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  • 1
    Electronic Resource
    Electronic Resource
    Polycythemia vera (1980)
    Springer
    Virchows Archiv 389 (1980), S. 307-324 
    Details
    ISSN: 1432-2307
    Keywords: Polycythemia vera ; Secondary polycythemia ; Histopathology ; Ultrastructure ; Cytogenetics ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and morphological studies including light microscopy, electron microscopy and karyotyping of the bone marrow, were performed on a total of 164 patients with polycythemic conditions. A final diagnosis was obtained from clinical findings and histopathology of plastic embedded core biopsies of the bone marrow including sequential examinations. 51 patients revealed a secondary polycythemia whereas 113 displayed polycythemia vera (P. vera). In this last group 83 cases have persisting P. vera. 30 showed a transgression towards chronic myeloid leukemia with or without accompanying myelofibrosis — osteomyelosclerosis (so called chronic megakaryocytic-granulocytic myelosis — CMGM). The histopathology of the bone marrow in P. vera revealed consistent alterations which are useful in distinguishing this disorder from secondary polycythemia (SP) and CMGM: depletion of iron storage, increased neutrophilic granulopoiesis but no gross atypia in maturation, polymorphism of megakaryocytes with conspicuous giant forms and dilatation and increased branchings of venous sinusoids. Electron microscopic findings were in agreement and showed further abnormalities of cytological maturation in the erythrocytic and granulocytic lineage. Cytogenetic studies in 27 non-treated patients with P. vera revealed the Philadelphia chromosomes in 2 cases, whereas in SP only minor chromosomal anomalies have been encountered in a few patients. It is concluded that histopathology of trephine biopsies of the bone marrow is an invaluable aid to establish a correct diagnosis, differentiating P. vera from the other potentially polycythemic disorders and helping to detect a possible progression towards leukemia at an early stage. Cytogenetic investigations may show early structural and numerical abnormalities of the karyotype and possibly precede a presumptive transgression towards myeloid leukemia (CMGM). A simultaneously performed histological and chromosomal examination of bone marrow samples is therefore desirable in each case of a polycythemic condition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430657
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  • 2
    Electronic Resource
    Electronic Resource
    Polycythemia vera (1980)
    Springer
    Virchows Archiv 389 (1980), S. 325-341 
    Details
    ISSN: 1432-2307
    Keywords: Polycythemia vera ; Myeloid leukemia ; Histopathology ; Ultrastructure ; Cytogenetics ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Of 113 Patients with polycythemia vera (P. vera) who had been followed for the last 8 years, 30 cases (27%) developed myeloid leukemia with fibrosis of the bone marrow. Core biopsies of the bone marrow including sequential examinations in several cases revealed neoplastic proliferation of neutrophil granulopoiesis and an atypical megakaryopoiesis with accompanying fibrosis of varying degrees. These alterations were consistent with a subtype of chronic myeloid leukemia — the so called chronic megakaryocytic-granulocytic myelosis (CMGM) — and correspond to (agnogenic) myeloid metaplasia with osteomyelofibrosis/-sclerosis. 5 of those 30 patients showed spontaneous transgression into myeloid leukemia, none of them had received any ionizing radiation or cytostatic therapy. A blast crisis or so called acute leukemia in P. vera was seen only in one patient who was treated by an overdose of radioactive phosphorus and later evolved into osteomyelosclerosis with blastic transformation. These findings of a chronic leukemia or CMGM arising from P. vera was further confirmed by atypia of ultrastructure and particularly by our cytogenetic evaluation. Chromosomal studies showed a Ph′-chromosome to be present in 5 of 8 patients with CMGM and myelofibrosis. Clinical and statistical evaluation of survival times showed a median survival expectation of all P. vera patients of 15 years. Life expectancy of the patients who still displayed P. vera was more favorable than those cases with transformation into CMGM, disregarding any therapy. Transformation of P. vera into CMGM occurred about 8 years after the onset of disease and following transgression into leukemia, half of these patients were dead after 2.5 years. Our results demonstrate that P. vera represents a “panmyelosis” with an inherent malignant nature, or a neoplastic proliferation of all three cell lines. This concept is supported by several facts: atypia of cytological differentiation as observed by light- and electron microscopy of the bone marrow, chromosomal anomalies with aneuploidy and an infrequent Ph'-marker, spontaneous transgression into chronic myeloid leukemia or its subtype CMGM without relevant therapy and a clonal evolution as shown by enzymatic studies reported in the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430658
