Biomedical subjects

A Georgii

Publications and source records attributed to A Georgii.

At least 55 records · Page 3Linked to original sources

PubMed1995

[The new Hannover method of synthetic embedding of bone marrow. Cold polymerization of methylmethacrylate].

A patented low-temperature polymerization method for methylmethacrylate (MMA) infiltrated bone marrow biopsies is described: it has been developed from our previous MMA technique and is a patented procedure. Differences from the previous method are (1) removal of stabilizer from the MMA monomer before its application, (2) the use of a different starter, (3) avoidance of O2 influence during polymerization by means of vacuum exchange with N2, and (4) polymerisation in a water bath to draw off residual heat. After this procedure, all immunohistochemical reactions are possible provided that the previous fixation is adequate. The effects of different fixatives are reviewed briefly without detailed analysis. Technically, this plastic embedding can be performed at least as rapidly as the classic paraffin embedding after decalcification. The advantages over the latter method are: (1) the cells can be better differentiated because semi-thin sections can be made; (2) the immunoreactions can also be performed on the basis of semithin sections, which means they can be interpreted more easily; (3) morphometric analyses yield more reliable results because of the constant thickness of sections; (4) osteological examination of bone trabeculae, especially the search for mineralisation deficiencies, is possible; (5) the plastic embedding procedure is less dependent on individual instabilities in the quality of performance of the staff members involved. Furthermore, it is worth mentioning that the costs for additional equipment necessary remain below DM 100,000 including an excellent microtome.

Biomarkers, Tumor↗

PubMed1995

[Morphometry of megakaryocytes for supporting the histologic diagnosis of chronic myeloproliferative diseases].

Morphometric analysis of sections of biopsy specimens from patients with chronic myeloproliferative disorders (CMPD) can complement the individual histological diagnosis and help to distinguish the four groups of CMPD. A total of 130 diagnostic biopsies from 29 cases of chronic myelocytic leukemia (CML.CT), 26 cases of (CML.MI), 28 of essential thrombocythemia (PTH), 26 cases of chronic megakaryocytic granulocytic myelosis (CMGM), and 21 of polycythemia vera (P. vera), and 30 from healthy control persons were evaluated morphometrically in sections of undecalcified plastic-embedded core biopsies. Clear distinctions were revealed in size of megakaryocytes, nuclear lobulation, clustering, and the nuclear size and shape of megakaryocytes. Nuclear size and cellular size were significantly less in CML (range of means of cellular size: 220-360 microns2) than in the other three Ph1-negative groups (range of means: 480-750 microns2). Nuclear lobulation was more distinct in PTH than in P. vera, and especially in CMGM. Clustering of megakaryocytes was more than twice as frequent in CMGM (8.0-10.5%) as in any of the other three groups (0.1-7.0%). Naked nuclei were more numerous in all groups of CMPD. The main topic of the study is the different size of megakaryocytes in the four main groups of CMPE, allowing a distinction between small-megakaryocytic Ph1-positive CML and large-megakaryocytic Ph1-negative forms of CMPD.

Biopsy↗

PubMed1995

[Cytogenetics and molecular studies confirm the histopathologic diagnosis of chronic myeloproliferative diseases].

The histopathological classification of chronic myeloproliferative disorders can be supported by applying cytogenetics and molecular genetics to the analysis of bone marrow or blood cells, as demonstrated in 253 cases evaluated. The Philadelphia translocation (9;22) is the most important genetic parameter, being specific for chronic myeloid leukemia. Conventional methods for the detection of the t(9;22) are karyotyping and Southern blot analysis of the bcr gene. The newly established technique of fluorescence in situ hybridization (FISH) allows visualization of bcr-abl fusion even in non dividing cells. Molecular cytogenetics for t(9;22) yield results that are rapid and reliable as well as easily quantifiable.

Biopsy↗

PubMed1995

[The histological picture of anemia in bone marrow biopsies].

A total of 41,553 bone marrow biopsies were collected for the Bone Marrow Registry from January 1989 to June 1994 included 6,366 taken from 5,011 patients referred because of unexplained anemia. An increasing percentage of biopsies submitted for examination are designated anemic: this rose from 7.2% in 1989 to 18.9% within the first 6 months of 1994, reflecting an increased need to find the reasons for anemic conditions. Histologically, seven main groups have been found: (1) myelodysplastic syndrome (MDS) accounting for 32% of all anemia patients seen, (2) infectious anemia (23.5%), (3) iron deficiency anemia ((22.7%), (4) hemolytic anemias (7.2%), (5) aplastic anemia (6.8%), (6) megaloblastic/pernicious anemia (5.0%), and (7) anemia due to bleeding (3.0%). These seven groups of anemia can be diagnosed in core biopsies on the basis of their particular histopathology, so that films of bone marrow smears are not always needed.

