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Biomedical subjects

G Williams

Publications and source records attributed to G Williams.

At least 19 recordsLinked to original sources
PubMed2006

Extraanatomic stents for transplant ureteric stenosis.

Surgical and standard endourology options are limited in transplant patients with severe ureteric stenosis, particularly when access to the transplant renal pelvis is limited. The use of a silicone-polytetrafluoroethelene (PTFE)-bonded extraanatomic urinary tract stent for urinary tract drainage is described in two patients. This technique of ureteric reconstruction in renal transplantation may be considered when standard approaches have failed. It appears to be safe when performed by radiologists and urologists with expertise in percutaneous renal access.

Adult↗
PubMed2006

Total laparoscopic versus open surgery for stage 1 endometrial cancer: the LACE randomized controlled trial.

PURPOSE: Endometrial cancer is the most common gynaecological malignancy in Australia and the US. Current standard treatment involves open surgery to remove the uterus, and both tubes and ovaries (TAH). The Laparoscopic Approach to Cancer of the Endometrium (LACE) trial was designed to assess equivalence of performing this in a total laparoscopic approach (TLH). METHODS: Patient recruitment was designed to proceed along two stages to accommodate for a potential increase in patient requests of laparoscopic surgery. During the first stage, patients are randomised in a 2:1 allocation to receive TLH or TAH, with the primary endpoint quality of life (QoL) at 6 month post-surgery, requiring 180 patients to be enrolled to have 80% power at alpha=0.05 to detect a clinically significant difference of 8 points on the Functional Assessment of Cancer General (FACT-G) QoL instrument. If additional recruitment of patients seems impossible after accrual of 180 patients, this cohort will be followed for 4 years, and disease free survival (DFS) of patients treated by TLH will be compared to DFS within the endometrial cancer population. During the second stage, recruitment will be extended to a total of 590 patients in a 1:1 TLH:TAH allocation, to assess the equivalence with respect to DFS with 80% power and alpha=0.05. Equivalence will be assumed if the difference in DFS does not exceed 7% at 4 years. Secondary outcomes include treatment related morbidity; costs and cost-effectiveness; patterns of recurrence; and overall survival. All data from this multicentre study will be entered using online electronic case report forms (e-CRF), allowing real time assessment of data completeness and patient follow-up. CONCLUSIONS: The LACE trial will establish the equivalence of a TLH approach for patients with stage 1 endometrial cancer following a two stage protocol to accommodate potential threats to patient recruitment through requests for laparoscopic surgery.

Adenocarcinoma↗
PubMed2006

A five-year audit of anal cancer in Wales.

OBJECTIVES: A retrospective audit has been undertaken of Squamous (epidermoid) type of anal cancer diagnosed and treated in the principality of Wales over a five-year period (1995-99) with follow-up until 2005. The referral pattern, distribution, presenting symptoms, predisposing conditions, clinical findings and staging modalities were documented. The surgical and oncological treatment together with their outcome was analysed. METHODS: Patients were identified from the Welsh Cancer Registry and the pathology databases of the 17 acute hospitals in Wales. Data was collected from the clinical and oncology case notes onto a purpose designed Microsoft access database. RESULTS: There was a wide variation in data quality from the individual units. Twenty-six anal cancers were diagnosed per year in the region. Median age was 69 years. Ten percent had documented perianal Human Papilloma Virus related disease. Radiology was inconsistently used for staging. Eighty percent were referred for an oncology opinion; 50% had chemo-radiotherapy with a curative intent. The over-all Stoma rate was 35% and of these 18% had an abdomino perineal resection. The overall five-year survival was 45%. CONCLUSIONS: This is a unique regional audit of anal cancer. Improvements need to be made in documentation particularly of staging, treatment, pathology reporting and outcome. This study concurs that Human Papilloma Virus appears to predispose to Squamous anal cancer. Radiological staging needs to be standardized according to best clinical practice. As recommended by NICE all patients should be referred to a multidisciplinary anal cancer team, which can provide individual treatment plans. Increased specialization could mean specialist regional MDTs for anal cancer.

Adult↗
PubMed2006

Maternal exposure to low levels of ambient air pollution and preterm birth in Brisbane, Australia.