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  • 3
    Electronic Resource
    Electronic Resource
    Histopathology of the bone marrow in toxic myelopathy (1985)
    Springer
    Virchows Archiv 405 (1985), S. 225-235 
    Details
    ISSN: 1432-2307
    Keywords: Myelopathy ; Drug effect ; Toxicity ; Histopathology ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Following the introduction of numerous highly effective drugs in recent decades, haematologists are confronted with a panmyelopathy or “toxic myelopathy” originating from the exhibition of certain therapeutic regimens. Among 16,711 trephines referred to us in the last 5 1/2 years, 57 cases or 0.34 percent were found to have clear evidence of lesions caused by the ingestion of potentially toxic agents. The evaluation of the histopathology shows two groups of alterations which concern the haematopoietic parenchyma as well as the mesenchyme of the bone marrow. Different degrees of cellularity ranging from aplasia to regenerative hyperplasia and a pronounced mesenchymal reaction with proteinaceous oedema, perivascular plasmacytosis and frequent necrobiosis of neutrophilic granulocytes or cellular debris are the most conspicuous features. However, the histopathology of the bone marrow described gives no indication of the specific drug responsible and no specific suggestion of any group of drugs. Generally the histopathology allows the recognition of lesions which are induced by the toxicity of these agents. Therefore a bone marrow biopsy should be included in the diagnostic procedures whenever a toxic lesion is suspected of causing haematological disorders, particularly in all cases of uncertain pancytopenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00704374
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  • 4
    Electronic Resource
    Electronic Resource
    Die Differentialdiagnose „lymphoider Zellinfiltrate“ im Knochenmark (1995)
    Springer
    Der Pathologe 16 (1995), S. 106-119 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Maligne Lymphome ; Fokale reaktive lymphoide Hyperplasie ; Knochenmark ; Differentialdiagnose ; Histotopographie ; Fasergehalt ; Immunhistochemie ; Key words Malignant lymphomas ; Reactive lymphoid hyperplasia ; Bone marrow ; Differential diagnosis ; Histotopography ; Fiber content ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The purpose of this study was to provide criteria for the differentiation of reactive lymphoid hyperplasia (RLH) and focal involvement of the bone marrow by malignant lymphoma (ML). Using trephine bone-marrow biopsy specimens embedded in paraffin wax and unequivocally established samples with ML for comparison, all patients with questionable lymphoid or lymphohistiocytic marrow aggregates were re-examined, together with obviously reactive lesions. Following this procedure, a number of characteristics were found that differed in validity with regard to diagnosis. In addition to cytology, which is preferably assessed in Giemsa-stained specimens and evaluated by the Kiel classification, histotopography, fiber content, and immunohistochemical reactions are the most valuable tools for differential diagnosis. RLH is consistent with a central-perivascular localization, a distinctive border and the presence of germinal centers, no or only minimal reticulin fibrosis and a polyclonal reaction pattern with a mixed population of B- and T-lymphocytes, following staining with appropriate antibodies. In uncertain cases (i. e., extensive lymphoproliferations in HIV-myelopathy) the results of immunohistochemical staining are of definite importance for the diagnostic evaluation of these lesions.
    Notes: Zusammenfassung Die vorliegende Studie verfolgt das Ziel, Kriterien für die differentialdiagnostische Abgrenzung zwischen fokaler reaktiver lymphatischer Hyperplasie (RLH) und nodulären Infiltraten von malignen Lymphomen (ML) im Knochenmark festzulegen. Im Vergleich zu klinisch und histologisch gesicherten Fällen von ML und offensichtlich reaktiven Veränderungen wurden alle in ihrer diagnostischen Zuordnung fraglichen lymphoiden bzw. lymphohistiozytären Läsionen anhand von Beckenkammbiopsien nach Paraffineinbettung noch einmal untersucht. Als wesentliches Ergebnis konnte eine Reihe von diagnostischen Merkmalen herausgearbeitet werden, die allerdings von sehr unterschiedlicher Wertigkeit waren. Neben der Zytologie, welche besonders gut in nach Giemsa gefärbten Präparaten auswertbar ist und sich problemlos nach den entsprechenden Maßgaben der Kiel-Klassifikation zuordnen läßt, sind Histotopographie, Fasergehalt und Immunhistochemie von besonderer nosologischer Bedeutung. Für eine RLH sprechen eine zentral-perivaskuläre Lokalisation mit scharfer Abgrenzung sowie Keimzentren, keine oder allenfalls eine minimale Retikulinfibrose sowie schließlich nach Anwendung immunhistochemischer Verfahren ein polyklonales Reaktionsmuster mit einer Mischpopulation aus B- und T-Lymphozyten. Im Zweifelsfall (z. B. bei ausgedehnter Lymphoproliferation im Rahmen einer HIV-Myelopathie) ist alleine die Immunhistochemie in der Lage, diagnostisch wegweisende Anhaltspunkte zu geben.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050083
