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Biomedical subjects

T J Hamblin

Publications and source records attributed to T J Hamblin.

At least 127 records · Page 7Linked to original sources

Antibodies to shared idiotypes as agents for analysis and therapy for human B cell tumors.

Monoclonal anti-idiotypic antibodies generated against idiotypic immunoglobulin (Ig) of neoplastic B lymphocytes can be selected from growing hybridoma clones by their ability to recognize idiotypic but not normal IgM. This group of antibodies can be subdivided into those that bind to the target tumor cells in the presence of normal human serum (approximately 85% of the clones) and those in which binding is inhibited by serum (approximately 15%). The former appear to be specific for private idiotypic determinants whereas the latter recognize cross-reacting idiotypic determinants. Such cross-reactivity is reflected both in recognition of a small percentage of normal Ig and also in binding to other lymphomas. The anti-idiotypes specific for private determinants can be used for therapy, with only idiotypic Ig secreted by tumor cells able to block its access to cells. The cross-reacting anti-idiotypes will face in addition the barrier of the proportion of normal Ig with which it reacts. The attraction of using a single monoclonal reagent for more than one patient has led us to develop an assay that measures the level of such blocking and to propose that those recognizing less than 30 micrograms/mL of normal Ig could be placed in a panel for possible therapy for several patients; less restriction need apply to antibodies for monitoring tumor progress. The assay is described, and examples of such antibodies raised against lymphoma cells from two patients are given together with comparisons with them of anti-idiotypes specific for private determinants.

Aged↗

Circulating stem cell autografts.

The role of autologous bone marrow transplantation in the treatment of malignant disease is currently being evaluated. The peripheral blood represents an alternative source of haemopoietic progenitors and the use of circulating rather than bone marrow stem cells permits autografting in patients with infiltrated bone marrows. It may also offer a lower risk of tumour contamination, although this is not yet proven. Several autografts using circulating stem cells (CSCs) have recently been reported. These are reviewed and current uncertainties and future prospects are discussed.

Animals↗

Hairy cell leukaemia and Legionnaires' disease.

A 69-year-old man who had recently returned from a holiday in Majorca, presented with haemoptysis and fever. Chest radiograph showed right lower lobe consolidation. A diagnosis of Legionnaires' disease was made. He was treated with erythromycin and made an uneventful recovery.

Aged↗

Myelodysplastic syndromes: a scoring system with prognostic significance.

141 patients with MDS were classified according to the FAB criteria and followed up for a period of 4-192 months. It was recognized that patients with RAEBT had a uniformly poor prognosis. However, there was a wide variation in survival among the other subgroups. A score of 1 was assigned to each of the following presenting haematological features: bone marrow blasts greater than or equal to 5%, platelets less than or equal to 100 X 10(9)/l, neutrophils less than or equal to 2.5 X 10(9)/l and Hb less than or equal to 10.0 g/dl. Therefore the score for each patient ranged between 0 and 4. There were no statistically significant differences between those patients who scored 0 or 1, or between those who scored 2 and 3. Therefore patients were put into three groups: Group A (score 0 or 1), Group B (score 2 or 3), Group C (score 4). The differences in survival between each of the three groups are highly significant (P less than 0.00001). This system further separates patients with RA, RAS, RAEB into good and bad prognostic groups. This study also confirms that deaths due to cytopenias are more common than those due to transformation to AML. The use of this scoring system in conjunction with the FAB criteria for MDS should serve as a prognostic tool on which to base treatment.

Aged↗

Successful treatment of post-transfusion purpura with high dose immunoglobulins after lack of response to plasma exchange.

A 77-year-old woman with post-transfusion purpura failed to respond to two 2.5-litre plasma exchanges with albumin as a replacement fluid. However, intravenous infusion of high-dose human immunoglobulin produced a response within 4 h. It is suggested that plasma exchange and exchange transfusion are effective in this condition mainly because they have allowed large doses of immunoglobulin to be infused in the form of plasma or whole blood.

Aged↗

Reciprocal translocation between chromosomes 8 and 9 in atypical chronic myeloid leukaemia.

A balanced translocation t(8;9) (p11;q34) was present in the peripheral blood, bone marrow, and spleen cells of a patient with Ph negative chronic myeloid leukaemia. Subsequent transformation into acute leukaemia was associated with the emergence of trisomy 8 and der(8)(8qter----cen----8p11::9q34----9qter). This is the third reported case of t(8;9) (p11;q34) and raises the question of the role of c-abl in the pathogenesis of this myeloproliferative disorder.

Adult↗

Angio-immunoblastic lymphadenopathy with hypogammaglobulinaemia complicated by miliary tuberculosis.

