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Biomedical subjects

M M Reid

Publications and source records attributed to M M Reid.

At least 19 recordsLinked to original sources
PubMed2001

A demographic study of the clinical significance of minimal residual disease in children with acute lymphoblastic leukemia.

BACKGROUND: Minimal residual disease (MRD) detected during remission might predict outcome in children with acute lymphoblastic leukemia. No population-based studies have been carried out. We studied all children with ALL presenting over 5 years within a defined population to determine its clinical importance. PROCEDURE: Patients were investigated for the presence of unique clonal rearrangements of IgH and T-cell receptor genes. Unique patient specific probes were used to detect, by polymerase chain reaction, the presence of clonal markers indicating MRD in mononuclear cells obtained from marrow samples at 1, 3, 5, and 24 months. The effect of MRD on event-free survival was determined. RESULTS: Seventy-seven of 120 children with ALL had informative markers and samples of remission marrow suitable for testing. Presence or absence of MRD did not significantly affect outcome. Gender (P < 0.04) and white cell count (P < 0.04) were independent prognostic factors. Analysis of only those cases with detectable MRD showed that cases with one blast per 100 mononuclear cells, or more, 28 days after starting treatment did worse than those with lower levels (hazard ratio 7.77, P < 0.02). CONCLUSIONS: Mere presence or absence of MRD is probably too crude a measure to be useful and worse than other standard prognostic indicators. A threshold of 10(-2) blasts at 28 days might be discriminatory, but should not be over-interpreted. The number of patients available for this analysis (31) was small, the threshold and sampling points were arbitrary and any effects could be treatment regimen-specific. Large prospective studies are needed.

Adolescent↗
PubMed2001

Topoisomerase II alpha and II beta expression in childhood acute lymphoblastic leukaemia: relation to prognostic factors and clinical outcome.

BACKGROUND/AIMS: Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase II alpha and II beta might be of predictive value in ALL. METHODS: Cellular expression of topoisomerases II alpha and II beta was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase II alpha and II beta expression were assessed. RESULTS: Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase II alpha and II beta expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase II alpha expression was found to be related to sex, with expression being lower in girls (p = 0.002). CONCLUSIONS: These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase II alpha and II beta expression as defined by immunohistochemistry.

Adolescent↗
PubMed2001

Erythroleukaemia in the north of England: a population based study.

AIMS: To evaluate the incidence and outcome of acute myeloid leukaemia (AML), FAB M6 (erythroleukaemia). METHODS: A demographic study in the Northern Health Region of England between 1983 and 1999. RESULTS: Thirty three cases were diagnosed and registered prospectively. The overall incidence was 0.077 cases/100,000/year. There was a pronounced rise in incidence in patients aged 56 years or more: 6.6 times higher than that in younger patients. Overall survival was poor; median survival was 11 months for those aged less than 56 years, and three months for patients aged 56 years and above (p = 0.045). Acquired karyotypic abnormalities were found in 17 of 27 patients where analysis was attempted. When classified according to the criteria of the Medical Research Council AML trials, karyotype predicted survival, with a median overall survival of 14 months for those with "standard risk" cytogenetic results and two months for "poor risk" results (p = 0.005). CONCLUSION: This study demonstrates a worse survival for patients with erythroleukaemia than that reported in some published trials of selected patients.

Adult↗
PubMed2001

How complete and accurate are cancer registrations notified by the National Health Service Central Register for England and Wales?

STUDY OBJECTIVE: To assess the completeness and accuracy of notification of cancers by the National Health Service Central Register (NHSCR) for England and Wales. DESIGN: Comparison of 720 cancer registrations ascertained from NHSCR up to May 1999 with those ascertained for the same cohort from six other sources and a pathology review of the NHSCR cancer registrations. PARTICIPANTS: People born in Cumbria, north west England, 1950-89, and diagnosed with cancer throughout the UK, 1971-1989. MAIN RESULTS: Cancer diagnoses notified by NHSCR differed substantially from those determined by this pathology review for 47 of the 688 notified cases reviewed (7%; 95% CI 5%, 9%). Over one third of these discrepancies were attributable to failures in data capture or coding by the cancer registration system and almost half to changes in diagnosis; 26 of the 47 discrepant cases were reclassified as non-malignant and 21 as malignancies but with a substantially different diagnosis. The 694 confirmed malignancies represented 94% (95%CI 92%, 95%) of the 740 cancers ascertained from all sources. CONCLUSIONS: It is estimated that the cancer registration system missed at least 10% (95%CI 6%, 15%) of all incident cases of malignant disease. Without additional ascertainment from multiple sources and diagnostic review, it would be incautious to use NHSCR cancer registrations as the sole basis of an epidemiological study.

Adolescent↗
PubMed2000

Population-based study of the pattern of molecular markers of minimal residual disease in childhood and adult acute lymphoblastic leukemia: an assessment of the practical difficulty of representative sampling for trial purposes. Northern Region Haematology Group.