Adult↗

PubMed1995

[Histopathology and clinical aspects of primary myelodysplastic syndrome].

The histopathology of bone marrow in primary myelodysplastic syndromes (MDS) is described, with reference to the FAB classification. Variants such as hypoplastic, thrombocythemic and fibrotic MDS are recognized from their histopathology and must be incorporated in the FAB classification. The clinical significance of hypoplastic, thrombocythemic and fibrotic variants is illustrated by the survival rates and leukemic transformation in these patients. Histopathological classification according to the FAB system corresponds with cytological classification, as proven by the distribution of the subtypes, blood values, leukemic transformation rates and survival times. Finally it is even possible to elaborate a prognostic score for survival based on histological features of diagnostic biopsies, which emphasizes the importance of histopathological examination of bone marrow in MDS patients.

Adult↗

PubMed1995

[Histopathology of Ph1-negative chronic myeloproliferative diseases].

The Ph1-negative groups of chronic myeloproliferative diseases (CMPD) are described, and histopathological criteria that distinguish them from each other are given. These are based upon observations in primary biopsies from 2,331 patients with CMPDs among a total of 34,160 patients referred between 1 January 1989 and 30 June 1994 to the Bone Marrow Registry. These cases of CMPD break down into the main groups as follows: CML 23.2%, megakaryocytic myelosis consistent with agnogenic myeloid metaplasia 22.3%, essential thrombocythemia 22.1%, and polycythemia vera 20.4%; 12.0% of cases were unclassifiable. Histological progress in each group is characterized by (1) increasing number and pleomorphy of megakaryocytes, (2) increasing fibrosis, and (3) excess of blasts. These three features can be observed in diagnostic biopsies before any therapy. Therefore, it is recommended that such alterations be reported semiquantitatively. A staging system with four stages from 0 to 3 for each of the three features is introduced. Its application allows staging for the individual patient on the basis of diagnostic biopsies.

Bone Marrow↗

PubMed1995

[Histopathology of chronic myeloid leukemia in diagnostic biopsies of bone marrow].

Histopathology of the bone marrow of diagnostic biopsies prior to any therapy is described in a total of 412 Ph1-positive patients. Special attention is paid to the distribution of megakaryocytes, increase of fibres and blasts, and occurrence of storing histiocytes of pseudo-Gaucher type. Megakaryocytes were significantly increased in 31.6% of diagnostic biopsies, myelofibrosis was found in 15.8%, significant increase of blasts in 2.4%. Pseudo-Gaucher cells were detected in 57.8% of a total of 412 biopsies. These histiological features are considered as an indication of the progress of the disease. A semiquantitative specification of CML by this criteria is described which can be performed rather reliably and defines the stage of CML at diagnosis prior to substantial treatment.

Biopsy↗

PubMed1995

Monoclonal antibodies against inhibin represent key markers of adult granulosa cell tumors of the ovary even in their metastases. A report of three cases with late metastasis, being previously misinterpreted as hemangiopericytoma.

Antibodies against human inhibin, a peptide hormone produced by ovarian granulosa cells to inhibit FSH, are widely applied to determine serum inhibin levels. Recently, they were, however, proved also to stain follicle cells in ovarian tissue by immunoreactions in histological sections. The commercially available inhibin antibody produced by Serotec, applied to sections of paraffin blocks, stained follicle epithelia in 6/6 samples of ovarian tissue from females under the age of 40 recruited from the archives. Adult granulosa cell tumor tissue samples from primary tumors of the ovary showed positive reaction in 6/6 cases. No positive reaction was found in staining tissues from hemangiopericytomas from males (0/3), leiomyomas, leiomyosarcomas, and a malignant melanoma (0/5), serving as negative controls. No positive reactions could be observed in tumor cells of 10 ovarian carcinomas, whereas in two of these cases single cells of the specialized ovarian stroma stained positively with inhibin. Positive immunostainings were revealed in three late metastases (two within the liver) from granulosa cell tumors in females, primarily misinterpreted as hemangiopericytomas or leiomyosarcomas, because the previously resected primaries of the ovary were not known at the time of liver surgery. The recognition of granulosa cell tumors, especially the distinction of the sarcomatoid growth type from soft tissue tumors, may be difficult, even if immunostaining for intermediate filaments are applied. Immunostaining by antibodies against inhibin, which can be applied reliably in histopathology, may therefore provide a useful tool to distinguish between granulosa cell tumors and genuine soft tissue tumors. This is also of clinical importance, because treatment of the former by cisplatin-based polychemotherapy and antisex hormone therapy proved to be helpful. Furthermore, the inhibin antibody can be used as an early serum marker for detecting tumor recurrence months before clinical evidence.

