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Biomedical subjects

S Ward

Publications and source records attributed to S Ward.

At least 19 recordsLinked to original sources
PubMed2006

Calcification inhibitors and Wnt signaling proteins are implicated in bovine artery smooth muscle cell calcification in the presence of phosphate and vitamin D sterols.

Administration of active vitamin D sterols to treat secondary hyperparathyroidism in patients with chronic kidney disease receiving dialysis has been associated with elevated serum calcium and phosphorus levels, which may lead to increased risk of vascular calcification. However, calcimimetics, by binding to the parathyroid gland calcium-sensing receptors, reduce serum parathyroid hormone, calcium, phosphorus, and the calcium-phosphorus product. Using cultured bovine aorta vascular smooth muscle cells (BASMCs), an in vitro model of vascular calcification, we compared calcification levels and gene expression profiles after exposure to the phosphate source ss-glycerolphosphate (BGP), the active vitamin D sterols calcitriol and paricalcitol, the calcimimetic R-568, or BGP with the active vitamin D sterols or R-568. Cells exposed to BGP (10 mM) alone or with calcitriol or paricalcitol showed dose-dependent BASMC calcification. No change in calcification was observed in cultures exposed to BGP with R-568, consistent with the observed lack of calcium-sensing receptor expression. Microarray analysis using total cellular RNA from cultures exposed to vehicle or BGP in the absence and presence of 10(-8) M calcitriol or paricalcitol for 7 days showed that cells exposed to BGP with calcitriol or BGP with paricalcitol had virtually identical gene expression profiles, which differed from those of cells treated with BGP or vehicle alone. Several osteoblast- and chondrocyte-associated genes were modulated by BGP and vitamin D exposure. In this study, exposure of BASMCs to phosphate and active vitamin D sterols induced calcification and changes in expression of genes associated with mineralized tissue.

Alkaline Phosphatase↗
PubMed2006

Which orthodontic archwire sequence? A randomized clinical trial.

The aim of this study was to compare three orthodontic archwire sequences. One hundred and fifty-four 10- to 17-year-old patients were treated in three centres and randomly allocated to one of three groups: A = 0.016-inch nickel titanium (NiTi), 0.018 x 0.025-inch NiTi, and 0.019 x 0.025-inch stainless steel (SS); B = 0.016-inch NiTi, 0.016-inch SS, 0.020-inch SS, and 0.019 x 0.025-inch SS; and C = 0.016 x 0.022-inch copper (Cu) NiTi, 0.019 x 0.025-inch CuNiTi, and 0.019 x 0.025-inch SS. At each archwire change and for each arch, the patients completed discomfort scores on a seven-point Likert scale at 4 hours, 24 hours, 3 days, and 1 week. Time in days and the number of visits taken to reach a 0.019 x 0.025-inch SS working archwires were calculated. A periapical radiograph of the upper left central incisor was taken at the start of the treatment and after placement of the 0.019 x 0.025-inch SS wire so root resorption could be assessed. There were no statistically significant differences between archwire sequences A, B, or C for patient discomfort (P > 0.05) or root resorption (P = 0.58). The number of visits required to reach the working archwire was greater for sequence B than for A (P = 0.012) but this could not be explained by the increased number of archwires used in sequence B.

Adolescent↗
PubMed2006

Do antiviral CD8+ T cells select hepatitis C virus escape mutants? Analysis in diverse epitopes targeted by human intrahepatic CD8+ T lymphocytes.

