O B Eden

Great Ormond Street Hospital for Children NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (175)992.94 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: A review of the cytogenetic analyses of a cohort of unselected patients with acute lymphoblastic leukemia from a single institution (1981-1989) confirmed hyperdiploidy > 50 as a favorable prognostic feature and pseudodiploidy, especially with chromosomal rearrangements, as an adverse one. In the early years of the study, a high incidence of diploid karyotype was identified, but with time (better banding and more intensive search) the incidence has fallen to 7.7%. Many such patients have been shown to be pseudodiploid. Molecular genetic techniques are increasingly identifying clonal abnormalities.
    Pediatric Hematology and Oncology 07/2009; 10(1):25-30. · 0.90 Impact Factor
  • M P Shaw, O B Eden, E Grace, P M Ellis
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    ABSTRACT: We report two children with acute lymphoblastic leukemia (ALL) who in initial cytogenetic investigation were coincidently found to have a 47, XXY karyotype. In one patient 100% of peripheral blood lymphocytes showed a 47,XXY complement, but in the other only 30% of cells had such a complement, the remainder having a normal male karyotype (46, XY). In neither case was the diagnosis of Klinefelter's syndrome clinically obvious. Antileukemic therapy may exacerbate both the hypogonadism and the learning difficulties seen in this condition. Routine cytogenetic investigations on peripheral blood and bone marrow should be performed in all new cases of leukemia. Cytogenetic analysis of cultured fibroblasts is essential in all cases in which the abnormal X line did not disappear after initial therapy. Evidence of an increased risk of leukemia in association with Klinefelter's is beginning to accumulate.
    Pediatric Hematology and Oncology 07/2009; 9(1):81-5. · 0.90 Impact Factor
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    ABSTRACT: Patients with a 47, XXY karyotype (Klinefelter syndrome) appear to have an increased risk of developing a malignancy in adulthood, usually cancer of the breast, extragonadal germ cell tumor, and acute nonlymphoblastic leukemia. There is growing evidence to show that these patients also have an increased risk of developing a malignancy in childhood. There are reports describing the development of acute lymphoblastic leukemia, retinoblastoma, and rhabdomyosarcoma in children with a 47, XXY or mosaic 47, XXY/46, XY karyotype. We report a child with a bone metastasizing, B-cell lineage, non-Hodgkin's lymphoma (NHL) who was found to have a 47, XXY karyotype in both the tumor and constitutional cells.
    Pediatric Hematology and Oncology 07/2009; 11(2):197-200. · 0.90 Impact Factor
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    ABSTRACT: The cytological technique of cytocentrifugation and millipore filter collection of cells allows accurate identification of cells in the CSF. This study reports the changing CSF cell-populations during 26 episodes of ventriculitis in children with shunts to control hjydrocephalus. There was a significant discordance between lymphocytes and macrophages in the CSF. Neurosurgery led to a 20 per cent increase in neutrophils on the first postoperative day, with a progressive decline to a mean of 10 cells on the fourth postoperative day. There was a small decrease in lymphocytes on the first postoperative day, followed by an increase on the second day. Macrophages were reduced by 12 per cent on the first postoperative day and then steadily increased from the second to the fourth day. A mean number of two peaks (of all cells) occurred during the treatment for ventriculitis: there was a greater number of neutrophils in the first peak, with less lymphocytes and macrophages than in the second peak. This study supports the advantages of this technique in the diagnosis and management of ventriculitis.RÉSUMÉCytomorphologie sédimentaire du LCR dans I'infection ventriculaire La technique cytologique de cytocentrifugation et le recueil de cellules á travers un filtre millipore permet une identification précise des cellules du LCR. Cette étude rapporte les modifications de population cellulaire du LCR durant 26 épisodes d'infection ventriculaire chez des enfants porteurs de valves pour contrôler une hydrocéphalie. Il