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Biomedical subjects

R Williams

Publications and source records attributed to R Williams.

At least 37 records · Page 2Linked to original sources

Best evidence topic report. Ultrasound placement of needle in three-in-one nerve block.

A short cut review was carried out to establish whether ultrasound placement of three-in-one block is better than placement using a nerve stimulator. 137 papers were found, of which two presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. The clinical bottom line is that ultrasound guidance is better than electrical nerve stimulation at obtaining a good quality three in one femoral block.

Humans↗

Increased urinary dopamine excretion in association with bilateral carotid body tumours-- clinical, biochemical and genetic findings.

This report describes a rare case of a patient with increased urinary dopamine excretion in association with bilateral carotid body tumours. Excretion of adrenaline, noradrenaline, metadrenaline, normetadrenaline and 4-hydroxy-3-methoxymandelic acid (HMMA) were within the reference ranges, and an (123)I-meta-iodobenzylguanidine (MIBG) scan showed uptake in the neck masses, with no other abnormal uptake anywhere else in the body. The patient is being managed conservatively as the tumours are not amenable to resection on account of their size and vascularity. There are only four previous case reports of dopamine-secreting tumours of the carotid body described in the literature, all of whom were women. The tumours were unilateral in three cases and bilateral in the fourth case. Familial cases of carotid body tumours have a higher prevalence of bilateral tumours than non-familial cases. Recent reports in the literature have suggested that a significant number of patients with extra-adrenal catecholamine-secreting paragangliomas have a genetic mutation in one of the identified susceptibility genes for catecholamine-secreting tumours, despite having no other affected family members, and a mutation has been found in the succinate dehydrogenase gene for this patient.

3-Iodobenzylguanidine↗

Practical experiences of moving molecular diagnostics into routine use at the Veterinary Laboratories Agency.

The practical bench application of molecular tests (here defined as nucleic acid-based tests) in a routine testing situation is not without its challenges. This paper outlines the approaches we take at the Veterinary Laboratories Agency (VLA) and highlights some of the practical issues which we have found to be important for the successful introduction and use of molecular tests in a routine testing environment. The potential advantages of molecular tests, and factors which dictate which tests are adopted for routine testing, are discussed before giving some examples of molecular tests in routine use at the VLA. The instrumentation, reagents and assays we use are outlined, followed by sections of how we approach validation and how we manage and resource the transfer of molecular tests into routine use.

Laboratories↗

Role of cytosolic phospholipase A2 in the enhancement of alpha2-adrenoceptor-mediated vasoconstriction by the thromboxane-mimetic U46619 in the porcine isolated ear artery: comparison with vasopressin-enhanced responses.

Pre-contraction with the thromboxane-mimetic U46619 enhances the subsequent alpha(2)-adrenoceptor-mediated vasoconstriction in the porcine ear artery through an enhanced activation of ERK-MAP kinase. In this study we determined the role of cPLA(2) in this enhanced response, and determined whether vasopressin is also able to enhance alpha(2)-adrenoceptor-mediated vasoconstriction through the same pathway. The cPLA(2) inhibitors AACOCF3 (50 microM) and MAFP (50 microM) both inhibited the U46619-enhanced alpha(2)-adrenoceptor response, but had no effect on the direct alpha(2)-adrenoceptor response. AACOCF3 also inhibited the enhanced ERK activation associated with the enhanced alpha(2)-adrenoceptor-mediated vasoconstriction. Pre-contraction with arachidonic acid mimicked the effect of U46619 by enhancing the contractile response to the alpha(2)-adrenoceptor agonist UK14304 (1 microM) and enhancing the alpha(2)-adrenoceptor-mediated ERK activation. Pre-contraction with vasopressin also enhanced the contractile response to UK14304, but neither PD98059 (50 microM) nor AACOCF3 (50 microM) had any effect this vasopressin-enhanced response, indicating that neither the ERK pathway, nor cPLA(2) are involved in vasopressin-enhanced responses. The alpha(2)-adrenceptor-stimulated activation of ERK was also unaffected by pre-contraction with vasopressin. On the other hand, inhibition of PKCzeta inhibited the enhanced alpha(2)-adrenoceptor contraction after pre-contraction with both U46619 and vasopressin. This study demonstrates that alpha(2)-adrenoceptor-mediated vasoconstriction can be enhanced through two different pathways-one dependent upon the enhanced activation of ERK-MAP kinase through activation of cPLA(2), and the other through a different, ERK/cPLA(2)-independent pathway.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

A controlled trial of ondansetron in the pruritus of cholestasis.