Adult↗

PubMed1995

Demonstration of the Philadelphia translocation by fluorescence in situ hybridization (FISH) in paraffin sections and identification of aberrant cells by a combined FISH/immunophenotyping approach.

The Philadelphia translocation was demonstrated by two-colour fluorescence in situ hybridization (FISH) in decalcified paraffin sections of bone marrow from patients with chronic myelogenous leukaemia. FISH was combined with immunocytochemical detection of different membrane-bound or cytoplasmic antigens. With this new technique, the cells bearing the 9:22 translocation can be identified morphologically, as well as immunocytochemically, in tissue sections.

Antigens, CD↗

PubMed1995

Prognostic relevance of a histologic classification system applied in bone marrow biopsies from patients with multiple myeloma: a histopathological evaluation of biopsies from 153 untreated patients.

A total of 153 diagnostic bone marrow biopsies from patients with advanced stages of multiple myeloma corresponding to stages II and III according to the Durie/Salmon classification were evaluated prior to any treatment in a prospective therapy trial of the German Myeloma Treatment Group. Histologic sections were analyzed according to a pre-defined system of criteria microscopically by 2 observers, determining three criteria: 1) grading by histopathology, regarding the cytologic differentiation of neoplastic cells and quantifying the percentage of plasmacytic, pleomorphic, and plasmablastic myeloma cells distributed within the sections; 2) the volume of infiltration; and 3) the pattern of neoplastic growth. Furthermore, four other criteria, namely hematopoiesis, fiber increase, osteomalacia, and micro-osteo-lesions, were evaluated. A cluster analysis using the three histological criteria revealed three groups of patients with significantly different survival times based on histological criteria only; the three criteria were mentioned above. It is concluded from these results that bone marrow biopsies, when evaluated histologically by grading and staging according to the three criteria, provide most valuable prognostic parameters in myeloma patients.

Bone Marrow↗

PubMed1995

Clinical significance of E-cadherin as a prognostic marker in thyroid carcinomas.

The aim of this study was to evaluate the expression of E-cadherin as a potential marker for the prognosis of thyroid carcinomas. In normal thyroid (n = 8), the expression of E-cadherin messenger ribonucleic acid levels was uniformly high and seemed to be restricted to thyrocytes. Steady-state messenger ribonucleic acid levels and immunostaining were both completely lost in undifferentiated thyroid carcinomas (n = 7) and were variably reduced in differentiated thyroid carcinomas (n = 44). In a follow-up study during a mean of 4.5 +/- 1.4 yr, E-cadherin messenger ribonucleic acid and immunohistochemical expression were compared with the initial clinicopathological parameters and with locoregional recurrence and the development of nodal or distant metastases in differentiated thyroid carcinomas. Immunohistochemical expression of E-cadherin was greatly reduced with the progression to primary tumor stage 4 (pT4) tumors. In parallel, patients with pT4 tumors had a higher rate of locoregional tumor recurrence and distant metastasis than did the group of patients with pT1-3 tumors. In 5 of 29 patients with pT4 tumors, positive E-cadherin staining of more than 30% of the cells was detected. None of these patients showed signs of a regional recurrence or distant metastases during an observation period of 4.3 +/- 1.1 yr. In 13 patients with E-cadherin-positive tumors, none developed new distant metastases which was in contrast to 7 of the group of 31 patients with less than 30% E-cadherin-positive cells. Thus, E-cadherin expression seems to be associated with the dedifferentiation, progression, and metastatic spread of thyroid carcinomas and may be a useful marker for the prognosis of these tumors.

Adenocarcinoma, Follicular↗

PubMed1995

Karyotype findings and molecular analysis of the bcr gene rearrangement supplementing the histologic classification of chronic myeloproliferative disorders.

