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Biomedical subjects

J Bright

Publications and source records attributed to J Bright.

At least 19 recordsLinked to original sources
PubMed2006

Severe vocal cord dysfunction resistant to all current therapeutic interventions.

Vocal cord dysfunction (VCD) is characterised by paradoxical vocal cord adduction during inspiration or throughout the respiratory cycle, it results in wheeze, stridor, cough and dyspnoea. Although asthma and VCD can coexist, patients with VCD are frequently misdiagnosed with refractory asthma. It can severely restrict an individual's level of activity and effective therapeutic control can be difficult to achieve. We report the case of a patient who was treated with all available therapeutic interventions, including intralaryngeal botulinum toxin injection, but failure resulted in a permanent trachesotomy.

Adult↗
PubMed2004

Metabonomics, dietary influences and cultural differences: a 1H NMR-based study of urine samples obtained from healthy British and Swedish subjects.

The aim of this study was to assess the feasibility and comparability of metabonomic data in clinical studies conducted in different countries without dietary restriction. A (1)H NMR-based metabonomic analysis was performed on urine samples obtained from two separate studies, both including male and female subjects. The first was on a group of healthy British subjects (n = 120), whilst the second was on healthy subjects from two European countries (Britain and Sweden, n = 30). The subjects were asked to provide single, early morning urine samples collected on a single occasion. The (1)H NMR spectra obtained for urine samples were visually inspected and analysed chemometrically using principal components analysis (PCA). These inspections highlighted outliers within the urine samples and displayed interesting differences, revealing characteristic dietary and cultural features between the subjects of both countries, such as high trimethylamine-N-oxide (TMAO)-excretion in the Swedish population and high taurine-excretion, due to the Atkins diet. This study suggests that the endogenous urinary profile is subject to distinct cultural and severe dietary influences and that great care needs to be taken in the interpretation of 'biomarkers of disease and response to drug therapy' for diagnostic purposes.

Adolescent↗
PubMed2004

Cyclosporin A-induced changes in endogenous metabolites in rat urine: a metabonomic investigation using high field 1H NMR spectroscopy, HPLC-TOF/MS and chemometrics.

The model nephrotoxin cyclosporin A was administered to male Wistar-derived rats daily for 9 days at a dose level of 45 mg/kg per day. Urine samples were collected daily and the excretion pattern of low molecular mass organic molecules in the urine was studied using 1H NMR spectroscopy and HPLC-TOF/MS. Distinct changes in the pattern of endogenous metabolites, as a result of the daily administration of cyclosporin A, were observed by 1H NMR from day 7 onwards. The NMR-detected markers included raised concentrations of glucose, acetate, trimethylamine and succinate and reduced amounts of trimethylamine-N-oxide. In parallel studies by HPLC-TOF/MS a reduction in the quantities of kynurenic acid, xanthurenic acid, citric acid and riboflavin present in the urines was noted, together with reductions in a number of as yet unidentified compounds. In addition, signals resulting from the polyethylene glycol, present in the dosing vehicle, and cyclosporin A metabolites were detected by MS. However, these were excluded from the subsequent multivariate data analysis in order to highlight only changes to the endogenous metabolites. Analysis of both the 1H NMR and HPLC-MS spectroscopic data using pattern recognition techniques clearly identified the onset of changes due to nephrotoxicity.

Animals↗
PubMed2004

A metabonomic investigation of the biochemical effects of mercuric chloride in the rat using 1H NMR and HPLC-TOF/MS: time dependent changes in the urinary profile of endogenous metabolites as a result of nephrotoxicity.

The effects of the administration of a single dose of the model nephrotoxin mercuric chloride (2.0 mg kg(-1), subcutaneous) to male Wistar-derived rats on the urinary metabolite profiles of a range of endogenous metabolites has been investigated using (1)H NMR and HPLC-MS. Urine samples were collected daily for 9 days from both dosed and control animals. Analysis of these samples revealed marked changes in the pattern of endogenous metabolites as a result of HgCl(2) toxicity. Peak disturbances in the urinary metabolite profiles were observed (using both NMR and HPLC-MS) at 3 days post dose. Thereafter the urinary metabolite profile gradually returned to a more normal composition. Markers of toxicity identified by (1)H NMR spectroscopy were raised concentrations of lactate, alanine, acetate, succinate, trimethylamine (TMA), and glucose. Reductions in the urinary excretion of citrate and alpha-ketoglutarate were also seen. Markers identified by HPLC-MS, in positive ion mode, were kynurenic acid, xanthurenic acid, pantothenic acid and 7-methylguanine which decreased after dosing. In addition an ion at m/z 188, probably 3-amino-2-naphthoic acid, was observed to increase after dosing. As well as these identified compounds other ions at m/z 297 and 267 decreased after dosing. In negative ion mode a range of sulfated compounds were observed, including phenol sulfate and benzene diol sulfate, which decreased after dosing. As well as the sulfated components an unidentified glucuronide at m/z 326 was also observed to decrease after dosing. The results of this study demonstrate the complementary nature of the NMR and MS-based techniques for metabonomic analysis.