BACKGROUND: [corrected] There is evidence that maternal exposure to ambient air pollution during pregnancy is associated with adverse birth outcomes. OBJECTIVE: To assess preterm birth (PTB) in relation to maternal exposure to ambient air pollution. DESIGN: Retrospective cohort. SETTING: Brisbane, Australia. POPULATION: A total of 28,200 singleton live births for the period of 1 July 2000 to 30 June 2003. METHODS: Average maternal exposure estimates for ambient particulate matter (PM(10) and bsp), ozone (O(3)) and nitrogen dioxide were calculated over the first 3 months after last menstrual period (LMP) and the last 3 months prior to birth (individually and combined as trimesters). MAIN OUTCOME MEASURES: PTB was defined as gestation <37 weeks and odds ratios (OR) were calculated for PTB per interquartile range increase in the maternal exposure estimate for each pollutant. Various covariates were controlled for, including season of birth. RESULTS: Exposure to PM(10) and O(3) during trimester one was associated with an increased risk of PTB (OR = 1.15, 95% CI 1.06-1.25 and OR = 1.26, 95% CI 1.10-1.45, respectively). The PM(10) exposure effect associated with trimester one was strongly related to exposure during the first month post-LMP (PM(10), month one; OR = 1.19, 95% CI 1.13-1.26). CONCLUSION: These results suggest that maternal exposure to low levels of ambient air pollution is associated with PTB.

Air Pollutants↗
PubMed2006

Invasion of host cells by JC virus identifies a novel role for caveolae in endosomal sorting of noncaveolar ligands.

Invasion of glial cells by the human polyomavirus, JC virus (JCV), leads to a rapidly progressing and uniformly fatal demyelinating disease known as progressive multifocal leukoencephalopathy. The endocytic trafficking steps used by JCV to invade cells and initiate infection are not known. We demonstrated that JCV infection was inhibited by dominant defective and constitutively active Rab5-GTPase mutants that acted at distinct steps in endosomal sorting. We also found that labeled JCV colocalized with labeled cholera toxin B and with caveolin-1 (cav-1) on early endosomes following internalization by clathrin-dependent endocytosis. JCV entry and infection were both inhibited by dominant defective mutants of eps15 and Rab5-GTPase. Expression of a dominant-negative scaffolding mutant of cav-1 did not inhibit entry or infection by JCV. A single-cell knockdown experiment using cav-1 shRNA did not inhibit JCV entry but interfered with a downstream trafficking event important for infection. These data show that JCV enters cells by clathrin-dependent endocytosis, is transported immediately to early endosomes, and is then sorted to a caveolin-1-positive endosomal compartment. This latter step is dependent on Rab5-GTPase, cholesterol, caveolin-1, and pH. This is the first example of a ligand that enters cells by clathrin-dependent endocytosis and is then sorted from early endosomes to caveosomes, indicating that caveolae-derived vesicles play a more important role than previously realized in sorting cargo from early endosomes.

Biomarkers↗
PubMed2005

CRT improves the exercise capacity and functional reserve of the failing heart through enhancing the cardiac flow- and pressure-generating capacity.

BACKGROUND: While information on how cardiac resynchronisation therapy (CRT) affects cardiac performance at rest is readily available, the mechanisms whereby CRT alters cardiac function during maximal exercise are unclear. AIMS: We examined the medium-term effects of CRT on cardiac and physical functional reserve of patients with severe heart failure (CHF) and prolonged QRS duration. METHODS: Seventeen consecutive patients with severe CHF (NYHA III-IV) and widened QRS underwent maximal cardiopulmonary exercise testing with non-invasive central haemodynamic measurements before and 6-8 weeks after CRT pacemaker implantation. RESULTS: After CRT there were significant increases in exercise cardiac output by 19.3% (P=0.0048) from 9.5+/-3.4 l min(-1), peak mean arterial blood pressure by 14.1% (P=0.0001) from 91.3+/-13.6 mm Hg, and peak cardiac power output by 37.2% (P=0.0008) from 1.92+/-0.74 W. There were no significant changes in these variables at rest. Exercise duration (+42.3%, P=0.0002), NYHA functional class (P=0.0001) and SF-36 symptom score (P=0.0006) were also significantly improved. Powerful surrogate indicators of prognosis were also significantly improved with CRT: peak O(2) consumption (+20.9%, P=0.0007), VE/VCO(2) slope (-20.0%, P=0.005) and circulatory power (+42.0%, P=0.0012). CONCLUSION: In this cohort of patients, post-implant CRT significantly improved the flow-, pressure- and power-generating capacity of the failing hearts. This may be causally related to the improvements observed in exercise capacity, functional class and symptom scores.

Aged↗
PubMed2005

Retinal toxicity during pegylated alpha-interferon therapy for chronic hepatitis C: a multifocal electroretinogram investigation.

