An examination of the reproducibility of three tests for identifying patients at risk of diabetic foot complications is reported. One thousand and one patients attending a general diabetic outpatient clinic at the Royal Liverpool University Hospital underwent screening using the Semmes‐Weinstein monofilaments, the biothesiometer, and palpation of pedal pulses. Two hundred and fifty‐nine patients who were found to have a deficit on at least one of these tests were given a second appointment where the tests were repeated. Two hundred and twenty‐nine patients attended for their second appointment. The expected range of variation in readings for the biothesiometer was 5 log hertz, sufficient variation to make the biothesiometer unacceptable as a screening instrument. The range of reproducibility for the four pedal pulses was from 68 % to 81 %, also an unacceptable level of variation. Over 85 % of the results for the Semmes–Weinstein monofilaments were the same on the first and second measurement. Of the three instruments examined in this study, only the Semmes–Weinstein monofilaments have sufficient reproducibility in the clinical setting for them to be recommended for general use as a screening test for risk of diabetic foot complications.
There have been significant advances in our understanding of carcinogenesis at the molecular level over the last 25 years. Oncogenes are of major interest as part of our search for knowledge surrounding the aetiology of cancer. There are several oncogenes associated with thyroid cancer. Detailed investigation of the nature and function of these tumour genes has provided important insights into both the tumour biology and the complex biochemical pathways of normal cellular functioning. Our knowledge of oncogene biology offers the hope of better diagnostic, therapeutic and prognostic modalities in our fight against this and other common cancers. Development of specific thyroid tumour markers and gene therapy is now a realistic prospect to supplement our present armamentarium of surgery and radiotherapy. This review aims to outline the pertinent information gained so far from studies of these oncogenes and provides both clinical relevance and fuel for further interest amongst the ENT thyroid community in this exciting area of research.
The key mitotic regulator securin is expressed at low levels in fetal brain compared with adult, and modulates the proliferation of human embryonic neuronal N-Tera2 (NT2) cells. We now examine the function and expression of securin's interacting partner separase, along with Rad21, the functional component of cohesin, which is cleaved by separase following interaction with securin. In contrast to securin, the cleaved forms of separase and Rad21 were highly expressed in human fetal cerebral cortex compared with adult. In a murine model of absent securin expression - the PTTG knock-out mouse - separase and Rad21 were over-expressed in multiple brain regions. In addition, cDNA array analysis of other key mitotic regulators additionally identified cyclin C and sestrin 2 to be induced in the brains of securin-null mice compared with wild type. Further, Rad21 mRNA expression was highly correlated with that of securin, separase, cyclin C and sestrin 2 in fetal brains. In embryonic neuronal NT2 cells, siRNA repression of separase failed to significantly alter cell turnover, whereas repression of securin expression resulted in increased levels of the activated forms of Rad21 and separase, and promoted cell proliferation. Our data suggest that the co-ordinated expression of separase, securin and Rad21 is fundamental for the developing brain.
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