a été observé une discordance significative entre lymphocytes et macrophages du LCR. La neuro-chirurgie conduit à une augmentation de 20 pour cent des neutrophiles au premier jour postopératoire avec un déclin progressif jusqu'á une moyenne de dix cellules au quatriéme jour post-opératoire. Le taux des lymphocytes décroit Légèrement au premier jour post-opératoire puis s'accroit au second jour. Les macrophages sont rétduits de 12 pour cent au premier jour post-opératoire et sont ensuite nettement accrus du second au quatribme jour. Un nombre moyen de deux pics (de toutes les cellules) survient durant le traitement de l'infection ventriculaire: il y a un plus grand nombre de neutrophiles durant le premier pic, avec moins de lymphocytes et de macrophages que durant le second pic. Cette étude favorise les avantages de cette technique dans le diagnostic et le traitement de I'infection ventriculaire.ZUSAMMENFASSUNGSedimentationscytomorphologie von Liquor bei Ventrikulitis Die Technik der Cytozentrifugation und Milliporfilterkollektion von Zellen erlaubt die genaue Identifizierung von Zellen im Liquor. Diese Studie berichtet uber wechselnde Zellpopulationen bei 26 Episoden einer Ventrikulitis bei Kindern mit Ventilen wegen eines Hydrocephalus. Es fand sich eine signifikante Diskordanz zwischen Lymphocyten und Makrophagen im Liquor. Der neurochirurgische Eingriff fuhrte zu einer Zunahme der Neutrophilen von 20 Prozent am ersten postoperativen Tag, mit einem zunehmenden Abfall bis zu einem Mittelwert von 10 Zellen am vierten postoperativen Tag. Die Lymphocyten fielen am ersten postoperativen Tag etwas ab und stiegen dann am zweiten Tag an. Die Makrophagen waren am ersten postoperativen Tag um 12 Prozent reduziert und stiegen dann stetig vom zweiten bis vierten Tag an. Unter der Behandlung der Ventrikulitis traten im Durchschnitt zwei Peaks auf (von allen Zellen): im ersten Peak fanden sich mehr Neutrophile mit weniger Lymphocyten und Makrophagen als im zweiten Peak, Diese Studie unterstreicht die Vorteile dieser Technik bei der Diagnose und Therapie der Ventrikulitis.RESUMENCitomorfologia de sedimentación del LCR en las ventriculitis La técnica citólogica de la centrifugación y del filtro miliporo para la recogida células permite una identificación precisa de las células en el LCR. Este estudio aporta los cambios en la población celular del LCR durante 26 episodios de ventriculitis en niños con derivation para controlar una hidrocefalia. Habia una discordancia significativa entre linfocitos y macrófagos en el LCR. La neurocirugia dio lugar a un aumento del 20 por ciento en los neutrófilos en el primer dia del postoperatorio, con una disminución progresiva hasta un promedio de 10 céculas en el cuarto dia postoperatorio. Habia una pequefla disminución en los linfocitos en el primer dia postoperatorio, seguido, de un aumento en el segundo dia. Los macrófagos se redujeron en un 12 por ciento en el primer dia postoperatorio para aumentar despues continuamente desde el segundo al cuarto dia. Durante el tratamiento de la ventriculitis tuvo lugar un promedio de dos picos para todas las células, habiendo un mayor número de neutrófilos en el primer pico, con menos linfocitos y macrofagos que en el segundo pico. Este estudio refuerza las ventajas de esta técnica en el Diagnóstico y vigilancia de las ventriculitis.
    Developmental Medicine & Child Neurology 11/2008; 28(2):213 - 219. · 2.68 Impact Factor
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    ABSTRACT: The effect of randomly allocated testicular irradiation on the subsequent incidence of testicular infiltration and disease-free survival was assessed in two Medical Research Council Childhood Leukaemia Trials, UKALL VI and UKALL VII. None of the 83 boys who actually received testicular radiotherapy subsequently developed gonadal disease, whereas 18 of the 163 who were not irradiated did. Despite this there is no apparent difference in disease-free survival for those randomized to receive testicular irradiation compared to those who were not. after a minimum of 8 years follow up. Although prophylactic testicular irradiation appears to prevent subsequent gonadal relapse there is no evidence that it improves overall prognosis when adequate systemic chemotherapy is used. As it has considerable long-term side effects it cannot be recommended as routine therapy.
