Prevention and treatment of acute graft-versus-host disease.
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Biomedical subjects
Publications and source records attributed to N Ramsay.
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To date, median duration of second and subsequent remissions in childhood acute lymphocytic leukemia (ALL) has been short, with most studies reporting median remission duration less than 6 months. In May 1979, the Childrens Cancer Study Group (CCSG) undertook a pilot study to assess the efficacy of a vincristine, methotrexate, and L-asparaginase regimen (modified Capizzi) for maintenance in children with ALL in second or subsequent remission. Thirty patients were treated with this maintenance regimen. By life table analysis, predicted median duration of hematologic remission was 57 weeks. Ten patients (33%) were in continuous hematologic remission at 1 year and three (10%) continue in remission greater than 2 years from maintenance onset. Major toxicity included leukoencephalopathy in four patients, three of whom had experienced at least one central nervous system relapse prior to study entry. Allergic reactions to Escherichia coli L-asparaginase were common. Nine of 30 patients experienced at least one CNS relapse during therapy. We conclude that a modified Capizzi regimen is the most effective regimen reported to date for maintaining second and subsequent remission in childhood ALL. CCSG is currently utilizing this regimen in an ongoing open study.
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Regressing atypical histiocytosis (RAH) of skin is a cutaneous noduloulcerative proliferation of atypical neoplastic histiocytes with concomitant polymorphous inflammation, frequently pronounced epidermal hyperplasia, and an unexpectedly indolent biologic course. Spontaneous regression and recurrence without systemic spread were the course in follow-up periods of over six years. Histopathologically, characteristic-appearing atypical mononuclear and multinucleated "RAH" cells showed erythrophagocytosis as well as ultrastructural, surface marker, and enzyme cytochemical features indicating histiocytic differentiation. Cytogenetic analysis showed aneuploidy and several marker chromosomes including 14q+. Its benign biologic course clearly distinguished this entity from malignant histiocytosis, large cell lymphoma, and Hodgkin's disease. The histiocytic atypical cells further distinguished it from the T-cell lesions of the skin, such as mycosis fungoides and lymphomatoid papulosis. This entity is readily confused with malignant lymphoreticular disease, melanoma, or squamous carcinoma.
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To our knowledge, 20 cases of retinoblastoma associated with a chromosome #13 aberration have been reported. The present study utilized high-resolution prophase banding analysis of 12 additional retinoblastoma patients to determine the occurrence of chromosome aberrations and identify consistently associated clinical abnormalities. Six male and six female patients were studied representing seven cases of bilateral and five cases of unilateral retinoblastoma. One case of unilateral and two cases of bilateral retinoblastoma and detectable cytogenetic abnormalities, all involving an interstitial deletion of 13q14 on the long arm of one chromosome #13. In all five unilateral cases the tumor manifested in the left orbit, and in all seven bilateral cases the left eye was at a more malignantly advanced stage than the right eye. All three cases with a chromosome abnormality had varying degrees of developmental and/or mental retardation, along with at least one other congenital abnormality. In addition to the 12 cases of retinoblastoma, a patient with severe ophthalmologic abnormalities and mild congenital anomalies was studied by the prophase banding technique and found to be partially trisomic for the 13q14 region with gene loci for optic development and indicate that cytogenetic abnormalities may occur even more frequently in retinoblastoma than indicated by the small number of cases reported in the literature.
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A restriction map has been constructed for the DNA of coliphage T1 which locates the cleavage sites of the restriction endonucleases, BglI (6 cuts), BglII (16 cuts), EcoRI (2 cuts), HindIII (2 cuts) and PstI (2 cuts). Digestions with BglI and BglII reveal fragments which are present in sub-molar quantities. Two methods, one using the selective removal of molecular ends with exonuclease III and the other involving the comparison of digestion patterns of concatemeric and virion DNA, have shown that the submolar fragments are at or close to the ends of the molecules. Digestions with BglI show that one terminal fragment has a very precise molecular weight whereas all the others are of heterogenous molecular weight. These results are consistent with the model for DNA packaging in which maturation is initiated at a precise site on a concatemeric precursor and proceeds by the encapsidation of up to four successive 'headfuls' of 1.065 genome equivalents (MacHattie and Gill 1977).
Two patients with retinoblastoma and an interstitial deletion of the long arm of chromosome 13 were studied using G-banded metaphase and prophase chromosomes. One patient showed several congenital defects, developmental retardation, and deletion of bands q14 and q21. The second patient showed mild developmental delay, a few minor congenital defects, and a loss of approximately half of band q14. On the basis of this study and nine others from the literature, it is now possible to tentatively assign a predisposition to retinoblastoma to deletion of a specific small region of chromosome 13.
Second bone marrow transplants have been used successfully to treat marrow graft failure or relapse following the original marrow transplantation. Hospital records of 16 related two-time bone marrow donors were reviewed to determine what risks a person faces in making a second marrow donation. One donor suffered a minor complication following the first collection, but no donors suffered complications during the second donation. The volume of marrow collected for the first and second donations (1253 +/- 504 vs. 1261 +/- 471 mL) was similar. However, more marrow donors received transfusions of homologous red cells during the second collection than during the first collection (5/16 compared to 1/16; p = 0.06). To determine what factors might contribute to the high incidence of homologous red cell transfusion during second donations, the experiences of donors who received homologous blood during the second donation were compared to the experiences of donors who received only autologous blood. Persons receiving homologous blood during the second collection received more red cell units than persons receiving autologous blood (2.0 +/- 0.7 units compared to 0.9 +/- 0.5 units; p less than 0.01). Their precollection hemoglobin levels were lower (12.3 +/- 1.2 vs. 14.4 +/- 1.4 g/dL [123 +/- 12 vs. 144 +/- 14 g/L]; p less than 0.01), and the time between the first and second collections was significantly less (45 +/- 8 days vs. 342 +/- 432 days; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)