Search PubMed⌕ Search

Biomedical subjects

M M Reid

Publications and source records attributed to M M Reid.

At least 73 records · Page 4Linked to original sources
PubMed1994

Secondary chronic myelomonocytic leukemia with t(9;11) in a child.

Chronic myelomonocytic leukemia (CMMol) developed in a 10-year-old girl after treatment of non-Hodgkin's lymphoma with a regimen which did not contain epipodophyllotoxins. t(9;11)(p22;q23) was found in the leukemic cells. This case highlights the fact that secondary hemopoietic malignancies with 11q23 abnormalities are not restricted to patients treated with epipodophyllotoxins, expands the number of documented cases of secondary myelodysplasia in children, and adds CMMoL to the spectrum of hemopoietic malignancies associated with t(9;11).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Cytogenetic abnormalities of small round cell tumours.

Between 1987 and 1991, cytogenetic studies were carried out on small round cell tumours of 68 patients from the Northern Health Region of England. Clonal chromosome abnormalities were found in 30, comprising 15 neuroblastomas, 7 Ewing's tumours, 7 rhabdomyosarcomas, and 1 granular cell tumour. Characteristic rearrangements were found in five cases of Ewing's tumour [all with translocation t(11;22) (q24;q12)] and in four cases of rhabdomyosarcoma [all with evidence of translocation t(2;13) (q35-37;q14)]. In one case of Ewing's tumour and three of rhabdomyosarcoma, the cytogenetic findings were important in diagnosis. Within the neuroblastomas, examples were found of hyperdiploidy, 1p rearrangements, double minute chromosomes, and homogeneously staining regions, but too few cases were available for prognostic associations to be assessed. Our findings confirm the diagnostic importance of chromosome abnormalities in small round cell tumours and indicate that cytogenetic analysis should be an intrinsic part of the initial investigations of all patients with such tumours.

Adolescent↗
PubMed1994

Assessing iron status in children with chronic renal failure on erythropoietin: which measurements should we use?

Iron deficiency severely limits the efficacy of recombinant human erythropoietin (EPO). In order to determine how best to identify and monitor children at risk of developing iron deficiency, we serially measured several parameters of iron status in nine children before and during a 24-week period of EPO therapy. Serum ferritin was the best predictor of development of iron deficiency, five of the nine children developed iron deficiency, characterised by a poor haemoglobin response or evidence of microcytosis and hypochromia; all had a serum ferritin of 60 micrograms/l or less at the start of EPO. Haemoglobin response was also related to change in mean red cell volume (MCV); a falling MCV, irrespective of absolute value, accompanying a poor response to EPO. Iron treatment in five children resulted in significant improvements in haemoglobin and iron status parameters. Although MCV remained low, there was a marked increase in red cell volume distribution width after iron, which may be of value in monitoring the response to iron therapy. We suggest that children with a serum ferritin of 60 micrograms/l or less and those who develop a falling MCV during EPO treatment should receive high-dose oral iron supplementation before and during treatment with EPO.

Administration, Oral↗
PubMed1994

Rapid detection of prognostic genetic factors in neuroblastoma using fluorescence in situ hybridisation on tumour imprints and bone marrow smears. United Kingdom Children's Cancer Study Group.

A number of biological factors have been identified which correlate with prognosis in neuroblastoma. Among these are genetic aberrations, including ploidy, deletions of chromosome 1p and N-myc amplification. Conventional methods of detecting these changes, such as tissue culture for karyotyping and Southern blotting, are time-consuming and yield interpretable results in only a small proportion of cases. We have developed interphase fluorescence in situ hybridisation for use on tumour imprints and bone marrow smears, allowing rapid visualisation of the relevant genetic changes. Valuable prognostic information is therefore available in a few days: the results in our cases were later confirmed by conventional methods. In the foreseeable future it will be possible to define distinct prognostic categories on the basis both of this genetic information and other parameters, and separate therapeutic strategies may then be employed for the different patient groups.

Bone Marrow↗
PubMed1994

The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia.

Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16 children and six adults at presentation and three children and three adults on relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13 with de novo AML, 11 at presentation and two on relapse, and seven secondary to myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the percentage of positive cells and for the intensity of staining using a five-point scale. There was a statistically significant increase in both the percentage of positive cells seen (P < 0.002) and the intensity of staining (P < 0.01) between samples obtained at relapse and those at presentation in ALL. There was a significantly greater intensity of staining in cells from patients with ALL (P < 0.05) and AML (P < 0.05) who failed to achieve remission after chemotherapy than in those who responded. The intensity of staining in cases of secondary AML was lower than that in de novo disease (P < 0.01). These results suggest that expression of bcl-2 may be an important prognostic feature in both de novo AML and in ALL, but not in secondary AML.

Adolescent↗
PubMed1994

Variable detection of myeloid antigens in childhood acute lymphoblastic leukaemia.