BACKGROUND: In patients with pruritus of cholestasis, response to conventional drug treatment may be unsatisfactory. Activation of 5-hydroxytryptamine receptors on dermal sensory nerve-endings plays a role in the perception of pruritus. The 5-hydroxytryptamine(3) receptor antagonist, ondansetron, has been used in the treatment of pruritus of cholestasis, but there are few controlled data. AIM: To determine whether ondansetron is effective in treating the pruritus of cholestasis. METHODS: A total of 19 patients with resistant pruritus were randomized, double blind, to receive either ondansetron 8 mg or placebo as a single intravenous bolus, followed by oral ondansetron 8 mg or placebo twice daily for 5 days. Patients' perception of pruritus was recorded hourly using a visual analogue scale, and scratching activity measured by means of a piezo-electric crystal attached to the fingernail. RESULTS: Mean pruritus score using visual analogue scale and scratching activity were reduced on the first treatment day compared with baseline in both the ondansetron and placebo groups (P < 0.05), but there were no significant differences in mean pruritus perception or scratching activity between the two groups. CONCLUSION: Ondansetron was of no benefit in this group of pruritic patients during short-term treatment.

Adult↗

Arsenic levels in the soils and macrophytes of the 'Entremuros' after the Aznalcóllar mine spill.

In April 1998, a holding lagoon containing pyrite ore processing waste rich in arsenic, failed and released 5-6 million m(3) of highly polluting sludge and acidic water. Over 2700 ha of the internationally important Doñana National and Natural Parks were contaminated. The area of Natural Park to sustain the greatest impact was known as the Entremuros. This paper presents 0-5 cm soil monitoring data from the Entremuros, from sampling campaigns 6 and 18 months after the disaster; as well as macrophyte root, rhizome and stem data from samples taken 18 months after the spill. Results show a clear, decreasing, north-south arsenic soil pollution trend, both 6 and 18 months after the spill, and suggest a small reduction in total soil arsenic levels occurred over time; although a significant increase in extractable arsenic is also noted. The two macrophytes (Typha dominguensis and Scirpus maritimus) studied herein are not accumulating arsenic in stem parts, however, accumulation of arsenic on iron plaque on the roots of these plants may be occurring. Further work is recommended in order to determine the ecotoxicological significance of this process in relation to the avian food-chains of Doñana, and elsewhere.

Accidents↗

Long-term outcome of immunosuppression withdrawal after liver transplantation.

Eighteen liver transplant recipients were followed up for 10 years after a trial of immunosuppression withdrawal. Three groups were identified according to the early outcome of complete (group A, n = 5), partial (group B, n = 9), and unsuccessful (group C, n = 4) withdrawal of immunosuppression. The indications for liver transplantation (LT) (August 1983-December 1988) were as follows: primary biliary cirrhosis (n = 3), primary sclerosing cholangitis (n = 3), Budd-Chiari syndrome (n = 3), acute liver failure (n = 3), hepatitis C virus (HCV) cirrhosis (n = 1), HCV and autoimmune hepatitis (n = 1), HCV and alcohol-related cirrhosis (n = 1), HCV and hepatocellular carcinoma (HCC) (n = 1), cystic fibrosis (n = 1), and liver metastases from testicular teratoma (n = 1). Immunosuppression was based on cyclosporine. All patients experienced 1 or more complications of prolonged immunosuppression (median, 7 years; range, 5-11). Thirteen patients (72%) are alive at a median interval of 17 years (range, 16-21) after LT. Of the 5 patients in group A, 2 currently have normal graft function with no rejection episodes, and 3 have restarted immunosuppression following late low-grade acute rejection (n = 1), retransplantation for chronic rejection (n = 1), and kidney transplantation (n = 1). Of the 9 patients in group B, 5 died. The deaths were due to ruptured arterial pseudoaneurysm following retransplantation, HCC recurrence, cardiac failure, renal failure, and posttransplant lymphoma at 5, 7, 7, 14, and 17 years after LT, respectively. All 4 patients in group C are alive on a full immunosuppressive regimen. Long-term follow-up of 18 LT recipients withdrawn from immunosuppression has shown that at a median of 17 years 10% of patients remain off all immunosuppression.

Adolescent↗

Evolution of atherogenic diets in South Asian and Italian women after migration to a higher risk region.

