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A Georgii

Publications and source records attributed to A Georgii.

At least 91 records · Page 5Linked to original sources

Histologic findings in bone marrow biopsies of patients with thrombocythemic cell counts.

Histologic diagnoses from bone marrow biopsies were analyzed in a total of 1165 patients presenting with thrombocythemic platelet counts at initial examination. Two cut-off points suggested by the Polycythemia Vera Study Group to define thrombocythemia by platelet counts were compared: the former limiting value of 1000 x 10(9)/l platelets versus the recently proposed value of 600 x 10(9)/l. The percentage of all nonproliferative disorders was 41% under the lower, dropping to 11% under the high cut-off point. The respective figures for myeloproliferative disorders increased from 49% under the lower to 74% under the high limiting value. Primary thrombocythemia was included in 72% by the lower, and in only 40% by the high limiting value when classified by its histologic pattern in bone marrow biopsy. A striking decrease of platelet counts occurs, related to fiber increase, among each of three main groups of myeloproliferative disorders: in CML with megakaryocytic predominance from 40% down to 25%, in megakaryocytic-granulocytic myelosis (primary, i.e., agnogenic myelofibrosis) from 36.6% to 10%, and in primary thrombocythemia from 72.6% to 28.6% in cases with reticulin sclerosis.

Biopsy↗

Immunohistochemical examination of routinely processed bone marrow biopsies.

Immunohistochemistry was performed on paraffin sections of 169 bone marrow biopsies fixed in a buffered methanol-formalin solution and decalcified with EDTA. The biopsies included specimens with normal hematopoiesis, and specimens that were affected by various hematological disorders as well as some metastatic carcinomas. The results demonstrate that a wide spectrum of antigens was preserved in routinely processed bone marrow biopsies, even after long-term fixation up to 12 days. Markers for granulopoietic cells were lysozyme, elastase, DAKO-M 1, and MT 1. Megakaryopoiesis was stained with glycoprotein IIIa, von Willebrand factor, and Ulex europaeus agglutinin (UEA), and erythropoiesis with LN 1. Normal lymphocytes as well as lymphoma cells of all non-Hodgkin's lymphomas tested were positive for leukocyte common antigen (LCA), and at variable degree, for MB 1, 4 KB 5, LN 1, LN 2, UCHL 1, or MT 1. Reed-Sternberg and Hodgkin's cells in Hodgkin's lymphomas were reactive with Ber-H 2, LN 2 and Dako-M 1. In plasma cell disorders, staining for immunoglobulin light chains gave best results. Metastatic carcinomas showed predominantly staining with EMA, and KL 1. A selected panel of specific cell markers is proposed, which proved to be helpful in routine bone marrow diagnosis in most cases.

Biopsy↗

Histopathological classification of Hodgkin's lymphomas. Results from the reference pathology of the German Hodgkin Trial.

Diagnostic biopsies of 1,140 previously untreated patients with Hodgkin's lymphoma from the German Hodgkin Therapy Trial were evaluated by a panel of 4 histopathologists. Each case was classified by consensus of the four according to an extended Rye-System including the diversifying of NS.HD and the unclassifiable cases. The interobserver agreement rate was 92.1% among the panel members regarding the final classification. Primary Hodgkin diagnosis was approved in 91.7% (1045/1140 cases). The distribution of the 1,140 cases within this system was (in %) as follows: 2.7 LP.HD, 57.9 NS.HD, 17.3 MC.HD, 0.7 LD.HD, 13 HD of unclassifiable subtypes, 6.3 of not certain HD, 1.9 Non-Hodgkin Lymphoma, 1 case of non malignancy. Grading of NS.HD into 2 subgroups according to the British classification differed conspicuously by 84.5% versus 15.5% and 71.6% versus 28.4% in British results. This divergency is explained by interobserver disagreement ranking from 43% to 85%.

Biopsy↗

[Borderline between Hodgkin and non-Hodgkin lymphomas with unfavorable clinical course: a clinical, histological and immunohistochemical analysis of 33 cases within the German Hodgkin Lymphoma Study].

