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Biomedical subjects

N Williams

Publications and source records attributed to N Williams.

At least 109 records · Page 6Linked to original sources
PubMed1999

Radial scar and carcinoma of the breast: microscopic findings in 32 cases.

We retrospectively reviewed the microscopic findings in 32 histologically confirmed radial scars in 31 women diagnosed in our unit during 1994-1998. The median age at diagnosis was 53 years (range 47-63 years). Thirty-one (97%) of 32 lesions presented as screen detected mammographic abnormalities (28 stellate lesions, 2 microcalcifications and only 1 architectural distortion). One lesion presented as a palpable breast mass. Stereotactic or ultrasound-guided fine needle aspiration cytology (FNAC) was performed in 28 cases. Cytological analysis of FNAs revealed malignant cells (C5) in 8 (29%) cases, highly suspicious cells (C4) in 3 (11%) cases, atypical benign cells (C3) in 7 (25%) cases and benign epithelial cells (C2) in 10 (35%) cases. All non-palpable lesions were surgically excised following wire localization. Histological examination of the breast specimens (mean weight=16 g) demonstrated, in addition to a radial scar, 6 invasive carcinomas (2 infiltrating ductal, 2 tubular, 1 mixed ductal/lobular and 1 secretory carcinoma) and 4 ductal carcinoma in situ lesions (2 high grade, 1 high grade with micro-invasion and 1 low grade) arising in the radial scar. Of the remaining cases the radial scar was associated with atypical epithelial hyperplasia in 2 cases and regular epithelial hyperplasia in 17 cases (4 florid and 13 mild to moderate). In the 10 cases associated with malignancy, 9 had FNAC and was reported as malignant (C5) in 6 (67%) cases, highly suspicious (C4) in 2 (22%) cases and atypical (C3) in 1 (11%). False positive FNAC (C5) occurred in two patients, one of whom presented with pleomorphic microcalcifications suggestive of ductal carcinoma in situ. This patient was treated with a wire guided segmental mastectomy. All invasive tumours were less than 20 mm in size (T1) and of these 4 were grade I and 2 were grade II. Axillary dissection was performed in 4 patients none of whom had axillary node metastases. Our study demonstrates a significant incidence of malignancy associated with radial scars (31%) suggesting that radial scars may be premalignant lesions. This is supported by detecting various stages of mammary carcinogenesis (atypical epithelial hyperplasia, ductal carcinoma in situ, and early invasive malignancy) in these lesions. Fine needle aspiration cytology seems to be unreliable in the diagnosis of radial scar associated malignancy (67% sensitivity and 91% specificity). Stellate lesions, therefore, should be excised to obtain an histological diagnosis regardless of cytological findings. Further studies examining the biology of radial scars are required.

Journal Article↗
PubMed1999

A full genome scan for late onset Alzheimer's disease.

We have genotyped 292 affected sibling pairs (ASPs) with Alzheimer's disease (AD) according to NINCDS-ADRDA diagnostic criteria and with onset ages of >/=65 years using 237 microsatellite markers separated by an average distance of 16.3 cM. Data were analysed by SPLINK and MAPMAKER/SIBS on the whole sample of 292 ASPs and subsets of 162 ASPs where both members possessed an apolipoprotein E (APOE)straightepsilon4 allele and 63 pairs where neither possessed anstraightepsilon4 allele. Sixteen peaks with a multipoint lod score (MLS) >1 either in the whole sample, the straightepsilon4-positive or -negative subgroups were observed on chromosomes 1 (two peaks), 2, 5, 6, 9 (two peaks), 10 (two peaks), 12, 13, 14, 19, 21 and X (two peaks). Simulation studies revealed that these findings exceeded those expected by chance, although many are likely to be false positives. The highest lod scores on chromosomes 1 (MLS 2.67), 9 (MLS 2.38), 10 (MLS 2.27) and 19 (MLS 1.79) fulfilLander and Kruglyak's definition of 'suggestive' in that they would be expected to occur by chance once or less per genome scan. Several other peaks were only marginally less significant than this, in particular those on chromosomes 14 (MLS 2.16), 5 (MLS 2.00), 12, close to alpha2-macroglobulin (MLS 1.91), and 21, close to amyloid precursor protein (MLS 1.77). This is the largest genome scan to date in AD and shows for the first time that this is a genetically complex disorder involving several, perhaps many, genes in addition to APOE. Moreover, our data will be of interest to those hoping to identify positional candidate genes using information emerging from neurobiological studies of AD.

Age of Onset↗
PubMed1999

Evaluation of a local cooperative project to improve postoperative pain management in Wisconsin hospitals.

The effectiveness of a local collaborative quality improvement project in improving the management of postoperative pain for Wisconsin Medicare patients was assessed. Six quality indicators were evaluated on the basis of baseline data from 714 subjects at 15 collaborating hospitals and follow-up data from 406 subjects from the same 15 hospitals. After efforts to improve postoperative pain management, there was statistically significant improvement in all six quality indicators.

