Search PubMed⌕ Search

Biomedical subjects

S Williams

Publications and source records attributed to S Williams.

At least 37 records · Page 2Linked to original sources
PubMed2005

Association between hormonal genetic polymorphisms and early-onset prostate cancer.

We investigated the association between seven polymorphisms in four candidate genes involved in vitamin D and androgen metabolism with early-onset prostate cancer (CaP) risk. The polymorphisms were genotyped in 288 UK males who were diagnosed with CaP at the age of 55 y or younger and up to 700 population-based controls. An additional 50 cases (not selected for age) and 76 controls were also genotyped. Short (< or =22 repeats) AR (CAG)(n) repeats were associated with a significantly reduced risk of early onset CaP (OR 0.68, 95% CI 0.50-0.91) compared with men with long (> 22) repeats. Men homozygous for the leucine variant of SRD5A2 p.89V > L were also found to be at a significantly increased risk of CaP compared with men who were homozygous for the valine allele (OR 1.84, 95% CI 1.15-2.98). No associations were found with the AR (GGC)(n), CYP17 Msp A1 I, VDR Taq I, SRD5A2 (TA)(n) and p.49A >T polymorphisms and CaP risk. These findings suggest that common polymorphisms in the AR and SRD5A2 genes may be associated with early-onset CaP in British men.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

Is tamoxifen associated with high-risk endometrial carcinomas? A retrospective case series of 196 women with endometrial cancer.

Tamoxifen therapy is associated with an increased risk of endometrial cancer. There is controversy regarding the incidence of high-grade endometrial malignancies associated with tamoxifen therapy. This retrospective study assesses pathological features of endometrial malignancy in patients with and without a history of tamoxifen therapy. This is a retrospective case analysis from a district general hospital. The cases were identified from the pathology database and the medical notes reviewed. The period of the study was January 1994 to December 2001. One hundred and ninety six women with endometrial cancer were identified. 20 patients had a history of breast cancer being treated with adjuvant tamoxifen therapy and developed subsequently endometrial cancer. The histology in women who had not taken tamoxifen showed: adenocarcinoma (97.1%), 1.7% had mixed mullerian tumour. Women in the tamoxifen-treated group had: adenocarcinoma (85%), sarcoma (5%), mixed mullerian tumour (5%). In this study the tamoxifen-treated group of patients developed endometrial malignancies with a higher incidence of poor prognostic malignancies (p = 0.01). Further research is needed to analyse the precise tumour types and pathophysiology.

Adenocarcinoma↗
PubMed2005

Relationship of neurofibrillary pathology to cerebral amyloid angiopathy in Alzheimer's disease.

Over 90% of patients with Alzheimer's disease (AD) develop cerebral amyloid angiopathy (CAA). Severe dyshoric CAA, in which amyloid extends into the surrounding brain parenchyma, may be associated with adjacent clustering of tau-immunopositive neurites but the relationship of CAA to neurofibrillary pathology has not been systematically investigated. In the present study this relationship was examined in sections of frontal, temporal and parietal cortex from 25 AD patients with moderate to severe CAA and 26 with mild or absent CAA. We measured immunolabelling of abnormally phosphorylated tau adjacent to A beta-laden and non-A beta-laden arteries and arterioles, and in cortex away from arteries and arterioles. We also analysed the possible influence of APOE genotype on these measurements. There were no significant differences between the lobes in measurements of tau labelling, either around blood vessels or elsewhere in the cortex. However, tau labelling around A beta-laden arteries and arterioles significantly exceeded that around non-A beta-laden blood vessels (P<0.001) and this, in turn was greater than the labelling of cortex away from blood vessels (P<0.001). There was no association between APOE epsilon 4 and the immunolabelling density for tau, whether around amyloid- or non-amyloid-laden arteries and arterioles, or in the cerebral cortex away from these. We propose that both CAA and peri-vascular accumulation of hyperphosphorylated tau may be a consequence of elevated levels of soluble A beta around cortical arteries and arterioles.

Aged↗
PubMed2005

HLA-DQB1 sequencing-based typing using newly identified conserved nucleotide sequences in introns 1 and 2.

