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Biomedical subjects

D Williams

Publications and source records attributed to D Williams.

At least 19 recordsLinked to original sources
PubMed2007

Anaplastic large cell lymphoma of bone--is it a bad tumor?

A teenage boy presented with a CD30-positive anaplastic large cell lymphoma (ALCL) affecting his scapula and was successfully treated with chemotherapy. His clinical features and outcome were compared with other cases described in the literature. A further review of 11 ALCL cases with bony involvement treated in the UK since 1990, including two with primary bone disease, did not suggest an unfavorable treatment outcome. This finding will need to be confirmed by further study on a larger patient cohort with primary bone ALCL.

Activin Receptors, Type II↗
PubMed2006

Flax seed oil and flax seed meal reduce the formation of aberrant crypt foci (ACF) in azoxymethane-induced colon cancer in Fisher 344 male rats.

Flax seed oil and flax seed meal are good sources of omega-3 fatty acids. The objective of this study was to explicate the effects of feeding flax seed oil and flax seed meal on AOM-induced aberrant crypt foci (ACF) in Fisher 344 male rats. Following an acclimatization period, rats were divided into six groups and fed AIN 93G diet Control (C), C+7 and 14% soybean oil (SBO), C+7 and 14% flax seed oil (FSO) and C+10 and 20% flax seed meal (FSM). All rats received 16 mg/kg body weight of AOM at 7 and 8 weeks of age. The rats were euthanized with CO2 at 17 weeks of age. FSM and FSO reduced the incidence of ACF which are putative precursor lesions in the development of colon cancer in the distal colon by 88% and 77%, in the proximal colon by 86% and 87% with a total reduction of 87.5% and 84%, respectively. Glutathione-S-transferase (GST) activities were significantly (P<0.05) higher in rats fed C+7 and 14% FSO and C+10 and 20% FSM, as compared to rats fed C+SBO diets. Results of this study showed that FSO and FSM reduced the incidence of AOM-induced ACF formation and may therefore be effective chemopreventive agents.

Animals↗
PubMed2006

Anaesthesia for pituitary surgery.

The anaesthetic care of patients undergoing pituitary surgery involves an understanding of the varied presentations of pituitary disease and their implications for the patient's perioperative condition and management. The neuroanaesthetist must also have an appreciation of the issues relevant to the surgical approach (either transsphenoidal or, less commonly, transcranial) and be able to anticipate and manage them accordingly.

Anesthesia↗
PubMed2006

The prevalence of a raised aldosterone-renin ratio (ARR) among new referrals to a hypertension clinic.

The wider application of the plasma aldosterone to renin activity ratio (ARR) test has led independent groups to report a 10-fold or higher prevalence in the detection and prevalence of primary aldosteronism than previously suggested, although such figures have been contested. We determined the prevalence of a raised ARR in an unselected group of patients who were referred to the hypertension clinic at Aberdeen Royal Infirmary. Over a 4-month period, all newly referred patients had an ARR, urea and electrolytes, and 24-h ambulatory blood pressure monitoring (ABPM) performed in addition to a detailed clinical examination. One hundred and twenty-two patients (mean age 51 +/- 16 years) were examined over the study period; 57 (47%) were receiving no anti-hypertensive medication, 32(26% of total) had a normal 24-h ABPM of which 15 patients were receiving antihypertensive medication ("controlled" hypertensives) and 17(14%) were receiving no anti-hypertensive medication ("white-coat hypertensives). Twenty patients (mean age 58 +/- 11 years) were found to have a raised ARR (> 750), of which 10 patients were receiving beta-blocker therapy as part of their anti-hypertensive regimen. Patients with a raised ARR were more likely (odds ratio 3.6, 95% confidence interval 1.2-13.2, p < 0.05) to be classified as a "non-dipper" compared with those whose blood pressure fell at night. The proportion of newly referred hypertensive patients with a raised ARR is still significant and confirms that of previous studies The ratio appears to be significantly driven by a suppressed renin value and further investigation is required to clarify the status of those patients receiving anti-hypertensive medications, particularly beta-blockers.