BACKGROUND: Histologic examination of bone marrow is important in establishing diagnoses among chronic myeloproliferative disorders (CMPD). Only a few studies, however, have compared cytogenetic or molecular genetic findings to histopathology in CMPD. Diverging results on the presence of the Ph1-translocation in patients with myelofibrosis have been reported. EXPERIMENTAL DESIGN: Cytogenetic studies and molecular analysis of the bcr gene were performed in bone marrow cells of patients with CMPD simultaneously with histopathologic examination of plastic-embedded bone marrow biopsies. RESULTS: The Ph1-chromosome was found in 120/128 (93%) cases with histopathologic diagnosis of chronic myeloid leukemia (CML), including a notable proportion of cases with an increase of megakaryocytes and/or myelofibrosis; the latter was associated with a significant increase of chromosome aberrations, in addition to Ph1. Among those additional changes in myelofibrosis of Ph1-positive CML were del (13q) and t(1;11) in one case each. A bcr gene rearrangement was detected in 92% (24/26) of the CML cases examined. All other groups of CMPD, comprising cases of myelofibrosis and unclassifiable cases, were Ph1-negative by both cytogenetics (n = 102) and molecular analysis (n = 18). Karyotype changes associated with myelofibrosis in various CMPD concerned mainly balanced translocations involving 1p36 and 11q11, deletions of 5q13-34, 3p, 11q23, 13(q12,q22), and 20q12 as well as gain of 1q and trisomy 3, 8, 19, or 21. In histologically unclassifiable CMPD, karyotyping provided additional information for the differential diagnosis. CONCLUSIONS: The correlation of cytogenetic findings and histopathologic features is helpful in confirming or supporting histopathologic diagnoses and in characterizing new marker chromosomes in CMPD.

Aged↗

PubMed1995

Which is the best surgery for Budd-Chiari syndrome: venous decompression or liver transplantation? A single-center experience with 50 patients.

The optimal treatment of Budd-Chiari syndrome (BCS) remains an open question. It is still a matter of controversial discussion whether venous decompression or liver transplantation is superior. To elucidate the role and prognosis of both surgical options in our own experience, a consecutive series of 50 patients treated between 1981 and 1993 was retrospectively analyzed. Twelve patients had different types of portosystemic shunts or local decompressive procedures, and transplantation was performed in 43 cases, including five with previous conventional surgery. The overall mortality of 18 of 50 was conventional surgery. The overall mortality of 18 of 50 was concentrated within the early postoperative period, with no patient lost after 1 year. In the venous decompression group, the success rate was only 29%, and treatment failure was closely related to the finding of cirrhosis or technical problems like vascular thrombosis. After transplantation, early complications were rejection, primary nonfunction, or graft necrosis, and contributed significantly to the risk of sepsis. Thirty of 43 liver recipients are currently alive, including four rescued after failed decompressive surgery, with 1- and 10-year survival of 69%, and excellent recurrence-free rehabilitation. These results clearly indicate that patient selection plays a dominant prognostic role in the treatment of BCS. Venous decompression and liver transplantation should both be integrated in a common therapeutic concept, and the individual decision for the preferred approach must be based on the leading clinical symptom: portal hypertension or liver failure, together with the assessment of reversibility of hepatic damage, and the potential of cure of the underlying disease.

Adolescent↗

PubMed1995

[Mesenchymal tumors of the liver: their frequency and histopathological diagnostic problems in surgical investigations].

BACKGROUND: Primary mesenchymal tumors of the liver are rarely observed. Histopathological diagnosis can be very difficult, in needle biopsies especially. This is a great difference to epithelial tumors of the liver. The frequency of their occurrence within surgical pathology will increase in the near future, since image analysis and improvement of liver surgery technics raise their recruiting. DESIGN: A total of 1102 primary liver tumors were evaluated from the files of this laboratory between 1981 and 1993, reclassified histologically and in cases of mesenchymal tumors compared with clinical data and course. RESULTS: 208/1102 (19%) mesenchymal tumors were revealed. When 177 cavernous hemangiomas were omitted for its choristomatous character and unproblematically diagnostic approach, a substantial group of 31/1102 (3%) mesenchymal tumors does remain. These were classified as: epithelioid hemangioendotheliomas (EHE) (8/31), angiosarcomas (7/31) infantile hemangioendotheliomas (5/31), mesenchymal hamartomas (5/31), angiomyolipomas (3/31), malignant mesenchymomas (2/31) and schwannoma (1/31). Among other misdiagnoses, 3 of hemangiopericytoma are remarkable, since they had to be reclassified as metastases from adult granulosa cell tumor of the ovary and meningeoma respectively. The histological distinction of EHE's is discussed versus angiosarcoma, since therapy and prognosis are different. CONCLUSIONS: These results reconfirm that mesenchymal neoplasms of the liver in adults are usually angiomatous differentiated. Diagnostic approach to probably mesenchymal derived masses of the liver does often request additional information from immunostaining and image analysis, especially when based on needle biopsies. Metastases are to be considered in this procedure. Primary pericytomas were not reconfirmed among this total of 1102 primary liver tumors.

Adenoma↗

PubMed1995

Transforming growth factor beta 1 in human liver tumors.