BACKGROUND: The prevalence, in unselected patients with acute lymphoblastic leukaemia (ALL), of clonal rearrangements suitable for minimal residual disease (MRD) studies has not been formally investigated. PROCEDURE: This was a prospective, demographic study of the frequency of molecular markers of MRD in all patients with ALL presenting over 5 years within the Northern Health Region of England (population 3.1 million). Presentation marrow samples were examined to detect informative markers. RESULTS: One hundred twenty-four children (age <15 years) developed non-Burkitt ALL. No material was available for study in 21. Eighty-six had clonal gene rearrangements (BCR/ABL, immunoglobulin heavy chain (IGH) and/or T cell receptor (TCR) gene rearrangements). All entered remission; 84 (68% of the original cohort) survived to become eligible for MRD studies. One hundred sixteen adults developed ALL, of whom 48 were not studied due to insufficient cellular material in the bone marrow aspirate or to logistical problems in central referral of samples from other hospitals. Material from elderly adults (age >55 years) was less likely to be sent for analysis, 36% vs. 59% (P = 0.024). Thirty-eight had BCR/ABL and/or IGH/TCR gene rearrangements. Thirty-one (27% of the original cohort) entered remission and became eligible for MRD studies. Informative gene rearrangements were more common in children than adults (83% vs. 63%, P < 0.003). CONCLUSIONS: The results reveal substantial potential, unintentional, selection bias. Large-scale multicentre studies of MRD in children may well produce clinically relevant and representative data. Those who mount similar studies in adults should not assume they will be similarly representative or as successful in accrual of material.

Adolescent↗
PubMed2000

A comparison of molecular and enzyme-based assays for the detection of thiopurine methyltransferase mutations.

S-Methylation by thiopurine methyltransferase (TPMT) is an important route of metabolism for the thiopurine drugs. About one in 300 individuals are homozygous for a TPMT mutation associated with very low enzyme activity and severe myelosuppression if treated with standard doses of drug. To validate the use of molecular genetic techniques for the detection of TPMT deficiency, we have determined red blood cell TPMT activity in 240 adult blood donors and 55 normal children. Genotype was determined by restriction fragment length analysis of polymerase chain reaction products in a cohort of 79 of the blood donors and five cases of azathioprine-induced myelosupression, and this confirmed a close relationship between genotype and phenotype. In 17 of the 24 cases in which mutations were found, DNA was also available from remission bone marrow. In one of these cases, DNA from the remission marrow sample indicated the presence of a non-mutated allele that had not been seen in the blast DNA sample obtained at presentation. These results indicate that polymerase chain reaction-based assays give reliable and robust results for the detection of TPMT deficiency, but that caution should be exercised in relying exclusively on DNA obtained from lymphoblasts in childhood leukaemia.

Adolescent↗
PubMed2000

Anti-E in pregnancy.

Since the introduction of anti-Rhesus (Rh) D prophylaxis for RhD-negative women, other Rh and non-Rh red cell alloantibodies have become relatively more important and are now responsible for the greater proportion of haemolytic disease of the newborn. Anti-C and anti-E are the most commonly implicated non-D Rh antibodies in the pathogenesis of haemolytic disease of the newborn'. In 1977 Pepperell et al. reported the outcome of 44 women with anti-E. This is the only published series that investigates the implications of anti-E during pregnancy. The present report presents a retrospective study of the outcome of 122 pregnancies in which anti-E was the sole alloantibody detected.

Erythroblastosis, Fetal↗
PubMed1999

Posttransplantation B lymphoblastic leukemia with Burkitt-like features.

BACKGROUND: Posttransplantation Epstein-Barr virus-associated lymphoproliferative disease (PTLPD) occurs as a spectrum of disease ranging from benign, polyclonal, localized lymphoid hyperplasia to malignant, monoclonal, disseminated lymphoma, sometimes involving the bone marrow. To our knowledge, PTLPD has not been previously reported to present as acute lymphoblastic leukemia. METHODS: We report the case of a boy who developed PTLPD in the form of acute lymphoblastic leukemia 6 years after cardiac transplantation. He had greater than 90% bone marrow invasion by Epstein-Barr virus-positive B lymphoblasts with Burkitt-like features and a t(8;14) translocation. RESULTS: He was successfully treated with combination chemotherapy but unfortunately died, 6 months after completing treatment, from ischemic heart disease. CONCLUSIONS: B lymphoblastic leukemia may occur as a manifestation of PTLPD and should be included in the classification of these diseases. Bone marrow examination should be an essential part of the investigation of patients suspected of having PTLPD.

Administration, Oral↗
PubMed1999

Glucocorticoid resistance and the AP-1 transcription factor in leukaemia.