BACKGROUND: Ocular side-effects in the form of retinal ischaemia and haemorrhages have been reported in patients undergoing standard alpha-interferon therapy. AIM: To assess the ocular impact of therapy with sustained release pegylated alpha-2a interferon (Pegasys) for chronic hepatitis C. METHODS: Ten patients receiving Pegasys and ribavirin and 10 healthy volunteers were recruited. Patients underwent full ophthalmic investigations and multifocal electroretinogram testing at baseline, at regular intervals during treatment and post-treatment. The multifocal electroretinogram maps retinal function. Responses were compared with sequential recordings from healthy volunteers. RESULTS: All patients had normal clinical ophthalmic investigations at baseline. During therapy a single patient experienced central visual disturbance lasting 24 h with no prolonged ill effect. No other patient was aware of any change in vision. Fundal abnormalities appeared in five patients during treatment. The multifocal electroretinogram showed reductions in retinal function in five patients. Nine of 10 patients exhibited abnormalities on at least one multifocal electroretinogram or fundoscopic investigation. CONCLUSIONS: Subclinical retinal toxicity during anti-viral therapy with pegylated alpha-interferon and ribavirin was frequent in this study and it suggests that patients should be warned of this risk and monitored during therapy.

Adult↗
PubMed2005

Autoimmune pancreatitis: an underdiagnosed condition in Caucasians.

Unlike in Japan, autoimmune pancreatitis is uncommon in the Western world, particularly in Europe. We report the first case of a Caucasian male with typical features of autoimmune pancreatitis in the UK. Recognizing autoimmune pancreatitis as a new clinical entity in Europe will change the management of many patients who have been labelled as having acute or chronic pancreatitis.

Aged↗
PubMed2005

Histological evaluation of Permacol as a subcutaneous implant over a 20-week period in the rat model.

This study assessed the suitability of Permacol (a porcine derived, isocyanate cross linked collagen based biomaterial) as an alternative to autologous tissue in soft tissue reconstruction. The Sprague-Dawley rat was used as a model for subcutaneous implantation over a 20 week period and comparison made with two other porcine biomaterials (small intestinal submucosa and glycerol treated-ethylene oxide sterilised porcine dermis). Implants were scored histometrically on the degree of acute inflammation, chronic inflammation, fibrosis and stromal response. The vascularity and percentage composition of collagen within Permacol were assessed by stereology and seescan image analysis, respectively. In general terms, Permacol was well tolerated as a subcutaneous implant, with only a minor chronic inflammatory response remaining after a 20 week period of implantation. There was evidence of collagen degradation during this period and vascular ingrowth into Permacol was limited. Permacol has the potential for a broad range of applications in plastic surgery, but may benefit from modification to promote a more rapid degree of vascularisation.

Acute Disease↗
PubMed2005

Validation of a food-frequency questionnaire assessment of carotenoid and vitamin E intake using weighed food records and plasma biomarkers: the method of triads model.

BACKGROUND: Reliability or validity studies are important for the evaluation of measurement error in dietary assessment methods. An approach to validation known as the method of triads uses triangulation techniques to calculate the validity coefficient of a food-frequency questionnaire (FFQ). OBJECTIVE: To assess the validity of an FFQ estimates of carotenoid and vitamin E intake against serum biomarker measurements and weighed food records (WFRs), by applying the method of triads. DESIGN: The study population was a sub-sample of adult participants in a randomised controlled trial of beta-carotene and sunscreen in the prevention of skin cancer. Dietary intake was assessed by a self-administered FFQ and a WFR. Nonfasting blood samples were collected and plasma analysed for five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene) and vitamin E. Correlation coefficients were calculated between each of the dietary methods and the validity coefficient was calculated using the method of triads. The 95% confidence intervals for the validity coefficients were estimated using bootstrap sampling. RESULTS: The validity coefficients of the FFQ were highest for alpha-carotene (0.85) and lycopene (0.62), followed by beta-carotene (0.55) and total carotenoids (0.55), while the lowest validity coefficient was for lutein (0.19). The method of triads could not be used for beta-cryptoxanthin and vitamin E, as one of the three underlying correlations was negative. CONCLUSIONS: Results were similar to other studies of validity using biomarkers and the method of triads. For many dietary factors, the upper limit of the validity coefficients was less than 0.5 and therefore only strong relationships between dietary exposure and disease will be detected.

Adult↗
PubMed2005

Age-related factors that confound peripheral pulse timing characteristics in Caucasian children.