AIMS: To determine whether the use of different sources of anti-CD13 and anti-CD33 monoclonal antibodies leads to discrepant results in childhood acute lymphoblastic leukaemia (ALL), which might contribute to the wide variation in the reported incidence of myeloid antigen expressing ALL in childhood. METHODS: Stored leukaemic cells from 10 children with previously defined myeloid positive ALL were examined. A range of commercially available anti-CD13 and anti-CD33 monoclonal antibodies, directly conjugated with phycoerythrin or fluorescein isothyocyanate, or both, was used. Positively reacting cells were detected by flow cytometry. RESULTS: There was a noticeable discordance between the different commercial sources of antibody and between the two fluorochromes in their ability to detect myeloid antigens, as well as variation in the intensity of staining. For CD13, one antibody reacted with eight cases and another with only four. Similarly, CD33 was detected in all 10 cases by one antibody and in only three by another. CONCLUSIONS: The lack of any consistent pattern of results suggests that various commercial antibodies against the same CD antigen might recognise different epitopes and that the number of molecules per cell might vary from case to case. These observations partly explain the variation in reported incidence and the failure to establish the clinical importance of myeloid positivity, and they highlight the importance of standardisation in multicentre studies in which immunophenotypic data are collected.

Antibodies, Monoclonal↗
PubMed1994

Glutathione S-transferase in bone marrow metastases of disseminated neuroblastoma.

Antisera to each of the three main cytosolic forms of glutathione S-transferase (GST; alpha, mu, and pi) has been used to characterise GST expression by metastatic neuroblastoma in bone marrow trephine biopsies taken from 15 patients at presentation and from five of this group at relapse. There was no correlation between expression of extra-nuclear alpha or mu GST and outcome, and no consistent pattern at relapse. Seven of eight expressing nuclear pi GST at presentation died of resistant disease. Three of five cases with no detectable nuclear pi class GST remain alive and disease free. The results provide no encouragement for further investigation of alpha or mu GST in this disease but larger studies of uniformly treated patients may show whether nuclear pi GST expression at presentation indicates likely relapse.

Adolescent↗
PubMed1994

Research on leukaemia cells surplus to diagnostic needs in children.

The ability to improve diagnosis and refine prognosis in children with acute leukaemia is improving steadily. A growing number of tests can and are being performed on leukaemic cells. These include surface-marker analysis, DNA content, cytogenetics and studies of gene rearrangements. Increasingly large bone-marrow samples, now usually obtained under general anaesthesia, are required to make secure diagnoses. Ethical issues arise from three major areas. 1) Current research on leukaemia cells requested by the Medical Research Council is considered by local research ethics committees, but parents are not regularly given detailed information about or asked specifically to consent to such research; 2) substantial quantities of excess cells are stored indefinitely. This archive of stored material is a valuable resource for research but there has been little consideration of the ethical issues which arise from this practice, and 3) there is a potential for pressure to obtain increasingly large samples. 'Creeping growth' in sample size is likely to continue unless ethics committees consider future research proposals in more detail. These issues deserve attention in order that worthwhile research and its publication are not impeded for want of ethical consideration. The implications extend beyond the field of childhood leukaemia.

Acute Disease↗
PubMed1994

Acute lymphoblastic leukaemia in the elderly.

Acute lymphoblastic leukaemia (ALL) is rare in adults over the age of 60 years, with an incidence of 1 per 100,000 per year. We review the current (sparse) literature and our Regional experience of 62 consecutive cases of ALL in this age group collected over a ten year period. The patterns of cytogenetic abnormalities and immunophenotypes differs from those seen in ALL in childhood and young adults, but are similar to those reported in previous studies. B-ALL was found at twice the rate observed in younger adults (9/51 versus 6/99) and T-ALL was rare (2/51). In our patients we had few cytogenetic results but in the literature up to 50% of patients have been found to be Philadelphia positive, supporting the hypothesis that ALL in this group is often a stem cell disorder. In our patients treatment results were disappointing, with only 30% of those given 'curative' treatment achieving a complete remission, and a relapse rate of 92%, mirroring other published series. The overall four year survival was 4%. We conclude that ALL in the elderly is a rare condition with an extremely poor prognosis. Aggressive treatment may prolong life but it seldom cures.

Adult↗
PubMed1994

Edinburgh drug users: are they injecting and sharing less?

OBJECTIVE: To describe epidemiological trends in injecting and equipment sharing among a sample drawn from a drug-using population with a high rate of HIV infection. DESIGN: A structured interview was administered prior to treatment to cross-sectional samples of drug users over the period 1988-1991. Reports of injecting, sharing and HIV infection were compared annually. SETTING: Lothian Health Board's Community Drug Problems Service is a secondary level service offering harm reduction and treatment of dependency. PARTICIPANTS: A total of 734 consecutively referred drug users resident in Edinburgh. Re-referrals in the same calendar year were excluded. MEASURES: History of injecting and sharing, recent injecting and sharing, HIV testing history, drugs used in previous month and substitute prescription status. RESULTS: Large reductions in the frequency of injecting were found over the 4 years even among those who were not receiving oral substitutes. More participants in latter years were receiving prescriptions combining opioids and benzodiazepines. Fewer of those interviewed latterly had ever shared injecting equipment. Among recent injectors just as many share equipment as previously. HIV prevalence did not vary significantly over the period. An HIV prevalence of 19% was reported among recent injectors. CONCLUSIONS: Edinburgh's drug users are engaging in far safer drug-taking behaviour than previously. Levels of HIV in this population suggest that the epidemic is being contained. A small number persist in high risk drug-related activities. Further investigation of the characteristics of these individuals and the need to develop novel methods of influencing their behaviour are recommended.

