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Biomedical subjects

J A Copplestone

Publications and source records attributed to J A Copplestone.

At least 37 records · Page 2Linked to original sources
PubMed1994

Avascular necrosis of bone following intensified steroid therapy for acute lymphoblastic leukaemia and high-grade malignant lymphoma.

Five out of nine adults (55%) with lymphoblastic disease developed severe avascular necrosis of bone (AVN) when treated with a Berlin-Frankfurt-Munster (BFM) ALL protocol similar to the current joint MRC-ECOG ALL trial (UKALL XII). The principal purpose of these intensified regimens is to improve long-term disease-free survival without necessarily increasing toxicity and secondary morbidity. The presentation of all five was non-specific bone pain occurring after the re-intensification block of chemotherapy containing high doses of dexamethasone. Three types of diagnostic imaging were performed and magnetic resonance imaging (MRI) proved superior in demonstrating AVN and showed it at an earlier stage than plain radiographs or isotopic scans. We believe that the dose of corticosteroids was the major factor in the development of AVN. The five men in our series all remain in first remission with a median disease-free survival of 3.5 years (range 2-8 years) but with varying degrees of disability due to AVN. Clinicians involved in UKALL XII and similar trials should be aware of this debilitating and potentially crippling complication when using high-dose steroid-containing regimens, perform MRI scan early and modify treatment if necessary.

Adolescent↗
PubMed1994

Stability studies on admixtures of 5-fluorouracil with carboplatin and 5-fluorouracil with heparin for administration in continuous infusion regimens.

The therapeutic index of several anticancer agents may be improved by replacing rapid infusion/bolus injection schedules with prolonged continuous infusion regimens. Admixtures of 5-fluorouracil (5FU) with carboplatin and 5FU with heparin were subjected to stability studies to establish the feasibility of administering these infusions on an in-patient and out-patient basis, respectively. In the first study the stability of carboplatin was determined in an admixture of carboplatin and 5FU for neoadjuvant treatment of in-patients with oesophageal carcinoma by 5-day infusion. A previous study had reported significant carboplatin degradation in 5FU/carboplatin admixtures. Our results were consistent with this study and demonstrated that under ward conditions (25 degrees C) carboplatin also degraded (16% in 24 h) in dilute admixtures with 5FU. However, the addition of a citric acid buffer, which reduced infusion pH from 8.65 to 6.5, increased the stability of carboplatin (4.8% degradation in 24 h), without compromising 5FU solubility or stability. In a second study, the stability of an infusion containing 5FU and heparin was determined. Prolonged continuous infusion is routinely used for adjuvant treatment of colorectal carcinoma but episodes of thromboses and occlusion of the central venous catheter have been associated with this treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Carboplatin↗
PubMed1994

HLA-DR typing for kidney transplants: advantage of polymerase chain reaction with sequence specific primers in a routine hospital laboratory.

AIMS: To determine whether the polymerase chain reaction with sequence specific primers (PCR-SSP) can assign HLA-DR type more accurately than serology in a routine hospital laboratory. METHODS: The 93 patients currently awaiting kidney transplants have been DR typed by serology over the past 14 years, 82% within the past five years. They have now been retyped using the PCR-SSP method described by Bein et al. Where the two results differed, PCR-SSP was repeated, once by the same method and once using the primer set of Olerup and Zetterquist. RESULTS: There were 13 (14%) discrepancies between the results. Of these, two were PCR-SSP failures, later overcome: three were failure to detect DRB1*0103 by serology; five assignment of other alleles by PCR-SSP to serological "blanks"; and three alleles were differently assigned by serology and PCR. The serological typing of the final patient when repeated for this study was at variance with the original findings (14 years ago), but in agreement with PCR. In the remaining patients, serology had not determined the split of 36 DR3 alleles (all DR17 by PCR-SSP) or 13 DR6 alleles (12 DR13 and one DR14 by PCR-SSP). One patient in each case had their antigen splits of DR2 and DR5 assigned by PCR-SSP (DR15 and DR11, respectively) but not by serology. CONCLUSIONS: PCR-SSP provides more reliable and detailed information on HLA-DR polymorphism than serology, and does so within a routine tissue typing laboratory.

HLA-DR Antigens↗
PubMed1993

Acute non-lymphocytic leukemia with t(16;21).

A patient with ANLL FAB subtype M1 was found to possess a t(16;21)(p11;q22) and trisomy 10. The 16;21 translocation has been reported in 12 other cases of ANLL, of various subtypes, and its relationship to the disease profile is discussed.

Adult↗
PubMed1993

Inaccurate haemoglobin estimation in Waldenström's macroglobulinaemia: unusual reaction with monomeric IgM paraprotein.

Automated blood counts from a patient with Waldenström's macroglobulinaemia repeatedly failed critical limit standards set for mean cell haemoglobin concentration and mean cell haemoglobin. Haemoglobin estimation was higher than that suggested by clinical examination, symptoms, and the spun haematocrit. This was found to be due to an interaction between the Coulter lysing agent and monomeric IgM paraprotein in the patient's plasma, creating a precipitate which was optically dense at 525 nm.

Diagnostic Errors↗
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1988

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↗