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Biomedical subjects

R Burkhardt

Publications and source records attributed to R Burkhardt.

At least 91 records · Page 5Linked to original sources

[Bone marrow diagnostic in hairy cell leukaemia (author's transl)].

Evaluation of the histologic changes of the bone marrow and clinical data of twelve male and two female patients with hairy cell leukamia before treatment. Mean age of the patients was 46 years, time from the onset of symptoms 5.5 months. 13 of the patients were anaemic, showing splenomegaly, 12 suffered from thrombopenia, 9 from granulocytopenia, and 8 from hepatomegaly. In all of the cases, the relative numbers of lymphocytes in the blood had been increased together with various amounts of characteristic hairy cells. All of the cases had a typical histologic picture of lymphocytic bone marrow infiltration, mostly of the diffuse type. In 50% of the cases not only the well known rod-like intracellular inclusions could be seen, but also ring-shaped figures whose significance is discussed. Decrease of the granulopoiesis, disintergration of the marrow sinusoids, and osteoporosis are the most important additional signs. The progression of the disease is marked by increasing bone marrow infiltration, by splenohepatomegaly, anaemia, thrombopenia, and increasing numbers of typical lymphocytes in the blood. The bone marrow being considered to be the origin of the disease for good reasons, the histobiopsy of this organ ranks among the diagnostic and prognostic measures to be taken at first sight.

Adult↗

[Bone marrow biopsy investigation: an important prognostic factor in aplastic anaemia (author's transl)].

In thirty-five patients with aplastic anaemia initial bone marrow biopsy investigations were performed. 25 patients showed partial bone marrow aplasia whereas in ten patients complete myeloid aplasia could be demonstrated. Probability of survival was approximately ten times higher in patients with partial than in patients with complete bone marrow aplasia. The results of bone marrow biopsy investigations had a greater predictive value than the degree of diminution of single cellular blood components. Initial bone marrow biopsy investigation facilitates the selection of poor risk patients who should be treated by bone marrow transplantation rather than by conventional therapy.

Adolescent↗

[Megakaryocytic myelosis--cause of "idiopathic" thrombocythemia].

Primary thrombocythaemia is to be distinguished from the secondary type by higher counts of megakaryocytes especially of atypic and gigantic forms of these cells, showing up in adequate histological preparations of bone marrow biopsies. From the analysis of those preparations the autonomous proliferation of the megakaryocytopoiesis clearly is to be understood as the reason of the socalled primary thrombocythaemia, occurring in the forms of isolated or mixtcellular megakaryocytic myelosis of the well differentiated type. Both of these forms can convert into thrombocytopenia when atypical and immature megakaryocytes start to overcrowd the picture or when myelofibrosis develops. The latter is to be considered in causal connections with the ineffective dislocated thrombopoiesis, a common finding among megakary-ocytic myelosis complicated with myelofibrosis. Megakaryocytic myelosis therefore is the clue of three different clinical syndromes, which are alternatively marked by the haemostaseologic or the histologic consequences of the overproduction of platelets, or by the proliferation of the megakaryocytes themselves.

Bone Marrow Examination↗

Methyl-methacrylate as an embedding medium in histopathology.

Methyl-methacrylate embedding makes it possible to obtain semi-thin sections rich in detail and without tissue shrinkage. The procedure requires considerable time and labour, and great care must be taken to prevent heat damage to the tissue during the exothermic polymerization process. The original method given by Burkhardt (1966) and later modifications are described and discussed, with special attention to the practical problems encountered and their solutions.

Histological Techniques↗

[The significance of histologic assessment of the bone marrow in Hodgkin's disease].