    British Journal of Haematology 03/2008; 75(4):496 - 498. · 4.94 Impact Factor
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    ABSTRACT: Blast cell morphology of children with lymphoblastic leukaemia (ALL) entering two national multicentre trials was prospectively reviewed by three haematologists to define the clinical importance of (a) French–American–British (FAB) classification, (b) the presence of cytoplasmic vacuoles, and (c) the presence of ‘hand-mirror’cells.Of 2135 evaluable children, 1907 (89%) had FAB L1 morphology and 228 (11%) L2. (L3 patients were not eligible for the trials in question). L2 patients more frequently had residual disease 14 d after starting treatment and had a significantly inferior disease-free survival, but not if the analysis was stratified for age, sex and diagnostic white cell count (WBC), 627 (29%) had blast cells with cytoplasmic vacuoles, and showed a significant survival advantage over the remainder. Vacuoles were positively associated with a low WBC, age range 1–6 years and blast cell positivity for CD10, but their benign influence was apparent even when these variables were taken into account. ‘Hand-mirror’(HM) cells were only studied in UKALL X, and were noted in 316/1402 (23%) children. There appeared to be an inverse correlation between HM cells and cytoplasmic vacuoles and a weak association with T-cell immunophenotype, but no prognostic significance was evident.FAB classification appears to be of less prognostic importance than has previously been supposed, though L2 disease is more resistant to current remission induction regimens. Hand-mirror cells may be more common in T-ALL, but are seen in all types and are not related to prognosis. Cytoplasmic vacuoles are predictive of a good response to current therapeutic schedules even allowing for other prognostic variables, and are the single most important morphological feature relating to prognosis in childhood ALL.
    British Journal of Haematology 03/2008; 81(1):52 - 57. · 4.94 Impact Factor
  • Chapter: Lymphomas
    O.B. Eden, Ross Pinkerton
    10/2007: pages 482 - 503; , ISBN: 9780470987001
  • Ejc Supplements - EJC SUPPL. 01/2007; 5(4):166-166.
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    ABSTRACT: Costello syndrome (CS) is a rare multiple congenital abnormality syndrome, associated with failure to thrive and developmental delay. One of the more distinctive features in childhood is the development of facial warts, often nasolabial and in other moist body surfaces. Individuals with CS have an increased risk of malignancy, suggested to be about 17%. Recently, mutations in the HRAS gene on chromosome 11p13.3 have been found to cause CS. We report here the results of HRAS analysis in 43 individuals with a clinical diagnosis of CS. Mutations were found in 37 (86%) of patients. Analysis of parental DNA samples was possible in 16 cases for both parents and in three cases for one parent, and confirmed the mutations as de novo in all of these cases. Three novel mutations (G12C, G12E, and K117R) were found in five cases. These results confirm that CS is caused, in most cases, by heterozygous missense mutations in the proto-oncogene HRAS. Analysis of the major phenotypic features by mutation suggests a potential correlation between malignancy risk and genotype, which is highest for patients with an uncommon (G12A) substitution. These results confirm that mutation testing for HRAS is a reliable diagnostic test for CS.
    Journal of Medical Genetics 06/2006; 43(5):401-5. · 5.70 Impact Factor
  • A Ng, G M Taylor, O B Eden
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    ABSTRACT: The ability of topoisomerase 2 inhibitors to induce DNA breakage is well recognized. Previous studies, however, have concentrated on the effects on individual genes. The effects of etoposide on the MLL, RUNX1, and MLLT3 genes were simultaneously studied in the same hemopoietic cell population. We found MLL to be more susceptible to etoposide-induced cleavage than RUNX1 and MLLT3, with maximum cleavage at a lower drug concentration. A higher level of MLL than other gene cleavage was also detected after cellular exposure to all drug concentrations. Greater susceptibility to topoisomerase 2 inhibitor-induced cleavage may explain the more frequent involvement of MLL in treatment-related leukemogenesis.