Acetates↗
PubMed2003

A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects.

The aim of the study was to assess the feasibility of metabonomics in clinical studies. A 1H nuclear magnetic resonance (NMR)-based metabonomic analysis was performed on plasma and urine samples obtained from a group of 12 healthy male subjects on two separate study days 14 days apart. The subjects were fed a standard diet and plasma and urine samples were obtained on both days. The 1H NMR spectra obtained for urine and plasma samples were analysed using principal components analysis (PCA) in order to generate metabonomic data. In plasma there was relatively little variability between subjects and study days. In the case of endogenous urinary metabolite profiles there was considerable inter-subject variability, but less intra-subject variation. In all subjects diurnal variation was seen with urine samples. This suggests the possibility to collect consistent metabonomics data in clinical studies.

Adult↗
PubMed1999

European medical device regulatory law and product liability.

The regulatory system for medical devices is quite different from that for pharmaceuticals and may catch many people unawares. For instance, it does not involve the grant of a marketing authorization by a medicines agency. Instead, a declaration of conformity is made by the manufacturer, but in many instances this is subject to approval by an independent certification house (known as a notified body). The Medical Devices Directive 93/42/EEC is applied in each EEA State by national Legislation. In the UK, for example, the relevant law is the Medical Devices Regulations 1994, and responsibility for enforcement rests with the Medical Devices Agency. Non-compliance with the regulations can incur a criminal penalty.

Device Approval↗
PubMed1998

Return to work after lung transplantation.

The social rehabilitation of lung transplant recipients becomes increasingly important as the results of lung transplantation improve. Although return-to-work (RTW) rates have been published for recipients of other organ transplants, no such data are available after lung transplantation. The purpose of this study was to determine what factors influence RTW after lung transplantation. Of 99 lung transplant recipients (43 single, 56 bilateral) surveyed from Denver, Colorado, (n = 49) and Toronto, Ontario, Canada (n = 50), 22% (n = 22) were employed, 38% (n = 38) were unemployed but medically able to work, 29% (n = 29) were medically disabled, and 10% (n = 10) had retired. The RTW rate for those medically able to work was 37% (22/60), and it was identical at each center (n = 11). Only Canadian lung transplant recipients (36%, 4/11) secured new jobs, whereas all Colorado lung transplant recipients returned to their previous employment (100%, 11/11). A stepwise discriminant analysis revealed that (1) pretransplantation employment, (2) a diagnosis of emphysema, cystic fibrosis, or primary pulmonary hypertension, (3) a self-report of being physically able to work, (4) greater functional improvement as measured by post-lung transplantation percent predicted forced vital capacity, and (5) post-lung transplantation 6-minute walk > 550 m positively influenced RTW. This analysis accurately profiled 82% of the employed and 76% of the unemployed recipients for an overall effectiveness of 79%. The findings of this study are that (1) a 37% employment rate for those physically able was comparable to other types of organ transplant recipients, (2) employment was not determined by the type of lung transplantation procedure (single or bilateral), and (3) social factors remain employment barriers for some recipients, but their absence did not guarantee a better employment rate.

Adult↗
PubMed1997

NMR studies of a viral protein that mimics the regulators of complement activation.

