[Active euthanasia in The Netherlands--sharp internal criticism is discovered].
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Biomedical subjects
Publications and source records attributed to T Seidal.
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Eighteen light microscopically undifferentiated small and dark cell malignancies, previously studied ultrastructurally and immunohistochemically in terms of desmin, vimentin and myoglobin expression, were analyzed using mono- and polyclonal antibodies to muscle-specific isoforms of myosin and actin. For comparison, 10 characteristic rhabdomyosarcomas, 5 alveolar and 5 embryonal, were included in the study. A polyclonal antibody to skeletal myosin produced an indistinct staining in all the alveolar and embryonal rhabdomyosarcomas. The staining was most prominent in well-differentiated rhabdomyoblastic tumor cells. In the analysis of the small and dark cell malignancies, this antibody produced a weak and indistinct positivity which can not be interpreted with certainty as an expression of muscle-specific properties. An antibody directed at the alpha and gamma isoforms of actin, which are present in smooth and striated muscle, produced a distinct positive staining in all the alveolar and embryonal rhabdomyosarcomas and in 8/18 small and dark cell malignancies, 7 of which were also shown to express desmin. An antibody directed at the alfa-smooth muscle isoform of actin did not produce any positive staining in any of the tumors. The present study indicates that both muscle-specific actin and desmin can be expressed in tumors lacking ultrastructural evidence of a rhabdomyoblastic differentiation and that the combined use of monoclonal antibodies to desmin and muscle-specific actin is of value when it comes to recognizing rhabdomyosarcomas within the group of undifferentiated small and dark cell malignancies of soft tissue tumors.
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The expression of fine and intermediate filaments in 10 cases of leiomyosarcoma originating from a large vein, 9 cases of vascular leiomyoma (angiomyoma) and one case of a leiomyoma originating from the wall of the saphena magna vein was studied immunohistochemically by using 6 different anti-desmin antibodies, one anti-vimentin antibody and 2 antibodies to muscle-specific isoforms of actin. All the benign tumors and all the leiomyosarcomas of a large vein as well as the vein of origin were positively stained for desmin. The staining results obtained using the different anti-desmin antibodies varied considerably, however, and formaldehyde-fixed tissues were apparently inappropriate for some of them. No single anti-desmin antibody produced a positivity in all cases, and the extent and distribution of the positivity varied by being irregular and patchy in the leiomyosarcomas and in the muscle walls of the veins, while the benign tumors generally revealed a more uniform and strong positivity. Antibodies to muscle-specific and smooth muscle-specific actin produced a positive staining in all the benign tumors, as well as all the leiomyosarcomas and the veins from which they originated. A strong and uniform positivity was observed in the benign tumors and muscle walls of the veins, while the positivity in the leiomyosarcomas was more irregular, as it was for desmin. Vimentin was constantly expressed in the benign tumors and in the veins of origin, but only in 5/10 of the leiomyosarcomas. It is concluded from this study that the immunohistochemical demonstration of desmin, utilizing a monoclonal antibody appropriate to the type of fixation used, and muscle specific isoforms of actin, provide strong support to the light-microscopic diagnosis of leiomyosarcoma of venous origin.
In a review of a national series of malignant tumors in middle-aged and elderly individuals (over 40 years of age), in all 107 cases primarily diagnosed and reported to the Swedish Cancer Registry as rhabdomyosarcomas during the period 1972-1981, 4 cases were accepted as botryoid, embryonal or alveolar rhabdomyosarcoma, using light-microscopic criteria for the diagnosis. An electron-microscopic and immunohistochemical analysis was performed on the 4 cases along with 7 cases of botryoid, embryonal and alveolar rhabdomyosarcoma in patients of over 40 years of age obtained from our own files. Rhabdomyoblastic differentiation was established ultrastructurally by the presence of myofilaments and Z-like densities in 10 of these 11 cases. There were tumor cells in the formaldehyde-fixed, paraffin-embedded material which were positively stained for desmin in all cases, for myoglobin in 7/11 cases, for vimentin in 5/11 cases and for actin in all cases, using monoclonal antibodies. The demonstration of desmin by the monoclonal antibody which was used on the formaldehyde-fixed, paraffin-embedded material is of particular value in the diagnosis of rhabdomyosarcoma. Another tumor, located in the minor pelvis, lacked the light-microscopic features of botryoid, embryonal or alveolar rhabdomyosarcoma, but presented ultrastructural and immunohistochemical evidence of a rhabdomyoblastic differentiation. This tumor was epithelioid in appearance and shared features with alveolar soft part sarcoma. The label epithelioid rhabdomyosarcoma is proposed for this tumor. Nine pleomorphic sarcomas were selected from the national series as possible pleomorphic rhabdomyosarcomas because of the presence of ribbon-shaped tumor cells with an eosiniphilic cytoplasm. There was no electron-microscopic or immunohistochemical evidence of a myogenic differentiation in any of these 9 tumors. The present investigation indicates that a pleomorphic type of rhabdomyosarcoma, indistinguishable from embryonal, botryoid and alveolar rhabdomyosarcoma, is extremely rare or non-existent.
