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Biomedical subjects

E D Williams

Publications and source records attributed to E D Williams.

At least 19 recordsLinked to original sources
PubMed2006

Chernobyl and thyroid cancer.

The most dramatic effect of exposure to fallout from the Chernobyl accident on physical health has been the increase in thyroid cancer. When this was first reported 1,2, there was scepticism in Europe and the US, as it was not thought plausible that exposure to radio-isotopes of iodine in fallout could lead to such an increase in thyroid cancer with such a short latency. This review will discuss the lessons to be learnt from a re-examination of the reasons for the original scepticism, together with what is currently known about the factors that have influenced the development of excess thyroid cancers in those exposed, the number and type of cancers that have occurred, and the interaction between tumor morphology, molecular pathology, clinical behavior, and latent period.

Adult↗
PubMed2006

Alpha4beta2 nicotinic receptor status in Alzheimer's disease using 123I-5IA-85380 single-photon-emission computed tomography.

BACKGROUND: Loss of the alpha4beta2 nicotinic receptor subtype is found at autopsy in Alzheimer's disease. OBJECTIVE: To investigate in vivo changes in this receptor using single-photon-emission CT (SPECT) with 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (5IA-85380), a novel nicotinic acetylcholine receptor ligand which binds predominantly to the alpha4beta2 receptor. METHODS: 32 non-smoking subjects (16 with Alzheimer's disease and 16 normal elderly controls) underwent 123I-5IA-85380 and perfusion (99mTc-hexamethylenepropyleneamine oxime (HMPAO)) SPECT scanning. Region of interest analysis was performed with cerebellar normalisation. RESULTS: Significant bilateral reductions in nicotinic receptor binding were identified in frontal (left, p = 0.004; right, p = 0.002), striatal (left, p = 0.004; right, p = 0.003), right medial temporal (p = 0.04) and pons (p<0.001) in patients with AD compared to controls. There were no significant correlations with clinical or cognitive measures. The pattern of nicotinic binding significantly differed from that of perfusion in both patients with AD and controls. Both 123I-5IA-85380 and 99mTc-HMPAO SPECT imaging demonstrated similar diagnostic performance in correctly classifying controls and patients with AD. CONCLUSION: Using 123I-5IA-85380 SPECT we found changes consistent with significant reductions in the nicotinic alpha4beta2 receptor in cortical and striatal brain regions. This method could facilitate diagnosis and may be useful for monitoring progression of the disease and response to treatment in patients with AD and related diseases.

Aged↗
PubMed2006

Distinctive fluctuations in a confined geometry.

Spurred by recent theoretical predictions [Phys. Rev. E 69, 035102(R) (2004)10.1103/PhysRevE.69.035102; Surf. Sci. Lett. 598, L355 (2005)10.1016/j.susc.2005.09.023], we find experimentally using STM line scans that the fluctuations of the step bounding a facet exhibit scaling properties distinct from those of isolated steps or steps on vicinal surfaces. The correlation functions go as t0.15 +/- 0.03 decidedly different from the t0.26 +/- 0.02 behavior for fluctuations of isolated steps. From the exponents, we categorize the universality, confirming the prediction that the nonlinear term of the Kardar-Parisi-Zhang equation, long known to play a central role in nonequilibrium phenomena, can also arise from the curvature or potential-asymmetry contribution to the step free energy.

Journal Article↗
PubMed2006

A new form of familial multi-nodular goitre with progression to differentiated thyroid cancer.

We report a kindred with euthyroid multi-nodular goitre (MNG) of adolescent onset. Two of the seven subjects with MNG have progressed to papillary thyroid cancer. One affected male had nodular kidney disease, and breast cancer occurred in one affected female. Genes that were candidates on the basis of the associated kidney (PAX8) and breast diseases (sodium iodide symporter (NIS)), were sequenced. No mutations were found in the coding region, intron/exon splice sites or in the promoter sequences (from -1248 relative to the translation initiation codon) of PAX8. Similar results were obtained for NIS. Subsequently, microsatellite analyses were performed on 14 informative family members. We used 2 to 3 markers per locus for 6 loci (on chromosomes 1,2,3,14,19,X) previously reported to predispose to MNG and/or familial non-medullary thyroid cancer (FNMTC). On the basis of non-significant logarithm of the odds ratio (LOD) scores or inheritance of different alleles in affected individuals, all loci have been excluded. Thyroidectomy specimens from three members of the kindred show multiple benign lesions, with papillary cancer in two. The morphological features do not resemble those seen in familial adenomatous polyposis, Cowden syndrome, or in multiple oxyphil lesions. From these findings and from the absence of any linkage to any of the known loci associated with MNG or FNMTC, we suggest that this represents a new form of inherited MNG with a significant risk of progression to papillary carcinoma.