Vaccinia virus complement control protein (VCP) is a 243-residue protein that is similar in sequence to the regulators of complement activation; its role is to defend the virus against attack by the host complement system. A fragment of this protein spanning the two complement protein (CP)-modules (residues 126 to 243) which make up the C-terminal half of VCP has been expressed in Pichia pastoris. A 15N-labelled sample was purified for the purposes of structure determination and measurements of dynamics in solution using NMR. Structures were calculated on the basis of 1767 NMR-derived distance and angle restraints, with a longer than normal high-temperature simulated annealing (SA) protocol which improved convergence. The viral CP-modules are structurally very similar to the 15th and 16th CP-modules of human factor H (fH; average r.m.s.d., for invariant Trp and Cys, four pair-wise comparisons,=1.2 A) but less similar to the fifth CP-module of fH (average r.m.s.d.=2.2 A). In the VCP fragment, the orientation of one module with respect to the other is clearly defined by the experimental data, and T1 measurements are consistent with only limited flexibility at the module-module interface. The r.m.s.d. over all of the 118 residues (backbone atoms) is 0.73 A. The intermodular orientation is better defined than, and significantly different from, that observed in a CP-module pair from fH (re-calculated using the extended SA protocol). In VCP the long axis of the second module is tilted by 59(+/-4) degrees with respect to the first module (50(+/-13) degrees in the fH pair), and twisted with respect to the first module by 22(+/-6) degrees (223(+/-17) degrees in fH). The differences between the human and viral proteins may be rationalised in terms of the lack of hydrogen-bond stabilised secondary structure in the N-terminal portion of fH module 16, and the number and type of amino acid side-chains which make up the interface. A similar intermodular interface may be predicted between the third and fourth module of human C4 binding protein and, probably, between the third and fourth modules of the guinea pig acrosomal matrix protein 67; but the formulation of general rules for predicting the structure of interfaces between CP-modules awaits further experimental data.

Amino Acid Sequence↗
PubMed1997

House-dust mite allergen Der p 1: amount or concentration?

There is a lack of consensus as to the best way to quantify settled house-dust mite Der p 1 allergen from planar and nonplanar surfaces. To investigate the most appropriate measure of settled house-dust mite Der p 1 allergen, we determined the relationship between Der p 1 allergen content and collected dust weight from planar-surface (mattress) and nonplanar-surface (living-room) samples in 58 homes. There was a direct relationship between Der p 1 content and dust weight for both planar-surface (mattress, n = 217) samples (r = 0.50, P < 0.0001) and nonplanar-surface (living-room, n = 48) samples (r = 0.61, P < 0.0001). Correction for the surface area of the planar surface (mattress) vacuum-cleaned resulted in no additional benefit. We conclude that expression of Der p 1 levels per weight of collected dust appears to be the best method for both planar and nonplanar surfaces.

Allergens↗
PubMed1996

Radial cortical and trabecular bone densities of men and women standardized with the European Forearm Phantom.

We previously showed that it is possible to cross-calibrate peripheral bone densitometers using the European Spine Phantom (ESP). We have now performed a multinational study of cross-calibrated radius bone density based on normal subjects of both sexes in eight European centers. Six centers were equipped with machines made by Scanco or Stratec for determining distal radial trabecular bone density by quantitative computed tomography (QCT) and two were equipped with Lunar SP2 single photon absorptiometry (SPA) equipment for measuring midshaft cortical bone density. Subjects recruited ranged from 20 to over 80 years of age. Over one hundred and fifteen men were studied by QCT and a different cohort of 104 men were studied with SPA; the equivalent figures for women were 235 and 123. Reference ranges were derived for bone density against age for each of the four groups, and their applicability is discussed in relation to between-center differences in the results obtained. There were insignificant differences (P > 0.05 with Bonferroni correction) between centers in the values obtained by QCT in the different populations. However, there were considerably larger and highly statistically significant differences between midshaft cortical bone density values of about 10% of overall means between subjects from eastern Finland and central Belgium (P < 0.001), with higher Finnish values. Women had considerably lower radial trabecular bone density values than men at all ages, a result that differentiates the radius from the spine. This sex difference widened after menopause. These results have important implications for understanding the contribution of bone density to the differential risk of Colles' fracture in the two sexes and suggest that further work is needed to establish young normal reference ranges for radial bone density in Europe.

Absorptiometry, Photon↗
PubMed1995

Decreased CD3-mediated interferon-gamma production in relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that has been postulated to be T-cell mediated. We examined the proliferation and cytokine secretion of mononuclear cells after stimulation with OKT3 (anti-CD3) monoclonal antibody concanavalin A, or ionomycin plus myristic acid palmityl ester in subjects with stable relapsing-remitting MS. Control subjects demonstrated good proliferation to anti-CD3 monoclonal antibody whereas subjects with relapsing-remitting MS showed a significantly decreased anti-CD3 monoclonal antibody-mediated response. There was no difference in concanavalin or ionomycin plus myristic acid palmityl ester stimulation between control subjects and MS subjects. Secretion of interferon-gamma was significantly decreased and transforming growth factor-beta was significantly increased from cultures stimulated with anti-CD3 monoclonal antibody, but not ionomycin plus myristic acid palmityl ester or concanavalin A, in MS patients compared to control subjects. Secretion of interleukin-10 and tumor necrosis factor-alpha was not different between control subjects and MS patients following stimulation with anti-CD3 monoclonal antibody, concanavalin A, or ionomycin plus myristic acid palmityl ester, or of interleukin-2 and interleukin-4 following stimulation with anti-CD3 monoclonal antibody or concanavalin A. An abnormality of signal transduction and secretion of the immunomodulatory molecule interferon-gamma may exist in MS via the CD3 T-cell receptor complex.