Reevaluation of diagnostic biopsies from 502 patients who entered the German Hodgkin Therapy trial was performed by a panel of four pathologists. Classification revealed 90% of unambiguous Hodgkin-lymphomas (HL), 1.6% of Non-Hodgkin-lymphomas (NHL) and 8.4% of cases difficult to evaluate, reflecting to the well-known problem of the border between these 2 groups of lymphoma. As these cases had the worst prognosis, a second attempt of reclassification, including immunohistochemical studies, was made, resulting in final classifying of 25% of these cases as NHL, 50% as HL, and 25% as further unclassifiable. The most common differential diagnostic problem was separating pleomorphic nodular sclerosing HL from large cell NHL's and HL with rather few Hodgkin- or Reed-Sternberg-cells from Lennerts lymphoma or angioimmunoblastic lymphadenopathy. Immunohistochemistry was helpful for the differential diagnostic decisions in these individual cases. A very high percentage of these problem cases had initially entered the trial as lymphocyte depleted HL, and the large majority of deaths came from the large cell NHL group.

Diagnosis, Differential↗

Elliptic Fourier analysis of megakaryocyte nuclei in chronic myeloproliferative disorders.

Elliptic Fourier analysis was applied to megakaryocyte nuclei in bone marrow biopsies from 15 patients with chronic myelocytic leukemia with megakaryocyte predominance and from 15 patients with chronic megakaryocytic granulocytic myelosis. To assess the reliability of this procedure, the biopsies were evaluated also by the semiautomatic measurement of nuclear area and form factor, and both methods were compared with respect to the degree of morphologic differences obtained between these two types of chronic myeloproliferative disorders (CMPDs). Discriminant analysis revealed correct reclassification of all cases both for elliptic Fourier analysis and for semiautomatic planimetry, whereas discriminant scores were much higher for Fourier analysis. Thus, simple planimetric features such as nuclear area and form factor, in contrast to Fourier analysis, are not able to detect the full degree of morphologic differences between megakaryocyte nuclei in different CMPDs. Elliptic Fourier analysis therefore seems to be a useful procedure for the accurate description of such complicated structures as megakaryocyte nuclei in CMPD.

Analysis of Variance↗

[Carcinoid of the middle ear: a rare tumor with biphasic differentiation. Case report with special reference to immunohistochemistry and electron microscopy].

Progressive unilateral sensorineural deafness and tinnitus developed in a 59-year-old woman over a 1-year period. Clinical examination showed a tumor mass which almost completely filled the tympanic cavity, and grew around the auditory ossicular chain. Histological findings revealed the tumor to be a primary carcinoid of the middle ear. Neuro-endocrine differentiation was confirmed immunohistochemically by positivity for neuron-specific enolase, chromogranin, pancreatic polypeptide and synaptophysin. Using electron microscopy, neuroendocrine granules could be visualized. In addition, both light and electron microscopy revealed that cells had an epithelial differentiation with mucin granules while immunohistochemistry showed a positivity for cytokeratins. The detection of intermediary filaments (immunohistochemically with vimentin and under electron microscopy) was unique to this neoplasm and has to be considered in distinguishing the carcinoid tumor from the papillary adenoma of the middle ear. Tumor prognosis is excellent with radical extirpation from the middle ear. In the case presented, there has been no evidence for either recurrence or metastases 10 months after surgical resection.

Biomarkers, Tumor↗

[The clinical course of oxyphilic carcinoma of the thyroid].

In a total of 1665 patients with malignant thyroid neoplasms 90 oxyphilic thyroid carcinomas (OTC) were found of whom 55 could be re-examined and newly classified. Morphological and clinical parameters influencing the clinical course were determined. During a mean follow-up period of 6.5 y metastases or local recurrent disease occurred in 12 patients (24%). Apart from 3 early manifestations of metastases, 9 patients developed recurrent disease within, on average, 4.7 y after thyroidectomy: local lymph node metastases and local recurrences occurred within an average of 5.4 y, distant metastases after only 2.7 y. Thyroglobulin proved to be reliable for follow-up with a sensitivity of 88% on levothyroxine and 75% on endogenous TSH-stimulation (specificity: 98%). The frequency of metastases and local recurrences correlated with age at the time of tumor diagnosis, the degree of invasiveness and the local tumor extension (pT4 vs. pT1-3), whereas other factors such as the absolute diameter of the tumor or patient's sex had no influence on the clinical course. The survival probability for 5 and 10 years was 95 and 75%, respectively. All OTC patients should be examined regularly at least once a year by cervical sonography and thyroglobulin measurement. Because 18% recurrences occurred within 4.7 y such examinations should be repeated beyond year 5 after thyroidectomy.

Aged↗

Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients.

