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Biomedical subjects

J A Copplestone

Publications and source records attributed to J A Copplestone.

At least 19 recordsLinked to original sources

Acquired factor XI inhibitor in chronic lymphocytic leukaemia.

A 71 year old man with chronic lymphocytic leukaemia (CLL) experienced excessive bleeding following transurethral resection of the prostate. Investigations showed a prolonged kaolin cephalin clotting time (KCCT) with low concentrations of factor XI. The prolonged KCCT was largely corrected by mixing with normal plasma but this correction was lost on incubation, confirming the presence of an inhibitor. He was treated with pulsed methylprednisolone and chlorambucil which resulted in the resolution of the bleeding problem and the loss of detectable circulating inhibitor.

Aged

Asymptomatic thrombocytopenia developing during pregnancy (gestational thrombocytopenia)--a clinical study.

During pregnancy some women develop unexplained thrombocytopenia (gestational thrombocytopenia). Previous studies have detected abnormal platelet antibodies, suggesting an autoimmune aetiology. To determine whether gestational thrombocytopenia is associated with increased maternal bleeding or adversely affects the fetus, 31 pregnant women with asymptomatic thrombocytopenia were compared with 12 women with thrombocytopenia associated with pre-eclampsia and 34 normal pregnant controls. There was no increase in maternal bleeding in those with asymptomatic thrombocytopenia compared with the normal controls, but pre-eclamptic women experienced more bleeding (mean difference 181 ml, 95 per cent confidence limits 50-312 ml, p < 0.01). There was no difference in the mean weights of the babies or placenta, nor in the APGAR scores between infants born to controls and those with asymptomatic thrombocytopenia. Cord blood platelet levels were measured in 26 women with asymptomatic thrombocytopenia and were normal in 25 and mildly reduced in one. Thus measures used for the treatment and delivery of pregnancies complicated by autoimmune thrombocytopenia are not indicated in gestational thrombocytopenia. Pregnant women should not be considered thrombocytopenic unless the platelet count has fallen below 120 x 10(9)/l.

Adult

Haematological toxicity compromises MOPP/ABVD chemotherapy in Hodgkin's disease.

A total of 23 patients with previously untreated Hodgkin's disease received MOPP/ABVD hybrid chemotherapy and response to treatment and toxicity were assessed. Of these 14 (61% (95% confidence limits 38.5%-80%] achieved complete remission with chemotherapy alone, six (26% (10.2%-48.4%)) achieved partial remission and there were three treatment failures (13%). Toxicity was mainly haematological resulting in treatment delays and dose reductions. Those in partial remission after chemotherapy achieved complete remission with additional radiotherapy. So far five of the 20 who remitted (25%) have relapsed. We conclude that the haematological toxicity from this regimen compromises dose intensity. The results from using this hybrid regimen are not superior to those using MOPP or ABVD alone in our experience.

Adolescent

Comparison of the multiple dose pharmacokinetics of two formulations of itraconazole during remission induction for acute myeloblastic leukaemia.

This double-blind cross-over study compares the serum pharmacokinetics of a polyethylene glycol formulation of itraconazole (ITRA-PEG; 4 x 50 mg once daily) with a new pelleted formulation (ITRA-PEL; 2 x 100 mg once daily) during remission induction for acute myeloblastic leukaemia. Each formulation was administered for 28 days with a seven day washout period. Five of eight patients (median age 52 years, range 18-65) entering completed both arms of the study. At day 7 for ITRA-PEL (n = 8) the mean +/- one standard deviation and median maximum concentrations (Cmax) were 307 +/- 155 ng/mL and 275 ng/mL respectively and for ITRA-PEG (n = 6) 272 +/- 212 ng/mL and 193 ng/mL. At day 14 for ITRA-PEL (n = 8) the mean +/- S.D. and median Cmax were 412 +/- 227 ng/mL and 375 ng/mL respectively and for ITRA-PEG (n = 5), 315 +/- 177 ng/mL and 327 ng/mL. The Cmax mean and median values were therefore greater with ITRA-PEL but the differences between the two formulations were not statistically significant. Adequate therapeutic levels of itraconazole can be achieved in this clinical setting. However, the wide variation within and between patients suggests that an ITRA-PEL dosage of 400 mg/day may ensure earlier and more consistent therapeutic levels. Measurement of serum levels may be indicated in suspected failure of prophylaxis or treatment.

Adolescent

Acute myeloblastic leukaemia in the elderly.