Sequencing-based typing (SBT) human leukocyte antigen (HLA) class I and II genes should examine entire exon sequences where polymorphisms lie. Primers for the amplification of complete exons therefore anneal in introns and their design relies on accurate intron sequences being available. We decided to develop a SBT method for HLA-DQB1 using amplification primers which anneal in introns 1 and 2, yet the amount of intron sequence data previously available in databases was sparse. Therefore, we undertook a systematic sequencing of introns 1 and 2 using DNA from cell lines homozygous for DQB1. This study confirmed an earlier report that the non-coding regions of this gene are the most polymorphic seen in the human genome. Intron sequences within an allele group were largely identical, the exceptions being DQB1*0301 differing from other DQB1*03 allele groups and DQB1*0601 differing from all other DQB1*06 alleles. A retroviral Alu element, related to the AluYa5a2 subfamily, was identified uniquely inserted in intron 2 of DQB1*02 alleles. For the typing approach, six amplification primers were designed based on conserved allele group sequences covering all of the HLA DQB antigens, and two sequencing primers were also designed which anneal in intron 2. This method has proved to be very robust and has been used as part of a referral DNA sequencing service for a number of years.

Alleles↗
PubMed2005

Adverse events and near miss reporting in the NHS.

OBJECTIVES: To conduct a multicentre study on adverse event and near miss reporting in the NHS and to explore the feasibility of creating a national system for collecting these data. DESIGN: Prospective voluntary reporting by staff with anonymised transfer of data was used by a national system to collect data from 18 NHS trusts. PARTICIPANTS: Staff from 12 acute trusts, three mental health trusts, two ambulance trusts, and one primary care trust. MAIN OUTCOMES MEASURED: Number of incidents, date and time of incident, patient age and sex, clinical speciality, location, outcome, risk rating, type and description of incident. RESULTS: A total of 28 998 incidents were reported including 11 766 (41%) slips, trips and falls, 2514 (9%) medication management incidents, 2429 (8%) resource issues, and 2164 (7%) treatment issues. 138 catastrophic and 260 major adverse outcomes were reported. Slips, trips and falls (n = 11 766) were the most common type of incident. CONCLUSIONS: Voluntary reporting by staff when linked to a multicentre data collecting system can yield information on a large number of incidents. This provides support for the principle of creating a national IT system to collect and analyse incident data.

Accidental Falls↗
PubMed2004

Homologues of the maize rust resistance gene Rp1-D are genetically associated with a major rust resistance QTL in sorghum.

As part of a comparative mapping study between sugarcane and sorghum, a sugarcane cDNA clone with homology to the maize Rp1-D rust resistance gene was mapped in sorghum. The cDNA probe hybridised to multiple loci, including one on sorghum linkage group (LG) E in a region where a major rust resistance QTL had been previously mapped. Partial sorghum Rp1-D homologues were isolated from genomic DNA of rust-resistant and -susceptible progeny selected from a sorghum mapping population. Sequencing of the Rp1-D homologues revealed five discrete sequence classes: three from resistant progeny and two from susceptible progeny. PCR primers specific to each sequence class were used to amplify products from the progeny and confirmed that the five sequence classes mapped to the same locus on LG E. Cluster analysis of these sorghum sequences and available sugarcane, maize and sorghum Rp1-D homologue sequences showed that the maize Rp1-D sequence and the partial sugarcane Rp1-D homologue were clustered with one of the sorghum resistant progeny sequence classes, while previously published sorghum Rp1-D homologue sequences clustered with the susceptible progeny sequence classes. Full-length sequence information was obtained for one member of a resistant progeny sequence class ( Rp1-SO) and compared with the maize Rp1-D sequence and a previously identified sorghum Rp1 homologue ( Rph1-2). There was considerable similarity between the two sorghum sequences and less similarity between the sorghum and maize sequences. These results suggest a conservation of function and gene sequence homology at the Rp1 loci of maize and sorghum and provide a basis for convenient PCR-based screening tools for putative rust resistance alleles in sorghum.

Amino Acid Sequence↗
PubMed2004

Wear of surface engineered metal-on-metal hip prostheses.

