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Biomedical subjects

Alan Davidson

Publications and source records attributed to Alan Davidson.

14 recordsLinked to original sources
PubMed2006

Wilms tumour experience in a South African centre.

BACKGROUND: In Africa, Wilms tumour frequently presents with advanced disease. This study reports our results over 25 years using the National Wilms Tumour Study Group (NWTSG) approach of primary surgery followed by chemotherapy. PROCEDURE: A retrospective analysis was performed on all patients diagnosed with unilateral Wilms tumour between January 1979 and December 2003. RESULTS: The records of 188 children with newly diagnosed Wilms tumour were examined. Of these 57 (30.3%) were stage I, 33 (17.6%) were stage II, 60 (31.9%) were stage III and 38 (20.2%) were stage IV. Twenty-four patients (12.8%) had unfavourable histology (UFH). The estimated 5-year overall survival (OS) for the whole group was 80.5% (84.8% for favourable histology (FH) and 51.6% for UFH). Among those with FH, estimated 5-year OS was 94.4% for stage I, 96.2% for stage II, 84.9% for stage III and 54.2% for stage IV. There was no difference in OS between those FH stage III tumours that were operable and those deemed inoperable. Intra-operative spillage was uncommon (8%), and did not increase local relapse rate. CONCLUSIONS: National Wilms Tumour Study Group protocols employed in an African setting with highly competent and experienced surgical care, produced results for non-metastatic FH Wilms tumour comparable to those of the NWTSG.

Adolescent↗
PubMed2006

Intraocular rhabdomyosarcoma in the sibling of a patient with a cerebellar medulloepithelioma.

A 12-year-old girl with a three-year history of right eye disease was referred to our service after enucleation of her right eye. Histology showed a pleomorphic high-grade rhabdomyosarcoma. As there was extrascleral extension, we elected to treat her with local radiotherapy and adjuvant vincristine, dactinomycin, cyclophosphamide, and adriamycin. She remains disease free 35 months from diagnosis. Notably, a younger sibling died in early childhood as a result of a cerebellar medulloepithelioma. Although there were no teratoid elements in the rhabdomyosarcoma, our patient's unusual disease course would be consistent with rhabdomyosarcomatous differentiation in a teratoid medulloepithelioma.

Cerebellar Neoplasms↗
PubMed2006

The evolving management of Burkitt's lymphoma at Red Cross Children's Hospital.

BACKGROUND: Treatment for Burkitt's lymphoma at Red Cross Children's Hospital has evolved from the use of aggressive surgery and less intensive chemotherapy to a conservative surgical approach with more intensive chemotherapy. METHODS: The study was a retrospective folder review of patients diagnosed with Burkitt's lymphoma at RCCH between 1984 and 2004. RESULTS: Ninety-two children were treated for Burkitt's lymphoma at RCCH between 1984 and 2004. There were 10 patients with group A or fully resected disease, 52 with group B or extensive localised disease, and 30 with dissemination to the bone marrow and/or central nervous system or group C disease. Protocol 1 (less intensive chemotherapy based on the COMP regimen) was used from 1984, with protocol 2 (more intensive chemotherapy based on the LMB regimen) introduced in 1988 for group C disease, 1991 for group B disease and 1996 for group A disease. Overall 5-year survival increased from 20% with protocol 1 to 66% with protocol 2 for group C disease, and from 76.5% with protocol 1 to 88.2% with protocol 2 for group B disease. There were more admissions for neutropenic fever in patients on protocol 2 and more episodes of mucositis, and these patients required more red cell and platelet transfusions. With a more conservative surgical approach, biopsy largely replaced attempts to partially resect the tumour at primary surgery, and there was a consequent decline in surgical complications. CONCLUSIONS: Intensive chemotherapy with protocol 2 has resulted in improved survival for group C and group B patients, but with more morbidity. Protocol 1, which is less intensive with less morbidity, remains a viable strategy for group A and group B disease in resource-poor settings.

Adolescent↗
PubMed2005

Bilateral Wilms' tumors: a single-center experience with 19 cases.