BACKGROUND: To identify differences in the evolution of the diets of South Asian and Italian migrants, a cross-sectional, multiethnic study was undertaken in Glasgow, Scotland. METHODS: Five groups of women aged 20-42 years comprising general population (n = 35), South Asian migrants (n = 35) British-born controls (n = 37), Italian migrants (n = 30) and British-born (n = 38) participated in an interviewer administered structured questionnaire on issues relating to health, diet and food selection. Anthropometric measurements were made and subjects completed a 7-day weighed diet inventory. RESULTS: Compared with the general population, dietary differences were greatest amongst first generation migrant groups. There were major differences between the two migrant groups. South Asian migrants tended to display a more atherogenic profile (fat 42.4% energy, saturated fat 15.0% energy, vitamin C 5.1 mg per 1000 kJ) than the general population (fat 39.1% energy, saturated fat 13.5% energy, vitamin C 6.8 mg per 1000 kJ), and Italian migrants (fat 35.7% energy, saturated fat 12.1% energy, vitamin C 10.9 mg per 1000 kJ). However, South Asian groups had higher intakes of polyunsaturated fatty acids which may be cardioprotective. CONCLUSIONS: South Asian migrants to Scotland appear to develop adverse dietary elements in the first generation, which are modified in subsequent generations, whereas Italians' diets remain cardioprotective in the migrant generation but deteriorate in subsequent generations.

Acculturation↗

Monitoring trends in obesity in South Wales using routine data.

AIM: To use existing data on height and weight of 5 year old children, routinely recorded annually as part of the school entry medical, to monitor trends in obesity over the last 16 years in three South Wales localities. METHODS: Body mass index (BMI) and percentage of children over the cut off points for being overweight or obese proposed by the International Obesity Task Force were determined in 46,073 children who had height, weight, and sex recorded each school year (between 1986/87 and 2001/02) on the National Child Health Computer System held at the Swansea NHS Trust. RESULTS: With the exception of one year, the coverage for BMI measurements ranged between 87% and 99%. The accuracy of measurement and data entry was identified as suspect in some cases, and although some data entry errors could be corrected, 14% of BMI measurements were inadmissible. Logistic regression analysis of BMI trends in the remainder showed that the percentage of 5 year olds classified as overweight or obese had increased significantly over the time period and that the rate of change in girls was significantly greater than that in boys. CONCLUSION: Overweight and obese children have increased in frequency in this population. The Child Health Computer System is potentially a valuable source of information on the health status of populations and should be capable of monitoring trends in obesity. However, accuracy of measurement and data entry need to be improved, and the system, to be useful on a national basis, needs to be amalgamated at a higher level than individual NHS Trusts.

Body Height↗

Effect of photoperiod on body mass, food intake and body composition in the field vole, Microtus agrestis.

Many small mammals respond to seasonal changes in photoperiod by altering body mass and adiposity. These animals may provide valuable models for understanding the regulation of energy balance. Here, we present data on the field vole (Microtus agrestis) - a previously uncharacterised example of photoperiod-induced changes in body mass. We examined the effect of increased day length on body mass, food intake, apparent digestive efficiency, body composition, de novo lipogenesis and fatty acid composition of adipose tissue in cold-acclimated (8 degrees C) male field voles by transferring them from a short (SD, 8 h:16 h L:D) to long day photoperiod (LD, 16 h:8 h L:D). During the first 4 weeks of exposure to LD, voles underwent a substantial increase in body mass, after which the average difference between body masses of LD and SD voles stabilized at 7.5 g. This 24.8% increase in body mass reflected significant increases in absolute amounts of all body components, including dry fat mass, dry lean mass and body water mass. After correcting body composition and organ morphology data for the differences in body mass, only gonads (testes and seminal vesicles) were enlarged due to photoperiod treatment. To meet energetic demands of deposition and maintenance of extra tissue, voles adjusted their food intake to an increasing body mass and improved their apparent digestive efficiency. Consequently, although mass-corrected food intake did not differ between the photoperiod groups, the LD voles undergoing body mass increase assimilated on average 8.4 kJ day(-1) more than animals maintained in SD. The majority (73-77%) of the fat accumulated as adipose tissue had dietary origin. The rate of de novo lipogenesis and fatty acid composition of adipose tissue were not affected by photoperiod. The most important characteristics of the photoperiodic regulation of energy balance in the field vole are the clear delineation between phases where animals regulate body mass at two different levels and the rate at which animals are able to switch between different levels of energy homeostasis. Our data indicate that the field vole may provide an attractive novel animal model for investigation of the regulation of body mass and energy homeostasis at both organism and molecular levels.

Adaptation, Physiological↗

The computer-aided design and rapid prototyping fabrication of removable partial denture frameworks.