Adult↗
PubMed2006

The effect of the withdrawal of rofecoxib on prescribing patterns of COX-2 inhibitors in Scotland.

BACKGROUND: Concerns have been raised regarding the cardiovascular safety of the COX-2 inhibitors. In September 2004, rofecoxib was withdrawn from the market as a result of concerns regarding its cardiovascular safety. AIMS & METHODS: We set out to examine the effect of the withdrawal of rofecoxib on the prescription of other COX-2 inhibitors and nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) in Scotland, using a national prescription database. RESULTS: The withdrawal of rofecoxib led to an initial increase in the prescription of celecoxib as prescribers presumably switched to this alternative agent. However, this rise was short-lived, presumably as a result of concerns that the safety concerning rofecoxib may be a class effect. A parallel increase in the prescription of diclofenac and ibuprofen was also noted, suggesting that prescribers were prescribing these medications as alternatives to COX-2 inhibitors. CONCLUSIONS: While prescribers and their patients may have initially interpreted safety concerns regarding rofecoxib to be drug specific, prescribers appear to have interpreted this effect to be class specific.

Cardiovascular Diseases↗
PubMed2006

Management of minor head injuries according to NICE guidelines and changes in the number of patients requiring computerised tomography imaging in a district general hospital: a retrospective study.

The objective of this study was to investigate how many patients with minor head injury would have required computerised tomography (CT) imaging if they were to be managed according to the National Institute of Clinical Excellence (NICE) guidelines (June 2003) and the difference in workload for patients presenting out of hours at Calderdale Royal Hospital, Halifax. The study was a retrospective cohort analysis of patient's notes presenting with head injury at Calderdale Royal Hospital, Halifax. The data set comprised case notes of 844 patients with head injuries, 400 adults and 444 children attending the Accident and Emergency department from January to June 2003. The case notes were evaluated according to the NICE guidelines for the indications for CT imaging for the time that they presented to the Accident and Emergency department, and how many of them actually underwent CT imaging. The number of patients who required CT imaging and how many of them presented out of hours (between 17:00 and 21:00 hours on weekdays and at any time on weekends). Ten patients underwent CT imaging for minor head injuries from January to June 2003. Eighty-eight patients required CT imaging if they were to be managed according to the NICE guidelines. Sixty-three per cent of these patients presented out of hours when a radiologist was not available in the hospital. Adhering to the NICE guidelines would significantly increase the number of patients requiring CT imaging. A significant proportion of these patients would present out of hours.

Adult↗
PubMed2006

The use of a probiotic in captive cheetahs (Acinonyx jubatus).

Juvenile captive cheetahs (Acinonyx jubatus) often present with diarrhoea that is commonly associated with bacterial infections. A species-specific probiotic containing Lactobacillus Group 2 and Enterococcus faecium was prepared from healthy adult cheetahs. Juvenile cheetahs (n = 27) between 8 and 13 months of age were included in the probiotic trial. The animals were observed prior to and after feeding of the probiotic which was made available for 28 days. Feeding of the probiotic resulted in a significantly increased body weight in the treatment group (P = 0.026), while there was no increase in the control group. A relative improvement in the faecal quality in the probiotic group during the treatment period compared with the pre-treatment (P = 0.0363) and post-treatment (P = 0.004) period was observed. This was accompanied by an absence of blood and mucus in the faeces during the treatment period in the probiotic group.

Acinonyx↗
PubMed2005

Evidence for age and sex differences in the secondary prevention of stroke in Scottish primary care.