Angio-immunoblastic lymphadenopathy is a systemic disease of unknown aetiology. It carries a high mortality mainly from infection which results both from the intrinsic immunodeficiency and its exacerbation by treatment with steroids and or cytotoxics. We report a case of angio-immunoblastic lymphadenopathy with the unusual feature of hypogammaglobulinaemia who died of miliary tuberculosis. We suggest that all patients with angio-immunoblastic lymphadenopathy who have inactive tuberculous foci should be given antituberculous prophylaxis.

Agammaglobulinemia↗

Mechanisms of tumour cell escape encountered in treating lymphocytic leukaemia with anti-idiotypic antibody.

Four patients with chronic lymphocytic leukaemia were treated by one or more infusions of polyclonal antibody specific for the immunoglobulin idiotype expressed on their leukaemic cells. The antibody was in the form of IgG from sheep antiserum. Three of the 4 cases showed a significant fall in blood lymphocyte count. On one occasion most of the residual circulating lymphocytes were apparently dead. However on all occasions the cell counts rebounded to near pre-infusion levels within one week. Viable lymphocytes recovered from the blood after infusion always showed evidence of antigenic modulation: a diminished level of surface idiotype in a patched distribution, with an accompanying refractoriness to lysis by anti-idiotype plus complement. When cultured in vitro blood lymphocytes from three of the four patients revealed an appreciable export of idiotypic Ig. These 3 patients showed plasma levels of idiotypic Ig up to 400 micrograms ml-1, reduced by plasma exchange prior to infusion. The fourth patient had a level of less than 4 micrograms ml-1, and was the only one in whom free antibody could be found in the plasma after infusion. These cases demonstrate two major factors which thwart antibody attack on leukaemic cells--extracellular antigen and antigenic modulation--as well as problems relating to sparseness of surface antigen, recruitment of effectors, and exhaustion of effectors.

Aged↗

Serous effusions in monocytic leukaemias.

We report four patients who either presented with or developed serous effusions during the course of monocytic leukaemia. This finding has not been documented previously. All the patients had very high peripheral blood monocyte counts when effusions developed. The effusions resolved after the patients were treated with anti-leukaemic therapy. It is therefore likely that the effusions were disease related. Two of the patients have been treated with razoxane, one with etoposide and the other with cytarabine.

Aged↗

Polymyalgia rheumatica and antimitochondrial antibodies.

Antimitochondrial antibodies (AMA) were detected in the sera of 11 of 36 patients with a clinical diagnosis of polymyalgia rheumatica (PMR) in whom comprehensive autoantibody screening had been performed. AMA did not correlate with biochemical changes of hepatic dysfunction, which are common in PMR, nor with parameters of musculoskeletal inflammation. Possible explanations are discussed.

Aged↗

Relapse of lymphoma in the heart after a 10-year remission.

A 71-year-old woman presented with intractable cardiac failure 10 years after receiving treatment for lymphoma. Extensive investigations failed to demonstrate a recurrence of her disease, but resolution of her cardiac failure following a trial of chemotherapy and subsequently a cross-sectional echocardiogram suggested intracardiac relapse. This was later confirmed at autopsy. Cardiac metastases should be suspected in patients with malignant disease who develop signs or symptoms related to the heart.

Aged↗

Angiodysplasia of the colon in patients with hemostatic defects: risk of secondary hemorrhage after electrocoagulation treatment.

Angiodysplasia of the colon is a relatively common cause of blood loss in the elderly. Electrocoagulation through a colonoscope is a common mode of treatment for this condition. Three patients are presented who had associated hemostatic defects and electrocoagulation resulted in life threatening secondary hemorrhage. In two of these patients a right hemicolectomy was performed. On the basis of these findings we suggest that patients with angiodysplasia and associated hemostatic disorders have a greatly increased risk of secondary hemorrhage following electrocoagulation treatment. These patients should be followed closely for two-three weeks following this treatment.

Aged↗

Apheresis in rheumatoid arthritis.

Plasmapheresis was first introduced as a means of treating the rheumatic diseases in 1976. The rationale of its use was the removal of circulating immune complexes, thus preventing their deposition in the tissue. In rheumatoid arthritis circulating immune complexes do indeed occur and are responsible for some of the serious complications such as vasculitis. Since the T cells are implicated in tissue damage, lymphapheresis and lymphoplasmapheresis were introduced with various success rates. Controlled trials in rheumatoid arthritis have found no value for intensive plasmapheresis, limited value for lymphapheresis and possible, though suspect, value for lymphoplasmapheresis.

Arthritis, Rheumatoid↗

Immunological reason for chronic ill health after infectious mononucleosis.

In a group of patients who suffered from chronic ill health after an attack of acute infectious mononucleosis a disorder of T cell regulation was found. By means of cytochemical reactions the staining pattern associated with T suppressor cells was found in a greater percentage and that associated with T helper cells in a smaller percentage than in normal subjects. In a few patients this finding was confirmed in a functional suppressor assay. The patients were unwell for at least a year but most later made a complete recovery, which was associated with return to normal of the lymphocyte subsets.

Adolescent↗