    Cancer Genetics and Cytogenetics 02/2006; 164(2):164-7. · 1.93 Impact Factor
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    ABSTRACT: Fanconi anemia (FA) is a rare autosomal recessive disorder characterized by congenital and developmental abnormalities, hypersensitivity to DNA cross-linking agents such as mitomycin C (MMC), and strong predisposition to acute myeloid leukemia (AML). In this article, we describe clinical and molecular findings in a boy with a severe FA phenotype who developed AML by the age of 2. Although he lacked a strong family history of cancer, he was subsequently shown to carry biallelic mutations in the FANCD1/BRCA2 gene. These included an IVS7 splice-site mutation, which is strongly associated with early AML in homozygous or compound heterozygous carrier status in FA-D1 patients. Myeloid leukemia cells from this patient have been maintained in culture for more than 1 year and have been designated as the SB1690CB cell line. Growth of SB1690CB is dependent on granulocyte macrophage colony stimulating factor or interleukin-3. This cell line has retained its MMC sensitivity and has undergone further spontaneous changes in the spectrum of cytogenetic aberrations compared with the primary leukemia. This is the second AML cell line derived from an FA-D1 patient and the first proof that malignant clones arising in FA patients can retain inherited MMC sensitivity. As FA-derived malignancies are normally not very responsive to treatment, this implies there are important mechanisms of acquiring correction of the cellular FA phenotype that would explain the poor chemoresponsiveness observed in FA-associated malignancies and might also play a role in the initiation and progression of cancer in the general population.
    Genes Chromosomes and Cancer 05/2005; 42(4):404-15. · 3.55 Impact Factor
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    A Ng, G M Taylor, R F Wynn, O B Eden
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    ABSTRACT: The molecular effects of etoposide in haemopoietic cells suggest that mixed lineage leukaemia (MLL) abnormalities can be biomarkers of patient susceptibility to the genotoxic effects of topoisomerase 2 (topo 2) inhibitors. We have prospectively studied treatment-related MLL cleavage and rearrangement in serial samples from 71 children receiving chemotherapy, using Southern blot analysis and panhandle PCR. The results were related to patient demographics, treatment details and outcome. MLL cleavage was identified in six bone marrow samples from five patients 2-10 months after the start of therapy. There was no obvious relationship between the degree of MLL cleavage and cumulative dose or schedule of topo 2 inhibitors. Three children with low percentage (23-30%) cleavage remained well and two were still receiving treatment at study completion. One child with two consecutively positive samples and higher level of MLL cleavage (45-48%) died from treatment-related toxicities and relapsed leukaemia. A patient with haemophagocytic lymphohistiocytosis developed the highest level of MLL cleavage (50%) at 3 months and a treatment-related leukaemia with MLL rearrangement 6 months after the start of treatment. It would appear that some patients are inherently more susceptible to the genotoxic effect of topo 2 inhibitors. The degree and persistence of MLL cleavage may identify patients at risk.
    Leukemia 03/2005; 19(2):253-9. · 10.16 Impact Factor
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    ABSTRACT: Treatment-related acute myeloid leukaemia (t-AML) is a serious complication of topoisomerase 2 inhibitor therapy and is characterised by the presence of mixed lineage leukaemia (MLL) rearrangement. By molecular tracking, we were able to show that MLL cleavage preceded gene rearrangement by 3 months and before the clinical diagnosis of t-AML in a patient with haemophagocytic lymphohistiocytosis. This is the first report on the sequential detection of the two biomarkers in treatment-related leukaemogenesis.