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  • 5
    Electronic Resource
    Electronic Resource
    Dreidimensionale Rekonstruktion von Serienschnitten in der Lichtmikroskopie (1995)
    Springer
    Der Pathologe 16 (1995), S. 128-138 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Dreidimensionale Rekonstruktion ; Lichtmikroskopie ; Serienschnitte ; Megakaryozyten ; Primäre Osteomyelofibrose ; Knochenmark ; Key words Three-dimensional reconstruction ; Light microscopy ; Serial sections ; Megakaryocytes ; Primary osteomyelofibrosis ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Computer-based three-dimensional reconstruction of serially cut light microscopic sections is being increasingly used in medical and biological research. Compared with conventional two-dimensional evaluation of histological sections, complex histotopographical relationships and structural details are easy to assess and could be imposingly visualized on the graphics screen. Because of the rapid progress in modern computer hardware, uncomplicated and fast reconstruction systems are available on standard personal computers. Therefore, 3D reconstruction is applicable for a wide range of investigations that warrant 3D exploration. Own results are presented and the principles of 3D reconstruction, as well as the problems and difficulties in this new technique, are discussed. The complex ameboid morphology of megakaryocytes in bone marrow of primary (idiopathic) osteomyelofibrosis is examined with this new method in combination with selective immunohistochemical staining procedures. 3D reconstruction can visualize the complexity of cytoplasmic and nuclear formation impressively. Moreover, the models generated permit exact quantitative measurements of cell morphology. The technique presented is a powerful tool for anatomical-morphological investigations and can furthermore increase our comprehension of complex histomorphological objects.
    Notes: Zusammenfassung Computergestützte dreidimensionale Rekonstruktionsverfahren von lichtmikroskopischen Serienschnitten haben sich in den letzten Jahren in allen Bereichen der medizinisch-biologischen Forschung etablie-ren können. Im Vergleich zur konventionellen zweidimensionalen Schnittbetrachtung lassen sich komplexe histotopographische Beziehungen sowie Strukturcharakteristika besser erfassen und auch eindrucksvoll darstellen. Aufgrund der schnell fortschreitenden Entwicklung im Bereich der Computertechnik sind heutzutage Rekonstruktionssysteme auch auf preisgünstigen Rechnersystemen verfügbar, so daß sich dieser neuen Methode ein zunehmendes Anwendungsgebiet erschließt. Anhand von eigenen Befunden werden die Grundlagen der 3 D-Rekonstruktion besprochen sowie Schwierigkeiten und Probleme dieser neuen Technik diskutiert. In Kombination mit kontrastreichen und selektiven immunhistochemischen Färbungen wird beispielhaft die komplexe amöbenartige Morphologie der Megakaryozyten bei der primären (idiopathischen) Osteomyelofibrose durch lichtmikroskopische Serienschnitte aus dem Knochenmark vorgestellt. Die erzeugten 3 D-Modelle vermitteln einen plastischen Eindruck von der Komplexität der Zell- und Kernstrukturen dieser Zellen und stellen die Basis für exakte quantitative Analysen der Zellmorphologie dar. Die vorgestellte Technik beinhaltet ein ergänzendes Werkzeug für anatomisch-morphologische Analysen und ist in der Lage, entscheidende Erkenntnisse bei der Untersuchung vielschichtiger histomorphologischer Objekte zu liefern.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050085
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  • 6
    Electronic Resource
    Electronic Resource
    Polycythemia vera: Electron microscopy of the bone marrow in 10 non-treated patients (1979)
    Springer
    Annals of hematology 38 (1979), S. 407-420 
    Details
    ISSN: 1432-0584
    Keywords: Polycythämia vera ; Ultrastruktur des Knochenmarkes ; Kernspalten ; Mikromegakaryozyten ; myeloproliferative Erkrankungen ; Polycythemia vera ; Bone marrow ultrastructure ; Nuclear clefts ; Micromegakaryocytes ; Myeloproliferative disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Electron microscopy (thin sections and freeze-fracture replicas) was performed on the bone marrow of ten patients with Polycythemia vera prior to any treatment. In addition to a hyperplasia of all three cell lineages and the sinuses, atypias were observed in the maturing erythroblasts. These aberrations of normal development consisted mainly of deep invaginations of the nuclear envelope in proerythroblasts and conspicuous nuclear clefts in erythro- and normoblasts. In comparison with similar changes in dyserythropoietic and aplastic anemia as well as leukemia these alterations are discussed in connection with disturbances of DNA synthesis. Further atypias involved megakaryopoiesis which displayed microforms probably as an evidence for maturation arrest. These ultrastructural abnormalities with their morphological features of a neoplastic proliferation of all three cell lineages in Polycythemia vera are in good agreement with the new concept of a transformation of a pluripotent stem cell with clonal character.