Hepatitis C virus (HCV) is a variable RNA virus that can readily establish persistent infection. Cellular immune responses are important in the early control of the virus. Evidence from animal models suggests that mutation in epitopes recognized by CD8+ T lymphocytes may play an important role in the establishment of persistence but in human persistent infection, equivalent evidence is lacking. We investigated this by analysing a unique resource: viruses from a set of chronically HCV-infected individuals in whom the CD8+ T-cell responses in liver had previously been accurately mapped. Virus was sequenced in seven individuals at 10 epitopes restricted by 10 human leucocyte antigen (HLA) molecules. Two main patterns emerged: in the majority of epitopes sequenced, no variation was seen. In three epitopes, mutations were identified which were compatible with immune escape as assessed using phylogenetic and/or functional studies. These data suggest that - even where specific intrahepatic T cells are detectable - many epitopes do not undergo mutation in chronic human infection. On the contrary, virus may escape from intrahepatic CD8+ T-cell responses in a 'patchy' manner in certain specific epitopes. Furthermore, longitudinal studies to identify the differences between 'selecting' and 'nonselecting' intrahepatic CD8+ T-cell responses are needed in HCV infection.

CD8-Positive T-Lymphocytes↗
PubMed2005

Heat transfer and the energetic cost of singing by canaries Serinus canaria.

Sexually selected displays, such as male passerine bird song, are predicted to be costly. However, most measurements calculated the rate of oxygen consumption during singing using respirometry have shown that bird song has a low energetic cost. Since birds are reluctant to sing when enclosed inside a respirometry chamber, the energetic cost of singing could differ from that under more normal circumstances. We used heat transfer modelling, based on thermal images, to estimate the energetic cost of singing by canaries (Serinus canaria) that were not enclosed in respirometry chambers. Metabolic rate calculated from heat transfer modelling was 0.70 +/- 0.02 W (N = 10 birds) during singing, which was 14+/-5% greater than during standing (0.62 +/- 0.02 W). The energetic cost of singing did not differ significantly from that measured previously using respirometry when we took into account that birds sang for a greater proportion of the time during the current experiments. These conclusions were not sensitive to potential errors in the heat transfer model. Heat transfer modelling would be especially useful to obtain measurements of the energetic cost of activities that animals do not perform readily inside respirometry chambers, such as singing in birds.

Animals↗
PubMed2005

Randomised controlled trial of non-invasive ventilation (NIV) for nocturnal hypoventilation in neuromuscular and chest wall disease patients with daytime normocapnia.

BACKGROUND: Long term non-invasive ventilation (NIV) reduces morbidity and mortality in patients with neuromuscular and chest wall disease with hypercapnic ventilatory failure, but preventive use has not produced benefit in normocapnic patients with Duchenne muscular dystrophy. Individuals with nocturnal hypercapnia but daytime normocapnia were randomised to a control group or nocturnal NIV to examine whether nocturnal hypoventilation is a valid indication for NIV. METHODS: Forty eight patients with congenital neuromuscular or chest wall disease aged 7-51 years and vital capacity<50% predicted underwent overnight respiratory monitoring. Twenty six with daytime normocapnia and nocturnal hypercapnia were randomised to either nocturnal NIV or to a control group without ventilatory support. NIV was started in the control group if patients fulfilled preset safety criteria. RESULTS: Peak nocturnal transcutaneous carbon dioxide tension (Tcco2) did not differ between the groups, but the mean (SD) percentage of the night during which Tcco2 was >6.5 kPa decreased in the NIV group (-57.7 (26.1)%) but not in controls (-11.75 (46.1)%; p=0.049, 95% CI -91.5 to -0.35). Mean (SD) arterial oxygen saturation increased in the NIV group (+2.97 (2.57)%) but not in controls (-1.12 (2.02)%; p=0.024, 95% CI 0.69 to 7.5). Nine of the 10 controls failed non-intervention by fulfilling criteria to initiate NIV after a mean (SD) of 8.3 (7.3) months. CONCLUSION: Patients with neuromuscular disease with nocturnal hypoventilation are likely to deteriorate with the development of daytime hypercapnia and/or progressive symptoms within 2 years and may benefit from the introduction of nocturnal NIV before daytime hypercapnia ensues.

Abdominal Wall↗
PubMed2005

Maxillary incisor palatal erosion: no correlation with dietary variables?