    British Journal of Cancer 01/2005; 91(12):1990-2. · 5.08 Impact Factor
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    ABSTRACT: Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder resulting from mutations in the NBS1 gene, which encodes for the DNA double strand break repair protein nibrin. NBS is clinically characterized by microcephaly, dysmorphic features, immunodeficiency, and increased susceptibility to malignancy, mainly of lymphoid origin. Here, we describe a 7-year-old girl with NBS who is homozygous for the NBS1 698del4 mutation. She had been diagnosed with perianal rhabdomyosarcoma (RMS) and experienced severe toxicity from chemotherapy. RMS arising perianally is extremely uncommon but has been previously described in two cases with NBS. The strong association of perianal RMS with NBS should, therefore, be considered when confronted with a perianal RMS, as this carries important clinical implications in terms of potential need for therapy modification and follow up investigations. In addition, it suggests a role for the NBS1 gene and the nibrin dependent pathway in the pathogenesis of RMS, especially those arising perianally.
    Cancer Genetics and Cytogenetics 11/2004; 154(2):169-74. · 1.93 Impact Factor
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    ABSTRACT: The Sixth International Childhood ALL Workshop was made possible by unrestricted educational grants from Sanofi-Synethelabo Inc., Glaxosmithkline, Enzon Inc., and Ilex. Preparation of the Meeting Report was supported in part by the Österreichische Kinderkrebshilfe and private donations to the Children's Cancer Research Institute; the Associazione Italiana Ricerca sul Cancro, Fondazione Tettamanti, and Consiglio Nazionale Ricerche-Ministero Instruzione Universitá Ricerca); the Deutsche Krebshilfe, Bonn, and Madeleine Schickedanz Foundation, Fürth, Germany; Cancer Research UKJ; grants from the US National Institutes of Health (CA-21765, CA-51001, CA-31566, CA-78824, CA-29139, CA-37379, GM-61393, and GM61374), a Center of Excellence grant from the State of Tennessee, and the American Lebanese Syrian Associated Charities (ALSAC). C-H Pui is the American Cancer Society – FM Kirby Clinical Research Professor.
    Leukemia 07/2004; 18(6):1043-53. · 10.16 Impact Factor
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    ABSTRACT: We have examined space-time clustering amongst cases of lymphoma in children, aged 0-14 years, using population-based data from the North West of England for the period 1954-2001. There was little or no evidence for space-time clustering amongst all the lymphomas or amongst those sub-groups identified in advance.
    European Journal of Cancer 04/2004; 40(4):585-9. · 5.06 Impact Factor
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    ABSTRACT: Concern about late adverse effects of cranial radiotherapy (XRT) has led to alternative approaches to eliminate leukaemia from the central nervous system (CNS) in childhood acute lymphoblastic leukaemia (ALL). The Medical Research Council UKALL XI trial recruited 2090 children with ALL between 1990 and 1997. Median follow-up is 7 years 9 months; event-free survival (EFS) and overall survival were 63.1% and 84.6%, respectively, at 5 years and 59.8% and 79.4% at 10 years. The isolated CNS relapse rate was 7.0% at 10 years. Patients were randomized for CNS-directed therapy within white blood cell (WBC) groups. For WBC <50 x 10(9)/l, high-dose intravenous methotrexate (HDMTX) (6-8 g/m2) with intrathecal methotrexate (ITMTX) was compared with ITMTX alone, and was significantly better at preventing isolated and combined CNS relapse, but non-CNS relapses were similar. There was no significant difference in EFS at 10 years, 64.1% [95% confidence interval (CI) 60.4-67.8] with HDMTX plus ITMTX, and 63.0% (95% CI 59.5-66.5) with ITMTX alone. For WBC >/=50 x 10(9)/l, HDMTX with ITMTX was compared with XRT and a short course of ITMTX. CNS relapses were significantly fewer with XRT, but there was a non-significant increase in non-CNS relapses. EFS was not significantly different, being 55.2% (95% CI 47.8-62.6) at 10 years with XRT and 52.1% (95% CI 44.8-59.4) with HDMTX plus ITMTX.