    Notes: Zusammenfassung Elektronenmikroskopische Untersuchungen (Dünnschnitte und Gefrierbrechungen) wurden am Knochenmark von zehn Patienten mit Polycythämia vera vor der Behandlung durchgeführt. Au\er der Hyperplasie aller drei Zellreihen und der Sinus wurden vor allem Atypien der reifenden Erythroblasten gesehen. Diese Abweichungen der normalen Entwicklung bestanden hauptsächlich aus tiefen Einstülpungen der Kernhülle im Proerythroblasten und in auffallenden Kernspalten in Erythro- und Normoblasten. Im Vergleich zu ähnlichen Veränderungen bei dyserythropoetischen und aplastischen Anämien ebenso wie bei Leukämien werden diese Anomalien im Zusammenhang mit Störungen der DNA-Synthese diskutiert. Weitere Atypien betrafen die granulocytäre Reihe mit abnormen Kernschleifen und die Megakaryopoese, die Mikroformen aufwies, was wohl als ein Ausdruck der Reifungshemmung zu werten ist. Diese ultrastrukturellen Anomalien mit ihren morphologischen Kriterien der neoplastischen Proliferation aller drei Zellreihen bei der Polycythämia vera passen gut in das neue Konzept der Transformation einer pluripotenten Stammzelle mit klonalem Charakter.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01007902
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  • 7
    Electronic Resource
    Electronic Resource
    Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling (1997)
    Springer
    Annals of hematology 75 (1997), S. 33-39 
    Details
    ISSN: 1432-0584
    Keywords: Key words Apoptosis ; PCNA-labeling ; Idiopathic thrombocytopenia ; Polyglobuly ; Reactive thrombocytosis ; Primary thrombocythemia ; Polycythemia vera ; AML ; Hematopoietic turnover index ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050309
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  • 8
    Electronic Resource
    Electronic Resource
    Prognostic impact of apoptosis and proliferation in idiopathic (primary) myelofibrosis (1999)
    Springer
    Annals of hematology 78 (1999), S. 65-72 
    Details
    ISSN: 1432-0584
    Keywords: Key words Idiopathic myelofibrosis ; PCNA labeling ; Apoptosis ; Dynamic disease features ; Prognosis ; Proportion of life loss ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A retrospective study of 120 patients with the clinically and histologically established diagnosis of idiopathic (primary) myelofibrosis (IMF) was performed to determine prognostic factors of predictive value, including parameters characterizing the dynamics of hematopoietic cell kinetics. In contrast to previous studies, our cohort comprised the full spectrum of the disease, from initial prefibrotic to advanced osteosclerotic stages. The in situ end-labeling (ISEL) technique was used to demonstrate apoptosis, in order to determine dynamic parameters of predictive value. Cell proliferation was evaluated by employing the monoclonal antibody PC10 directed against proliferating cell nuclear antigen (PCNA). Proliferative activity (PCNA index) and frequency of apoptosis showed significant differences between early and advanced fibrosclerotic stages of disease. Decrease in proliferation indicated a significantly shorter survival, whereas a higher frequency of apoptotic cells was associated with a better prognosis. It may be speculated that a normal or enhanced proliferation rate expressed by PCNA positivity (late G1- and S-phase of the cell cycle) that is accompanied by a higher incidence of apoptosis reflects the regenerative (turnover) capacity of hematopoiesis. This may apply especially to early hypercellular stages without relevant myelofibrosis. In consideration of a recently published multivariate risk model, a simplified synthesis score for stratification of a patient's prognosis was constructed. Age, degree of anemia, leukocytes, and platelet count were regarded as the most important parameters. A substantial improvement of prognostic efficiency was further achieved by including PCNA index and frequency of apoptosis. Our results are in keeping with the assumption that generalization, indicated by myeloid metaplasia, has a prodigious impact on prognosis in IMF. Furthermore, in this context dynamic features such as proliferative activity and frequency of apoptosis exert an additional predictive value.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002770050474
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