The objectives of the study were to examine a relationship between tooth erosion affecting the palatal aspects of permanent maxillary central incisors with dietary, behavioral and medical variables. The methods included, 251 schoolchildren aged 11 to 13 years were recruited to participate. Each subject had dental impressions of the palatal aspects of both upper central incisors recorded at baseline, 9 and 18 months intervals. From these, electroconductive replicas were fabricated, mapped and compared using a surface matching technique. At the end of the study all participants underwent a structured interview that sought to assay the level of potential erosive dietary, behavioral and medical risk factors. Correlation analyses of the responses given in the final structured interview with the degrees of palatal tooth substance loss (both previous and measured) were under taken. The results showed: (1) The degree of previous erosion did not predict the level of measured ongoing erosion. (2) Brushing the teeth more frequently with fluoridated toothpaste correlated significantly with lower levels of ongoing erosion (P = 0 011). It was concluded that: (1) Evidence of previous palatal erosion did not predict future erosion. (2) The application of topical fluoride as a by-product of tooth brushing may provide an element of protection against palatal erosion. (3) In view of the lack of correlation between exposure to potential risk factors and the level of ongoing palatal tooth surface loss in this study, other factors (such as an individual's susceptibility and salivary buffering power) may well be more important predictors. The clinical relevance included: Preventive advice to patients with dental erosion should not only include the use of topical fluoride, in the form of toothpaste, but recognize individual susceptibility to this condition.

Adolescent↗
PubMed2004

Training pathways.

Explore the source record for details and available documents.

Educational Measurement↗
PubMed2004

Rationalization of quantitative tooth surface loss data for epidemiological research.

Recent UK National Surveys have revealed a high prevalence of tooth surface loss (TSL) because of erosion in Children and Adolescents. Although digital surface mapping and surface matching techniques may be used to quantify its progression with time, reporting TSL of individuals as a function of either mean depth loss or volume loss, this can be inadequate when transferred for epidemiological analysis. For example, a tooth displaying multiple regions of depth loss may deserve to be distinguished from a tooth with a single localised area of erosion, although the total volume change may be the same. A potential solution, explored here, is to use both the quantitative wear data and colour coded surface representation plots generated by such methods to arrive at a single categorical wear score [1 (< or = 5% of surface exhibits TSL) to 5 (> or = 51% of surface exhibits TSL)]. Two examiners independently categorized, on two separate occasions, the TSL of 53 maxillary incisors (26 subjects observed at baseline and 9 months). Their performance was assessed for intra- and inter-examiner agreement by; (i) calculating the percentage of agreement, (ii) a Wilcoxon matched-pairs signed rank test. Thereafter, in cases of disagreement a consensus score was allocated and a regression analysis of this versus the numerically derived percentage of the surface that had undergone change was carried out. Intra- and inter-examiner agreement was 100 and 88.7% respectively and for the inter-examiner comparison P = 0.0456. The categorical scores and the quantitative wear data correlated linearly (R = 0.82). It is concluded that the method used to rationalize the quantitative TSL data is both reproducible and reflects the quantitative data. Its use should be helpful in epidemiological TSL studies but continued vigilance is required in cases of examiner disagreement.

Adolescent↗
PubMed2004

A novel approach to evaluating the reproducibility of a replication technique for the manufacture of electroconductive replicas for use in quantitative clinical dental wear studies.

The assessment of the progression of tooth surface loss has until recently been limited to either the application of subjective ranking scales or visual comparison of sequential study casts. The development of quantitative measuring techniques offers the potential of greater accuracy and sensitivity. As direct intra-oral measurement is problematical such approaches often utilize impressions of the teeth, recorded at different epochs, to construct replicas for mapping and comparison. This in vitro investigation sought to determine the reproducibility of such an approach taking into account the total process chain. Two inlay cavities (one large, one small) were prepared in the palatal aspect of a plastic maxillary central incisor and restored with two flush fitting inlays. A series of impressions of this tooth were recorded, using a special tray and an addition cured light bodied silicone impression material (President, Coltene, Switzerland), with (a) both inlays in (b) both inlays out (c) large inlay out and small inlay in (d) large inlay in and small inlay out - a total of 16 impressions. Electroconductive replicas were fabricated from these and mapped using a computer controlled probe. Each series simulated wear of the tooth. A surface matching and difference detection algorithm was then used to compare each series of replicas and calculate the proportion of the surface undergoing simulated wear by a direct comparison of (a) matched to (b) or, indirectly as the summation of the results of matches of (a) with (c) and (a) with (d). The mean proportion of the surface with wear calculated directly was 26.6% (s.d.=0.6) and indirectly 26.1% (s.d. = 0.5). A one-way anova revealed no significant difference (P > 0.05). It is concluded that determining wear by this method is highly reproducible.