Glucocorticoids have been used in the treatment of acute lymphoblastic leukaemia (ALL) for many years, initially as the only agent and then as part of multiagent chemotherapy. In ALL 20% of patients are resistant to glucocorticoids at presentation but this rises to greater than 70% on relapse. It has recently been reported that the glucocorticoid receptor inhibits activity of the AP-1 transcription factor by the ligand-dependant binding of glucocorticoid receptor (GR) to the fos and jun components of AP-1. Since AP-1 is necessary for cell proliferation, the upregulation or over-expression of AP-1 may be a mechanism of resistance to glucocorticoids. The aim of the study was to investigate whether AP-1 levels correlate with in vitro glucocorticoid resistance. In vitro sensitivity to glucocorticoids was measured using the MTT assay. AP-1 levels were quantified using gel shift analysis: a consensus sequence for the AP-1 binding site was synthesised, labelled with 32P and incubated with nuclear extracts of leukaemic blasts from 14 ALL and 26 CLL patients. Leukaemic blasts were treated with prednisolone or with vehicle alone before preparation of nuclear extracts. The gels were dried and bands quantified using a phosphorimager, using an appropriate internal standard and correcting for protein loading and cytoplasmic contamination of nuclear extracts. The patient samples fell into two distinct groups with respect to their sensitivity to glucocorticoids: AP-1 levels were significantly higher (p < 0.02) in sensitive blasts than resistant ones. There was no significant change in AP-1 levels after treating blasts for 4 hours with 0.2 mM prednisolone. No change was seen in CLL samples. These data show that glucocorticoid resistance is not associated with increased AP-1. Conversely, glucocorticoid resistance in these samples was apparently associated with decreased AP-1 levels in ALL samples. Whether this has any causal relationship to glucocorticoid resistance is unknown. Clearly, further studies on the role of AP-1 and related transcription factors is essential for understanding the control of proliferation and apoptosis in ALL.

Adult↗
PubMed1999

Iron nutritional status in preterm infants fed formulas fortified with iron.

AIMS: To prospectively evaluate the iron nutritional status of preterm infants fed either a term (0.5 mg/dl iron) or preterm (0.9 mg/dl) formulas fortified with iron after hospital discharge. METHODS: Healthy low birthweight preterm infants were randomly assigned into three groups at the time of hospital discharge. Group A were fed an iron fortified preterm formula (0.9 mg/dl iron) until 6 months corrected age; group B, a fortified term formula (0.5 mg/l iron) until 6 months corrected age group C, the preterm formula between hospital discharge and term, then the term formula until 6 months corrected age. RESULTS: Seventy eight infants were followed up to 6 months corrected age. Iron intake from formula differed significantly between the groups (A, 1.17 mg/kg/day (SD 0.32) > C, 0. 86 mg/kg/day (SD 0.40) = B, 0.81 mg/kg/day (SD 0.23); p < 0.0001). Haemoglobin concentrations were similar to those of iron sufficient preterm infants of the same postnatal age, and term infants of the same postmenstrual age (after 3 months of age). There were no significant differences in haemoglobin concentration (p = 0.391), plasma ferritin (A vs B, p = 0.322), or in the incidence of iron deficiency (A vs B, p = 0.534). CONCLUSIONS: Iron fortified formulas containing between 0.5 and 0.9 mg/dl iron seem to meet the iron nutritional needs of preterm infants after hospital discharge.

Analysis of Variance↗
PubMed1999

Deterioration in performance in obtaining bone marrow trephine biopsy cores from children. European Neuroblastoma Study Group.

AIM: To complete an audit of bone marrow trephine biopsy adequacy in children MATERIAL: 605 specimens from children with neuroblastoma submitted by 25 centres were reviewed centrally. This reassessment ran between January 1995 and August 1998. RESULTS: 25% of specimens (95% confidence interval (CI) 21% to 29%) were inadequate compared with 17% (95% CI 14% to 20%) in a previous study. Variation between individual centres' performance remains high (5-54% of specimens inadequate). Had five centres performed as well as previously, the inadequate biopsy rate would have been unchanged from that found in the previous study. There was no important improvement in any centre's performance. Earlier suggestions about change in practice have had no discernible impact on centres' ability to obtain adequate bone marrow trephine biopsies from children. CONCLUSIONS: The responsibility for improving the rate of adequate biopsies lies with individual centres. Reporting pathologists might help by making even more positive attempts to influence operators within their own centres.

Biopsy↗
PubMed1998

Methadone treatment in the Scottish context: outcomes of a community-based service for drug users in Lothian.

Few studies investigating the effectiveness of methadone treatment for opiate dependence have emanated from the UK. The core feature of treatment offered by Lothian Health's Community Drug Problems Service involves the prescribing of methadone by the client's general practitioner. Of a cohort of 494 daily users of opiates attending the service, 39% remained in treatment for at least 12 months. Up to 2 years in-treatment follow-up revealed significant improvement in injecting and criminal behaviour. There were no HIV seroconversions reported during the treatment period. There was no improvement in injection equipment sharing, condom use, illicit drug use or employment status. 'Satisfactory' discharge was achieved for 40% of those in treatment for at least 6 months. These results are largely consistent with the outcomes of methadone programmes elsewhere.

Adolescent↗