A case of primary tracheal rhabdomyosarcoma is presented--the second in the English-language literature. The treatment policy is discussed on the basis of this case and the literature is reviewed.
A correlated cytologic and histologic study of seven cases of embryonal rhabdomyosarcoma is presented. The diagnosis of rhabdomyosarcoma was established by light and electron microscopy and immunohistochemistry of the operative specimens. The cytologic appearance of the smears corresponded well with the histopathologic findings. Cytologically, two main cell types were distinguished: a predominant primitive, small round cell with scant cytoplasm and a large cell with an abundant cytoplasm, sometimes tadpole- or ribbon-shaped. The tumor cells were often enclosed in a background of mucosubstances. The lack of cytologic features proving rhabdomyoblastic differentiation, such as cross-striation, necessitates the use of additional methods in the cytologic diagnosis of embryonal rhabdomyosarcoma. The value of the embedding technique for ultrastructural analysis and immunohistochemistry in the demonstration of desmin in aspirates is emphasized in the diagnosis of embryonal rhabdomyosarcoma.
Eighteen poorly differentiated, small and dark cell malignancies afflicting young individuals without light-microscopic evidence of a rhabdomyoblastic differentiation or a growth pattern characteristic of rhabdomyosarcoma were analyzed and compared with a series of 30 alveolar rhabdomyosarcomas of varying differentiation, where the diagnosis could be established light-microscopically. The study comprised clinical data, light and electron microscopy and immunohistochemistry, using a battery of mono- and polyclonal antibodies against intermediate filaments, myoglobin, epithelial membrane antigen, neuron-specific enolase, S-100 and leucocyte common antigen. All 30 alveolar rhabdomyosarcomas were positive for desmin, while a minority were positive for myoglobin, using monoclonal antibodies. In 8 of the 18 small and dark cell malignancies, support for a rhabdomyoblastic differentiation was obtained by a positive staining for desmin. In only 3 of these 8 cases was there ultrastructural evidence of rhabdomyosarcoma. The results of the investigation indicate that immunohistochemistry is a more useful tool than electron microscopy in the diagnosis of poorly differentiated rhabdomyosarcoma and that the criteria for the diagnosis of poorly differentiated rhabdomyosarcoma may need to be reformulated.
The present study is an immunohistochemical analysis utilizing a series of mono- and polyclonal antibodies to myoglobin, desmin and vimentin in smooth and striated control muscle tissues, 7 alveolar and 7 embryonal rhabdomyosarcomas and 1 adult and 1 fetal rhabdomyoma with ultrastructurally proven rhabdomyoblastic differentiation in all the tumors. Formaldehyde-fixed and paraffin-embedded tissue was used for the immunohistochemical analysis of all the tumors, while ethanol fixation was also used for the analysis of the control tissues. The staining for myoglobin with the poly- and monoclonal antibody used was positive in both formaldehyde- and ethanol-fixed skeletal and cardiac control muscle. Trypsin treatment abolished the positive staining when the monoclonal antibody was used. Both the striated and smooth control muscle tissues were positively stained by the antidesmin antibodies. The influence of the fixative that was used and the trypsin treatment depended on the antibody used and the type and origin of the muscle tissue. All the tumors were positively stained with the polyclonal antimyoglobin and 8/14 rhabdomyosarcomas and the 2 rhabdomyomas were positively stained with the monoclonal antimyoglobin. All the tumors were positively stained with the polyclonal and 3 of the 5 monoclonal antidesmin antibodies used. Well-differentiated tumor cells were usually positively stained for both myoglobin and desmin. There were small, poorly differentiated tumor cells in the rhabdomyosarcomas and the fetal rhabdomyoma which were positively stained for desmin, whereas very few or no such cells were positively stained for myoglobin. A varying number of mostly small, poorly differentiated tumor cells were positively stained for vimentin in 12 of 14 rhabdomyosarcomas and in the fetal rhabdomyoma. The study showed that one of the monoclonal antidesmin antibodies produced the most consistent result with a positive staining in all cases. The monoclonal antimyoglobin antibody, which is a specific marker of rhabdomyoblastic differentiation, is also considered to be of value, although it did not produce positivity in all cases. It remains to be shown whether desmin can help in the diagnosis of poorly or undifferentiated rhabdomyosarcomas without light- or electron-microscopic evidence of rhabdomyoblastic differentiation.
An ultrastructural study is presented of 8 alveolar rhabdomyosarcomas and 8 embryonal rhabdomyosarcomas, and one mesenchymoma with predominantly rhabdomyoblastic differentiation. Thin and thick myofilaments and Z-lines or Z-like densities were found in all. Intermediate filaments were found in 4 alveolar and 4 embryonal rhabdomyosarcomas. A correlation was noted between the light- and electron microscopic appearance of the tumours regarding the degree of differentiation. A wide differentiation spectrum of the tumour cells was observed which could be correlated partly with normal fetal myogenesis. Ultrastructural differences were demonstrated in the alveolar and embryonal types. Electron microscopy is considered to play an important role in the characterization and diagnosis of rhabdomyosarcoma and is a valuable tool in the differential diagnosis.