In a retrospective study of 352 patients with primary myelodysplastic syndromes, 61 (17.3%) revealed myelofibrosis in bone marrow biopsies. The fibrosis was observed to occur mostly focally (41/61 cases), and collagen deposits were found very rarely (4/61). The histopathology of bone marrow biopsies revealed hyperplasia and disturbed differentiation in megakaryopoiesis; the frequency and grade of dysplasia in megakaryopoiesis increased with advancing myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelo-monocytic leukaemia (CMMoL). The frequency of cytogenetic aberrations was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly lower values of haemoglobin and lower platelet counts in MDS with myelofibrosis. Life expectancy was reduced to 9.6 months, compared with 17.4 months in MDS without fibrosis. In refractory anaemia, the survival times were 10.0 months in MDS with myelofibrosis, compared to 28.9 months in MDS without myelofibrosis. 36.6% of the patients with MDS and myelofibrosis developed a transformation into ANLL during the course of the disease. Myelofibrosis therefore seems to herald a poor prognosis.

Adult↗

Chronic myelogenous leukemia: recent developments in prognostic evaluation and chemotherapy. The German CML Study Group.

Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Bone Marrow Transplantation↗

Megakaryocytes in chronic myeloproliferative disorders: numerical density correlated between different entities.

A morphometric evaluation of number and grouping of megakaryocytes (MK) in five different groups of chronic myeloproliferative disorders (CMPD) was performed by counting 60 high power fields equaling approximately 14.28 mm2 of haematopoiesis in each case. Twenty-one up to 29 cases were evaluated for each of five categories of CMPD and one control group; a total of 132 cases of CMPD and 33 control cases were used. The mean number of MK per square millimetre was 15.54 +/- 1.53 in chronic myeloid leukaemia of common or granulocytic type (CML.CT), 69.91 +/- 5.85 in CML with megakaryocytic increase (CML.MI), 59.59 +/- 3.27 in polycythaemia vera (P. vera), 59.85 +/- 4.59 in primary thrombocythaemia (PTH), 67.58 +/- 4.11 in chronic megakaryocytic granulocytic myelosis (CMGM), and 19.7 +/- 3.07 in controls. The distinction between free or isolated MK, and between clustered or grouped MK corresponds to the total cell counts of MK in the various groups of CMPD. Clustering of MK was significantly higher in CMGM and PTH compared to other groups, but the difference between them was not statistically significant. Significant differences in the mean number of MK were obtained between controls and CML.CT on the one hand and all other groups of CMPD on the other. The results further support the histological sub-classification of CMPD according to the primary disorders of the Hannover classification (not advanced by sclerosis, fibrosis or excess of blasts, respectively).

Blood Cell Count↗

Cytogenetics of chronic myelogenous leukemia (CML) correlated to the histopathology of bone marrow biopsies.

Cytogenetic findings were correlated to histopathological bone marrow findings evaluated simultaneously in 103 patients with chronic myelogenous leukemia (CML). CML was subtyped histologically according to the number of megakaryocytes and increase of fibers or blasts within the bone marrow. The Philadelphia chromosome (Ph 1) was found in 88.3% of all patients (91/103). Chromosome aberrations additional to the Ph 1-chromosome were noticed in 20 of 91 (22%) cases. The additional karyotype changes occurred significantly more frequently among patients with increase of fibers in the bone marrow compared with patients without increase of fibers or blasts (p less than 0.05). Karyotype changes associated with increase of fibers in Ph 1-positive cases of CML were trisomy 8 and 19, +Ph1, t (1; 11), and i (17q). Ph 1-positive CML patients with additional karyotype changes had a significantly shorter survival (p less than 0.04) than Ph 1-positive patients without additional chromosome aberrations. Our results suggest that histopathological examination of the bone marrow should be considered in the evaluation of cytogenetic markers in chronic myeloproliferative disorders.

Adult↗

Planimetric analysis of megakaryocytes in the four main groups of chronic myeloproliferative disorders.

