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Biomedical subjects

T Hamblin

Publications and source records attributed to T Hamblin.

At least 37 records · Page 2Linked to original sources
PubMed1992

Clinical features of MDS.

MDS is primarily a disease of the elderly. Cases who give a history of exposure to X-rays, cytotoxic drugs or leukaemogenic chemicals may be younger. Many cases of MDS present because of an incidental blood count. The most prominent clinical features are those of anaemia, neutropenia, thrombocytopenia. Because haemopoietic tissue is also dysfunctional the pathological effect is often greater than the figures would suggest, even leading to infection of bleeding with normal neutrophil or platelet counts. Occult abscesses are a particular feature. Despite documented abnormalities of the lymphoid system, neither infections characteristic of T-cell immunodeficiency nor autoimmunity is a problem. The proliferation of monocytes in CMML leads to organomegaly, leukaemia cutis, serous effusions and vasculitic lesions caused by the mishandling of circulating immune complexes. Cancer is no commoner than in age-matched controls, but coincident lymphoid tumours do occur. Many patients require long-term blood transfusion and will run into problems of iron overload unless precautions are taken.

Anemia↗
PubMed1992

The treatment of acute myeloid leukaemia preceded by the myelodysplastic syndrome.

Most cases of acute myeloid leukaemia in the elderly and about 15% of the cases in younger patients follow a myelodysplastic disease. This disease may differ biologically from de novo AML making cure more difficult. Understanding post-MDS AML is difficult because of its preponderance in the elderly and the many complicating factors of treating old people. However, it is likely that post-MDS AML is more resistant to chemotherapy than de novo AML, that periods of pancytopenia last longer following chemotherapy and remissions are shorter. In younger patients high complete remission rates are achievable with aggressive chemotherapy and good supportive care. Such patients are best served by subsequent allogeneic bone marrow transplantation if possible, and if not then bone marrow autograft or a maintained remission should be considered. For older patients cure is unlikely and the choice between low-dose cytarabine and aggressive chemotherapy must be made if treatment is to be contemplated at all. The former leads to less hospitalisation and fewer side effects, but the latter gives a greater chance of a complete remission. This will not be long lasting.

Acute Disease↗
PubMed1992

Initial experience in treating human lymphoma with a combination of bispecific antibody and saporin.

Results are presented showing the use of bispecific F(ab')2 antibodies (bsAbs) in the delivery of saporin for the treatment of 2 human B-cell malignancies. BsAbs delivering saporin through CD22, but not through CD19, were effective at inhibiting the uptake of [3H]leucine by Daudi and Raji cells. Furthermore, a combination of 2 anti-CD22 bsAbs, selected to bind simultaneously to saporin, bound saporin 20 times more avidly and inhibited protein synthesis far more efficiently than any single bsAb. In the first patient, with end-stage chronic lymphocytic leukaemia (CLL), treatment with 10 mg of saporin complexed to 100 mg of anti-CD19 bsAb over 43 days showed no therapeutic effect. In contrast, the second patient, with end-stage non-Hodgkin's lymphoma (NHL), given 5 mg of saporin complexed with a pair (50 mg) of anti-CD22 bsAbs over 15 days showed a marked clinical response, including complete clearance of tumour from the blood, clearance of ascites and shrinkage of tumour masses. Neither patient experienced any toxic side-effects, either during or after treatment. However, the second patient developed a strong anti-mouse Fab (HAMA) response 28 days after the treatment started. No anti-saporin response could be detected.

Adult↗
PubMed1992

Immunologic abnormalities in myelodysplastic syndromes.

In myelodysplastic syndromes, several autoimmune phenomena are more common than expected. Lymphocyte subsets are sometimes abnormal in number and function. Associated lymphoid malignancies and lymphoblastic evolution have occasionally been reported. Molecular studies suggest that the lymphoid system may be involved in the dysplastic process.

Autoimmune Diseases↗
PubMed1988

Activation of Ha-ras in human chronic granulocytic and chronic myelomonocytic leukaemia.

DNAs from chronic granulocytic leukaemia (CGL) and chronic myelomonocytic leukaemia (CMML) were assayed for transforming genes by transfection into NIH 3T3 cells. Foci DNA was tagged with a geneticin-resistance cosmid, then followed through a drug selection and tumorigenicity assay. Activated Ha-ras genes, with point mutations at codon 12 (glycine to valine) were subsequently detected. The mutation was detected in the original samples by either MspI/HpaII digestion or polymerase chain reaction (PCR). Although mutations in the ras gene family may occur frequently in leukaemias, these are the first examples of Ha-ras mutations in CGL (blast crisis) and CMML.

Animals↗
PubMed1988

Heterogeneity in neoplastic cell populations in chronic lymphocytic leukaemia defined by immunoglobulin expression and secretion in vitro.

Neoplastic cell populations were prepared from peripheral blood and bone marrow samples of four patients with typical B-cell chronic lymphocytic leukaemia (CLL). Lymph node biopsies were also performed and used as a source of neoplastic cells for two of these patients. Using sensitive ELISA systems to determine unstimulated immunoglobulin (Ig) secretion of these tissue-derived populations in culture, a discrepancy between the nature of the secreted Ig products was found. Peripheral blood and lymph node-derived populations from each patient secreted both whole molecules of Ig and a large molar excess of Ig light chains (free LC), whereas all bone marrow-derived population secreted only free LC. The isotypic expression of intrinsic, cell-surface immunoglobulin (sIg), determined using immunofluorescence microscopy and flow cytometry, was, however, indistinguishable between different tissue-derived populations for any one patient. The absolute amounts of LC secretion were not markedly different between the tissue-derived populations (blood = 5.3 +/- 1.7; marrow = 3.5 +/- 1.3; lymph node = 11.5 ng per 2 X 10(7) cells per h) and thus failure of detection could not account for this discrepancy. Furthermore, the presence of sIgM and sIgD on each tissue-derived population indicated that all were at least capable of synthesizing whole Ig for membrane insertion. These results suggest that the assessment of a B-cell function, Ig secretion, is a valuable technique for determining small differences within neoplastic populations from individual patients. These functional differences may be related to the maturity of different cells within clonal populations.

B-Lymphocytes↗
PubMed1978

Polyarteritis presenting with thrombocytosis and palliated by plasma exchange.

A 66-year-old patient with polyarteritis nodosa presented with thrombocytosis and was found to have circulating immune complexes. Treatment by plasma exchange produced symptomatic improvement and lowered both the platelet count and the level of immune complexes. While plasma exchange is a useful technique in investigating the pathogenesis of the disease, predisolone is a more convenient way of treating it.

Aged↗
PubMed1977

Chronic lymphatic leukaemia: correlation of immunofluorescent characteristics and clinical features.

60 patients with chronic lymphatic leukaemia (CLL) were classified according to the immunofluorescent characteristics of their lymphocytes. A group expressing surface membrane (Sm) IgM had a significantly less aggressive disease than those expressing a mixture of SmIgM and SmIgD or those without surface immunoglobulin. The patients were older than in most comparable series and had a 2:I preponderance of women. It is suggested that especially among old ladies there is a benign variety of CLL which expresses SmIgMK, and that determination of the SmIg class in CLL has prognostic value.

Aged↗