This study explores the application of computer-aided design and manufacture (CAD/CAM) to the process of electronically surveying a scanned dental cast as a prior stage to producing a sacrificial pattern for a removable partial denture (RPD) metal alloy framework. These are designed to retain artificial replacement teeth in the oral cavity. A cast produced from an impression of a patient's mouth was digitally scanned and the data converted to a three-dimensional computer file that could be read by the computer-aided design (CAD) software. Analysis and preparation were carried out in the digital environment according to established dental principles. The CAD software was then used to design the framework and generate a standard triangulation language (STL) file in preparation for its manufacture using rapid prototyping (RP) methods. Several RP methods were subsequently used to produce sacrificial patterns, which were then cast in a chromium-cobalt alloy using conventional methods and assessed for accuracy of fit. This work demonstrates that CAD/CAM techniques can be used for electronic dental cast analysis, preparation, and design of RPD frameworks. It also demonstrates that RP-produced patterns may be successfully cast using conventional methods and that the resulting frameworks can provide a satisfactory fit.

Computer-Aided Design↗

Development of the Safe Tractor Assessment Rating System.

We describe the development of the Safe Tractor Assessment and Rating System (STARS), a design-based tractor safety rating system that can be applied to new or used tractors to provide an objective assessment of their inherent safety features. A predictive rating system model, based on technical inspection, was used. Key principles underlying the system included the potential for design features to reduce the risk of an injury event occurring, and to reduce the risk of injury if such an event did occur. The rating system was based on current standards, research literature, injury and fatality data, and farmer input via focus groups. Development was an iterative process involving field, pilot, and inter-rater reliability tests. The final system was divided into six domains: rollover protection, runover protection, user protection, information and controls, pedestrian protection, and options. Within each domain, optimum design features were described for the common or serious potential injury risks, and a score was assigned for each feature. Scores were translated into a star rating, from zero stars for virtually no inherent safety features to five stars for the highest inherent safety, for each of the six domains. STARS distinguished well between older tractor models known to have few inherent safety features and newer tractor models known to have higher levels of inherent safety. STARS can provide tractor manufacturers, dealers, and users with information critical for managing tractor-associated injury risk. In Australia, it is initially being implemented within the curriculum of the technical education and training sector.

Accidents, Occupational↗

15th Seah Cheng Siang Memorial Lecture: Liver transplantation--lessons learnt and future horizons.

The first clinical successes with liver transplantation by Starzl in 1967 were based on studies showing that in man, organ allografts could induce self-tolerance with the aid of immunosuppression. Overall survival figures were poor until 1983, when cyclosporine was introduced into immunosuppressive regimes, and with the introduction of tacrolimus, results improved even further. With figures for 1-year survival now up to 90%, more attention is being directed to quality of life and the side effects of immunosuppression. Nephrotoxicity along with hypertension and diabetes are of major concern, and a significant number of long-term liver transplant patients are now facing end-stage renal failure. In the majority of conditions transplanted there is also a significant chance of disease recurrence in the graft. Owing to the shortage of cadaver organs, split liver and domino techniques are increasingly utilised. Living donor liver transplantation has also come to the fore, and to minimise potential harm to the donor, new techniques are being developed which will allow greater use of left lobe grafts.

Humans↗

Low myo-inositol and high glutamine levels in brain are associated with neuropsychological deterioration after induced hyperammonemia.

The neuropsychological effect of hyperammonemia is variable. This study tests the hypothesis that the effect of ammonia on the neuropsychological function in patients with cirrhosis is determined by the ability of the brain to buffer ammonia-induced increase in glutamine within the astrocyte by losing osmolytes like myo-inositol (mI) and not by the magnitude of the induced hyperammonemia. Fourteen cirrhotic patients with no evidence of overt hepatic encephalopathy were given a 75-g amino acid (aa) solution mimicking the hemoglobin molecule to induce hyperammonemia. Measurement of a battery of neuropsychological function tests including immediate memory, ammonia, aa, and short-echo time proton magnetic resonance spectroscopy were performed before and 4 h after administration of the aa solution. Eight patients showed deterioration in the Immediate Memory Test at 4 h. Demographic factors, severity of liver disease, change in plasma ammonia, and aa profiles after the aa solution were similar in those that showed a deterioration compared with those who did not. In patients who showed deterioration in the memory test, the mI-to-creatine ratio (mI/Cr) was significantly lower at baseline than those that did not deteriorate. In contrast, the glutamate/glutamine-to-Cr ratio was significantly greater in the patients that deteriorated. The observation that deterioration in the memory test scores was greater in those with lower mI/Cr supports the hypothesis that the neuropsychological effects of induced hyperammonemia is determined by the capacity of the brain to handle ammonia-induced increase in glutamine.

Adult↗

The distribution of arsenic in soils affected by the Aznalcóllar mine spill, SW Spain.

