosis not apoptosis.

OBJECTIVES: Ventricular conduction disturbances following cardioplegic arrest remains a serious, yet unsolved problem. In the present study we examined whether myocardial conduction cells (MCC, Purkinje fibers) are more vulnerable to ischemia/reperfusion injury than working myocardial cells and whether the damage is due to necrosis or apoptosis. METHODS: Mini-pigs were subjected to 60 min of crystalloid (St Thomas; n = 15 group I) or blood (Buckberg; n = 6 group II) cardioplegic arrest followed by 3 h of reperfusion. Animals not subjected to either procedures served as controls (n = 5). Ventricular myocardial specimens were investigated by hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining and immunohistochemical labeling of apoptosis-associated proteins (Bax, Bcl-2, Caspase-3). DNA-breaks were visualized by in situ end labeling (terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling, TUNEL). Electron microscopy confirmed apoptosis or necrosis. RESULTS: MCC of control hearts intrinsically expressed Bax, Bcl-2, and Caspase-3 without signs of either apoptotic or necrotic damage. Subendocardial Purkinje fibers of groups I and II hearts exhibited focal damage, with reduced labeling of apoptosis-associated proteins, glycogen loss, karyopycnosis and increased eosinophilia (15/21 hearts). The majority of damaged MCC displayed nuclear TUNEL-positivity (2.8+/-2.5% of MCC), whereas the average TUNEL-rate of the adjacent working myocardium was low (<0.1%). Electron microscopy demonstrated ischemic changes in MCC consistent with cellular necrosis. CONCLUSIONS: Ischemia/reperfusion injury due to cardioplegic arrest inflicts significant damage on subendocardial MCC, but not on working myocardium. Ultrastructural and light-microscopic findings are consistent with coagulation necrosis, rather than apoptosis.

Animals↗
PubMed2003

Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a chronic hypercholesterolemic porcine model.

OBJECTIVE: The value of prophylactic brachytherapy on vein graft disease is unknown. METHODS AND RESULTS: Vein bypass grafts in 23 hypercholesterolemic pigs after ex vivo gamma irradiation of the vein grafts (10, 20, and 40Gy) and 16 control veins were analyzed regarding: (1) expression of platelet-derived growth factor (PDGF-AA and -BB, ELISA); (2) smooth muscle cell (SMC) proliferation/cell death (double-immunohistochemistry Mib-1/TUNEL/SMC alpha-actin); and (3) vessel wall dimensions. Planimetric data on vessel wall dimensions revealed no positive effect of gamma radiation on neointima formation and inner lumen diameter. On the contrary, vein grafts subjected to 40Gy were significantly more likely to be occluded and to have reduced inner lumen and increased neointima formation. Radiation therapy had no effect on PDGF expression and SMC proliferation/cell death. The mean inner lumen diameter decreased as PDGF-AA expression increased. CONCLUSIONS: Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a hypercholesterolemic porcine model. High-dose radiation (40Gy) resulted in more frequent graft occlusion and vein sclerosis.

Anastomosis, Surgical↗
PubMed2003

Histopathological grading of ascending aortic aneurysm: comparison of patients with bicuspid versus tricuspid aortic valve.

BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is a common inherited condition that is often accompanied by ascending aortic aneurysm. A high level of histological wall abnormalities was reported to be present in non-dilated aortas of patients with BAV. In patients with tricuspid aortic valve, there appears to exist a direct relationship between the diameter of the ascending aorta and degree of histopathological aortic wall abnormalities. Whether this situation exists in patients with BAV has not yet been investigated. METHODS: Surgical and medical records of all patients undergoing surgery of the ascending aorta were reviewed. A total of 65 patients was identified in whom an aortic wall specimen was obtained intraoperatively. These specimens were systematically re-evaluated, and graded according to the severity of seven histopathological conditions: fibrosis, atherosclerosis, medionecrosis, cystic medial necrosis, smooth muscle cell orientation, elastic fiber fragmentation, and inflammation. RESULTS: BAVs were present in 26 patients (40%). Patients with BAV had significantly less aortic wall alterations than patients with tricuspid aortic valves (p < 0.001) in all variables examined. The severity of aortic wall abnormalities was significantly dependent on aortic diameter in patients with BAV as well as tricuspid aortic valve (p = 0.036 and 0.019), but dependent on age (p = 0.009) only in patients with tricuspid aortic valve. CONCLUSION: The study results provide evidence that ascending aortic aneurysm in patients with BAV differs clinically and histologically from that in patients with tricuspid aortic valve. Further studies are needed to elucidate the impact of inherited and acquired aortic wall abnormalities on the development of aneurysms.