BACKGROUND AND PURPOSE: Secondary preventive measures play an important role in the reduction of stroke, the third largest cause of death in Scotland. We investigated whether sex, age, or deprivation differences existed in the secondary prevention of stroke in primary care. METHODS: A retrospective cross-sectional study using a computerized database with 61 practices (377,439 patients) to identify group differences in secondary preventive therapy between March 2003 and April 2004 for 10,076 patients with a diagnosis of any stroke. RESULTS: Women with any stroke were more likely than men to be prescribed a thiazide (odds ratios [OR], 1.60; 95% confidence interval [CI], 1.46 to 1.75) but less likely to be prescribed an angiotensin-converting enzyme inhibitor (OR, 0.73; 95% CI, 0.67 to 0.81). Women with ischemic stroke were less likely to receive either an antiplatelet or warfarin (OR, 0.84; 95% CI, 0.75 to 0.94) or statin therapy (OR, 0.82; 95% CI, 0.74 to 0.90) than men. Women with atrial fibrillation received less warfarin (OR, 0.62; 95% CI, 0.48 to 0.81) but more antiplatelet therapy than men (OR, 1.30; 95% CI, 1.00 to 1.68). The oldest patients (older than 75 years) with ischemic stroke received more antiplatelet therapy than the youngest patients (younger than 65 years) (OR, 1.83; 95% CI, 1.64 to 2.06). No significant differences in secondary preventative treatment across deprivation groups were found. CONCLUSIONS: Important sex and age differences exist in the care of patients with stroke and suggest that women and the elderly need to be targeted for secondary prevention therapy.

Age Factors↗
PubMed2005

Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid.

Oxyphil or Hurthle cell tumours of the thyroid are characterised by their consistent excessive number of mitochondria. A recently discovered gene, GRIM-19 has been found to fulfil two roles within the cell: as a member of the interferon-beta and retinoic acid-induced pathway of cell death, and as part of the mitochondrial Complex I assembly. In addition, a gene predisposing to thyroid tumours with cell oxyphilia (TCO) has been mapped to chromosome 19p13.2 in one family. A cluster of genes involved in mitochondrial metabolism occurs in this region; one of these is GRIM-19. We have searched for GRIM-19 mutations in a series of 52 thyroid tumours. Somatic missense mutations in GRIM-19 were detected in three of 20 sporadic Hurthle cell carcinomas. A germline mutation was detected in a Hurthle cell papillary carcinoma arising in a thyroid with multiple Hurthle cell nodules. No mutations were detected in any of the 20 non-Hurthle cell carcinomas tested, nor in any of 96 blood donor samples. In one of the sporadic Hurthle cell papillary carcinomas positive for GRIM-19 mutation, we have also detected a ret/PTC-1 rearrangement. No GRIM-19 mutations were detected in any of the six cases of known familial Hurthle cell tumour tested, so that our results do not support the identification of GRIM-19 as the TCO gene. The GRIM-19 mutations we have detected are the first nuclear gene mutations specific to Hurthle cell tumours to be reported to date; we propose that such mutations can be involved in the genesis of sporadic or familial Hurthle cell tumours through the dual function of GRIM-19 in mitochondrial metabolism and cell death.

Adenoma, Oxyphilic↗
PubMed2005

Large tunneling anisotropic magnetoresistance in (Ga,Mn)As nanoconstrictions.

We report a large tunneling anisotropic magnetoresistance (TAMR) in (Ga,Mn)As lateral nanoconstrictions. Unlike previously reported tunneling magnetoresistance effects in nanocontacts, the TAMR does not require noncollinear magnetization on either side of the constriction. The nature of the effect is established by a direct comparison of its phenomenology with that of normal anisotropic magnetoresistance (AMR) measured in the same lateral geometry. The direct link we establish between the TAMR and AMR indicates that TAMR may be observable in other materials showing room temperature AMR and demonstrates that the physics of nanoconstriction magnetoresistive devices can be much richer than previously thought.

Journal Article↗
PubMed2005

Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration.

