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Biomedical subjects

R Burkhardt

Publications and source records attributed to R Burkhardt.

At least 37 records · Page 2Linked to original sources
PubMed1986

Working classification of chronic myeloproliferative disorders based on histological, haematological, and clinical findings.

Bone marrow biopsies of 850 patients with chronic myeloproliferative disorders were taken at initial diagnosis; and 169 sequential biopsies over periods of one to 188 months. Three micron sections of all biopsies were evaluated semiquantitatively with reference to the proliferating cell lines, anomalies of megakaryocytes, and fibrosis or osteosclerosis. Correlations between initial histological findings, clinical, haematological, and survival data were analysed statistically. The predominant cell lines distinguished the classical entities of polycythaemia vera, primary thrombocythaemia, and chronic myeloid leukaemia and correlated with their different prognoses, while megakaryocytes characterised subgroups that were prone to fibrotic or blastic transformation. Based on the initial histological, clinical, and haematological data analysed a working classification of chronic myeloproliferative disorders was proposed that permits recognition of both typical and atypical cases of chronic myeloproliferative disorders.

Adolescent↗
PubMed1985

Quantitative monitoring of fundus changes.

The proposed method allows to discover and quantify small changes in series of fundus photographs which are normally not directly comparable. The principle of geometric conformality of small parts between the fundus and its photographs is developed into a practical method of stereoscopic measurement, numerical adjustment and quantitative evaluation. Very high accuracy is possible without special conditions on repeated fundus photography. The aim is to create a theoretical and methodical basis for ophthalmoscopic change detection with image-processing computers.

Fundus Oculi↗
PubMed1984

Chronic myeloproliferative disorders (CMPD).

The wide clinical range of CMPD can be understood as leukaemia of pluripotent stem cells according to the pathogenic concepts reviewed above. Blastic metamorphoses of CMPD are regressions to a more primitive level of cellular differentiation. The predominant proliferative cell line characterizes the classical entities of PV, PT and CML, and their different prognoses. Pure erythrocytic and megakaryocytic proliferations are more compatible with sustained physiologic bone marrow functions than granulocytic proliferations. The combinations of granulocytic and megakaryocytic growth are especially prone to develop MF/OMS, in which participation of immune reactions, of granulocytic and of platelet factors is probable. An etiologic role for ineffective thrombocytopoiesis is supported by experimental as well as by histologic evidence. Myelofibrosis and osteomyelosclerosis may have similar causes, but develop independently. The prevalence of the female sex among thrombocythaemic patients was proven statistically also for the increase of giant type megakaryocytes in the form of clusters in the bone marrow, and for longer median survival of females in CMPD, especially when there is megakaryocytosis in the bone marrow. It is assumed that females may be better protected against the detrimentous effects of abnormal platelet production. An arbitrary classification according to haematologic and histologic criteria was applied to PV, PT and CML, and groups with typical and atypical haematologic and histologic signs were distinguished. The latter cannot be separated from each other by their various haematologic manifestations, but by histology and their different propensity to progress into more immature and/or fibrotic stages. Three major groups are characterized by histology: mixed granulocytic-megakaryocytic myelosis with giant megakaryocytic clusters, a similar variant with diffuse distribution of giant megakaryocytes, and immature and/or pleomorphic megakaryocytic myelosis. Transitions from each of these groups have been observed as well as transitions from each of the typical CMPD-entities into these less typical forms. CML, frequently accompanied by dwarf-megakaryocytes, often develops into pleomorphic megakaryocytic or blastic myelosis. Blastic dedifferentiation and myelofibrosis manifest themselves as closely related end stages, to which principally all groups proceed after a longer or shorter period of time, modified by the proliferating cell lines in each group. Clinical, experimental and histologic evidence of this natural history has been reviewed, with special emphasis on the re-evaluation of technically optimal bone marrow biopsies of untreated patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1984

Lymphoproliferations in the bone marrow: identification and evolution, classification and staging.

