Medical Education - Research Publications
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ItemLate recovery of renal failure after autologous haematopoietic stem cell transplantation for multiple myeloma: a report of two cases.(Oxford University Press (OUP), 2009-06)Acute renal failure is a frequent feature in patients with multiple myeloma (MM). MM-related renal insufficiency may improve after autologous haematopoietic stem cell transplantation (autoHSCT) even in patients initially requiring dialysis. Herein, we report on two unusual cases of late improvement in renal function occurring over more than 5 years after autoHSCT for MM. Clinicians must be aware that slow and progressive improvement in renal function may occur over years in patients with MM-associated renal failure. Our data underline the need for an aggressive treatment, including autoHSCT, in MM patients presenting with severe renal dysfunction.
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ItemIntraosseous angiosarcoma with secondary aneurysmal bone cysts presenting as an elusive diagnostic challenge.(Springer Science and Business Media LLC, 2008-05-20)Angiosarcoma of bone is an exceedingly rare primary bone malignancy that can present as an aggressive osteolytic lesion. Histological diagnosis can be extremely challenging, as the pathological features often resemble that of aneurysmal bone cysts. We report an interesting and peculiar case of an intraosseous angiosarcoma that presented as a diagnostic dilemma and discuss the relevant radiological and pathologic findings.
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ItemTerminal osteoblast differentiation, mediated by runx2 and p27(KIP1), is disrupted in osteosarcoma(Rockefeller University Press, 2004-12-06)The molecular basis for the inverse relationship between differentiation and tumorigenesis is unknown. The function of runx2, a master regulator of osteoblast differentiation belonging to the runt family of tumor suppressor genes, is consistently disrupted in osteosarcoma cell lines. Ectopic expression of runx2 induces p27KIP1, thereby inhibiting the activity of S-phase cyclin complexes and leading to the dephosphorylation of the retinoblastoma tumor suppressor protein (pRb) and a G1 cell cycle arrest. Runx2 physically interacts with the hypophosphorylated form of pRb, a known coactivator of runx2, thereby completing a feed-forward loop in which progressive cell cycle exit promotes increased expression of the osteoblast phenotype. Loss of p27KIP1 perturbs transient and terminal cell cycle exit in osteoblasts. Consistent with the incompatibility of malignant transformation and permanent cell cycle exit, loss of p27KIP1 expression correlates with dedifferentiation in high-grade human osteosarcomas. Physiologic coupling of osteoblast differentiation to cell cycle withdrawal is mediated through runx2 and p27KIP1, and these processes are disrupted in osteosarcoma.
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ItemThe role of thallium-201 and pentavalent dimercaptosuccinic acid for staging cartilaginous tumours.(Springer Science and Business Media LLC, 2004-11-08)INTRODUCTION: Heterogeneity of cartilage tumours may confound accurate diagnosis and grading resulting in under and over treatment. Improved preoperative assessment of malignancy and grade would be invaluable for developing a rational plan for treatment. We examined correlations between nuclear tracer avidity and malignancy grade in cartilage tumours. METHODS: Between 1996 and 2000, 92 consecutive patients with cartilaginous tumours (50 benign, 42 non-metastatic malignant) underwent nuclear scanning. Thallium-201 (TL-201) and pentavalent dimercaptosuccinic acid (DMSAV) were used as nuclear isotopes. Scanning with these agents was performed on separate days 48 hours apart. Static and SPECT images were obtained at 30 m and 4 h after injection of nuclear tracer. Pathology review was undertaken blinded to the results of the nuclear scans and correlations between histologic results and trace uptake at 4 hours examined. RESULTS: 25 patients with negative DMSAV had benign tumours. 15/17 tumours with positive TL-201 had malignant tumours. 11/13 patients with both positive DMSAV and TL-201 scans had intermediate or high grade tumours and 4 of these developed metastases. We have developed an algorithm for the management of patients with tumours that aims to avoid over treatment of low grade tumours and under treatment of high grade tumours. CONCLUSION: Functional nuclear scanning with TL-201 and DMSAV complements other imaging modalities in the management of cartilaginous tumours.