The sequential timing of cell-cycle transitions is primarily governed by the availability and act... more The sequential timing of cell-cycle transitions is primarily governed by the availability and activity of key cell-cycle proteins. Recent studies in yeast have identified a class of ubiquitin ligases (E3 enzymes) called SCF complexes, which regulate the abundance of proteins that promote and inhibit cell-cycle progression at the G1-S phase transition. SCF complexes consist of three invariable components, Skp1, Cul-1 (Cdc53 in yeast) and Rbx1, and a variable F-box protein that recruits a specific cellular protein to the ubquitin pathway for degradation. To study the role of Cul-1 in mammalian development and cell-cycle regulation, we generated mice deficient for Cul1 and analysed null embryos and heterozygous cell lines. We show that Cul1 is required for early mouse development and that Cul1 mutants fail to regulate the abundance of the G1 cyclin, cyclin E (encoded by Ccne), during embryogenesis.
Distal femoral osteotomy (DFO) is successful in treating painful valgus arthritis of the knee. We... more Distal femoral osteotomy (DFO) is successful in treating painful valgus arthritis of the knee. We present a case where painless recurrent knee effusion was attributed to constitutional valgus. The absence of pain made the indication for surgery atypical so DFO was carefully considered and planned. A small correction was performed, bringing alignment closer to neutral with complete resolution of the recurrent effusion. We suggest that the indications for knee osteotomy can be expanded to include recurrent joint effusion in carefully selected patients.
We present a case of distal radius fracture. Several sequential unfortunate events resulted in a ... more We present a case of distal radius fracture. Several sequential unfortunate events resulted in a poor outcome. The patient was poorly selected because the degree of early dementia was not fully appreciated, due to intermittent periods of lucidity. Having elected to treat this distal radius fracture with Kirschner wires, a wire snapped during the procedure and was deemed safe to leave within the medullary cavity. Subsequently, the patient was left in a cast for 4 weeks without regular pin site inspection. When the cast was removed a gross osteomyelitis had developed. This series of events, led to unnecessary morbidity and extended the immobilisation time with reduced wrist function. This case highlights the importance of careful patient selection, surgical tactics and continuity of care.
High tibial osteotomy (HTO) is successful in treating symptomatic varus arthritis of the knee. We... more High tibial osteotomy (HTO) is successful in treating symptomatic varus arthritis of the knee. We present a case where ankle pain and instability were attributed to varus ankle malalignment. This was found to be secondary to constitutional varus of the proximal tibia but the patient's knee was asymptomatic. The decision to operate on an asymptomatic knee in the hope of improving ankle symptoms took a period of careful consideration, planning and discussion. HTO was performed without immediate complication and the patient reported an excellent outcome with marked improvement in Mazur's foot and ankle score from 18 to 85. In well selected and planned cases, HTO may be considered as an instrument of deformity correction with improvement in symptoms from joints distant to the surgical site.
Deficiencies in oxygenation are widespread in solid tumors. The tran- scription factor hypoxia-in... more Deficiencies in oxygenation are widespread in solid tumors. The tran- scription factor hypoxia-inducible factor (HIF)-1a is an important medi- ator of the hypoxic response of tumor cells and controls the up-regulation of a number of factors important for solid tumor expansion, including the angiogenic factor vascular endothelial growth factor (VEGF). We have isolated two cell lines nullizygous for HIF-1a, one
Influence of BMI upon patient outcomes and complications following THA was examined across a nati... more Influence of BMI upon patient outcomes and complications following THA was examined across a national cohort of patients. Outcomes were compared by BMI groups (19.0-29.9kg/m(2) [reference], 30.0-34.9kg/m(2) [obese class I], 35.0kg/m(2)+ [obese class II/III]), adjusted for case-mix differences. Obese class I patients had a significantly smaller improvement in OHS (18.9 versus 20.5, P<0.001) and a greater risk of wound complications (odds ratio [OR]=1.57, P=0.006). For obese class II/III patients, there were significantly smaller improvements in OHS and EQ-5D index (P<0.001), and greater risk of wound complications (P=0.006), readmission (P=0.001) and reoperation (P=0.003). Large improvements in patient outcomes were seen irrespective of BMI, although improvements were marginally smaller and complication rates higher in obese patients.