Bone marrow biopsies from 3229 patients with lymphoproliferative disorders and 1156 patients with benign or reactive lymphoproliferations were investigated and criteria for distinguishing between them are given. Bone marrow involvement was found in 89% of multiple myeloma, 64% of non-Hodgkin's lymphomas and 8% of Hodgkin's disease. According to the predominant proliferative cell type there were five major entities in multiple myeloma and non-Hodgkin's lymphomas: (1) plasmacytic; (2) lymphocytic; (3) hairy cell; (4) immunocytic; (5) centrocytic. These were further classified into distinct subtypes each of which had independent prognostic significance. The mode of spread of the lymphoproliferative disorders in the bone marrow showed one of six architectural patterns, which together with the quantity of infiltration in the biopsy (reflecting the tumour cell burden) had significant predictive value. These results demonstrate the value of bone marrow biopsies in the identification, classification and staging of lymphoproliferative disorders, as well as in monitoring the course of disease and the response to therapy.

Bone Marrow↗
PubMed1984

Scope and value of bone marrow biopsies in metastatic cancer.

The results of examination of 1,810 bone marrow biopsies of 1,725 patients with known or suspected carcinomas are presented. The frequency of positive biopsies was 72% for unknown primaries, 42% for mammary, 32% for prostatic, 14% for pulmonary and 19% for other cancers; the overall rate of detection of metastases was 35%. The mode of spread, the grade of tumour cell differentiation and the host response to the presence of the metastases were investigated by light and electron microscopic studies and by means of antibody reactions on fresh-frozen sections. The results are presented and their relevance to the fundamental understanding of the metastatic process is outlined. Implications for clinical oncology and patient management are discussed.

Biopsy↗
PubMed1984

Histologic criteria for classification and differential diagnosis of chronic myeloproliferative disorders.

The chronic myeloproliferative disorders (MPD) are well characterized clinical entities comprising polycythaemia vera (PV), idiopathic thrombocythaemia (IT) (also called megakaryocytic myelosis, mature type; MegM), chronic myeloid leukaemia (CML), and myelofibrosis/osteomyelosclerosis (MF/OMS). Three thousand one hundred and eight bone biopsies of 2629 patients with established MPD were examined to investigate the histologic features of MPD in a large material in order to identify criteria for the histologic classification and differential diagnosis of these disorders. Detailed histologic characteristics were defined for each of the disorders and the results showed that in the majority of cases MPD may be recognized and classified by the initial bone marrow histology. Utilizing the predominant proliferative cell(s) in the bone marrow, PV was categorized into 4 types: 1. the classic, tri-linear type; 2. a bi-linear type with hyperplasia of the erythroid and granulocytic lines; 3. a bi-linear type with hyperplasia of the erythroid and megakaryocytic cell lines and 4. a uni-linear type with isolated increased erythrocytic proliferation. CML showed 2 sub-divisions: 1. the granulocytic, uni-linear type and 2. the bi-linear type with proliferation of myeloid and megakaryocytic lines. The former had a tendency to evolve into blastic crisis, while the latter was prone to develop into MF/OMS. It was primarily uni-linear exhibiting increased megakaryocytes. In most cases, MF/OMS was shown (by means of follow-up biopsies) to arise out of those entities of MPD which had included megakaryocytic hyperplasia and to which the proliferation of fibroblasts was secondary. The conclusion is drawn that an initial bone marrow biopsy provides additional diagnostic and prognostic data in this group of haematologic malignancies.

Adolescent↗
PubMed1984

Lymphoproliferative disorders in the bone marrow: histologic criteria for classification and staging.

Malignant lymphoproliferative disorders (LPD) were investigated in bone marrow biopsies of 1565 untreated patients. Marrow involvement was found in 90 per cent of multiple myeloma (MM), 70 per cent of non-Hodgkin lymphomas (NHL) and 10 per cent of Hodgkin disease (HD). In MM and NHL there were five major entities according to the predominant proliferative cell type: 1. plasmacytic, 2. lymphocytic, 3. hairy cell, 4. immunocytic and 5. centrocytic. On the basis of bone marrow histology they were classified into 3 distinct sub-types each of which had an independent prognostic significance. The mode of spread of all the LPD fell into one of six architectural patterns which together with the tumour cell burden (the quantity of infiltration in the biopsy) also had a significant predictive value. Consequently, bone marrow biopsy is a valuable diagnostic tool for histologic classification and clinical staging of any patient with LPD.

Biopsy↗
PubMed1983

Improvement of bone scintigraphy by quantitative evaluation compared with X-ray studies and iliac crest biopsy in malignant disease.