AIMS: Transforming growth factor beta 1 (TGF beta 1) is a multifunctional cytokine. The role of TGF beta 1 in hepatocarcinogenesis is still a matter of discussion. To assess the expression of TGF beta 1 in human liver tumors, the following study was conducted. MATERIAL AND METHODS: Formalin fixed, paraffin embedded sections of 50 hepatocellular carcinomas (HCC), 30 cholangiocellular carcinomas (CCC), 15 hepatocellular adenomas (HCA), 15 focal nodular hyperplasias (FNH), and 20 normal livers (NL) were immunostained with a monoclonal anti-TGF beta 1 antibody (clone TB-21). TGF beta 1 mRNA was measured in snap frozen tissue of 2 HCC, 3 HCA, 2 FNH, and 3 NL of the immunohistochemistry group using slot blot hybridizations. Total RNA was extracted, and slot blots were hybridized with 32P endlabeled TGF beta 1 oligonucleotides. TGF beta 1 mRNA was measured in cpm with a scintillation counter. RESULTS: TGF beta 1 protein was strongly expressed in 14/15 FNH and 13/15 HCA, whereas it was scarcely detectable in 46/50 HCC and 25/30 CCC. All NL were moderately positive. The 2 HCC cases contained far less TGF beta 1 mRNA than the HCA, FNH, and NL examined here. CONCLUSIONS: TGF beta 1 expression is markedly lower in malignant liver tumors than in benign tumors or NL. Therefore, TGF beta 1 down-regulation may be an important step in hepatocarcinogenesis. Additionally, TGF beta 1 immunostaining may be useful in distinguishing well-differentiated HCC from adenomas.

Adenoma↗

PubMed1994

Effects of antigen retrieval by microwave heating in formalin-fixed tissue sections on a broad panel of antibodies.

Formaldehyde fixation of biopsy specimens for routine purposes has often been held responsible for the poor reproducibility of immunohistochemical studies. Recently, antigen retrieval (AGR) using microwave irradiation was described as a potential tool to enhance immunostaining. A comparison of conventional staining and staining after microwave heating was performed for 52 markers, using tissues fixed in formaldehyde for 24 h, 1 to 6 weeks and 3 years respectively, as well as consultant case material. After adequate duration of fixation (24 h), only a few markers (17%) showed better results after AGR, but this percentage was increased to 50% when tissues were fixed for longer periods. Maximal enhancement was obtained in the group of consultant cases (58% of tested markers demonstrated better staining results), in which the period of fixation and tissue processing was unknown. To achieve reliable enhancement with AGR, continuous heating (100 degrees C) should not be shorter than 20 min. In conclusion, AGR may become the most important tool to simplify and equalize immunohistochemical techniques, if critically evaluated.

Antibodies, Monoclonal↗

PubMed1994

[Cytogenetics in addition to histopathology exemplified by myelodysplastic syndrome].

The value of cytogenetics performed simultaneously with histopathology was evaluated in patients with myelodysplastic syndrome (MDS). Clonal karyotype changes of the bone marrow cells supporting the histological diagnosis were found in 38/69 cases (55%). The chromosome aberrations, especially complex changes, were significantly correlated to distinct histopathological findings such as atypias of the haematopoietic cell lines and myelosclerosis. Complex karyotype changes were further associated with short survival of the MDS patients. Our results demonstrate that cytogenetic analyses are helpful in supplementing the histopathological diagnoses. Recent developments in molecular cytogenetics even allow the detection of chromosomal aberrations in non-dividing cells from cytological preparations or tissue sections which may become available for routine diagnosis.

Aged↗

PubMed1994

Mycobacterium genavense. Autopsy findings in three patients.

The authors report on the pathologic findings in three cases of disseminated infection with Mycobacterium genavense, a recently described nontuberculous mycobacterium, in human immunodeficiency virus (HIV)-I-positive patients. The mycobacterium was identified by amplification of a 16S rDNA gene fragment and subsequent sequence determination. The organs mainly involved were the small intestine, spleen, liver, and lymph nodes. In contrast, lungs, myocardium, and kidneys were not involved, or only minimally involved, in this generalizing disease. Histopathologically, infection with Mycobacterium genavense in HIV-positive patients was mostly characterized by masses of foamy histiocytes and, depending on the immunologic reactivity of the host, by ill-formed granulomas, rarely with small foci of necrosis. The pathologic findings and clinical features were similar to those presented by patients who had generalized infection with Mycobacterium avium-intracellulare complex. To obtain more precise information about the specific course of infection with Mycobacterium genavense, scrupulous microbiologic investigations, including molecular biologic techniques, are necessary in cases with mycobacterial infections.

AIDS-Related Opportunistic Infections↗