The spreading of Hodgkin's disease in the bone marrow is of primary diagnostic significance in respect of its quantity as well as its quality, and therefore has to be taken into account from the initial staging procedure. The iliac crest is the most suitable site of the biopsy, the diagnostic significance of which depends on the adequate size of the specimen and on the technical standard of the histologic embedding with methacrylate, affording perfect semithin sections without decalcification. The prognostic value of the statement of Hodgkin's disease spreading in the marrow deserves further careful evaluation. A nonspecific reaction of the marrow against extramedullary lymphogranulomatosis closely resembling to the so-called tumor myeopathy has to be distinguished from the localized marrow changes due to the tumor itself. The former is depending primarily of the progress of the disease, the latter of its type as well. The well-known histologic classification covers the changes of the bone marrow due to Hodgkin's disease also. The different histologic types however exhibit a varying tendency of expansion within the bone. Generally the marrow involvement is accompanied with more severe clinical and hematological symptoms. The bone is altered mostly in the very region of the infiltration. This is not the consequence of direct tumorous destruction but of stimulation of environmental mesenchymal activities. Parenchymal and mesenchymal changes of the bone marrow, either directly or indirectly connected with the lymphogranulomatosis, are considered primarily as sequelae of the basic disease. The very close structural relationship between the original lymphogranulomatosus growth and these changes is one of the characteristics of Hodgkin's disease. As yet, there is no unequivocal pointer to structural characteristics whose appearance can exert an obstructive or stimulating effect on the lymphogranuloma tissue, apart from the number of lymphocytes and normal histiocytes in the specific infiltrate itself. Our observations of a special role of megakaryocytes in this connection deserve further attention.

Biopsy, Needle↗

[Value of results of animal experiments for the evaluation of drugs. 3. Animal trials and subjective probability].

Inasmuch as the findings in pharmacology and toxicology are based on animal trials these disciplines have to be considered as subjective sciences, since the experimentally obtained objective data become medically relevant only on the basis of subjective probabilities. The value of pharmacological and toxicological tests is dependent on the quality of the investigator. Data obtained in animals trials are of no relevance for human medicine unless the investigator substantiates his subjective probabilities and at the same time demonstrates how the hypotheses won in animal trials can be verified in man. Toxicological testing methods allowing the "preselection" of drugs or any other kind of deductions without verification in man do not exist. Animal studies which are not based on the principles of decision theory serve merely as an alibi and may lead to wrong conclusions. Besides, they interfere with the German Animal Protection Law. Methodological problems can neither be solved by normative regulations of an administrative authority nor by increasing experimental activity.

Animals↗

[Value of the results of animal experiments for the evaluation of drugs. 2. Methodology and prediction of effects].

The efficiency of animal trials is critically examined against the background of the new EC drug regulations. The present contributions deal with the problem of predictability of qualitative events. It is established that the so-called "pharmacological properties" of substances do not exist. Further it must be taken into account that observations made on test animals are reductionistic in relation to man. The study also shows that it is difficult to predict events with reasonable certainty even within one particular animal species. The problem of extrapolation is being viewed under three different aspects: when there is no previous experience at all, when there is relevant previous experience, and when there are animal models available. In the first case, it is impossible to make any prediction at all. In the second case, only subjective suppositions are possible. As to the third case, it is an open question at the moment whether animal models do exist at all. According to the present state of science it is not possible to make objective predictions for man on the basis of animal trials. In regard to animal trials, the EC regulations stand in contrast to science and the methodology of statistics. The subjective nature of prediction will be discussed in the following contributions.

Animals↗

[Histological examinations of late changes of bone marrow and bone following local fractionated gamma irradiation in patients with genital carcinoma (author's transl)].

In 25 patients iliac crest biopsies have been taken after radiation therapy of genital carcinoma. The radiation doses in the biopsied region ranged up to about 3,000 rads. The time interval from the end of radiation until the control biopsy was 2 months or longer, up to 25 years. The immediate consequences of the radiation, compared with the pretherapeutic picture, have been analyzed in an earlier study (Beil et al., 1974). By histomorphotometric analysis of the samples it can be shown that a more or less severe atrophy of the bone marrow is persisting in the irradiated area for years. The atrophy is accompanied either by normal or increased bony trabecularization, together with increased osteoblastic and -clastic activity. These disturbances are likely to depend of a chronic distortion of the marrow capillarization, which may be influenced by the individual RES activity; different types of the reticuloendothelial response can be demonstrated in our material. Whether this response has a bearing regarding the prognosis of the tumours condition itself remains a matter of speculation, to be proved by further investigations.

Aged↗

[Immunosuppressive therapy in pure red cell aplasia].

Acquired erythroblastic aplasia of adults is a rare disease characterised by the absence of red cell precursors in the bone marrow. In a 34-year-old female patient the disease has been known for seven years. A partial remission had at first been achieved with glucocorticoids but regular transfusions had been necessary since 1971. Treatment with cyclophosphamide produced a remission which has lasted for over twelve months up to now. Histology of the bone marrow biopsy shows the appearance of active erythropoiesis after cyclophosphamide treatment which reflects well the clinical course.

Adult↗