The wear of existing metal-on-metal (MOM) hip prostheses (1 mm3/million cycles) is much lower than the more widely used polyethylene-on-metal bearings (30-100 mm3/million cycles). However, there remain some potential concerns about the toxicity of metal wear particles and elevated metal ion levels, both locally and systemically in the human body. The aim of this study was to investigate the wear, wear debris and ion release of fully coated surface engineered MOM bearings for hip prostheses. Using a physiological anatomical hip joint simulator, five different bearing systems involving three thick (8-12 microm) coatings, TiN, CrN and CrCN, and one thin (2 microm) coating diamond like carbon (DLC) were evaluated and compared to a clinically used MOM cobalt chrome alloy bearing couple. The overall wear rates of the surface engineered prostheses were at least 18-fold lower than the traditional MOM prostheses after 2 million cycles and 36-fold lower after 5 million cycles. Consequently, the volume of wear debris and the ion levels in the lubricants were substantially lower. These parameters were also much lower than in half coated (femoral heads only) systems that have been reported previously. The extremely low volume of wear debris and concentration of metal ions released by these surface engineered systems, especially with CrN and CrCN coatings, have considerable potential for the clinical application of this technology.

Biomedical Engineering↗
PubMed2004

Ideal or actual body weight to calculate CD34+ cell doses for allogeneic hematopoietic stem cell transplantation?

The number of CD34+ cells infused influences hematologic recovery after transplantation. Limited data suggest that cell dose should be based on ideal (IBW) rather than actual (ABW) body weight for autotransplantation, but none in allografts. We compared the correlation between recovery to 0.5 x 10(9)/l neutrophils and the CD34+ cell dose based upon ABW and IBW in 78 allograft recipients. ABW was > or =25% over IBW in 47% of patients. The median CD34+ cell dose was 5.1 x 10(6)/kg IBW and 4.4 x 10(6)/kg ABW. The time to neutrophil recovery was 8-26 days (median 12). There was a stronger inverse correlation between CD34+ cell dose/IBW and neutrophil recovery (r(2)=0.160; P<0.0001) than between CD34+ cell dose/ABW and neutrophil recovery (r(2)=0.138; P=0.001). When neutrophil recovery in patients receiving <3 or <5 x 10(6) CD34+ cells/kg was compared to those receiving > or =3 or > or =5 x 10(6) CD34+ cells/kg, respectively, separately by IBW and ABW, the magnitude and significance of the differences were greater for IBW-based comparisons. These data suggest the CD34+ cell dose based on IBW is a better predictor of neutrophil recovery after allografting. Further work in a larger, more homogeneous group of patients is required to confirm this observation.

Acute Disease↗
PubMed2004

How long after neutrophil recovery should myeloid growth factors be continued in autologous hematopoietic stem cell transplant recipients?

Growth factors are routinely used after autotransplantation to accelerate hematopoietic recovery, and are continued until the absolute neutrophil count (ANC) is >/=0.5 x 10(9)/l on 3 consecutive days. Since ANC often increases to very high levels with this strategy, we discontinued growth factor on the first day ANC reached 0.5 x 10(9)/l in 45 patients (Study Group), and compared their subsequent ANC to 108 historic controls who received growth factor longer. While ANC on the day after reaching 0.5 x 10(9)/l was comparable between groups, ANC on the third day was significantly higher in the Control Group (2.3 vs 4.9 x 10(9)/l; P=0.0003). When compared to the first day, ANC in the Study Group was higher by a median of 140% on the third day and by 450% in the Control Group (P=0.0002). A significantly higher proportion of patients experienced a decline in ANC after the first day in the Study Group. However, only one patient in the Study Group became neutropenic transiently and ANC recovered spontaneously the next day. The incidence of fever and hospitalization were comparable. We conclude that growth factors can be discontinued after autotransplantation the day the ANC reaches 0.5 x 10(9)/l, without compromising neutrophil recovery.

Adult↗
PubMed2004

Preparation and purification of synthetic protein nanoparticulates.