    British Journal of Haematology 02/2004; 124(1):33-46. · 4.94 Impact Factor
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    ABSTRACT: To investigate the association of acute parvovirus B19 infection with new onset of acute lymphoblastic and myeloblastic leukaemia. Cerebrospinal fluid (CSF) samples from patients with acute myelogenous leukaemia (AML) at diagnosis (n = 2) and acute lymphoblastic leukaemia (ALL) at diagnosis (n = 14) were analysed for parvovirus B19 DNA by means of nested polymerase chain reaction. In addition, samples from patients with benign intracranial hypertension (BIH) (n = 10) and hydrocephalus (n = 13) were tested as controls. Four leukaemia cases were positive-common ALL (n = 2), null cell ALL (n =1), and M7 AML (n = 1)-whereas all controls were negative (Yates corrected chi(2) value, 3.97; p = 0.046; odds ratio, 16.92; confidence interval, 1.03 to 77.18). All four patients were significantly anaemic, but none was encephalitic or had evidence of central nervous system leukaemia. In three of these patients, serum tumour necrosis alpha, interferon gamma, interleukin 6, granulocyte-macrophage colony stimulating factor (range, 34.93-3800.06 pg/ml), and macrophage chemoattractant protein 1 were detectable. All of these four patients carried at least one of the HLA-DRB1 alleles, which have been associated with symptomatic parvovirus B19 infection. Erythroid suppression and immune cell proliferation are both associated with B19 infection and may also be important in the pathogenesis of acute leukaemia.
    Journal of Clinical Pathology 12/2003; 56(11):873-5. · 2.44 Impact Factor
  • Cancer Research 11/2003; 63(19):6563-4; author reply 6565. · 8.65 Impact Factor
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    ABSTRACT: Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.
    British Journal of Haematology 11/2003; 123(1):60-5. · 4.94 Impact Factor

Publication Stats

4k Citations
992.94 Total Impact Points

Institutions

  • 2000–2007
    • Great Ormond Street Hospital for Children NHS Foundation Trust
      • Department of Haematology and Oncology
      Londinium, England, United Kingdom
    • The Royal Marsden NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2001–2006
    • The University of Manchester
      Manchester, England, United Kingdom
    • Institute of Cancer Research
      Londinium, England, United Kingdom
    • University of California, San Francisco
      San Francisco, California, United States
  • 2002–2005
    • Central Manchester University Hospitals NHS Foundation Trust
      • • Paediatric Oncology Unit
      • • Department of Adult Histopathology
      Manchester, England, United Kingdom
  • 2004
    • Birmingham Children's Hospital NHS Foundation Trust
      Birmingham, England, United Kingdom
  • 2003
    • University of Leeds
      Leeds, England, United Kingdom
    • Imperial College London
      • Section of Microbiology
      London, ENG, United Kingdom
  • 1997–2000
    • The Christie NHS Foundation Trust
      Manchester, England, United Kingdom
    • University of Wales
      Cardiff, Wales, United Kingdom
  • 1997–1999
    • Manchester Memorial Hospital
      Manchester, Connecticut, United States
  • 1998
    • St. Luke's Hospital
      Cedar Rapids, Iowa, United States
  • 1995
    • Institute for Child Health Policy (ICHP)
      Oxford, Ohio, United States
  • 1989–1995
    • SickKids
      • Division of Hematology/Oncology
      Toronto, Ontario, Canada
  • 1991–1994
    • Royal Society of Edinburgh
      Edinburgh, Scotland, United Kingdom
  • 1988
    • Riley Hospital for Children
      Indianapolis, Indiana, United States
  • 1978–1984
    • The University of Edinburgh
      • Department of Child Life and Health
      Edinburgh, Scotland, United Kingdom