Adolescent↗
PubMed2005

Spiral evolution in a confined geometry.

Supported nanoscale lead crystallites with a step emerging from a noncentered screw dislocation on the circular top facet were prepared by rapid cooling from just above the melting temperature. STM observations of the top facet show a nonuniform rotation rate and shape of the spiral step as the crystallite relaxes. These features can be accurately modeled using curvature driven dynamics, as in classical models of spiral growth, with boundary conditions fixing the dislocation core and regions of the step lying along the outer facet edge.

Journal Article↗
PubMed2005

Metallothionein crypt-restricted immunopositivity indices (MTCRII) correlate with aberrant crypt foci (ACF) in mouse colon.

Metallothionein (MT) crypt-restricted immunopositivity indices (MTCRII) are colonic crypt stem cell mutation markers that may be induced early and in abundance after mutagen treatment. Metallothionein is the endogenous reporter gene for MTCRII, but is not typically implicated in the classical pathway of colorectal tumorigenesis. Hence, the oncological relevance of MTCRII is unclear. This study tests the hypothesis that MTCRII induced by N-methyl-N-nitrosourea (MNU) and lambda carrageenan (lambdaCgN) associate with aberrant crypt foci (ACF) in mouse colon. Undegraded lambdaCgN and MNU were tested alone and in combination against MTCRII and ACF in Balb/c mice, at 20 weeks after the start of treatment. MTCRII were unaffected by lambdaCgN alone. Combined lambdaCgN/MNU treatments induced greater MTCRII (P < 0.01) as well as greater number (P < 0.001) and crypt multiplicity (P < 0.01) of ACF than MNU alone. MTCRII were approximately 10-fold more numerous than ACF, although linear correlations were observed between these parameters (r = 0.732; P < 0.01). MTCRII are induced by lambdaCgN/MNU interactions in sufficient numbers to provide statistical power from relatively small sample sizes and correlate with ACF formation. MTCRII could thus provide the basis for a novel medium-term murine bioassay relevant to early-stage colorectal tumorigenesis.

Animals↗
PubMed2005

Sampling-time effects for persistence and survival in step structural fluctuations.

The effects of sampling rate and total measurement time have been determined for single-point measurements of step fluctuations within the context of first-passage properties. Time dependent scanning tunneling microscopy has been used to evaluate step fluctuations on Ag(111) films grown on mica as a function of temperature (300-410 K) , on screw dislocations on the facets of Pb crystallites at 320 K , and on Al-terminated Si(111) over the temperature range 770-970 K . Although the fundamental time constant for step fluctuations on Ag and Al/Si varies by orders of magnitude over the temperature ranges of measurement, no dependence of the persistence amplitude on temperature is observed. Instead, the persistence probability is found to scale directly with t/delta t where delta t is the time interval used for sampling. Survival probabilities show a more complex scaling dependence, which includes both the sampling interval and the total measurement time t(m) . Scaling with t/delta t occurs only when delta t/ t(m) is a constant. We show that this observation is equivalent to theoretical predictions that the survival probability will scale as delta t/ L(z) , where L is the effective length of a step. This implies that the survival probability for large systems, when measured with fixed values of t(m) or delta t , should also show little or no temperature dependence.

Journal Article↗
PubMed2005

Effects of repeated drill use on temperature of bone during preparation for osteosynthesis self-tapping screws.

Drills used during preparation for osteosynthesis with self-tapping screws are often used repeatedly until they become blunt and ineffective. Because the sharpness of the drill is one of the most important factors in its cutting efficiency, blunt drills may require the application of extra force, which in turn may contribute to excessive frictional heat produced during preparation of screw holes. Large rises in temperature can impair bony regeneration around screws and contribute to failure of internal fixation. In an attempt to quantify the potential increase in temperature produced by blunt drills, we devised an in vitro experiment to simulate preparation for osteosynthesis by using drills with different degrees of wear. Three drills were used: one was new, one had drilled 600 holes, and the third drill had been in use in theatre for several months. The mean (range) rise in temperature for the three drills were: new drill 7.5 degrees C (0.6-20.5 degrees C); drill after 600 holes 13.4 degrees C (5.7-28.3 degrees C); and drill from theatre 25.4 degrees C (12.4-41.3 degrees C). There was a highly significant difference in the temperatures generated by the three drills, and the changes in temperature were related to the amount of wear. The cost of drills is low, and as their repeated use can compromise the results of the operation they must be discarded after single use.

