Treatment and prevention of spinal metastases of prostatic carcinoma with neurologic complications.
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Biomedical subjects
Publications and source records attributed to K Malkani.
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Giant osteoclasts and other cells were isolated from Pagetic bone tissue using 0.5 mM ethylene diamine tetraacetic acid on bone samples from 8 patients with Paget's disease. The cell suspension contained osteoclasts and osteoblasts as well as some mononuclear cells such as monocytes. The number of nuclei in isolated osteoclasts (33.85 +/- 20.92 nuclei/osteoclast) correlates fairly well (p less than 0.02) with the number of nuclei counted on histologic sections (15.88 +/- 11.80 nuclei/osteoclast) for samples from each patient. Enzyme histochemistry demonstrated acid phosphatase activity in isolated osteoclasts and in mononucleated cells, such as monocytes. Alkaline phosphatase was detected only in osteoblasts while succinate dehydrogenase was observed in osteoclasts, osteoblasts and monocytes. Esterases, such as nonspecific aliesterase and specific naphthol AS-D acetate esterase, were identified in osteoclasts and in macrophages. Inhibition of specific naphthol AS-D acetate esterase in osteoclasts by addition of sodium fluoride suggests that the enzyme could be of monocytic origin.
The efficiency of flow cytometric (FCM) DNA analysis in the diagnosis of lung carcinoma was compared with that of conventional cytologic techniques on bronchial brushing and fine needle aspiration samples from 461 patients. The main advantage of FCM was the rapid delivery of results. Unfortunately, this was offset by a poor sensitivity in the detection of bronchial tumors. Nevertheless, DNA analysis may still prove useful in determining the prognosis and in evaluating the effects of chemotherapy on known tumor stem lines.
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The ultrastructural discovery of microcylindric inclusions in the nuclei and cytoplasm of osteoclasts in tissue affected by Paget's disease of bone has created a new approach. The morphologic similarity of the inclusions to viral structures has stimulated further studies involving immunocytologic techniques and in situ hybridization. Polyclonal antibodies reveal the presence of paramyxovirus antigens and measles virus and respiratory syncytial virus in pagetic osteoclasts. Monoclonal and monospecific polyclonal antibodies demonstrate paramyxovirus antigens of measles virus, simian virus (SV5), and human parainfluenza virus (PF3). In situ hybridization carried out with a 3H-labeled DNA probe, specific for the measles nucleocapsid protein, detects measles virus nucleotide sequences in the nuclei and cytoplasm of pagetic osteoclasts, confirming ultrastructural and immunocytologic findings. Surprisingly, the tritiated probe also hybridizes with a large proportion of mononucleated cells: osteoblasts, osteocytes, fibroblasts, and lymphocytes. This suggests a very wide host cell range for measles virus genomic information which, however, would appear to undergo translation only in osteoclasts. The cause-effect relation between the viral information contained by diseased bone cells and Paget's disease of bone remains to be established.
Hundred forty-four correlations are reported between radiological simulation and CT-scan in cases of prostate adenocarcinoma without metastases treated from 1980 to 1986 exclusively by transcutaneous radiotherapy using the box technique with 25 MV photons. Forty-eight percent of the cases were intracapsular forms. On the basis of correlation criteria defined, the prostatic boost volume was shifted in the sagittal plan in 18% of the cases. Suspect seminal vesicles were found in 60% of the cases. Our treatment plans were considered "correct" in 65% of the cases, "acceptable" in 26% of the cases and "unsatisfactory" in 29% of the cases. The corrections applied to the treatment plan do not vary according to grade but according to stage and concern mainly the posterior limit of the boost volume and to a lesser extent the superior and anterior limits. The boost volume should be determined specifically for each case. CT-scans thus seem indispensable in establishing treatment plans in prostate cancer.
Diphosphonates have been used in the management of Paget's disease of bone because of their experimentally demonstrated antiosteoclastic activity. Light microscopic examination of bone tissue from 13 patients with Paget's bone disease who were receiving (EHDP) treatment showed considerably reduced osteoclastic resorption accompanied by gradual replacement of irregular woven bone by lamellar tissue. Electron microscopic examination confirmed that pagetoid osteoclasts are morphologically abnormal cells and degenerate after EHDP treatment. EHDP does not affect the measles nucleocapsid-like inclusions in the osteoclast nuclei. Immunocytologic analysis showed that during EHDP treatment viral antigens of the measles type persist in the cytoplasm and nuclei of osteoclasts even when these cells are greatly altered. These findings support the hypothesis of a viral etiology in Paget's disease of bone.
The etiology of Paget's disease of bone has long remained obscure. The recent discovery in electron microscopy of specific inclusions in the cytoplasm and nuclei of osteoclasts in tissue from patients with Paget's bone disease has been the starting point of investigations into a possible viral origin. The inclusions, made up of microcylinders, described by several authors as being found only in osteoclasts in Paget's bone disease, present a close morphological analogy with nucleocapsids of paramyxovirus of the measles group. Immunocytological methods have provided a complementary approach to the problem. It has been demonstrated that the osteoclasts in Paget's bone disease contain antigenic material which reacts positively with sera containing measles antibodies. Both the morphological and the immunocytological evidence is strongly in favour of a viral etiology for Paget's bone disease.
Ultrastructural observation in Paget's disease of bone clarify aspects of bone cells in bone tissue and demonstrate the presence of specific intranuclear inclusions composed of microcylinders in the osteoclasts. The morphologic analysis of these structures suggests an analogy with virus material of the measles group. Results obtained using indirect immunofluorescence and immunoperoxidase techniques lend further support to the hypothesis of a viral etiology in Paget's disease of bone.
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Comparison of biopsies from patients with Paget's bone disease before and during long-term treatment with calcitonin reveals that the ration of bone-adherent osteoclasts to free osteoclasts is not modified by the hormone. Nor does treatment alter the average number of nuclei in osteoclasts. Under electron microscopy, all the cytological anomalies of osteoclasts in Paget's bone disease and, in particular, the characteristic nuclear inclusions, persist through treatment. Thus, although such osteoclasts do react to calcitonin as demonstrated by several authors, the specific morphological anomalies remain unaffected by the treatment. It is likely that the osteoclast in Paget's bone disease is an abnormal cell with peculiarities which may be related to the yet unknown etiology of the disease.
The ultrastructural study of osteoclasts in biopsies from 12 patients with Paget's disease reveals several cytological anomalies. In Particular, nuclear inclusions, consisting essentially of striated filaments about 150 A in diameter, often organized in bundles and sometimes in paracrystalline arrays, appear to be specific to the disease. Morphologically, the inclusions are remarkably similar to those observed in various cases of viral attack, and the hypothesis of the action of a possible external agent in Paget's disease cannot be ruled out.
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An electron microscope study of 35 bone biopsies from patients with Paget's disease confirmed the constnat presence of intra-nuclear and intracytoplasmic inclusions, which seemed to be the most specific anomalies of the osteoclasts. The presence of these inclusions leads to their comparison with other inclusions described in certain affections for which the viral etiology is at present under discussion.
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