Aged↗
PubMed1999

Follow up of workers previously exposed to silver solder containing cadmium.

OBJECTIVES: To study longitudinal biological monitoring data on urinary and blood cadmium collected in a small cohort of nine workers who had been brazing for several years with solders containing cadmium. METHODS: Cadmium was measured by neutron activation analysis in livers and kidneys, and estimates of renal function were carried out in 1983 and 1995. During the intervening period exposure to cadmium was dramatically reduced by local exhaust ventilation control and substitution of the solder containing cadmium. RESULTS: From urinary protein measurements there was evidence within the group of increasing renal tubular damage over the 12 year period, even though exposure to cadmium was dramatically reduced over this period and almost eliminated by 1995. There was no evidence from serum creatinine of decreasing glomerular filtration rate, and the renal tubular handling of calcium, phosphate, or urate had not worsened significantly. Blood and urinary cadmium concentrations reduced significantly over the 12 year period but were still substantial in 1995. Blood cadmium concentrations tended to reflect cadmium body burden in 1995 when exposure had been low for several years, and decreased most significantly during 1983-90. By contrast urinary cadmium concentrations only decreased significantly from about 1990 onwards. Urinary cadmium was not significantly correlated with liver or kidney cadmium concentration in either 1983 or 1995. This may be due to the level of tubular dysfunction in the cohort. Calculated cumulative excretion of cadmium over the 12 year period was substantially greater than the loss of cadmium measured in livers and kidneys and the derived loss in body burden. Reasons for this are discussed. It is possible that in cohorts, where renal damage is apparent, urinary concentrations reflect a substantial component of current exposure rather than stored body losses. CONCLUSIONS: The data reinforce the concept that blood cadmium concentrations may not always reflect recent exposure, but may reflect body burden derived from historical exposure depending on the degree of current exposure; and that the decline in urinary and blood cadmium measurements after removal from, or reduction in, exposure will be slow and depend on the historical body burden.

Adult↗
PubMed1999

Fluorescence studies of lens epithelial cells and their constituents.

Steady-state and time-resolved fluorescence measurements have been made of human and rabbit lens epithelial cells and their total soluble protein. Excitation at 350 nm results in broad fluorescence spectra peaking at 450 nm and stretching into the visible past 650 nm. The fluorescence excitation spectra peak around 350 nm. We assign the species responsible for this absorption and fluorescence as NADPH. Because the absorption of near-UV light (300-400 nm) is responsible for cell damage and death, we postulate that excited states of NADPH are implicated in the mechanisms of cell damage. Preirradiation with 355 nm light leads to a loss of NADPH fluorescence but with no change in decay kinetics. Possible mechanisms for cell damage are explored.

Animals↗
PubMed1998

Genetic studies on chromosome 12 in late-onset Alzheimer disease.

CONTEXT: The only genetic locus universally accepted to be important as a risk factor for late-onset Alzheimer disease (AD) is the apolipoprotein E (APOE) locus on chromosome 19. However, this locus does not account for all the risk in late-onset disease, and a recent report has suggested a second locus on chromosome 12p11-12. OBJECTIVE: To look for evidence of linkage on chromosome 12 and to test for the presence of the new locus in an independent sample of familial late-onset AD cases. DESIGN: Retrospective cohort study. As part of a 20-centimorgan genome screen (approximately equal to 200 markers), we tested a series of 18 genetic markers on chromosome 12 and carried out multipoint, nonparametric lod score and exclusion analyses. SETTING: Clinic populations in the continental United States selected from the National Institute of Mental Health AD Genetics Consortium. PATIENTS: We selected samples for DNA analysis from affected sibling pairs, 497 subjects from 230 families with 2 or more affected individuals with probable or definite AD with onset ages older than 60 years (mean+/-SD, 75+/-6 years). Within the families, we used the 2 probable or definitely affected individuals. In families with more than 2 such cases available, we used all of them; in families with only 2 such cases in which unaffected individuals were available, we also sampled the oldest unaffected individual and used genotype data from this unaffected individual to check for nonpaternity and genotyping errors. MAIN OUTCOME MEASURE: Presence of linkage or locus on chromosome 12. RESULTS: Although linkage analyses confirmed the presence of a genetic susceptibility factor at the APOE locus in these families with late-onset AD, we were unable to confirm the presence of a locus close to the marker D12S1042. A moderate lod score (1.91) was found near D12S98 close to the alpha2-macroglobulin locus in the affected pairs in which both members did not possess an APOE epsilon4 allele. CONCLUSIONS: APOE remains the only locus established to be a risk factor for late-onset AD. We were unable to confirm that a locus on chromosome 12p11-12 has a major effect on risk for late-onset AD, although an effect smaller than that for APOE cannot be excluded.

Age of Onset↗