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Biomedical subjects

Craig Donaldson

Publications and source records attributed to Craig Donaldson.

6 recordsLinked to original sources

Retinoblastoma in New South Wales 1975 to 2001.

PURPOSE: To examine the epidemiology of retinoblastoma in New South Wales (NSW), from 1975 to 2001, comparing the incidence with other parts of the developed world. METHODS: Examination of medical files for patients presenting to NSW retinoblastoma treatment centers between 1975 and 2001. Comparisons to international data were made. RESULTS: One hundred twenty-eight patients [63 (49.2%) male and 65 (51.8%) female] presented. The mean annual incidence of retinoblastoma in NSW was 8 per million children aged 0 to 6 years, per year. CONCLUSIONS: The incidence of retinoblastoma in NSW is similar to other parts of the developed world.

Age of Onset↗

Bone marrow-derived mesenchymal stem cells.

Human mesenchymal stem cells (MSCs) contribute to the regeneration of mesenchymal tissues, and are essential in providing support for the growth and differentiation of primitive hemopoietic cells within the bone marrow microenvironment. Techniques are now available to isolate human MSCs and manipulate their expansion in vitro under defined culture conditions without change of phenotype or loss of function. Mesenchymal stem cells have generated a great deal of interest in many clinical settings, including that of regenerative medicine, immune modulation and tissue engineering. Studies have already demonstrated the feasibility of transplanted MSCs providing crucial new cellular therapy. In this review, many aspects of the MSC will be discussed, with the main focus being on clinical studies that describe the potential of MSCs to treat patients with hematological malignancies who are undergoing chemotherapy and/or radiotherapy.

Bone Marrow Cells↗

Adult bone marrow is a rich source of human mesenchymal 'stem' cells but umbilical cord and mobilized adult blood are not.

In postnatal life, mesenchymal stem cells (MSC) self-replicate, proliferate and differentiate into mesenchymal tissues, including bone, fat, tendon, muscle and bone marrow (BM) stroma. Possible clinical applications for MSC in stem cell transplantation have been proposed. We have evaluated the frequency, phenotype and differentiation potential of MSC in adult BM, cord blood (CB) and peripheral blood stem cell collections (PBSC). During culture, BM MSC proliferated to confluence in 10-14 d, maintaining a stable non-haemopoietic phenotype, HLA class-1+, CD29+, CD44+, CD90+, CD45-, CD34- and CD14 through subsequent passages. Using the colony forming unit fibroblasts assay, the estimated frequency of MSC in the BM nucleated cell population was 1 in 3.4 x 10(4) cells. Both adipogenic and osteogenic differentiation of BM MSC was demonstrated. In contrast, CB and PBSC mononuclear cells cultured in MSC conditions for two passages produced a population of adherent, non-confluent fibroblast-like cells with a haemopoietic phenotype, CD45+, CD14+, CD34-, CD44-, CD90- and CD29-. In paired experiments, cultured BM MSC and mature BM stroma were seeded with CB cells enriched for CD34+. Similar numbers of colony-forming units of granulocytes-macrophages were produced by MSC-based and standard stroma cultures over 10 weeks. We conclude that adult BM is a reliable source of functional cultured MSC, but CB and PBSC are not.

Adult↗

Questioning the need for routine bone marrow aspiration and lumbar puncture in patients with retinoblastoma.

PURPOSE: This study assesses the value of routinely investigating children with retinoblastoma with bone marrow aspiration and lumbar puncture, staging investigations not without risk and trauma to the patient, emotional stress on parents and financial cost to the community. METHODS: Medical files and specimens were obtained and examined for patients with retinoblastoma presenting to the Royal Alexandra Hospital for Children, Camperdown and the Children's Hospital at Westmead, Sydney, from 1975 to 2001. RESULTS: In total, 123 patients presented; 62 (50.4%) were boys and 61 (49.6%) were girls. Of these 123 patients, 74 (60.2%) had unilateral disease, 46 (37.4%) involving the left eye and 28 (22.8%) involving the right eye. There were 47 (38.2%) patients with bilateral disease, and two (1.6%) with trilateral disease. Mean age of presentation was 17.9 months (23.1 months for unilateral subjects; 10.3 months for bi-lateral subjects; 3.5 months for trilateral subjects). There were 13 (10.6%) with a positive family history. Of 74 unilateral subjects, 70 (94.6%) required enucleation and four (5.4%) were salvaged. Of 47 bilateral subjects, 13 (27.7%) did not require enucleation, 27 (57.4%) required unilateral enucleation and seven (14.9%) required bilateral enucleation. Both trilateral subjects died. Of all 123 subjects, 112 (91.1%) had bone marrow aspiration and lumbar puncture performed during initial assessment, and none showed evidence of malignancy. CONCLUSIONS: Given the small but significant risks associated with these procedures, the results of this study cannot support bone marrow aspiration and lumbar puncture as routine investigations in all patients presenting with retinoblastoma, suggesting a more limited usage of these investigations is warranted.

Biopsy, Needle↗

Chromosome translocations and covert leukemic clones are generated during normal fetal development.

Studies on monozygotic twins with concordant leukemia and retrospective scrutiny of neonatal blood spots of patients with leukemia indicate that chromosomal translocations characteristic of pediatric leukemia often arise prenatally, probably as initiating events. The modest concordance rate for leukemia in identical twins ( approximately 5%), protracted latency, and transgenic modeling all suggest that additional postnatal exposure and/or genetic events are required for clinically overt leukemia development. This notion leads to the prediction that chromosome translocations, functional fusion genes, and preleukemic clones should be present in the blood of healthy newborns at a rate that is significantly greater than the cumulative risk of the corresponding leukemia. Using parallel reverse transcriptase-PCR and real-time PCR (Taqman) screening, we find that the common leukemia fusion genes, TEL-AML1 or AML1-ETO, are present in cord bloods at a frequency that is 100-fold greater than the risk of the corresponding leukemia. Single-cell analysis by cell enrichment and immunophenotype/fluorescence in situ hybridization multicolor staining confirmed the presence of translocations in restricted cell types corresponding to the B lymphoid or myeloid lineage of the leukemias that normally harbor these fusion genes. The frequency of positive cells (10(-4) to 10(-3)) indicates substantial clonal expansion of a progenitor population. These data have significant implications for the pathogenesis, natural history, and etiology of childhood leukemia.

Base Sequence↗

Management of Duane retraction syndrome.

BACKGROUND: Duane retraction syndrome is the most common cause of congenital aberrant ocular innervation. We report referral practices, clinical characteristics and complications, prevalence of congenital and familial anomalies, and management outcomes from a clinic-based series. METHODS: Retrospective clinic-based study of 65 patients with Duane retraction syndrome seen between January 1994 and March 2004. RESULTS: The majority of patients were girls with type I Duane retraction syndrome associated with esotropia in primary gaze. Twenty percent of cases were complicated by absent binocular stereoacuity and 16.9% had amblyopia. Family history of any ocular disorder was reported in 38.5% of cases, while an associated congenital abnormality was found in 46% of patients. There was a significant delay between the age when ocular abnormalities were first noticed and the age when patients presented at our tertiary referral center (P < .001). Twenty-two percent of patients underwent surgical correction at a mean age of 6 years. Most procedures were unilateral or bilateral medial or lateral rectus recessions. Postoperative ocular alignment < or = 15 prism diopters (PD) was achieved in 86% of cases, with 50% of cases having < or = 5 PD. CONCLUSIONS: Amblyopia and absent binocular stereo vision affected one in five patients with Duane retraction syndrome. There was significant delay between identification of an abnormality and presentation at the eye clinic.

Amblyopia↗