The protein nanostructure used in this study (bovine serum albumin; BSA nanoparticles) were fabricated with an average nanoparticle diameter 150 nm based on the principle of coacervation. Practical recovery of nanoparticulate mimics, of products such as plasmid DNA and viruses as putative gene therapy vectors from model systems, has been studied. The adsorbents employed in this study for the recovery of nanoparticles had one of four discrete designs i.e. microporous (pore size <0.2 microm), macroporous (pore size >0.8 microm), solid phase (nonporous) and pellicular (pore size <0.5 microm). Soluble protein was included in the study to represent cellular components of complex feedstocks and the separation of assemblies from components, while particulate protein served as surrogate size and charge mimics of less easily sourced viral and plasmid gene therapy vectors. Candidate adsorbents were physically characterised to assess their suitability for fluidised-bed operation, biochemically characterised exploiting batch-binding experimentation and laser scanning confocal microscopy. The adsorptive capacity of nanoparticulate products was strongly influenced by the physical design of the adsorbents, and microporous adsorbents appeared to be less suited for the recovery of nanoparticulate products. The generic application of such adsorbents for the recovery of nanoparticulate bioproducts is discussed.

Journal Article↗
PubMed2004

Quantitation of transverse maxillary dimensions using computed tomography: a methodological and reproducibility study.

The present investigation was a methodological study of a new method of quantification of a series of factors in the transverse dimension of the maxilla including the nose, maxillary bones and dental arches, based on computer tomographic (CT) scanning. The aim was to investigate a series of parameters thought to be relevant in the differential diagnosis of discrepancies in the morphology of this area and probably affected by orthodontic appliances. Based on a standardized CT scanning registration of 10 subjects, a series of points on the scans were identified and then measured in a special cephalometric computer system (linear and angular values). The quantitation was repeated by each observer and inter- and intra-observer differences were calculated. The results demonstrated that virtually all the parameters showed a high degree of reproducibility at both levels and confirmed the statistical suitability of the method described. The method will be used in a series of ongoing studies regarding the morphology and treatment of discrepancies of the midface and therefore supplement the relatively sparse information based on quantitative reports concerning this important anatomical area.

Adult↗
PubMed2004

HLA-A*24020102L in the UK blood donor population.

The low-expression allele HLA-A*24020102L was identified on a likely haplotype bearing B*55, Cw*01 during the investigation of nine cases (four families and five unrelated subjects) of HLA-A*24 lacking the A24 specificity. A search was made of 70,007 HLA-A, HLA-B, and HLA-C DNA-based typed largely northwestern European Caucasoid blood donors on the British Bone Marrow Registry and Welsh Bone Marrow Donor Registry panels for phenotypes possessing A*24, B*55, Cw*01. Fifty three were found, and 12 of these were subsequently shown to possess A*24020102L by sequence-based typing or polymerase chain reaction with sequence-specific primers. This indicated that the likely A*24, B*55, Cw*01 haplotype has a frequency of 0.000378 in the UK and that approximately 22.6% of these will possess A*24020102L. Consequently, HLA-A*24020102L, B*55, Cw*01 is a principal A*24020102L-bearing haplotype, and the minimum carriage and gene frequencies of A*24020102L are 0.017% and 0.000086, respectively, in UK blood donors.

Blood Donors↗
PubMed2004

Vasopressin and terlipressin: pharmacology and its clinical relevance.

Vasopressin and its analogue, terlipressin, are potent vasopressors that may be useful therapeutic agents in the treatment of cardiac arrest, septic and catecholamine-resistant shock and oesophageal variceal haemorrhage. The aim of this article is to review the physiology and pharmacology of vasopressin and summarise its efficacy and safety in clinical trials and its subsequent therapeutic use. Recent studies indicate that the use of vasopressin during cardiopulmonary resuscitation may improve the survival of patients with asystolic cardiac arrest. Vasopressin deficiency can contribute to refractory shock states associated with sepsis, cardiogenic shock and cardiac arrest. Low doses of vasopressin and terlipressin can restore vasomotor tone in conditions that are resistant to catecholamines, with preservation of renal blood flow and urine output. They are also useful in reducing bleeding and mortality associated with oesophageal variceal haemorrhage. The long-term outcome of the use of these drugs is not known.

Animals↗
PubMed2004

Delivering cognitive therapy to people with psychosis in a community mental health setting: an effectiveness study.

OBJECTIVE: Cognitive therapy (CT) has been shown to be an efficacious treatment for persistent psychotic symptoms. However, there is some debate regarding whether this is transportable to real life clinical settings. This study aimed to evaluate the effectiveness of CT for psychosis in a community mental health team (CMHT) setting. METHOD: Patients referred for CT for psychosis were naturalistically allocated (determined by the availability of a therapist) to CT or waiting-list (WL)/treatment-as-usual (TAU). Outcome assessments were performed at WL, pre-CT, post-CT and 1-year follow-up. Data from 59 patients were analysed. RESULTS: Random effects regression analyses showed there was a significant improvement, attributable to CT, on most outcome measures, and that many of the symptomatic improvements were maintained at follow-up. Wilcoxon signed ranks tests indicated that there was a significant reduction in psychiatric hospital use following CT. CONCLUSION: These results confirm that CT is an effective treatment for psychosis that is generalizable to a community setting.