Animals↗
PubMed2004

Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness.

The large numbers of papillary thyroid carcinomas that have occurred in those exposed to high levels of short-lived isotopes in fallout after Chernobyl provide a unique opportunity to correlate latency and tumour biology. We show that short latency is associated with tumours with a phenotype that is significantly less structurally differentiated, shows significantly less peritumour fibrosis, and significantly more invasive spread when compared to tumours with a longer latent period. In contrast, the type of differentiation (papillary or follicular architecture) is associated with age at exposure. These findings suggest that the initial mutation at the time of exposure played a major role in tumour latency and aggressiveness. We and others have shown that RET-PTC3 rearrangements are associated with the solid morphology seen in these short latency tumours, while classical papillary carcinomas more often show RET-PTC1 rearrangements. Studies in transgenic mice show similar findings, and in vitro studies show that RET-PTC3 induces more rapid growth than RET-PTC1. We therefore suggest that the solid morphology, high frequency of RET-PTC3 rearrangements and aggressive behaviour noted in early investigations of post-Chernobyl tumours were characteristic of short latency rather than the nature of the mutagen, and that successive overlapping waves of papillary carcinoma with differing latency, differing patterns of mutations and differing clinical behaviour are occurring in those exposed to Chernobyl fallout.

Adolescent↗
PubMed2004

The application of serial MRI analysis techniques to the study of cerebral atrophy in late-onset dementia.

We have used a serial MR image analysis technique previously developed for studies of cerebral atrophy in early-onset dementia and applied it to a study of late-onset dementia patients with images acquired using a different scanner and scan sequence. Validation and optimisation tests showed that with only small changes to key analysis parameters the technique can successfully be applied to previously untested data with dissimilar image characteristics. The overall accuracy in estimation of cerebral atrophy using the technique was determined to be between 2 and 4 ml (1sigma) depending on the conditions during image acquisition. By comparing the results of alternative registration techniques we demonstrate the potential of using of fully automated 9 DOF image registration as an effective and efficient means of correcting for scanner pixel size variations, even in the presence of significant cerebral atrophy. Applied to the late-onset dementia study, patients were found to have significantly increased mean atrophy rates (p<0.001) compared to controls. In general the analysis technique is shown to be a robust, accurate and transferable tool of potential value for future studies of dementia and related neuro-degenerative disorders.

Adult↗
PubMed2003

Infinite family of persistence exponents for interface fluctuations.

We show experimentally and theoretically that the persistence of large deviations in equilibrium step fluctuations is characterized by an infinite family of independent exponents. These exponents are obtained by carefully analyzing dynamical experimental images of Al/Si(111) and Ag(111) equilibrium steps fluctuating at high (970 K) and low (320 K) temperatures, respectively, and by quantitatively interpreting our observations on the basis of the corresponding coarse-grained discrete and continuum theoretical models for thermal surface step fluctuations under attachment/detachment ("high-temperature") and edge-diffusion limited kinetics ("low-temperature"), respectively.

Journal Article↗
PubMed2003

Can monocortical miniplates provide bony compression?. An experimental model.

Some maxillofacial surgeons advocate that screws in monocortical plate systems be placed eccentrically in an attempt to provide compression between bony ends. We sought to quantify the degree of displacement and compressive forces made possible by such eccentric placement in an experimental model using five miniplates and Perspex blocks to simulate mandibular fractures. The maximum displacement obtained was 0.67 mm and the maximal compressive force 5.2N (SEM=0.9, range=2.7-7.1). This demonstrates that eccentric placement of screws can achieve some compression and displacement at the fracture interface and that the forces obtained are close to those predictable from the dimensions of the burr, screw, and miniplate.

Bone Plates↗
PubMed2003

Parathyroid hormone-related peptide modulates signal pathways in skin and hair follicle cells.

