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Biomedical subjects

P Alter

Publications and source records attributed to P Alter.

27 records · Page 2Linked to original sources

[Impediment of cellular immune response under treatment with ticlopidine in a patient with Staphylococcus aureus endocarditis].

A 52-year-old male with coronary artery disease was admitted with acute aortic valve endocarditis and a temperature up to 39.5 degrees C caused by Staphylococcus aureus. The patient was treated with ticlopidine (Tiklyd) after percutaneous transluminal coronary angioplasties to reduce restenosis by inhibiting thrombocyte aggregation. Upon admission c-reactive protein (CRP) was 389 mg/l. Interleukin-6 (IL-6) and Interleukin-2-receptor (IL-2-rec) were distinctly increased. Monoclonal antimyocardial antibodies were found. Leukocyte count never exceeded 9.8 G/l; however, transesophageal echocardiography validated a soft vegetation of the aortic valve. Antibiotic therapy was initiated with imipenem, gentamicin and vancomycin; clarithromycin was added after five days. Temperature normalized after 24 days. The c-reactive protein decreased from 389 mg/l to 6 mg/l, and the elevated cytokine levels decreased accordingly. Agranulocytosis or pancytopenia by ticlopidine through a toxic mechanism have been described, which are normally reversible within three weeks; there has not yet been a description of a missing leukocyte response in endocarditis as in this case report. This is a special situation with lack of or impeded immunological response, which limits the use of ticlopidine, especially since a therapeutic alternative with clopidogrel is available.

Agranulocytosis↗

[Cell death in inflammatory heart muscle diseases--apoptosis or necrosis?].

Cell death can be induced by 2 different mechanisms: necrosis and apoptosis. Necrosis, on the one hand, is usually caused by unphysiological stress factors such as hyperthermia or hypoxia, apoptosis, on the other hand, is part of the normal organ development and controls for example immune responses. Morphologically, necrosis is characterized by swelling of cells and their organelles leading to the disruption of the cell membrane, which in turn causes an inflammatory reaction in the surrounding tissue. Morphological and biochemical criteria (Figure 1, Table 1) of apoptosis are the condensation of chromatin leading to the development of apoptotic bodies or membrane-enclosed vesicles containing oligonucleosomal DNA fragments. Important diagnostic tools of cell death (Table 2), such as the TUNEL test (Figure 2) or gel electrophoresis of extracted DNA (Figure 3) are based on the above mentioned biochemical characteristics, but a reliable differentiation of apoptotic versus necrotic processes is not always possible. Experimental studies in animals and studies in various diseases of the cardiovascular system were able to show that apoptosis in myocytes can be induced, an issue that has long been discussed controversially. Ischemia, reperfusion, and myocardial infarction were also shown to lead to apoptosis in cardiomyocytes, whereas cell destruction was caused mainly by necrosis. Several authors (Table 3) demonstrated apoptotic indices in cardiomyocytes of patients with dilatated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and patients with acute infarction from 0.25 to 35% by the use of the TUNEL test. Others were able to demonstrate an elevated expression of Fas-receptor in cells of atheroslerotic plaques in patients with atherosclerosis and high indices of apoptotic cardiomyocytes in patients with chronic heart failure. We investigated endomyocardial biopsies of patients with inflammatory cardiomyopathy, DCM without inflammatory reaction but the presence of adenoviral or cytomegaloviral genome and idiopathic DCM using the TUNEL test. The percentage of apoptotic cardiomyocytes in biopsies of patients with DCMi was 1.03 and in biopsies of patients with adenoviral genome 0.25, whereas in all other groups no apoptosis was found. If apoptosis plays a major role in myocardial diseases such as heart failure, arrhythmia and others, blocking this mechanism will have to be considered as a therapeutical strategy. Therefore, studies on the extent of apoptotic processes in diseased versus healthy cardiac tissue are of great importance.

Animals↗

Comparison of geometry-based and CT voxel-based finite element modelling and experimental validation.

The objectives of the paper presented here is the comparison of a geometry-based and voxel-based finite element (FE) method preprocessor of the human femur. The models were experimentally validated by strain gauge measurements (principal stress). The correlation coefficients (r) between the three methods (geometry-based FEM, voxel-based FEM, strain gauge measurements) were found to be in the range 0.91-0.94 (r2: 0.84-0.88). The relationships between the samples are highly significant (P = 0.001), where the strain gauge results are the independent variables. These results suggest that the validity with respect to the principal stress of a voxel-based modelling is similar to the validity of geometry-based modelling. In summary, therefore, we conclude that voxel-based meshing allows a straightforward interfacing with computerized tomography (CT) scans and might contribute to a clinically applicable FEM technology.