Bone marrow biopsy of the iliac crest was performed on 268 patients (124 males; 144 females). Of these patients 206 had haematological systemic disorders (HSD) or carcinoma and suspected bone involvement, which was confirmed by biopsy on 66 patients. Bone biopsy was performed not longer than 3 weeks after X-ray examination and bone scintigraphy which, combined, had already raised the suspicion of skeletal involvement in 55% of the 66 patients with skeletal involvement diagnosed by biopsy. Additional quantitative evaluation of the bone scans using bone to soft tissue ratios was able to increase the overall accuracy to 67% in that group. Additional quantitative assessment of the scan yielded considerably more effective bone scintigraphy, particularly in cases with visually normal patterns. Available equipment should therefore be used in scintigraphic bone imaging on a routine basis. It was shown that the various methods of examination, i.e. X-ray, biopsy and scintigraphy with both visual and quantitative evaluation provide their own individual values for the final diagnosis. Therefore, if one of the methods shows a negative result, bone involvement is not excluded and the others should be used for confirmation.

Adult↗
PubMed1983

Bone marrow histology in hairy cell leukemia. Identification of subtypes and their prognostic significance.

Bone marrow biopsy specimens taken on initial investigation of 134 patients with hairy cell leukemia (HCL) were processed into plastic, and sections cut at 3 microns were used for histologic and histomorphometric evaluation. Twenty-four clinical, 10 histologic, and four histomorphometric variables were tested for their prognostic significance. Bone marrow involvement was found in all cases, and on the basis of their morphology, the hairy cells were divided into three types: ovoid (47%), convoluted (37%), and indented (16%); this classification proved to be highly significant in the test statistics, with median survivals for the three groups of 56, 12, and 5 months, respectively. The characteristic nuclear features of the three types also were identified in smears of peripheral blood, in sections of spleen, and by electron microscopy. In addition, significant differences were found when the patients were grouped according to the tumor cell mass (volume %) in the biopsy sections, with median survivals of 55, 21, and 8 months noted for less than 20 vol%, 20-50 vol%, and greater than 50 vol%, respectively. Other factors with prognostic relevance were cytoplasmic inclusion bodies in the hairy cells (HC) and a number of clinical variables, including initial values of Hb and ESR, and platelets and monocytes in the peripheral blood. These results confirm that the bone marrow always is involved in HCL and its histology is diagnostic; that HCL may be classified according to the predominant neoplastic cell type; and that the patients may be staged on the basis of the tumor cell burden in the bone marrow biopsy.

Adult↗
PubMed1983

Bone marrow histology in Waldenström's macroglobulinaemia. Clinical relevance of subtype recognition.

Bone marrow biopsies of 137 patients with Waldenström's macroglobulinaemia (WM), 26 with non-secretory immunocytoma and 32 with benign monoclonal gammopathy were processed for histologic evaluation. Bone marrow involvement was found in 110 (80%) initially, and in 24 (18%) in sequential biopsies. 3 types were distinguished: lymphoplasmacytoid (47%), lymphoplasmacytic (42%) and polymorphous (11%) with median survivals of 74, 25 and 12 months, respectively. When grouped according to the tumour cell mass in the biopsies, the median survivals were 55, 21 and 8 months for less than 20 vol%, 20-50 vol% and greater than 50 vol% respectively; in each subtype, the tumour cell mass correlated with the disease progression. 6 clinical variables were also found prognostically significant. These results demonstrate that (i) 98% of patients with WM have bone marrow involvement; (ii) the lymph node sub-classification is applicable to the bone marrow and has both clinical and prognostic significance; (iii) patients may be staged according to the tumour cell burden in the bone marrow biopsy.

Adult↗
PubMed1983

Basic problems in controlled trials.

On the basis of critical discussions which have taken place in recent years in the Federal Republic of Germany, certain methodological, ethical and legal problems arising in relation to controlled trials are discussed. Because of methodological inconsistencies inherent in the experimental approach, the efficacy of a drug must in any case be judged by physicians. This leads to major ethical and even--at least in Germany--legal problems which impose considerable limits on the feasibility of controlled trials in Germany. Editor's note: This paper is written at the invitation of the journal, following the considerable controversy on the ethics of clinical trials in the European Journal of Clinical Pharmacology (8-11). A critical commentary follows the paper with a short response from the authors and a further response from the commentator.

Clinical Trials as Topic↗