Desferrioxamine therapy induces clearance of iron deposits after bone marrow transplantation for thalassemia: case report.
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Biomedical subjects
Publications and source records attributed to P Muretto.
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A case of bronchogenic carcinoma involving the base of the right inferior lobe and causing Budd-Chiari syndrome in a 66-year-old woman is reported. It appears to be the second case in the literature with a similar clinical manifestation.
Published work suggests that cardiac tamponade occurs only occasionally after bone-marrow transplantation (BMT) but the worrying number of cases encountered in the transplant programme in Pesaro, Italy, has led to an analysis of this complication. Cardiac tamponade occurred in 8 (2%) of 400 consecutive thalassaemic patients during conditioning for or within a month of BMT. 6 cases were fatal; these represented 9% of all causes of death and 29% of those occurring between start of conditioning regimen and 30 days post transplant. The syndrome was characterised by sudden onset of circulatory shock and cardiac arrest. The only effective treatment was immediate fluid removal. The absence of myocardial lesions and the complete resolution of the syndrome after pericardiocentesis suggest that the pericardial membranes played the main part in the pathogenesis of the syndrome. Since irradiation was not part of the conditioning regimen and since 3 of the affected patients had bacteraemia, the triggering factor for the syndrome could have been the drugs used for conditioning, acting alone or together with bacteraemia and trauma. The frequency with which we encountered the syndrome, and the similarity among our patients in clinical picture, and in characteristics of the effusion, indicate that cardiac tamponade occurring in thalassaemic patients after start of chemotherapy as conditioning for BMT is a specific syndrome requiring rapid treatment.
Total body irradiation (TBI) is used in conditioning regimens prior to bone marrow transplantation (BMT) in haematologic diseases to achieve the objective of eradicating bone marrow stem cells. The dose deliverable to the whole body is limited by the radiation tolerance of the normal tissues, especially of the lung, which is the major dose limiting organ because of the high incidence of interstitial pneumonia. The dose rate is important to successfully affect the therapeutic ratio of TBI and BMT; two different dose-rate schedules have been compared to define radiation damages in all tissues. Twenty mini-pigs were lethally irradiated, TBI was performed with 750 cGy total dose, but with two different midplane dose rates: a low dose rate (LDR) of 5 cGy/min and a quite high dose rate (HDR) of 25 cGy/min. In mini-pigs lethally irradiated with HDR, microscopic examination showed severe hemorrhagic changes in bone marrow, lymphonodes, lung parenchyma and other tissues, more prominent than in LDR mini-pigs. Hystologic pictures showed moderate changes in kidney and liver parenchyma, in thyroid and brain tissue both in HDR and in LDR group. Tissue radiation damages are related not only to TBI total dose, but to the dose-rate; the selection of a low dose-rate is useful to reduce radiation cell killing by accumulation of lethal injury to normal tissues, especially to the lung.
We reviewed the results of transplantation of allogeneic marrow from HLA-identical donors in patients with beta-thalassemia who were less than 16 years old. Among the 222 consecutive patients who had received transplants since 1983, survival and event-free-survival curves leveled off about one year after transplantation, at 82 and 75 percent, respectively. Pretransplantation clinical characteristics were examined for their impact on survival, event-free survival, and the recurrence of thalassemia in the 116 consecutive patients who were treated with our current regimen, in use since June 1985. In a multivariate analysis, portal fibrosis and either the presence of hepatomegaly or a history of inadequate chelation therapy were significantly associated with reduced probabilities of survival and event-free survival. The patients were divided into three classes on the basis of the presence of hepatomegaly or portal fibrosis (class 1 had neither factor, class 2 had one, and class 3 had both). For class 1 patients the three-year probabilities of survival, event-free survival, and recurrence were 94, 94, and 0 percent, respectively. For class 2 patients the probabilities were 80, 77, and 9 percent, and for class 3 patients 61, 53, and 16 percent. We conclude that for patients under 16 years of age, transplantation of bone marrow from an HLA-identical donor offers a high probability of complication-free survival, particularly if they do not have hepatomegaly or portal fibrosis.
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The Authors report a case of regressing atypical histiocytosis (or lymphoma Ki-1 of the skin) a primary cutaneous neoplasm composed by atypical cells resembling histiocytes and proliferating on a inflammatory background. The course is more frequently indolent with healing, although cases with evolution to a systemic lymphoma are referred. The case reported concerns a 52 years old man with multiple lesions in several sites of the body. Ours immuno-histochemical investigations have shown positivity for Ber H2 (equivalent to Ki-1) and for T line monoclonal antibodies in the proliferating cells. Our results agree with the recent reports of literature and therefore that lesion, at first believed as composed by histiocytes, is more probably a neoplasia of the T cells lineage.
A case of Paget's disease and gynecomastia in a 70-year-old man is reported. Paget's disease was connected to an intraductal carcinoma, and the immunohistochemical study revealed similar positivity for cytokeratin A, carcinoembryonic antigen and epithelial membrane antigen in Paget cells and intraductal neoplastic cells whereas Paget cells resulted negative for cytokeratin B and C. The study using monoclonal anti-cytokeratin A (35 beta H11), B (34 beta E12) and C (34 beta B4) could represent a good tool, supporting the theory of a ductal origin of Paget cells. A review of the literature has shown the rarity of Paget's disease in the male breast and revealed only two previous reports with an associated gynecomastia, in 2 patients with Klinefelter's syndrome and infiltrating breast carcinoma.
There are many case reports of secondary neoplasms occurring after treatment with alkylating agents. A case of malignant melanoma of the glans penis in a chronic myeloid leukemia (CML) Ph'-positive patient after 13 years on busulfan treatment is described. Since neither impairment of immune status nor increased incidence of secondary neoplasm have hitherto been reported in CML, the suggestion that busulfan has a carcinogenetic effect is discussed.
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An "angioblastic" adamantinoma of the tibia is described in a 78-year-old man. The diagnosis was defined by immunohistochemical methods, which showed a positivity for keratin in the cells lining spaces with a vascular appearance.
A primary inflammatory malignant fibrous histiocytoma of the kidney is reported. The differential diagnosis from other sarcomas and pseudosarcomatous lesions is discussed on the grounds of the histologic, immunohistochemical and ultrastructural results. The neoplasm was made up of histiocytes, fibroblasts, myofibroblasts, foam cells and undifferentiated mesenchymal cells with admixed granulocytes, lymphocytes and plasma cells. The immunohistochemical study showed a positivity for alpha-1-antichymotrypsin and a weak positivity for alpha-1-antitrypsin in mononuclear and pleomorphic multinucleated tumor cells. PAS-positive, diastase-resistant intracytoplasmic hyaline globules in necrotic cells, examined by electron microscopy, most likely represent lysosomal structures, in accordance with the theories of De Duve, Vattiaux and Von Ardenne.
After the characterisation of the hematological and immunological status of the mini-pig fetus at different gestational ages of development was performed, two different groups of animals receiving 800 rads of TBI given by a radioactive cobalt source at a dose/rate of 5/6 rad/min or 750 rads of TBI given by a Linear Accelerator at a dose/rate of 25/26 rad/min, both in a single dose exposure, were transplanted with a pool of allogeneic fetal liver cells whose age ranged between 55 and 75 days of gestation. In the first group 1 animal out of 6 is alive and well 30 months post-transplant. In the second group one of the nine transplanted animals survived 78 days. Engraftment was proved by the presence of the donor chromosome in the proliferating bone marrow cells in one animal.
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