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Biomedical subjects

S J Wilkinson

Publications and source records attributed to S J Wilkinson.

10 recordsLinked to original sources

Model fitting in two dimensions to small angle diffraction patterns from soft tissue.

In our research programme small angle x-ray scattering (SAXS) is used to provide information on the axial arrangement of collagen molecules as well as data about the state of other components of the extra cellular matrix (ECM) in human tissues. Derivation of parameters to describe and simplify the data is required for much of the SAXS patterns analysis. A method is presented here to achieve function fitting to collagen diffraction peaks along with a representation of the underlying diffuse scatter. A simple model was used which proved reliable in fitting a variety of 2D diffraction patterns. The logarithm of the scatter intensity over the area of the scatter image was taken to reduce the range and improve fitting accuracy. Our model was then used to fit the log data. The model consisted of a radial exponential diffuse scatter component added to a specified number of Gaussian peaks. In 2D the peak model is toroidal, each component being rotated about a common specified centre. Initial search parameters from a 1D averaged sector were supplied to the iterative 2D fitting routine. With the aid of data weighting and basic wavelet filtering, successful and reliable fitting of a specified 2D model to real data is achievable. The process is easily automated. Multiple SAXS patterns can be fitted without operator intervention. As described the model is simple enough to converge rapidly and yet allows image data to be parameterized to a form suitable for extracting the requisite information. The fitting method is flexible enough to be extended to achieve a more comprehensive and complex pattern fitting in two dimensions if this turns out to be necessary. It is our intention to implement orientation distribution functions in the near future by including an angular scaling factor.

Animals↗

A preliminary study of breast cancer diagnosis using laboratory based small angle x-ray scattering.

Breast tissue collected from tumour samples and normal tissue from bi-lateral mastectomy procedures were examined using small angle x-ray scattering. Previous work has indicated that breast tissue disease diagnosis could be performed using small angle x-ray scattering (SAXS) from a synchrotron radiation source. The technique would be more useful to health services if it could be made to work using a conventional x-ray source. Consistent and reliable differences in x-ray scatter distributions were observed between samples from normal and tumour tissue samples using the laboratory based 'SAXSess' system. Albeit from a small number of samples, a sensitivity of 100% was obtained. This result encourages us to pursue the implementation of SAXS as a laboratory based diagnosis technique.

Algorithms↗

The development of a blend-sampling technique to assess the uniformity of a powder mixture.

This article discusses the challenges overcome during the development of a blend-sampling technique and the successful validation of the blending operation for a tablet dosage form containing 2% active ingredient. Content uniformity results are discussedfor three pilot-scale (15-kg) and seven commercial-scale (150-kg) batches of tablets. Blend and core content uniformity data from the pilot-scale batches were acceptable. For the initial commercial-scale batches, although the tablet core content uniformity data were acceptable, the blend uniformity results were poor. The blend data for these batches had very high mean values, but acceptable relative standard deviations (RSDs). This suggested that the drug was being preferentially sampled by the thief but in a consistent, reproducible manner. Extensive testing was performed on a commercial-scale development batch to identify potential causes of sampling error. The results of this testing helped define the blend-sampling technique and strategy used to validate the mixing operation.

Bias↗

Spinous process strength.

STUDY DESIGN: Mechanical testing of cadaveric lumbar spines and dual energy radiograph absorptiometry scanning were performed. OBJECTIVES: To devise a technique to measure the strength of lumbar spinous processes and to determine the bone mineral density of the vertebrae used. SUMMARY OF BACKGROUND DATA: The spinous process has been identified as the weakest part of the anatomy to which a flexible fixation device can be attached. It was unknown if the spinous processes could withstand the forces applied by the device. METHODS: A hook was fitted to the spinous process of 32 lumbar vertebrae. A custom-built rig was designed to secure a vertebra to a materials testing machine. A loop of cord was passed over a bar mounted on the crosshead of the machine and around the two bollards of the hook. As the crosshead was raised, a tension was applied to the cord. Each vertebra was tested to failure. The bone mineral density of each vertebra was then measured using dual energy radiograph absorptiometry. RESULTS: Failure of the specimens occurred by failure of the spinous process, pedicles, or vertebral body. The logarithm (base 10) of the load (N) at which failure occurred was 2.53 +/- 0.3, which corresponded to a mean failure load of 339 N. The bone mineral density of each vertebral body varied between 0.263 and 0.997 g/cm2. A significant linear correlation was found between bone strength and bone mineral density (P < 0.0001). CONCLUSIONS: Specimens with a bone mineral density in the range of 0.263-0.997 g/cm2 failed at a mean load of 339 N when the load was applied through the spinous process hook of a flexible fixation device.