Parathyroid hormone-related protein (PTHrP) is secreted by skin epithelial cells and is thought to play an important role in the development and function of the hair follicle. It was hypothesized that PTHrP binds to receptors in dermal papilla cells and modulates intracellular signaling systems in these cells. We tested the effects of PTHrP on protein synthesis, protein kinase A (PKA) and protein kinase C (PKC) activities as well as tyrosine phosphorylation in rat vibrissa dermal papilla and capsular fibroblast cells. Cells were cultured in the presence or absence of the N-terminal peptide PTHrP1-34 for 48 h and detergent extracts prepared. Proteins were separated by electrophoresis. Phosphotyrosine and the PTH/PTHrP receptor immunoreactivity was identified by Western blot analysis. PKC and PKA activities in the cells were measured using colorimetric enzyme assays. Extracts of both dermal papilla cells and capsular fibroblasts displayed immunoreactivity to the PTH/PTHrP receptor. Electrophoresis showed that PTHrP treatment reduced the density of a 50-kDa protein in dermal papilla cells but not in capsular fibroblasts. Media conditioned by the cells showed similar changes, indicating that the PTHrP-modulated 50-kDa protein was secreted. Furthermore, 2-D gel electrophoresis indicated that the protein had a number of phosphorylation sites. Western analysis with antiphosphotyrosine antibodies confirmed a significant decrease in the intensity of a phosphorylated 50-kDa protein in papilla cells and papilla cell-conditioned medium. PKC and PKA activities of papilla cells were unaffected by PTHrP. However, activities of PKC were increased and PKA reduced in capsular fibroblasts following peptide treatment. These cell-specific effects showed that endogenous PTHrP may activate different intracellular pathways in mesenchymal cells of skin and elicit changes in levels of locally secreted proteins that specifically modulate normal follicular function.

Animals↗
PubMed2003

Evaluation of calcaneus bone densitometry against hip and spine for diagnosis of osteoporosis.

Dual X-ray absorptiometry (DXA) is now widely available as a method for assessing bone density. However, the place of peripheral bone densitometry in clinical practice for diagnosis of osteoporosis is not yet clear. To examine the potential use in our district general hospital setting, we compared calcaneus measurements with conventional DXA of the hip and spine in 100 patients referred for assessment following identification of risk factors for osteoporosis. Measurements were made on both heels and the results were found to be similar but not completely interchangeable. Use of receiver operating characteristic curves confirmed that a threshold T-score of -1.6 could be used to identify many of the high risk subjects. However, there was only moderate agreement between fracture risk classifications derived from heel T-scores, and diagnostic classification (osteoporosis/osteopenia/normal) derived from axial DXA. The specificity of heel measurements was high, but sensitivity was poorer. Heel measurements could therefore be valuable in some circumstances for finding patients for whom treatment of osteoporosis would be appropriate, such as in a population with a low prevalence of osteoporosis. They may also be of value in a population with a high prevalence of disease, particularly if there were no alternative means of bone densitometry. However, with an intermediate prevalence, the relatively high risk of false negative values would mean that false reassurance could be given to many of those classed as "low risk". This could be a major drawback in clinical practice if heel densitometry were used as the initial investigation and axial measurements were also available, since they would give conflicting results for a substantial proportion of these patients.

Absorptiometry, Photon↗
PubMed2002

Experimental persistence probability for fluctuating steps.

The persistence behavior for fluctuating steps on the Si(111)-(sqrt[3]xsqrt[3])R30 degrees -Al surface was determined by analyzing time-dependent STM images for temperatures between 770 and 970 K. Using the standard persistence definition, the measured persistence probability displays power-law decay with an exponent of theta=0.77+/-0.03. This is consistent with the value of theta=3/4 predicted for attachment-detachment limited step kinetics. If the persistence analysis is carried out in terms of return to a fixed-reference position, the measured probability decays exponentially. Numerical studies of the Langevin equation used to model step motion corroborate the experimental observations.

Journal Article↗
PubMed2002

Assessment of the physical properties of endoscopic retrieval systems.

BACKGROUND: A reliable method of retrieval of laparoscopically resected organs is required. The physical properties of three commercial systems available for clinical use (two plastic, one woven fabric) were examined. METHODS: Pig abdominal walls and gallbladders containing steel balls to represent gallstones were used to simulate organ retrieval on 60 occasions. The performance of retrieval bags was measured in terms of the temporal profile of pressure developed inside the bag, the force on the bag during withdrawal, and whether or not the bag could be retrieved intact. The force versus elongation relationship was also determined for each bag. RESULTS: Although there was a wide range of maximum pressures recorded (14-320 mmHg) with each retrieval system, the mean pressures in the plastic systems were significantly higher. The forces recorded during attempted withdrawal of both plastic bags were significantly lower than those with the fabric system (BERT bag: mean (range) 87 (25-165) N; Endocatch: 40 (7-123) N; Endopouch: 40 (14-68) N; P = 0.005 Endocatch versus BERT, P = 0.004 Endopouch versus BERT). The BERT bags tore more easily at the site of the grasper. CONCLUSION: Plastic retrieval systems were less likely to burst than fabric systems when subjected to simulated retrieval, and required less force for withdrawal. Plastic systems may therefore be associated with less tumour seeding or gallstone spillage as a consequence of bag disruption.

Animals↗