Planimetry of megakaryocytes (MK) was performed in bone marrow biopsies (BMBs) from patients with chronic myeloproliferative disorders (CMPD) to substantiate cytomorphologic differences in this cell lineage between the four main groups of CMPD. The biopsy specimens were classified histologically prior to morphometry, according to the Hannover Classification of CMPD. Five histological groups were investigated, evaluating between 21 and 30 biopsies in each group. The five groups were as follows: (1) Chronic myelocytic leukemia (CML) of common type (CML.CT), (2) CML with megakaryocytic increase (CML.MI), (3) polycythemia vera (P. vera), (4) primary thrombocythemia (PTH), and (5) chronic megakaryocytic-granulocytic myelosis (CMGM). The results of five variables, i.e. the cellular and nuclear size, the cellular and nuclear form factor, and nuclear segmentation, were determined in at least 50 MK per BMB. The results reveal significant differences in MK nuclear and cellular size, as well as in nuclear segmentation between CML and the three other groups in that the nuclear and cellular size of the MK in CML are smaller than in P. vera, PTH, and CMGM. Moreover, the degree of nuclear segmentation or lobulation differs significantly between the three disorders characterized by large MK. Discriminant analysis permits 78-100% reliability of reclassification by morphometry compared with the histologic classification. A reduced reliability of the morphometric classification to around 80% was found between P. vera and PTH, as well as between P. vera and CMGM. In the design of this study, morphometry of MK lends added weight to the subjective classification of these disorders.

Biopsy↗

Immunohistochemical and biochemical characterization of the mucin-type tumor associated antigen TAG-12 by monoclonal antibody 7A9.

The reactivity of monoclonal antibody 7A9 with normal and neoplastic human tissues and some biochemical characteristics of the antigen (TAG-12) bound by 7A9 were evaluated. Antibody 7A9 showed broad reactivity with various carcinomas in paraffin sections. High percentages of positive tumor cells, displaying membrane and cytoplasmic staining, were noticed in adenocarcinomas of the breast (83/85), serous cystadenocarcinomas of the ovary (15/16), and lung adenocarcinomas (14/16). TAG-12 antigen was also detectable in normal adult and fetal tissues, but the reactivity of 7A9 was mainly restricted to the luminal surface of epithelial cells. For biochemical analyses, TAG-12 antigen purified from T47-D breast carcinoma cells by lectin affinity chromatography was treated with different glycosidases and proteases and analyzed by immunoblotting with 7A9. The data indicate that the antigen recognized by 7A9 is a heavily sialated mucin-type glycoprotein with a molecular weight of more than 200 KD. Similar to all other antibodies against tumor associated antigens, monoclonal antibody 7A9 is not tumor-specific but displays tissue staining patterns with a high carcinoma-to-normal ratio. The strong reactivity with the majority of tumor cells in several carcinoma types suggests that 7A9 is useful for in vitro and in vivo targeting of those tumors.

Adult↗

Hyperacute rejection in heart allografts. Case studies.

Hyperacute rejection in orthotopic heart allografts is a rare event. In our material from a total collective of 524 heart-transplanted patients, we have observed two cases of hyperacute rejection, which are presented in this case report. Histopathologically, this entity is characterized above all by the following triad: pronounced edema, hemorrhages, and regressive changes up to necroses of myocytes. Besides the well-known risk factors, our report draws attention to two further factors possibly associated with an increased risk of hyperacute rejection: 1) repeated cardiac surgery prior to the transplantation, and 2) presence of identical viral genomes in recipient's and donor's heart.

Adult↗

[Multicenter prospective controlled study of therapy of chronic myeloid leukemia. Comparison of busulfan, hydroxyurea and interferon alpha (April 1990 status)].

In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon alpha instead of busulfan prolongs the chronic phase of Philadelphia-positive CML. Additional goals are the examination, whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By September 5, 1990, 593 CML-patients had been randomized, 221 for busulfan, 228 for hydroxyurea and 144 for interferon alpha. The average age is about 51 years. By April 30, 1990, 106 patients had reached the end of the chronic phase, 126 had died. The median survival of Philadelphia-positive patients was 3.95 years, that of all patients 3.75 years. The median observation time of all patients was 1.34 years (mean 1.60 years). At present, no significant difference in survival is recognizable between the three treatment arms, although fewer adverse effects have been observed in the hydroxyurea arm.

Busulfan↗

Immunodetection of a tumor associated antigen (TAG-12): comparison of microwave accelerated and conventional method.

The microwave stimulated immunodetection of a tumor associated antigen (TAG-12) by monoclonal antibody 7A9 and an avidinbiotinylated alkaline phosphatase kit was compared with the conventional staining method. No difference in the staining pattern of antibody 7A9 was noticed in serial paraffin sections of 50 specimens including normal, benign and malignant breast tissues after microwave irradiated and conventional immunostaining. The results demonstrate that microwave stimulated immunostaining gives reliable results and can remarkably reduce the time of the staining procedure.

Alkaline Phosphatase↗