Characteristics obtained from peripheral pulses can be used to assess the status of cardiovascular system of subjects. However, nonintrusive techniques are preferred when prolonged monitoring is required for their comfort. Pulse transit time (PTT) measurement has showed its potentials to monitor timing changes in peripheral pulse in cardiovascular and respiratory studies. In children, the common peripheries used for these studies are fingers or toes. Presently, there is no known study conducted on children to investigate the possible physiologic parameters that can confound PTT measure at these sites. In this study, PTT values from both peripheral sites were recorded from 55 healthy Caucasian children (39 male) with mean age of 8.4+/-2.3 years (range 5-12 years). Peripheries' path length, heart rate, systolic blood pressure, diastolic blood pressure (DBP) and mean arterial pressure (MAP) were measured to investigate their contributions to PTT measurement. The results reveal that PTT is significantly related to all parameters (P<0.05), except for DBP and MAP. Age is observed to be the dominant factor that affects PTT at both peripheries in a child. Regression equations for PTT were derived for measuring from a finger and toe, (6.09 age+189.2) ms and (6.70 age+243.0) ms, respectively.

Aging↗
PubMed2005

Pulse transit time as a derived noninvasive mean to monitor arterial distensibility changes in children.

Changes in arterial distensibility have been widely used to identify the presence of cardiovascular abnormalities like hypertension. Pulse wave velocity (PWV) has shown to be related to arterial distensibility. However, the lack of suitable techniques to measure PWV nonintrusively has impeded its clinical usefulness. Pulse transit time (PTT) is a noninvasive technique derived from the principle of PWV. PTT has shown its capabilities in cardiovascular and cardiorespiratory studies in adults. However, no known study has been conducted to understand the suitability and utility of PTT to estimate PWV in children. Two computational methods to derive PWV from PTT values obtained from 23 normotensive Caucasian children (19 males, aged 5-12 years old) from their finger and toe were conducted. Furthermore, the effects of adopting different postures on the PWV derivations were investigated. Statistical analyses were performed in comparison with two previous PWV studies conducted on children. Results revealed that PWV derived from the upper limb correlated significantly (P<0.05) regardless of computing methods or postures adopted. The findings here suggest that PTT measurement can be used as a convenient and noninvasive surrogate measure of derived PWV in prolonged clinical studies, especially on younger or less cooperative children. Furthermore, the simple set-up and noninvasive nature of PTT can promote its usefulness in ambulatory monitoring.

Arteries↗
PubMed2005

The high-level mobility assessment tool (HiMAT) for traumatic brain injury. Part 1: Item generation.

PRIMARY OBJECTIVE: To generate a comprehensive list of items for a scale suitable for assessing high-level mobility in people with traumatic brain injury (TBI). RESEARCH DESIGN: High-level mobility items were generated following a critical evaluation of existing adult and paediatric mobility scales and by surveying expert clinicians for opinions about items appropriate for inclusion on a high-level mobility scale. MAIN OUTCOMES AND RESULTS: The critical evaluation identified 18 different items from 31 mobility scales. These included nine walking items in addition to higher level activities such as stair use, running, jumping and hopping. Expert clinicians generated 157 items that were collated and condensed to 88 items for ranking on a questionnaire. Fifteen items on the questionnaire were rated as very important by 80% of the expert clinicians. These included walking forwards, walking on slopes and different surfaces, changing direction, walking long distances and stair use. Running items included forwards, backwards, on slopes and over different surfaces, changing direction, stopping and starting as well as running long distances. Balancing in single limb stance was also included. CONCLUSION: The final list comprised walking, running, hopping, skipping, jumping and balance items. This initial version of the HiMAT has face and content validity although requires further testing to investigate whether it is uni-dimensional and valid for people with TBI.

Activities of Daily Living↗
PubMed2005

Mcm2 labelling of balloon cells in focal cortical dysplasia.

Balloon cells (BC) are the prominent and defining cellular component of type IIB Focal Cortical Dysplasia (FCD), a common cause of focal epilepsy in patients undergoing surgical treatment. BC are considered immature cells of uncommitted cellular differentiation having immunophenotypical characteristics of both neurones and glia. They are often located in the lower cortical layers and white matter underlying the dysplastic cortex, suggesting migratory arrest during development. We investigated the proliferative potential of BC in 15 cases of FCD from patients with a wide range of ages using immunohistochemistry for Mcm2 (mini chromosome maintenance protein) and Ki67. In the majority of cases, BC showed Mcm2 nuclear positivity. In addition, cells with intermediate neuronal-glial characteristics were labelled whilst the dysmorphic or hypertrophic pyramidal neuronal components of FCD were not. Ki67 labelled only occasional BC. These findings support the view that BC cells represent a pool of less differentiated glial cells with proliferative capacity which may have potential for delayed neuronal differentiation. Furthermore, as Mcm2 specifically identifies BC populations, this marker may be of diagnostic value in the subtyping of FCD lesions in patients with epilepsy.