Algorithms↗
PubMed2004

Metabolic power of European starlings Sturnus vulgaris during flight in a wind tunnel, estimated from heat transfer modelling, doubly labelled water and mask respirometry.

It is technically demanding to measure the energetic cost of animal flight. Each of the previously available techniques has some disadvantage as well advantages. We compared measurements of the energetic cost of flight in a wind tunnel by four European starlings Sturnus vulgaris made using three independent techniques: heat transfer modelling, doubly labelled water (DLW) and mask respirometry. We based our heat transfer model on thermal images of the surface temperature of the birds and air flow past the body and wings calculated from wing beat kinematics. Metabolic power was not sensitive to uncertainty in the value of efficiency when estimated from heat transfer modelling. A change in the assumed value of whole animal efficiency from 0.19 to 0.07 (the range of estimates in previous studies) only altered metabolic power predicted from heat transfer modelling by 13%. The same change in the assumed value of efficiency would cause a 2.7-fold change in metabolic power if it were predicted from mechanical power. Metabolic power did not differ significantly between measurements made using the three techniques when we assumed an efficiency in the range 0.11-0.19, although the DLW results appeared to form a U-shaped power-speed curve while the heat transfer model and respirometry results increased linearly with speed. This is the first time that techniques for determining metabolic power have been compared using data from the same birds flying under the same conditions. Our data provide reassurance that all the techniques produce similar results and suggest that heat transfer modelling may be a useful method for estimating metabolic rate.

Analysis of Variance↗
PubMed2003

Cost-utility analysis of imatinib mesilate for the treatment of advanced stage chronic myeloid leukaemia.

Imatinib mesilate (Glivec), Novartis Pharmaceuticals) is a novel therapy for the treatment of chronic myeloid leukaemia (CML). We evaluated the cost-effectiveness of imatinib (600 mg daily) when used for the treatment of patients in advanced stages of CML (accelerated phase and blast crisis) against conventional therapies of combination chemotherapy (DAT) and palliative care in hospital or at home. A Markov model simulated the transitions of hypothetical patient cohorts and outcomes were modelled for 5 years from the start of treatment. Costs were estimated from the perspective of the UK National Health Service. Over 5 years, a patient in accelerated phase will, on average, accrue an additional 2.09 QALYs with imatinib compared to conventional therapies, while patients in blast crisis will accrue an additional 0.58 quality-adjusted life-years (QALYs) with imatinib compared to conventional therapies. The costs per additional QALY gained from treatment with imatinib compared with conventional therapies were pound 29344 (accelerated phase) and pound 42239 (blast crisis). The results were particularly sensitive to the price of imatinib, improvements in quality of life, and the duration of haematological responses. We conclude that treatment of CML with imatinib confers considerably greater survival and quality of life than conventional treatments but at a cost.

Antineoplastic Agents↗
PubMed2003

Assessment of a procedure for detecting minute levels of tooth erosion.

Over a period of some years, the components of a system for discerning erosion on children's teeth have been progressively developed, for use in an extensive project seeking correlations between erosion and various perceived risk factors. The aim was the detection of minute levels of erosion, based on mappings of the palatal surfaces of the maxillary central incisors in children. Significant challenges were encountered, the primary problem being the impracticality of placing control marks that would aid the realignment of successive measurements. The paper describes the erosion detection system and initial experiences based on the results of the first 100 subjects measured after 9 months. The procedures detected the occurrence of erosion of 50 microm magnitude on about one-quarter of the teeth over the 9 month period, at a precision estimated to be +/- 15 microm. The occurrence of some anomalous incidents prevented the procedure from being fully automatic, and it necessitated human examination of a graphical diagram derived from the surface matching program, but it was nevertheless superior to current practices of examining impressions or replicas entirely by eye.