CD3 Complex↗
PubMed1995

Dual X-ray absorptiometry of the proximal femur: normal European values standardized with the European Spine Phantom.

Measurements of the proximal femur by dual X-ray absorptiometry (DXA) are assuming increasing importance in clinical and epidemiological studies. However, different DXA manufacturers have adopted varying approaches to measuring the femoral neck and trochanter regions with the result that there is as yet no agreement on normal ranges and how to cross-calibrate between different machines. In this Concerted Action (of the EU's 2nd Framework Programme), 12 clinical centers in eight countries recruited a total of 855 female and 517 male Caucasian subjects who were judged to be free of conditions known to cause secondary osteoporosis and who had not been treated with drugs known to affect bone mass. The DXA machines used were made by Hologic, Lunar, and Norland. Each machine was cross-calibrated with the European Spine Phantom prototype designed by Kalender. All femoral neck and trochanter results were expressed as standardized values and were first examined for possible bias due to between-brand differences in choice of areas for measurement. On average, trochanter areas were similar between brands but Norland chose a narrower neck region for analysis. Bone mineral density (BMA or BMD g/cm2) was log-normally distributed for all groups at the femoral neck but normally distributed at the trochanter in men and postmenopausal women. There were substantial between-center differences after cross-calibration in age-adjusted mean values at both sites and also in the rates of apparent bone loss with age and the amounts of scatter within populations about mean age-adjusted values. With the proviso that locally derived normal ranges would allow more accurate comparisons for clinical purposes, European normal ranges were derived for both neck and trochanter. Data obtained with the three individual brands of machine fitted these overall ranges well. Bone loss was apparent in premenopausal women at the femoral neck but not the trochanter. Postmenopausal women's data was somewhat better fitted by reference to years since menopause than to chronological age. This work provides a basis for conducting future epidemiological and clinical studies with more than one brand of machine as long as each individual subject, if measured consecutively, is measured on the same machine throughout.

Absorptiometry, Photon↗
PubMed1995

European semi-anthropomorphic spine phantom for the calibration of bone densitometers: assessment of precision, stability and accuracy. The European Quantitation of Osteoporosis Study Group.

Up to now it has not been possible to reliably cross-calibrate dual-energy X-ray absorptiometry (DXA) densitometry equipment made by different manufacturers so that a measurement made on an individual subject can be expressed in the units used with a different type of machine. Manufacturers have adopted various procedures for edge detection and calibration, producing various normal ranges which are specific to each individual manufacturer's brand of machine. In this study we have used the recently described European Spine Phantom (ESP, prototype version), which contains three semi-anthropomorphic "vertebrae" of different densities made of stimulated cortical and trabecular bone, to calibrate a range of DXA densitometers and quantitative computed tomography (QCT) equipment used in the measurement of trabecular bone density of the lumbar vertebrae. Three brands of QCT equipment and three brands of DXA equipment were assessed. Repeat measurements were made to assess machine stability. With the large majority of machines which proved stable, mean values were obtained for the measured low, medium and high density vertebrae respectively. In the case of the QCT equipment these means were for the trabecular bone density, and in the case of the DXA equipment for vertebral body bone density in the posteroanterior projection. All DXA machines overestimated the projected area of the vertebral bodies by incorporating variable amounts of transverse process. In general, the QCT equipment gave measured values which were close to the specified values for trabecular density, but there were substantial differences from the specified values in the results provided by the three DXA brands. For the QCT and Norland DXA machines (posteroanterior view), the relationships between specified densities and observed densities were found to be linear, whereas for the other DXA equipment (posteroanterior view), slightly curvilinear, exponential fits were found to be necessary to fit the plots of observed versus specified densities. From these plots, individual calibration equations were derived for each machine studied. For optimal cross-calibration, it was found to be necessary to use an individual calibration equation for each machine. This study has shown that it is possible to cross-calibrate DXA as well as QCT equipment for the measurement of axial bone density. This will be of considerable benefit for large-scale epidemiological studies as well as for multi-site clinical studies depending on bone densitometry.