In April 1998, a holding lagoon containing pyrite ore processing waste, failed and released an estimated 5-6 million m(3) of metal rich sludge and acidic waters into the Rio Guadiamar, SW Spain. Over 2700 ha of the internationally important Doñana National and Natural Parks were contaminated. The sludge component of the waste contained up to 0.6% arsenic. This paper presents an extensive set of 0-5 cm soil analyses results from samples taken 6-8 months after the spill. Data are presented on pseudo-total arsenic levels in these samples, and on arsenic removed by both single batch and sequential extraction techniques. Pseudo-total levels of arsenic in the sludge ranged from 1521 to 3510 mg kg(-1), and a mean 4.4% of this was found to be extractable using 2.5% acetic acid. Soils in the Guadiamar Valley and Entremuros areas (those worst affected by the spill) were found to contain 85.4-782 mg kg(-1) and 7.1-196 mg kg(-1) pseudo-total arsenic, respectively. The mean acetic acid extractable component in these areas was 2.5% and 4.9%, respectively. Background pseudo-total arsenic levels in the soils of the area have been found to be 4.2-13.6 mg kg(-1). Rapid input of acidic waters, and the acidic nature of the sludge itself, may have caused depletion of Mg, Na and K, and to a lesser extent Mn, Ca and PO(4) in the upper 5 cm of the worst affected soils. Sequential extraction results suggest clear As-Fe associations, and possible As-Mn associations within the more soluble phases.

Journal Article↗

Transdermal hormone replacement therapy improves vertebral bone density in primary biliary cirrhosis: results of a 1-year controlled trial.

BACKGROUND: Retrospective studies have suggested that hormone replacement therapy may reduce the rate of bone loss in primary biliary cirrhosis, but no controlled data are available. METHODS: Forty-two post-menopausal women with primary biliary cirrhosis were treated with calcium and vitamin D, either alone (n = 21) or together with transdermal hormone replacement therapy (n = 21). Bone densitometry was performed at baseline and at 1 year, and serum and urinary markers of bone turnover were measured at three-monthly intervals. RESULTS: At entry, 17 patients (40%) had spinal or femoral osteopenia (T score - 1 to - 2.5) and nine (21%) had osteoporosis (T < - 2.5). In those given hormone replacement therapy, there was a significant decrease in the mean urinary deoxypyridinoline :creatinine ratios at 3 months (7.8 vs. 6.1 nm/mm creatinine for no hormone replacement therapy vs. hormone replacement therapy; P = 0.04) and a 48% reduction in urinary calcium excretion at 1 year (0.66 vs. 0.32 mm/mm creatinine; P = 0.01). Repeat bone densitometry at 1 year revealed a 2.25% increase in the hormone replacement therapy group (P = 0.02), compared with a non-significant 0.87% decrease in L2-L4 bone mineral density in those not given hormone replacement therapy. Both treatment regimens were well tolerated, with no increase in cholestasis. CONCLUSIONS: Compared with calcium and vitamin D alone, supplemental treatment with transdermal hormone replacement therapy for 1 year improved the vertebral bone density and urinary markers of bone turnover in post-menopausal women with primary biliary cirrhosis.

Administration, Cutaneous↗

Actin-dependent motility of melanosomes from fish retinal pigment epithelial (RPE) cells investigated using in vitro motility assays.

Melanosomes (pigment granules) within retinal pigment epithelial (RPE) cells of fish and amphibians undergo massive migrations in response to light conditions to control light flux to the retina. Previous research has shown that melanosome motility within apical projections of dissociated fish RPE cells requires an intact actin cytoskeleton, but the mechanisms and motors involved in melanosome transport in RPE have not been identified. Two in vitro motility assays, the Nitella assay and the sliding filament assay, were used to characterize actin-dependent motor activity of RPE melanosomes. Melanosomes applied to dissected filets of the Characean alga, Nitella, moved along actin cables at a mean rate of 2 microm/min, similar to the rate of melanosome motility in dissociated, cultured RPE cells. Path lengths of motile melanosomes ranged from 9 to 37 microm. Melanosome motility in the sliding filament assay was much more variable, ranging from 0.4-33 microm/min; 70% of velocities ranged from 1-15 microm/min. Latex beads coated with skeletal muscle myosin II and added to Nitella filets moved in the same direction as RPE melanosomes, indicating that the motility is barbed-end directed. Immunoblotting using antibodies against myosin VIIa and rab27a revealed that both proteins are enriched on melanosome membranes, suggesting that they could play a role in melanosome transport within apical projections of fish RPE.

Actins↗