Adult↗
PubMed1994

Raised intracellular glutathione levels correlate with in vitro resistance to cytotoxic drugs in leukaemic cells from patients with acute lymphoblastic leukemia.

Lymphoblasts were separated from the peripheral blood or bone marrow of 19 children (age 1-15, median 4 years) and 13 adults (age 18-59, median 47 years) with acute lymphoblastic leukaemia (ALL). Twenty-one samples were examined at presentation (16 from children and five from adults) and 13 at relapse (three children and ten adults). Glutathione (GSH) levels in leukaemic blasts were compared with in vitro sensitivity to a variety of cytotoxic drugs assessed using 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) as an indicator of cell viability. There was a statistically significant positive correlation between GSH levels and in vitro sensitivity to daunorubicin (Spearman's rank correlation coefficient rs = 0.38, p < 0.04), melphalan (rs = 0.39, p < 0.04) and prednisolone (rs = 0.48, p < 0.01), but not mitozantrone, etoposide or 6-thioguanine. There was no statistically significant difference in median GSH levels between blasts from children and adults or between samples taken at presentation or relapse. The sample median GSH levels in blasts from patients who responded to therapy (n = 21) and those who did not (n = 7) were 1.05 fmol/cell (97.3% confidence interval (CI) 0.78-1.52) and 2.66 fmol/cell (98.4% CI 0.53-5) respectively, and this difference was statistically significant (p < 0.02, Mann-Whitney U test). In two patients for whom paired samples were available, GSH levels in blasts on relapse were greater than 2-fold higher than on presentation. These results provide evidence that elevation of GSH in leukaemic blasts may be associated with resistance to drugs used in the treatment of children and adults with ALL.

Adolescent↗
PubMed1994

Molecular heterogeneity of variant Philadelphia translocations in childhood acute lymphoblastic leukaemia.

In acute lymphoblastic leukemia (ALL), it is unclear whether variant Philadelphia (Ph) translocations have the same molecular and clinical implications as the classical translocation. Two children with Ph+ ALL with variant translocations are described. One, in whom cytogenetic remission was not achieved, had evidence of translocation of c-abl to chromosome 22, rearrangement of minor breakpoint cluster region (mBCR) and expression of hybrid bcr/abl transcripts. In the other case, no gene rearrangement was found and complete remission was achieved. Variant Ph translocations in childhood ALL are heterogeneous at the molecular level. Molecular studies coupled with observations of clinical outcome are needed in larger numbers of such children to determine whether poor clinical response correlates with bcr/abl involvement and to allow planning of appropriate therapeutic strategies.

Child↗
PubMed1993

Prohibitive toxicity of a dose-intense regime for metastatic neuroblastoma containing ifosfamide, doxorubicin and cisplatin.

Three patients with stage 4 neuroblastoma were treated with a schedule comprising alternating modules of myelosuppressive (ifosfamide, etoposide, doxorubicin) and less myelosuppressive (vincristine, cisplatin) drugs given every 10 days regardless of the neutrophil count. A partial response was seen in two patients, and a very good partial response, in one patient. Extensive blood-component support was required. Non-haemopoietic toxicity was severe and led to treatment delays in two patients. Ifosfamide-related encephalopathy was seen in one patient and nephrotoxicity, in two patients. Mucositis was severe in two patients, may have contributed to the high rate of sepsis observed, and precluded the use of doxorubicin in one patient. As ifosfamide and doxorubicin were felt to be responsible for much of the toxicity, a subsequent schedule did not include these agents.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

A regional experience of red cell aplasia.

The incidence and current management of red cell aplasia in children was determined from a retrospective survey of haematologists and paediatricians in the northern health region of England over a 7-year period. Thirty-three children were diagnosed: 4 had Diamond Blackfan anaemia, 22 transient erythroblastopenia of childhood, and 7 parvovirus B19 aplasia, with annual incidences of 1, 5 and 2 per 1,000,000 children respectively. Many were over-investigated. Three with Diamond Blackfan anaemia were steroid responsive. One with transient erythroblastopenia was retrospectively diagnosed because anaemia did not recur after steroids were stopped. Transient erythroblastopenia is the most common single cause of red cell aplasia in immunocompetent children. Time, observation and bone marrow examination before steroid therapy are the ways to distinguish transient erythroblastopenia from Diamond Blackfan anaemia or leukaemia. Interpretation of red cell indices using age-related percentiles may reduce the number of inappropriate investigations of the anaemia, but is often unhelpful in distinguishing the various causes of red cell aplasia.

Anemia↗