Adult↗
PubMed2002

HER2 overexpression in muscle-invasive urothelial carcinoma of the bladder: prognostic implications.

The HER2 (c-erbB-2) receptor is overexpressed in a variety of human malignant tumors and, in breast carcinoma, has been identified as a target for anti-HER2-directed therapy with the monoclonal antibody (MAb) trastuzumab. The aim of this retrospective study was to evaluate immunohistochemic HER2 expression in a large cohort of muscle-invasive urothelial cell carcinomas of the urinary bladder and to compare the results to pathologic characteristics and survival. Paraffin-embedded tumor specimens from 138 patients undergoing radical cystectomy for muscle-invasive bladder carcinoma were studied immunohistochemically with the Food and Drug Administration (FDA)-approved HercepTest (Dako, Glostrup, Denmark). HER2 overexpression was observed in 57 of 138 tumors (41%) and occurred more frequently in high-grade carcinomas than in low-grade carcinomas (p = 0.036). No significant relationship with HER2 overexpression was registered for tumor staging and lymph node status. Kaplan-Meier curves showed a significantly worse disease-related survival (p = 0.034) in patients with HER2-overexpressing tumors compared to those without HER2 overexpression. In addition to lymph node status (p = 0.0001; relative risk [RR] = 2.93), HER2 status (p = 0.020; RR = 2.22) was identified as an independent predictor for disease-related survival in a multivariate analysis. These results suggest that HER2 expression might provide additional prognostic information in patients with muscle-invasive bladder carcinomas. Because many of these patients harbor HER2-overexpressing tumors, clinical trials evaluating the efficacy of trastuzumab in bladder carcinoma are warranted.

Adult↗
PubMed2002

Overexpression of c-erbB-2 oncoprotein in muscle-invasive bladder carcinoma: relationship with gene amplification, clinicopathological parameters and prognostic outcome.

Amplification of the c-erbB-2 oncogene and protein overexpression are well-known in breast cancer and a basis for therapy with the monoclonal antibody trastuzumab, which binds to the receptor encoded by c-erbB-2. Regarding bladder carcinoma, several studies have examined c-erbB-2 expression, but their results are quite heterogeneous. In the present study, we evaluated the expression of this oncoprotein immunohistochemically in 203 muscle-invasive urothelial bladder carcinomas using the HercepTest. Additionally, 42 cases were studied for gene amplification by fluorescence in situ hybridization (FISH) using the PathVysion kit. Follow-up was known in 147 patients. The results were compared with pathologic characteristics and disease-related survival. Immunohistochemical c-erbB-2 overexpression was observed in 37% of the tumors (76/203). However, only 5% (2/42) showed amplification of the oncogene, indicating that predominantly other mechanisms than gene amplification may cause protein overexpression in bladder cancer. C-erbB-2 protein overexpression was significantly associated with high tumor grade (p=0.004) and infiltrative growth pattern (p=0.0001), and tendentiously associated with the presence of lymph node metastases (p=0.077). Regarding tumor stage, sex and age, no significant correlation was registered. Kaplan-Meier curves showed a significantly worse disease-related survival for patients with c-erbB-2 overexpressing tumors (p=0.0346 by log-rank test). Multivariate analysis revealed that, besides nodal status (p=0.0001) and tumor stage (p=0.028), c-erbB-2 overexpression was an independent predictor of disease-related survival (p=0.030). Thus, our results suggest that immunohistochemical c-erbB-2 detection might represent an additional tool in determining bladder cancer prognosis. Clinical trials evaluating the efficacy of trastuzumab therapy in bladder cancer patients are warranted.

Adult↗
PubMedDate not supplied

Omphalocoele-exstrophy-imperforate anus-spinal defects complex in dizygotic twins.

OEIS complex refers to a combination of defects consisting of omphalocoele, exstrophy of the cloaca, imperforate anus, and spinal defects. The incidence of the OEIS complex is very rare, estimated to occur in 1 of 200,000-400,000 pregnancies. The aetiology of the OEIS complex is still unclear, single defects in blastogenesis and mutations in homeobox genes, such as HLXB9, have been suggested to be responsible for the development of the OEIS complex. Moreover, higher incidence of OEIS in monozygotic twins suggests a possible genetic contribution to the occurrence of this multisystem defect. We here report the peculiar case of OEIS complex in a dizygotic twin pregnancy. Prenatal diagnosis of OEIS by ultrasound examination is possible but difficult. Sonographic detection of an omphalocoele in the presence of an open neural tube defect should prompt a search of OEIS-associated defects. Accurate prenatal diagnosis by ultrasound and/or diagnosis of the OEIS complex at autopsy are important for detailed counselling of the parents and perinatal management.

Abnormalities, Multiple↗