Child↗
PubMed2003

Slower rise of exhaled breath temperature in chronic obstructive pulmonary disease.

In chronic obstructive pulmonary disease (COPD) there is decreased vascularity of the bronchi and inflammation of the airways that may have opposite effects on the regulation of heat loss. Exhaled air temperature increase (delta(e) T) was measured in 23 patients with moderate COPD (18 male, mean age +/- SEM 70 +/- 1 yrs; forced expiratory volume in one second (FEV1) 45 +/- 3%, FEV1/forced vital capacity 54 +/- 4%) and 16 normal volunteers (64 +/- 4 yr) and compared to exhaled nitric oxide (eNO) and inflammatory cells in induced sputum as a marker of airway inflammation. Delta(e) T was measured during a flow- and pressure-controlled single exhalation with a fast-response thermometer. delta(e) T was reduced in patients with COPD (1.86 +/- 0.15 delta C x s(-1)) compared to normal subjects (4.00 +/- 0.26 delta C x s(-1)). There was no difference in delta(e) T between patients treated with inhaled steroids and those who were steroid naïve. Delta(e) T was correlated with eNO (r=0.60) but not with sputum neutrophilia. In COPD patients, delta(e) T was increased (2.26 +/- 0.16 delta C x s(-1)) after the inhalation of 200 microg of albuterol, which is a known vasodilator, indicating that delta(e) T and bronchial blood flow may be correlated. Exhaled temperature increase is reduced in chronic obstructive pulmonary disease patients and is increased by the inhalation of vasodilators and therefore may be related to changes of bronchial blood flow and tissue remodelling.

Aged↗
PubMed2003

Clinical and cost-effectiveness of capecitabine and tegafur with uracil for the treatment of metastatic colorectal cancer: systematic review and economic evaluation.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of capecitabine and tegafur with uracil (UFT/LV) as first-line treatments for patients with metastatic colorectal cancer, as compared with 5-fluorouracil/folinic acid (5-FU/FA) regimens. DATA SOURCES: Electronic databases, reference lists of relevant articles and sponsor submissions were also consulted. REVIEW METHODS: Systematic searches, selection against criteria and quality assessment were performed to obtain data from relevant studies. Costs were estimated through resource-use data taken from the published trials and the unpublished sponsor submissions. Unit costs were taken from published sources, where available. An economic evaluation was undertaken to compare the cost-effectiveness of capecitabine and UFT/LV with three intravenous 5-FU/LV regimens widely used in the UK: the Mayo, the modified de Gramont regimen and the inpatient de Gramont regimens. RESULTS: The evidence suggests that treatment with capecitabine improves overall response rates and has an improved adverse effect profile in comparison with 5-FU/LV treatment with the Mayo regimen, with the exception of hand-foot syndrome. Time to disease progression or death after treatment with UFT/LV in one study appears to be shorter than after treatment with 5-FU/LV with the Mayo regimen, although it also had an improved adverse effect profile. Neither capecitabine nor UFT/LV appeared to improve health-related quality of life. Little information on patient preference was available for UFT/LV, but there was indicated a strong preference for this over 5-FU/LV. The total cost of capecitabine and UFT/LV treatments were estimated at 2111 pounds and 3375 pounds, respectively, compared with the total treatment cost for the Mayo regimen of 3579 pounds. Cost estimates were also presented for the modified de Gramont and inpatient de Gramont regimens. These were 3684 pounds and 6155 pounds, respectively. No survival advantage was shown in the RCTs of the oral drugs against the Mayo regimen. Cost savings of capecitabine and UFT/LV over the Mayo regimen were estimated to be 1461 pounds and 209 pounds, respectively. Drug acquisition costs were higher for the oral therapies than for the Mayo regimen, but were offset by lower administration costs. Adverse event treatment costs were similar across the three regimens. It was inferred that there was no survival difference between the oral drugs and the de Gramont regimens. Cost savings of capecitabine and UFT/LV over the modified de Gramont regimen were estimated to be 1353 pounds and 101 pounds, respectively, and over the inpatient de Gramont regimen were estimated to be 4123 pounds and 2870 pounds, respectively. CONCLUSIONS: The results show that there are cost savings associated with the use of oral therapies. No survival difference has been proven between the oral drugs and the Mayo regimen. In addition, no evidence of a survival difference between the Mayo regimen and the de Gramont regimens has been identified. However, improved progression-free survival and an improved adverse event profile have been shown for the de Gramont regimen over the Mayo regimen. Further research is recommended into the following areas: quality of life data should be included in trials of colorectal cancer treatments; the place of effective oral treatments in the treatment of colorectal cancer, the safety mechanisms needed to ensure compliance and the monitoring of adverse effects; the optimum duration of treatment; the measurement of patient preference; and a phase III comparative trial of capecitabine and UFT/LV versus modified de Gramont treatment to determine whether there was any survival advantage and to collate the necessary economic data.