BACKGROUND/PURPOSE: Bilateral Wilms' tumors present a therapeutic challenge, particularly with delay in presentation, when there is poor response to chemotherapy and when associated with nephroblastomatosis. The primary aim of management is eradication of neoplasm, while at the same time preserving of renal function. METHODS: Nineteen bilateral Wilms' tumors were seen in our service between 1981 and 2003. This represented 10% of the 190 patients with Wilms' tumors seen during this period. There were 12 female and 7 male patients ranging in age from 7 months to 8 years. Fourteen had synchronous presentation, one of whom had liver metastasis at diagnosis. Of the 5 patients with metachronous tumors, 3 had their initial nephrectomies done elsewhere. Nephroblastomatosis was identified in 18 (95%) of the patients. Treatment was, in most cases, according to National Wilms Tumor Study Group protocols, with initial bilateral biopsy, neoadjuvant chemotherapy, and tumorectomy. Where indicated, nephrectomy (partial or complete) involved using ice dam topical cooling and vascular control, and in one case, bench surgery and extensive renal reconstruction with orthotopic autotransplantation. Revision tumorectomy was used on 3 occasions for recurrence in areas of nephroblastomatosis. There were 6 extrarenal relapses. RESULTS: Ten patients are alive and free of disease 1 to 15 years after treatment, all with well preserved renal function (lowest recorded glomerular filtration rate was 85 mL/min per 1.73 m2). Nine have died (2 of unrelated disease), including 6 of the 7 with spread outside the kidney. All 3 with unfavorable histology are alive. Of the 5 with metachronous presentations, 4 are alive, as are 7 of 10 who presented in the last decade. CONCLUSIONS: Appropriate chemotherapy and conservative nephron-sparing and innovative surgery can achieve good results with preservation of adequate renal function in nearly all cases. Nephroblastomatosis was an almost universal finding and requires close monitoring because Wilms' tumors developed in residual suspect areas. Revision surgery was effective. Unfavorable histology did not have a reduced survival in our series. Metastatic spread outside the kidney had a poor prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Advancing the population health agenda.

Using the case of the B.C. Interior Health Authority, the paper teases out some of the bases for practical success and failure in advancing population health in a regionalized health system.

British Columbia↗
PubMed2003

Binding of ATP as well as tetrahydrofolate induces conformational changes in Lactobacillus casei folylpolyglutamate synthetase in solution.

Folylpolyglutamate synthetase (FPGS) catalyzes the addition of glutamate to folate derivatives to form folate polyglutamates. FPGS is essential for folate biosynthesis in bacteria and retention of folate pools in eukaryotes. X-ray crystallographic analyses of binary and ternary complexes of Lactobacillus casei FPGS suggest that binding of folate triggers a conformational change that activates FPGS. We used EPR and CD spectroscopy to further characterize the conformational change in the FPGS reaction. For EPR spectroscopy, two cysteine residues were introduced into FPGS by site-directed mutagenesis, K172C in the N-terminal domain and D345C in the C-terminal domain. The mutant protein was expressed, purified, and labeled with methanethiosulfonate. Addition of ATP, tetrahydrofolate, or 5,10-methylenetetrahydrofolate but not glutamate to FPGS showed broadening of EPR spectra, which is due to stronger spin-spin interactions, suggesting that both ATP and tetrahydrofolates cause a conformational change. ATP binding had an EPR spectrum distinct from that of tetrahydrofolate binding, indicating that it caused a different conformational change. When both ATP and THF were bound, the spectrum was identical to that seen when THF alone bound to the enzyme, showing that the THF-induced conformation was dominant. The spectral broadening suggests that the conformation change involves the two domains moving closer together, which is consistent with the rigid-body rotation of the C-terminal domain observed in the FPGS crystal structure with AMPPCP and 5,10-methylenetetrahydrofolate bound. No changes in the CD spectra were observed with the addition of FPGS substrates, suggesting that the conformational changes did not affect the secondary structure elements of the enzyme. These studies confirm the conformational change seen in the crystal structure by an independent method but also show that ATP binds to the free enzyme and affects its conformation.

Adenosine Triphosphate↗
PubMed2003

Romanow, Kirby and Courchene: Canada's health system--a moral or a business enterprise?

This paper examines Thomas Courchene's argument that Senator Kirby was closer to the truth than Commissioner Romanow when Kirby argued that Canada's healthcare system is only sustainable though introducing more private investment. The paper finds that Romanow's position, and indeed the nature of Canada's healthcare system, have been misrepresented by those seeking a larger private market share. The paper concludes the balance of evidence supports Ramanow, not Kirby.

Canada↗
PubMed2002

The Sak polo-box comprises a structural domain sufficient for mitotic subcellular localization.

The small family of polo-like kinases (Plks) includes Cdc5 from Saccharomyces cerevisiae, Plo1 from Schizosaccharomyces pombe, Polo from Drosophila melanogaster and the four mammalian genes Plk1, Prk/Fnk, Snk and Sak. These kinases control cell cycle progression through the regulation of centrosome maturation and separation, mitotic entry, metaphase to anaphase transition, mitotic exit and cytokinesis. Plks are characterized by an N-terminal Ser/Thr protein kinase domain and the presence of one or two C-terminal regions of similarity, termed the polo box motifs. These motifs have been demonstrated for Cdc5 and Plk1 to be required for mitotic progression and for subcellular localization to mitotic structures. Here we report the 2.0 A crystal structure of a novel domain composed of the polo box motif of murine Sak. The structure consists of a dimeric fold with a deep interfacial cleft and pocket, suggestive of a ligand-binding site. We show that this domain forms homodimers both in vitro and in vivo, and localizes to centrosomes and the cleavage furrow during cytokinesis. The requirement of the polo domain for Plk family function and the unique physical properties of the domain identify it as an attractive target for inhibitor design.

Amino Acid Motifs↗