Adolescent↗
PubMed2005

Physical activity staging distribution: establishing a heuristic using multiple studies.

The purpose of this study was to identify the population prevalence across the stages of change (SoC) for regular physical activity and to establish the prevalence of people at risk. With support from the National Institutes of Health, the American Heart Association, and the Robert Wood Johnson Foundation, nine Behavior Change Consortium studies with a common physical activity SoC measure agreed to collaborate and share data. The distribution pattern identified in these predominantly reactively recruited studies was Precontemplation (PC) = 5% (+/- 10), Contemplation (C) = 10% (+/- 10), Preparation (P) = 40% (+/- 10), Action = 10% (+/- 10), and Maintenance = 35% (+/- 10). With reactively recruited studies, it can be anticipated that there will be a higher percentage of the sample that is ready to change and a greater percentage of currently active people compared to random representative samples. The at-risk stage distribution (i.e., those not at criteria or PC, C, and P) was approximately 10% PC, 20% C, and 70% P in specific samples and approximately 20% PC, 10% C, and 70% P in the clinical samples. Knowing SoC heuristics can inform public health practitioners and policymakers about the population's motivation for physical activity, help track changes over time, and assist in the allocation of resources.

Behavioral Research↗
PubMed2004

Pneumococcal conjugate vaccines for preventing vaccine-type invasive pneumococcal disease and pneumonia with consolidation on x-ray in children under two years of age.

BACKGROUND: Pneumonia, most commonly caused by Streptococcus pneumoniae (Pnc), is a major cause of morbidity and mortality among young children especially in developing countries. Recently, the prevalence of antibiotic-resistant Pnc has increased worldwide such that the effectiveness of preventive strategies, like the new pneumococcal conjugate vaccines (PCV) on rates of invasive pneumococcal disease (IPD) and pneumonia, needs to be evaluated. OBJECTIVES: To determine the efficacy of PCV in reducing the incidence of IPD due to vaccine serotypes (VT) and x-ray confirmed pneumonia with consolidation of unspecified etiology in children who received PCV before 12 months of age. SEARCH STRATEGY: We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2004), MEDLINE (1990 to March 2004) and EMBASE (1990 to December 2003). Reference list of articles, and books of abstracts of relevant symposia, were hand searched. Researchers in the field were also contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PCV with placebo, or another vaccine, among children below two years with IPD and clinical/radiographic pneumonia as outcomes. DATA COLLECTION AND ANALYSIS: Two reviewers independently identified eligible studies, assessed trial quality, and extracted data. Differences were resolved by discussion. The inverse variance method was used to pool effect sizes. MAIN RESULTS: We identified four trials assessing the efficacy of PCV in reducing the incidence of IPD, two on x-ray confirmed pneumonia as outcome, and one on clinical pneumonia, with or without x-ray confirmation. Results from pooling HIV-1 negative children from the South African study with the other studies were as follows: the pooled vaccine efficacy (VE) for vaccine-type IPD was 88% (95% confidence interval (CI) 73% to 94%; fixed effect and random effects models), the effect measure was statistically significant (p <0.00001) and there was no heterogeneity (p = 0.77I2 0%); the pooled VE for all-serotype IPD was 66% (95% CI 46% to 79%; fixed effect model), the effect measure was statistically significant (p <0.00001) and there was no statistical heterogeneity (p = 0.09, I2 51%); the pooled VE for x-ray confirmed pneumonia was 22% (95% CI 11% to 31%; both fixed effect and random effects models) and there was no statistical heterogeneity (p = 0.80, I2 0%). Analyses that included all the children in the South African study (HIV-1 negative and HIV-1 positive children) and pooled with data from the other studies gave very similar results. REVIEWERS' CONCLUSIONS: PCV is effective in reducing the incidence of IPD from all serotypes but exerts a greater effect in reducing VT IPD. Although PCV is also effective in reducing the incidence of x-ray confirmed pneumonia, there are still uncertainties about the definition of this outcome. Additional randomised controlled trials are currently in progress.

Humans↗