Antimetabolites, Antineoplastic↗
PubMed2002

The energetics of barnacle geese (Branta leucopsis) flying in captive and wild conditions.

Experimental data on the relationship between mean heart rate (f(H)) and mean rate of oxygen consumption (VO(2)) of captive barnacle geese during flights in a wind tunnel are assessed in terms of their capacity to predict the typical VO(2) of wild barnacle geese, based on the recordings of their f(H), while undertaking autumn migratory flights between Spitsbergen (78 degrees N) and Caerlaverock, Scotland (55 degrees N). A significant linear relationship has been demonstrated between the f(H) and simultaneously recorded VO(2) of a single barnacle goose (B-B) flying in the wind tunnel (VO(2)=1.42 f(H)-304, r(2)=0.82, P<0.001, N=12 flights). Data recorded from three additional geese (N=4 flights), lay within the 95% prediction intervals of the relationship for goose B-B. When these geese (mean body mass=2.06 kg, n=4) were flown in the wind tunnel (WT) without the mask, they had a mean f(H) of 451+/-23 beats min(-1), yielding an estimate for VO(2) of 336+/-33 ml min(-1). However, f(H) has also been recorded from wild barnacle geese (mean migratory f(H) of 253 beats min(-1)), and substitution of this value into the above calibration equation results in an unrealistically low value for mean migratory VO(2) of only 55 ml min(-1). Various factors, such as differences in heart mass, selective tissue perfusion, environmental temperature and flock formation, which might account for some of the difference in f(H) between the captive and wild geese are discussed. Comparison with other WT studies shows that inter-species minimum mass-specific VO(2) declines with increasing body mass (M(b); range 0.035-2.8 kg) as 173 M(b)(-0.224), r(2)=0.848.

Animals↗
PubMed2002

Cellular immune responses against hepatitis C virus: the evidence base 2002.

Hepatitis C virus (HCV) is an RNA virus which is estimated to persistently infect about 170 million people worldwide. After acute infection, there is an initial period during which long-term outcome is decided. There is strong evidence that the cellular immune responses, involving both CD4+ and CD8+ T lymphocytes, are involved at this stage and it is their effectiveness which determines outcome. What is not understood is what determines their effectiveness. The most important component of this is likely to be some aspect of epitope selection, itself dictated by host MHC. Thus, to understand host immunity to HCV, we need to have a detailed understanding of the peptides involved in T lymphocyte responses. In this review, we discuss the peptide epitopes that have been identified so far, and their potential significance. We relate this to a scheme of host defence which may be useful for understanding natural and vaccine-induced immunity.

CD4-Positive T-Lymphocytes↗