Absorptiometry, Photon↗

Two families with an autosomal dominant inheritance pattern for papillary carcinoma of the thyroid.

BACKGROUND: Papillary carcinoma of the thyroid (PTC) is the most prevalent malignancy of the thyroid gland. Although the majority of lesions are sporadic tumors, an established relationship exists between familial adenomatous polyposis (FAP) and PTC. Moreover, some authors postulate the existence of familial PTC as a distinct entity. Evidence for this is limited, however, there being few well characterized descriptions of pedigrees with high prevalence of PTC. AIMS: The objective of the present study was to examine an apparent heritable predisposition to PTC occurring in two Tasmanian families in which PTC occurs commonly. METHODS: Pedigree charts were constructed for both families and the medical records of the members reviewed. RESULTS: In Pedigree I, 7 of 25 members had PTC (6 of these had coexisting multinodular goiter (MNG), and 11 others had MNG. In Pedigree II, identical male twins and their daughters had PTC. CONCLUSIONS: In both families there is evidence of autosomal dominant inheritance of PTC. The association of PTC with MNG suggests a possible role for MNG in tumor pathogenesis in hereditary PTC. The majority of the patients were diagnosed with PTC before commencement of prospective screening, indicating clinically relevant disease in the families described.

Adult↗

Evidence that different regional sympathetic outflows vary in their sensitivity to the sympathoinhibitory actions of putative 5-HT1A and alpha 2-adrenoceptor agonists in anaesthetized cats.

1. An investigation was carried out to determine whether the centrally acting hypotensive drugs whose mechanisms of action are due either to activation of 5-HT1A receptors (flesinoxan, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and urapidil--also an alpha 1-adrenoceptor antagonist) or to activation of alpha 2-adrenoceptors (clonidine and moxonidine) cause differential sympathoinhibition. 2. Cats were anaesthetized with alpha-chloralose and simultaneous recordings were made of whole cardiac, splanchnic and renal nerve activity, blood pressure and heart rate. Cumulative dose-response (i.v.) curves were constructed in separate experiments for the above hypotensive agents on these parameters. 3. Renal nerve activity was found to be more sensitive to the sympathoinhibitory action of flesinoxan and 8-OH-DPAT when compared with cardiac nerve activity, whereas the reverse was observed for clonidine and moxonidine, cardiac being more sensitive than renal nerve activity. Splanchnic nerve activity was similarly affected by all drugs. Furthermore at the highest dose, all drugs tended to cause complete inhibition in all regional sympathetic nerve outflows. 4. Urapidil differed from all the above hypotensive drugs in that it caused a similar degree of sympathoinhibition in all sympathetic outflows at all doses. It is suggested that this may be due to the ability of urapidil to block central alpha 1-adrenoceptors in addition to stimulation of 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Global ratings of stress in the elderly.

The properties of four global ratings of life stress were investigated using data from 237 elderly subjects interviewed using the Brown & Harris life event and difficulties schedule. The global ratings had high one-year test-retest reliability and inter-rater reliability agreement. A summary measure of Adversity (based on contextual rating of all events and difficulties) may be reliably derived when a single index of life stress is desired. In the elderly sample Adversity was more closely related to chronic difficulties than to life-events.

Adaptation, Psychological↗

Comparison of the haemodynamic actions of neuropeptide Y, angiotensin II and noradrenaline in anaesthetised cats.

Blood pressure, heart rate, cardiac output, renal flow and femoral flow were recorded in open-chested anaesthetised cats. Dose-response curves were constructed for neuropeptide Y, angiotensin II and noradrenaline after pretreatment with atropine sulphate. Neuropeptide Y, on a molar basis, was 7 and 120 times less potent than noradrenaline and angiotensin, respectively, in producing a 50 mm Hg rise in mean arterial blood pressure. The pressor effect of neuropeptide Y was characterised by dose-dependent increases in total peripheral, renal and femoral resistance with little change in cardiac output. Neuropeptide Y had a similar potency to noradrenaline in causing these resistance changes. However, the pressor response to noradrenaline was associated with a dose-dependent increase in cardiac output. The pressor action of neuropeptide Y was not attenuated by adrenoceptor blockade by phenoxybenzamine (5 mg kg-1) and propranolol (1 mg kg-1).

Anesthesia↗

Rating reliability for life events and difficulties in the elderly.

The inter-rater reliability of Brown's measure of ongoing difficulties ('severity') is shown to be comparable with that of the measure of life events ('long-term threat') when using data from an elderly subject pool. Test-retest reliabilities for both the life event and difficulty measures are shown to be adequate if based on 'consensus' ratings. The question is raised of generalizability of the concepts of 'threat' and 'severity' across the lifespan.

Adaptation, Psychological↗