BACKGROUND: The haplotype H1 of the tau gene, MAPT, is highly associated with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). OBJECTIVE: To investigate the pathogenic basis of this association. METHODS: Detailed linkage disequilibrium and common haplotype structure of MAPT were examined in 27 CEPH trios using validated HapMap genotype data for 24 single nucleotide polymorphisms (SNPs) spanning MAPT. RESULTS: Multiple variants of the H1 haplotype were resolved, reflecting a far greater diversity of MAPT than can be explained by the H1 and H2 clades alone. Based on this, six haplotype tagging SNPs (htSNPs) that capture 95% of the common haplotype diversity were used to genotype well characterised PSP and CBD case-control cohorts. In addition to strong association with PSP and CBD of individual SNPs, two common haplotypes derived from these htSNPs were identified that are highly associated with PSP: the sole H2 derived haplotype was underrepresented and one of the common H1 derived haplotypes was highly associated, with a similar trend observed in CBD. There were powerful and highly significant associations with PSP and CBD of haplotypes formed by three H1 specific SNPs. This made it possible to define a candidate region of at least approximately 56 kb, spanning sequences from upstream of MAPT exon 1 to intron 9. On the H1 haplotype background, these could harbour the pathogenic variants. CONCLUSIONS: The findings support the pathological evidence that underlying variations in MAPT could contribute to disease pathogenesis by subtle effects on gene expression and/or splicing. They also form the basis for the investigation of the possible genetic role of MAPT in Parkinson's disease and other tauopathies, including Alzheimer's disease.

Aged↗
PubMed2005

The application of prescribing indicators to a primary care prescription database in Ireland.

OBJECTIVE: To develop appropriate prescribing indicators and apply these to Irish prescription data. METHODS: A postal survey of 145 randomly selected general practitioners working within the Eastern Health Board region of the State-supported General Medical Services scheme in Ireland regarding the applicability of selected prescribing indicators was carried out. Such indicators were then applied to aggregate prescription data. RESULTS: Prescribing indicators based on agents of questionable efficacy/poor quality prescribing and those based on good prescribing practice were thought to make suitable indicators. Low rates of prescribing were noted for indicators based on drugs of limited efficacy, e.g. cerebral and peripheral vasodilators (rate 3.1 per 1,000 prescriptions), whilst indicators based on drugs associated with good prescribing practice were associated with higher prescribing rates, e.g. the prescription of aspirin in patients receiving nitrate therapy(rate 7.13 per 1,000 patients). However, a low rate of generic prescribing (4.6%) was found amongst general practitioners in the study. The largest variability in prescribing was seen with the prescribing of peripheral and cerebral vasodilators (75th/25th centile=5.6) and the prescription of long-acting sulphonylureas (75th/25th centile=66.6). CONCLUSIONS: Quality indicators based on aggregate prescribing provide valuable information on prescribing standards and should be developed with the close involvement of prescribers.

Databases, Factual↗
PubMed2005

Factors influencing the use of single vs multiple fractions of palliative radiotherapy for bone metastases: a 5-year review.

AIMS: Evidence from a number of randomised trials and meta-analyses supports the use of single-fraction radiotherapy for the palliation of painful bone metastases. This study explores patient and treatment factors that influence the choice of single compared with multiple-fraction radiotherapy for the treatment of bone metastases in clinical practice. MATERIALS AND METHODS: The Princess Margaret Hospital Palliative Radiation Oncology Program Database served as the basis for our report. All courses of treatment delivered for bone metastases were extracted. Courses were classified into single or multiple fractions. Clinical characteristics were compared between the two groups. RESULTS: Between 1998 and 2002, 882 courses of radiotherapy were delivered for the treatment of bone metastases, of which 283 (32%) were a single fraction. The proportion of single-fraction treatments was 37% in 1998, 30% in 1999 and 43% in 2000, but dropped to 26% and 28% in 2001 and 2002, respectively (P = 0.02). Patients treated with single fractions were significantly older (68 +/- 12 years vs 64 +/- 12 years), and had more weight loss and poor performance status. Single fractions included 20% of treatments in palliative irradiation of the spine, 36% in the pelvis and long bones, and 59% in the chest wall (P < 0.001). There was no significant difference in patients' gender, primary cancers, number of metastatic sites, treating physicians, enrollment in a clinical trial and general radiotherapy waiting time in our department. Multivariate analysis indicated age (P = 0.001), performance status (P < 0.001), anatomical site (P < 0.001) and year of radiotherapy (P = 0.006) as significant. CONCLUSION: One-third of palliative radiotherapy courses for bone metastases in our programme were given as single fractions. Performance status, age and anatomical site were significant factors affecting single compared with multiple fractionation. The variation in the use of single fractions over time may reflect the dynamic process of interpretation and application of evidence from clinical trials to practice.

Aged↗