An immuno-histochemical investigation of the presence and localization of myoglobin was performed on cardiac and skeletal muscle tissue and on 9 embryonal and 9 alveolar rhabdomyosarcomas, utilizing an immunoperoxidase technique. Cardiac muscle fibres were evenly stained whereas staining of skeletal muscle fibres varied, giving a mosaic-like pattern. Of the fixatives used (4 percent formaldehyde, 4 percent paraformaldehyde, formaldehyde-glutaraldehyde, and Bouin's fixative), 4 percent formaldehyde gave the most prominent staining; short fixation-time slightly increased the staining intensity. All the 9 embryonal and 9 alveolar rhabdomyosarcomas contained positively-stained tumour cells. The number of cells positively-stained and the intensity of the staining varied with differentiation: the most differentiated rhabdomyoblasts stained most intensely. However, also many poorly-differentiated tumour cells in highly cellular areas were positive. Myoglobin is considered a suitable marker of rhabdomyoblastic differentiation, thus the method used in this study may be valuable in the diagnosis.
A correlative, histologic and cytologic study of seven cases of alveolar rhabdomyosarcoma and chromosome analysis using the G-banding technique (in case 1) is presented. The histologic pattern was characterized by pseudo-alveolar structures, separated by fibrous septa. Primitive, dark, round cells predominated, but differentiated rhabdomyoblasts were found in all cases, and so were multi-nucleated giant cells. Unequivocal cross striation was seen in two cases. Cytologically, the tumors were highly cellular and small, undifferentiated tumor cells predominated. Large polymorphous, sometimes multi-nucleated, cells often with an elongated cytoplasm and eccentric nucleus were observed in all cases. The cell-types found could be well correlated to those identified in the histologic sections. The cytogenetic study revealed a karyotype profile, showing three 2q markers and only one chromosome type No. 13. The observations are different from the karyotype profile of embryonal rhabdomyosarcoma. However, further studies are necessary to elucidate this question.
A clinico-pathologic study of a 69-year-old woman with a malignant giant cell tumor of the uterus compatible with malignant giant tumor of soft tissues is presented. The diagnosis was based mainly on light- and electron-microscopic findings, including the demonstration of phagocytic activity of the neoplastic cells. The tumor metastasized to the lung and the patient died a short time after clinical onset. The classification of uterine sarcomas and the differential diagnosis are briefly discussed.
We have examined the effects of chlorine gas inhalation (110 and 140 ppm) on cardiovascular and pulmonary function in nine anaesthetised and mechanically ventilated pigs. Four additional pigs, which were similarly treated but not exposed to gas, served as controls. Severe pulmonary dysfunction developed when the animals were exposed to 100 l of 140 ppm chlorine gas for 10 min. Five of six animals died within 6 h of exposure. This dose induced a rapid drop in arterial oxygen tension (P < 0.001 compared with controls, ANOVA), a biphasic decline in lung compliance (P < 0.001) and a gradual increase in pulmonary vascular resistance (P < 0.001) that eventually caused a significant reduction in cardiac output (P < 0.05). Microscopic examination showed sloughing of the bronchial epithelium and early infiltration with leukocytes, but largely intact alveoli. The sequence of events and the microscopic appearance suggested that the initial stage of pulmonary dysfunction (the first 1 or 2 h) was the result of mismatching of ventilation and perfusion. This was followed at a later stage by interstitial oedema and migration of immunocompetent cells into the tissue. We conclude that exposure to 100 l of 140 ppm chlorine gas induces a severe stereotypic lung injury with high mortality within 6 h in this anaesthetised animal model.
The prognosis of ovarian carcinoma, even in the early stages (FIGO I-II), continues to present a challenge despite advances in the understanding of pathophysiology and treatment. In a series of 106 patients with epithelial carcinomas in FIGO stages IA-IIC, a number of prognostic factors (age, FIGO stage, histopathologic type, and tumor grade) were studied in relation to important regulators of apoptosis (p53, bcl-2, and bax). Immunohistochemical techniques were used. All the patients received adjuvant radiotherapy after the primary surgery. Univariate analysis showed that expression of p53 was highly significantly associated with tumor grade (P = 0.007) and survival status (P = 0.046). Positive bcl-2 staining was associated with serous (P = 0.0002) and endometrioid tumor subtypes, but not with the survival rate. A positive bax status was associated with younger age (P = 0.012) and a more favorable probability of survival. A significant association between the bcl-2 and bax status of the tumors and histopathologic subtypes and grades was noted. The most favorable subgroup of tumors was that with a combination of positive bax staining and negative p53 staining. In a multivariate Cox analysis, tumor grade (P = 0.0006) and bax status (P = 0.020) were independent and significant prognostic factors.