Aged↗

[Fully automated generation of hip prosthesis voxel models of the femur for finite element analysis. Comparison of direct and subsequent prosthesis implantation].

Two means of generating implant-bearing FE voxel models of the human femur are described and compared. The first method consists in the fully automatic production of a femur model from CT data and subsequent implantation of a prosthesis stem on the basis of a redefinition of existing voxel elements using geometrical data control. The second method processes the CT data of a femur already bearing a prosthesis. Here, the prosthesis elements are generated separately from the surrounding bony elements on the basis of the differing CT density thresholds. Although the two implantation algorithms produce comparable results, they have different fields of application. The method of numerical stress analysis involving automatic generation of voxel models can be applied to implant-bearing femurs. Clinical follow-up observations of patients with prostheses made of titanium can be supported by FE calculations.

Algorithms↗

[Use of voxel-oriented femur models for stress analysis. Generation, calculation and validation of CT-based FEM models].

A means of interfacing computed tomography with the finite element method for the analysis of stress distribution in human femurs is described. With the aid of data transfer and image processing programs, three-dimensional voxel models of four macerated and a fresh-frozen cadaveric femur were generated from CT data sets. The underlying basic principle is direct generation of model elements from one or more adjacent CT-voxels, which are characterised by their coordinates and local absorption coefficients. A new algorithm was used for smoothing the edges of the model. All the models were analysed with respect to their stress distribution under different load situations, and the results were compared with the data of a parallel study utilizing the strain-gauge technique. Using the method of linear regression, a high correlation (coefficient of determination r2: 0.80-0.91) was found between the calculated and experimentally measured principal stresses at the surface of the bones.

Biomechanical Phenomena↗

Apoptosis in myocarditis and dilated cardiomyopathy: does enterovirus genome persistence protect from apoptosis? An endomyocardial biopsy study.

UNLABELLED: The purpose of this study was to examine the role of apoptosis in myocarditis and dilated cardiomyopathy. Apoptosis is an active energy-consuming mechanism of cell death in several cardiac diseases in different quality and quantity. METHODS: Endomyocardial biopsies from 81 patients with active (1) and chronic myocarditis (10), dilated cardiomyopathy with inflammation (DCMi; 10) and without inflammation (DCM; 20), with borderline myocarditis and positive PCR for cytomegalovirus-DNA (6), adenovirus-DNA, or enterovirus-RNA (7), and controls (17) were analysed. Apoptosis was detected by using the TUNEL method. The highest rate of apoptotic cardiocytes was found in active and chronic myocarditis. One patient with severe active myocarditis demonstrated 6.15% of apoptotic cardiocytes. Mean percentage of apoptotic cardiocytes in chronic myocarditis was significantly increased (0.61+/-1.25%) when compared to controls (0.01+/-0.04%, P<.05). Particularly, patients with cytomegalovirus-DNA persistence in borderline myocarditis had an elevated rate of apoptosis (0.34+/-0.68%, P<.05). Increased rates of apoptosis were found in borderline myocarditis with adenovirus-DNA persistence (0.20+/-0.57%) and in DCM (0.06+/-0.15%). Only a nonsignificant increase of apoptotic cardiocytes was found in DCMi (0.03+/-0.08%). No apoptosis was found in patients with enteroviral genome persistence in borderline myocarditis. CONCLUSIONS: Apoptosis of cardiac cells is increased in myocarditis and dilated cardiomyopathy, being highest in severe active myocarditis. Apoptosis thus contributes to cell death in active myocarditis and may play a role not to be neglected in dilated cardiomyopathy. Enteroviruses seem to have anti-apoptotic effects, because no apoptosis at all was found in the myocardium.

Apoptosis↗

[Stress analysis of an anatomically-adapted femur shaft prosthesis (Lubinus SPII)].

OBJECTIVE: Very good clinical long-term results of the Lubinus SP II hip prosthesis stem were reported in the literature. We therefore asked whether there is a relationship between these findings with biomechanical data of strain gauge measurements. METHOD: 14 strain gauges were applied at a femur being measured at 10 different load cases before and after implantation of the stem. RESULTS: After stem implantation a similar patterns of principal stress distributions was observed, however, the magnitude was markedly reduced. A striking reduction of the hoop stresses at the femoral calcar was seen in the case of a missing collar contact. Even in the case of a perfect collar contact the hoop stresses were diminished after strem implantation. The S-shaped physiological stem did not correspond with a specific stress pattern measured at the femoral surface. CONCLUSION: These results suggest that the stresses at the femoral calcar may be lower than the limits of bone growth while the other parts of the femur are more physiologically stressed. However, the prosthesis may tolerate a missing collar contact during a long follow-up period. The large experimental data file presented here could be used to validate future finite element analyses which could evaluate the stress distribution within internal parts of the bone and the cement layer.

Aged↗