Adolescent↗
PubMed2004

The emerging role of the emergency care practitioner.

OBJECTIVES: To examine the emerging role of the emergency care practitioner (ECP) with comparisons to paramedic practice. Key activities were identified of newly appointed ECPs using qualitative methodology and a qualitative and quantitative comparison of patient treatment was made. METHOD: A constructivist methodology taking account of stakeholder input and drawing upon the constant comparisons of different group's construction of reality. Four practitioners completed reflective patient case studies and adapted patient report forms, which were compared with a second case group of 11 paramedics. In addition individual and focus groups interviews were performed with key stakeholders. RESULTS: In the comparison between ECP and paramedic roles, 331 paramedic incidents were compared with 170 ECP reports. ECPs treated 28% of patients on scene compared with 18% by paramedics (p = 0.007). Fifty per cent of ECPs patients were conveyed compared with 64% of paramedics (p = 0.000). Analysis of the 269 reflective reports and 14 stakeholder interviews revealed four key themes. Firstly, ECPs had a beneficial impact on the deployment of resources, especially relating to non-conveyance. Secondly, their training and education improved their decision making repertoire and developed their confidence for a leadership role. Thirdly, inter-agency collaboration and cooperation was improved, and finally, care benefits were increased especially relating to immediacy of treatment and referral mechanisms. CONCLUSIONS: The results indicate that an investment in the ECP role could be beneficial, however, more work is required to evaluate the development of practice, the quality of care, and cost benefits.

Adolescent↗
PubMed2004

Reducing absenteeism in hospital cleaning staff: pilot of a theory based intervention.

AIMS: To develop, pilot, and evaluate a workplace intervention to reduce sickness absence, based on a demand-control-support model of job strain. METHODS: Changes in the working arrangements of hospital cleaning staff were introduced with the aim of increasing their control over work and the support received at work. The study design was quasi-experimental, with 221 cleaning staff in the intervention group and 91 catering staff in the control group. The dependent variable was the difference in percentage monthly sickness absence between the 12 months preceding and following the intervention. Differences in sickness absence between staff groups for each month after the intervention were compared with differences between staff groups for the equivalent month one year prior to it. RESULTS: There was a significant reduction in the difference in sickness absence rates between the intervention and control group of 2.3% in the six months after the intervention, compared to the six months before. The difference was not maintained at 12 months. CONCLUSIONS: These results suggest that a workplace intervention aimed at increasing control and support at work has a small effect on reducing sickness absence among hospital cleaning staff in the short term. Future research should seek to replicate this effect in larger, experimental studies, analyse postulated mediators of such theory based interventions, and develop interventions that maintain improvement.

Absenteeism↗
PubMed2004

Predictors of re-employment and quality of life in NHS staff one year after early retirement because of ill health; a national prospective study.

AIMS: To measure changes in health related quality of life and employment status of NHS staff one year after early retirement because of ill health, and to identify predictors of re-employment. METHODS: A national cohort of 1317 NHS staff taking early retirement because of ill health in 1998 was recruited. Postal questionnaires were used to assess their quality of life (SF-36) and employment status 12 months after retirement. RESULTS: A total of 1143 (87%) ill health retirees responded; 152 (13%) retirees were working at one year, mostly part-time, and 22% of them were re-employed by the NHS. Independent predictors of re-employment were: living in England rather than Wales and occupation of doctor. There was an increased likelihood of re-employment with reducing age and increasing quality of life at baseline. Retirees' quality of life improved from baseline to one year after ill health retirement, but at one year still remained lower than the general population. Improvements in physical and mental component scores were greater in those working at one year compared with those not working. CONCLUSION: Reducing ill health retirement is likely to be of benefit to the individual, the NHS, and the economy. Results suggest that such a reduction may be possible and the identified predictors of re-employment may help in this process.

Adult↗