Colorectal cancer risk assessment and screening recommendation: a community survey of healthcare providers' practice from a patient perspective

<p>Abstract</p> <p>Background</p> <p>Family history is a common risk factor for colorectal cancer (CRC), yet it is often underused to guide risk assessment and the provision of risk-appropriate CRC screening recommendation. The aim of this study was to identify from a patient perspective health care providers' current practice relating to: (i) assessment of family history of CRC; (ii) notification of "increased risk" to patients at "moderately/potentially high" familial risk; and (iii) recommendation that patients undertake CRC screening.</p> <p>Methods</p> <p>1592 persons aged 56-88 years randomly selected from the Hunter Community Study (HCS), New South Wales, Australia were mailed a questionnaire. 1117 participants (70%) returned a questionnaire.</p> <p>Results</p> <p>Thirty eight percent of respondents reported ever being asked about their family history of CRC. Ever discussing family history of CRC with a health care provider was significantly more likely to occur for persons with a higher level of education, who had ever received screening advice and with a lower physical component summary score. Fifty one percent of persons at "moderately/potentially high risk" were notified of their "increased risk" of developing CRC. Thirty one percent of persons across each level of risk had ever received CRC screening advice from a health care provider. Screening advice provision was significantly more likely to occur for persons who had ever discussed their family history of CRC with a health care provider and who were at "moderately/potentially high risk".</p> <p>Conclusions</p> <p>Effective interventions that integrate both the assessment and notification of familial risk of CRC to the wider population are needed. Systematic and cost-effective mechanisms that facilitate family history collection, risk assessment and provision of screening advice within the primary health care setting are required.</p

Interactions of D-amphetamine with the active site of monoamine oxidase A

Reversible monoamine oxidase A inhibitors (RIMA) are used as antidepressants but little is known about how they interact with the active site of the enzyme. Heterologous expression of human liver MAO-A in yeast provides sufficient protein for molecular studies and direct observation of the changes in the spectrum of the FAD co-factor when inhibitors bind. Using the reversible inhibitor, D-amphetamine, as a model compound, a concentration-dependent change in the spectrum with clean isosbestic points was observed. The decrease in absorbance between 400 and 500 nm gave a dissociation constant for binding similar to the K(i) value. Anaerobic reduction yielded the semiquinone spectrum only and the midpoint potential was the same as the free enzyme. Full reduction was not possible with dithionite as the reductant, suggesting that the semiquinone-reduced couple had a much lower midpoint potential than the free enzyme. In contrast, with substrate, which reduces the enzyme on an equimolar basis, the semiquinone is never seen. In anaerobic stopped-flow experiments, amphetamine inhibits completely the reoxidation of the reduced enzyme in contrast to a substrate such as 2-phenylethylamine (the desmethyl analogue of amphetamine) that accelerates the rate 12-fold. The spectral changes in MAO-A permit the examination of inhibitor interaction with the redox co-factor. Stacking of the inhibitor and flavin rings constitutes part of the interaction but, taking into account other evidence, steric factors may be the clue to the differences between substrate and inhibitor

Angular dependence of electron paramagnetic resonance of an azide-NO complex of cytochrome c oxidase: orientation of the haem-copper axis in cytochrome aa3 from ox heart

AbstractThe orientation dependence of the EPR signals arising from the azide–nitric oxide complex of cytochrome oxidase was investigated using oriented multilayers of mitochondrial membranes from ox heart. Variations in line shape of the ΔMS=1 signal of the triplet state were apparent, whilst the ΔMS=2 transitions between g=4.7 and 3.9 varied in intensity as the angle of the applied magnetic field was varied. These half-field signals were maximal with the field parallel to the membrane plane. A model of the bi-liganded azide–nitric oxide complex has been constructed, in which the nitric oxide is bound to the high-spin haem in a bent configuration, with the Fe–NO plane at 60–90° to the membrane plane and the azide bound to the copper, distal from the haem. In addition, angular variations of the signals at g′=11 and g′ around 3.5, derived from an integer–spin complex, were also observed

Analysis of the domain properties of the novel cytochrome P450 RhF

The properties of the heme, flavin mononucleotide (FMN) and FeS domains of P450 RhF, from Rhodococcus sp. NCIMB 9784, expressed separately and in combination are analysed. The nucleotide preference, imidazole binding and reduction potentials of the heme and FMN domains are unaltered by their separation. The intact enzyme is monomeric and the flavin is confirmed to be FMN. The two one-electron reduction potentials of the FMN are -240 and -270 mV. The spectroscopic and thermodynamic properties of the FeS domain, masked in the intact enzyme, are revealed for the first time, confirming it as a 2Fe-2S ferredoxin with a reduction potential of -214 mV