The sequential timing of cell-cycle transitions is primarily governed by the availability and act... more The sequential timing of cell-cycle transitions is primarily governed by the availability and activity of key cell-cycle proteins. Recent studies in yeast have identified a class of ubiquitin ligases (E3 enzymes) called SCF complexes, which regulate the abundance of proteins that promote and inhibit cell-cycle progression at the G1-S phase transition. SCF complexes consist of three invariable components, Skp1, Cul-1 (Cdc53 in yeast) and Rbx1, and a variable F-box protein that recruits a specific cellular protein to the ubquitin pathway for degradation. To study the role of Cul-1 in mammalian development and cell-cycle regulation, we generated mice deficient for Cul1 and analysed null embryos and heterozygous cell lines. We show that Cul1 is required for early mouse development and that Cul1 mutants fail to regulate the abundance of the G1 cyclin, cyclin E (encoded by Ccne), during embryogenesis.
Distal femoral osteotomy (DFO) is successful in treating painful valgus arthritis of the knee. We... more Distal femoral osteotomy (DFO) is successful in treating painful valgus arthritis of the knee. We present a case where painless recurrent knee effusion was attributed to constitutional valgus. The absence of pain made the indication for surgery atypical so DFO was carefully considered and planned. A small correction was performed, bringing alignment closer to neutral with complete resolution of the recurrent effusion. We suggest that the indications for knee osteotomy can be expanded to include recurrent joint effusion in carefully selected patients.
We present a case of distal radius fracture. Several sequential unfortunate events resulted in a ... more We present a case of distal radius fracture. Several sequential unfortunate events resulted in a poor outcome. The patient was poorly selected because the degree of early dementia was not fully appreciated, due to intermittent periods of lucidity. Having elected to treat this distal radius fracture with Kirschner wires, a wire snapped during the procedure and was deemed safe to leave within the medullary cavity. Subsequently, the patient was left in a cast for 4 weeks without regular pin site inspection. When the cast was removed a gross osteomyelitis had developed. This series of events, led to unnecessary morbidity and extended the immobilisation time with reduced wrist function. This case highlights the importance of careful patient selection, surgical tactics and continuity of care.
High tibial osteotomy (HTO) is successful in treating symptomatic varus arthritis of the knee. We... more High tibial osteotomy (HTO) is successful in treating symptomatic varus arthritis of the knee. We present a case where ankle pain and instability were attributed to varus ankle malalignment. This was found to be secondary to constitutional varus of the proximal tibia but the patient's knee was asymptomatic. The decision to operate on an asymptomatic knee in the hope of improving ankle symptoms took a period of careful consideration, planning and discussion. HTO was performed without immediate complication and the patient reported an excellent outcome with marked improvement in Mazur's foot and ankle score from 18 to 85. In well selected and planned cases, HTO may be considered as an instrument of deformity correction with improvement in symptoms from joints distant to the surgical site.
Deficiencies in oxygenation are widespread in solid tumors. The tran- scription factor hypoxia-in... more Deficiencies in oxygenation are widespread in solid tumors. The tran- scription factor hypoxia-inducible factor (HIF)-1a is an important medi- ator of the hypoxic response of tumor cells and controls the up-regulation of a number of factors important for solid tumor expansion, including the angiogenic factor vascular endothelial growth factor (VEGF). We have isolated two cell lines nullizygous for HIF-1a, one
Influence of BMI upon patient outcomes and complications following THA was examined across a nati... more Influence of BMI upon patient outcomes and complications following THA was examined across a national cohort of patients. Outcomes were compared by BMI groups (19.0-29.9kg/m(2) [reference], 30.0-34.9kg/m(2) [obese class I], 35.0kg/m(2)+ [obese class II/III]), adjusted for case-mix differences. Obese class I patients had a significantly smaller improvement in OHS (18.9 versus 20.5, P<0.001) and a greater risk of wound complications (odds ratio [OR]=1.57, P=0.006). For obese class II/III patients, there were significantly smaller improvements in OHS and EQ-5D index (P<0.001), and greater risk of wound complications (P=0.006), readmission (P=0.001) and reoperation (P=0.003). Large improvements in patient outcomes were seen irrespective of BMI, although improvements were marginally smaller and complication rates higher in obese patients.
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Papers by David Elson