Myelodysplastic syndrome with t(8; 12) (q22; q13) translocation.
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Biomedical subjects
Publications and source records attributed to C G Geary.
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AIMS: To extend the alkaline phosphatase-antialkaline phosphatase (APAAP) immunoenzyme single stain method to a more generally applicable double stain technique. This will allow two primary antibodies of the same isotype of IgG and specifically the nuclear antigen bromodeoxyuridine (BRdU) to be evaluated with a cell surface antigen identifier. METHOD: Sequential applications of the APAAP method showed two antigen sites by different dye couplings to a common alkaline phosphatase substrate, producing blue and red reaction products on the same slide. Antigens on different cell populations as well as those in different compartments of the same cell were analysed. The method allowed a surface antigen monoclonal to be revealed first, using an optimal fixative, before alcohol/gluteraldehyde fixation was used to start the second (BRdU) staining sequence. RESULTS: An analysis of double staining of T lymphocyte subsets (CD4 and CD8) showed no significant difference in the order of application of the primaries (n = 10) and no significant difference from their corresponding single stain results (n = 50), confirming the validity of the technique where antigens are exclusively distributed. Other examples, including antigens distributed in different compartments of the same cell, displayed discrete staining which implied validity. CONCLUSION: Double staining by APAAP with this technique seems to be applicable to those cases where antigens are exclusively distributed and includes cases where different compartments of the same cell are stained. It is especially useful in revealing antigens that require different fixation and preparation--that is DNA incorporated BRdU with a surface antigen. But it does seem to have a limited ability to produce a dual colour at a common site.
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Identification of a "cluster" of cases of acute myeloid leukaemia and chronic myeloproliferative disorders in Lytham St. Annes, Lancashire, prompted an analysis of the incidence of myeloid leukaemias in Lancashire (excluding Ormskirk Health District), as recorded by the Manchester Cancer Registry. Although statistically there was no significant difference in the trend of incidence between the whole former borough of Lytham St. Annes and the other districts studied, the reported incidence of these diseases in the area as a whole had almost doubled, and in two districts nearly trebled, between two consecutive 6 year periods, beginning in 1965. This represents a substantially larger increase than mortality data suggests has occurred nationally in the same period, and is unlikely to be due solely to more accurate diagnosis or reporting.
Serial trephine biopsies were performed in 45 cases of chronic granulocytic leukaemia (CGL) in order to determine the frequency and significance of secondary myelofibrosis in the evolution of the disease. Histological changes were graded 1-5b, ranging from no increase in reticulin to dense osteomyelosclerosis. Many cases showed a progressive increase from Grade 1 to Grade 3, and accelerated disease, or blast crisis, often supervened when Grade 3 changes were present. However, a significant number of cases showed Grade 4 and 5 changes, which were indistinguishable histologically from those found in agnogenic myeloid metaplasia (AMM) (idiopathic myelofibrosis), at the time of diagnosis. These patients did not always show a rapidly fatal course and may be considered as an example of 'transitional myeloproliferative disorder', with features intermediate between CGL and AMM.
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One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.
An example is described of the syndrome of refractory anaemia in association with the plasma cell variant of giant lymph node hyperplasia of the mediastinum; the anaemia responded to removal of the lymphoid mass. The entity of giant lymph node hyperplasia is discussed and its relationship to the haematological syndrome is considered.
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As an adjunct to conventional haematological and cytogenetic data, 22 cases of refractory cytopenia, and five with chronic myelomonocytic leukaemia, (CMML) were studied by bone marrow culture. Cultures from II such patients without an excess of marrow myeloblasts usually showed low, or undetectable, numbers of cells capable of giving rise to colonies of granulocytes and/or macrophages (CFUc) but near-normal numbers of cluster-forming cells and cells capable of forming erythroid colonies (CFUE). Those with similar blood pictures, but in whom the marrow contained a slight excess of myeloblasts (II cases), showed a more profound defect in growth patterns: low or undetectable numbers of CFUC, clusters and CFUE, results similar to those found in acute myeloblastic leukaemia, into which three of this group evolved. The patients with CMML gave comparatively normal CFUC, cluster and CFUE growth patterns.
Serum immunoglobulin levels were estimated in 19 patients with aplastic anaemia. Although the mean levels for IgG, IgA and IgM for the group as a whole were within the normal range, 8 individual cases showed low levels of one or more immunoglobulin class, suggesting a disturbance in immunoglobulin production. One of these patients had a thymoma, and another positive tests for anti-nuclear factor, but there was no evidence of auto-immune disease in the others. It is suggested that 'aplastic anaemia' may sometimes be a disease due to injury of a stem cell subserving both haemopoietic and immunological function.
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