Acute myeloblastic leukaemia (AML) is a disease of the elderly with a median age at presentation in the seventh decade and a peak incidence in the U.K. of greater than 20 patients per 100,000 population per yr between the ages of 80 and 84. Most major AML trials are carried out on a younger population of patients with low recruitment of the elderly. The results in older patients are much worse than younger patients and often no better than the natural history of the disease. These poor results may be partly due to poor tolerance of treatment in the elderly, but are also due to intrinsic differences between AML in the elderly and AML in younger patients. These problems all justify randomised, prospective trials designed specifically for elderly patients to test prognostic scoring and various levels of intensity of therapy.

Aged

An 8;14 translocation in a case of plasma cell leukemia.

We report a patient with plasma cell leukemia. Chromosomal analysis of bone marrow showed hypodiploidy with a modal number of 32, and a t(8;14). This is only the second reported case of t(8;14) in plasma cell leukemia.

Chromosomes, Human, Pair 14

Bleeding and coagulation disorders in the elderly.

Ageing does not bring with it any major changes in the coagulation or fibrinolytic proteins or platelets. It does bring a greater burden of disease, with less reserves, and so when haemorrhage occurs in the elderly it has more serious consequences. The cause of a bleeding diathesis can usually be determined after a careful history, and examination of the patient followed by simple tests--the platelet count, blood film, bleeding time, prothrombin time, partial thromboplastin time, thrombin time, fibrin degradation products and the euglobulin clot lysis time. Other confirmatory tests, assays and inhibitor titres, will seal the diagnosis. Treatment is mainly directed at removing the underlying cause, if possible, and remedying the defect, with platelet transfusion, fresh frozen plasma or factor concentrates. These treatments will not be effective where there is an inhibitor or antibody present; steroids, splenectomy (for ITP), plasma exchange or immunosuppression are needed. Two major advances have occurred in the early 1980s. One has been the introduction of high-dose intravenous immunoglobulin in the management of ITP, although worries remain about thrombotic events in elderly patients. The other is the spreading use of DDAVP, originally introduced for von Willebrand's disease and mild haemophilia, and now finding a role in uraemia and with cardiopulmonary bypass. Drugs are a significant and potentially preventable cause of bleeding in the elderly. The most frequent problems arise with anticoagulants. The risk of interactions increase with the number of other medications which are prescribed.

Aged

Immunological abnormalities in myelodysplastic syndromes. I. Serum immunoglobulins and autoantibodies.

The immunoglobulin levels and autoantibody profiles of 104 patients with primary myelodysplastic syndromes (MDS), classified according to the FAB criteria, were analysed. Eight patients, four with coexistent non-Hodgkin's lymphomas, three with chronic lymphocytic leukaemia and one with a lymphoplasmacytoma, were excluded from the final analysis of immunoglobulin levels. Serum protein electrophoresis and immunoelectrophoresis revealed the presence of monoclonal gammopathy in 12 patients (12.5%). Of the remaining 84 patients, a polyclonal rise in serum immunoglobulins was present in 27 (32%) while a further 16 (19%) had low immunoglobulin levels. The direct antiglobulin test was positive in eight out of 98 patients tested (8.1%), and organ and non-organ specific autoantibodies were present in 15 out of 67 patients tested (22.3%). Two patients had associated pernicious anaemia (PA), two hypothyroidism, and one PA with hypothyroidism. Three patients had sero-negative rheumatoid arthritis. These results demonstrate that there is a high incidence of immunological abnormalities in MDS.

Aged

Immunological abnormalities in myelodysplastic syndromes. II. Coexistent lymphoid or plasma cell neoplasms: a report of 20 cases unrelated to chemotherapy.

We report a series of 20 patients with the myelodysplastic syndrome (MDS) each with a coexistent lymphoid or plasmacytic neoplasm. In none of the patients did chemotherapy play a part in the pathogenesis. The possible reasons for the coincidence of these conditions are discussed. The frequency and variety of associated neoplasms reinforces the idea that in MDS there are genetically unstable progenitor cells liable to clonal differentiation along a variety of pathways given appropriate stimuli.

Aged

Monocytic skin infiltration in chronic myelomonocytic leukaemia.

Although leukaemic infiltration of the skin commonly occurs in acute monoblastic leukaemia, the association with chronic myelomonocytic leukaemia (CMML) has only been described recently. We confirm the association and report histologically proven monocytic infiltration of the skin in four patients with CMML. This did not herald a more aggressive phase of the disease as previously suggested. Treatment of the rash with low dose cytarabine or etoposide was effective but razoxane produced no benefit. Superficial radiotherapy was useful to control pruritus in one patient.

Aged