Absorptiometry, Photon↗
PubMed1995

Dual X-ray absorptiometry--cross-calibration and normative reference ranges for the spine: results of a European Community Concerted Action.

Bone density measurements by dual X-ray absorptiometry (DXA) of the spine can now be made precisely, but there is no uniformity in reporting results and in presenting reference data. A European Union Concerted Action therefore devised a uniform procedure for cross-calibrating and standardizing instruments, using the European spine phantom (ESP) prototype. This phantom differs in a number of respects from the final version of the ESP. Eighteen centers in nine countries obtained 1619 records (1035 women) from Caucasian subjects, aged 20-80 years, drawn from normal populations. The DXA machines used were made by the Hologic, Lunar, and Norland companies. Highly statistically significant differences were evident between populations, both in apparent rates of bone loss with age and in the spread of values about the age-adjusted means. There were small residual differences in the results obtained with the three machine brands which could have been due to the relatively large between-center population differences we observed. The alternative or additional explanation that they were attributable, in part, to the design differences between the ESP prototype and the definitive ESP, which became available after this study was completed, was shown to be a valid possibility. Results from postmenopausal women reported in relation to the years that have elapsed since menopause showed reduced population variance when compared with conventional reporting in relation to age. After cross-calibration, the center with the highest age-adjusted normal density value averaged 23% more than the center with the lowest. It is therefore crucially important to select appropriate reference data in clinical and epidemiological studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1994

Apoptosis: programmed cell death in health and disease.

Apoptosis is a normal physiological cell death process of eliminating unwanted cells from living organisms during embryonic and adult development. Apoptotic cells are characterised by fragmentation of nuclear DNA and formation of apoptotic bodies. Genetic analysis revealed the involvement of many death and survival genes in apoptosis which are regulated by extracellular factors. There are multiple inducers and inhibitors of apoptosis which interact with target cell specific surface receptors and transduce the signal by second messengers to programme cell death. The regulation of apoptosis is elusive, but defective regulation leads to aetiology of various ailments. Understanding the molecular mechanism of apoptosis including death genes, death signals, surface receptors and signal pathways will provide new insights in developing strategies to regulate the cell survival/death. The current knowledge on the molecular events of apoptotic cell death and their significance in health and disease is reviewed.

Acquired Immunodeficiency Syndrome↗
PubMed1994

European semi-anthropomorphic phantom for the cross-calibration of peripheral bone densitometers: assessment of precision accuracy and stability.

A semi-anthropomorphic 'distal radius like' phantom, developed by Kalender and Ruegsegger for use in peripheral bone densitometry using single photon (DPA) dual X-ray (DXA) and quantitative computed tomography (QCT) machines, has been studied with a view to cross-calibrating different types and brands of densitometers in current use. In the context of an EU 'Concerted Action' (second Framework Programme) the phantom was repeatedly measured on six SPA machines, three DXA machines and nine QCT machines (545 measurements). Linear regression equations were derived, individual to each machine, which allowed the derivation of 'standardized densities'. In this way we converted measurements made by machines of the same modality to a common scale of measurements. Two machines (one DXA, one SPA) showed statistically significant instability over time emphasising the need for rigorous quality control in the application of densitometry. In other respects these results provide an encouraging basis for the derivation of standardized normative ranges and the more effective use of peripheral densitometry in future clinical and epidemiological studies.

Absorptiometry, Photon↗
PubMed1993

The effect of a synthetic hexadentate iron chelator (CP130) and desferrioxamine on rabbit kidneys exposed to cold and warm ischaemia.

The effect of CP130 (a synthetic hexadentate pyridinone iron chelator) on the formation of two markers of lipid peroxidation (TBA-reactive material and Schiff's bases) in rabbit kidneys following a 72 h period of cold (0-4 degrees C) ischaemia was investigated by either adding CP130 to the flush/storage solution (hypertonic citrate solution) or by administering the agent intravenously 15 min before removal of the organs. In both cases, CP130 blocked the adverse rises in lipid peroxidation caused by ischaemia and subsequent reoxygenation of the homogenates in vitro. Both CP130 and desferrioxamine (DFX) (administered intravenously 15 min before ischaemia and 5 min before reperfusion) were also found to significantly reduce post-ischaemic rates of in vitro lipid peroxidation in kidneys rendered warm ischaemic for 90 min followed by reperfusion for 5 or 60 min in situ. Kidneys exposed to warm ischaemia and reperfusion developed interstitial and intracellular oedema, congestion and haemorrhage. DFX administration had little effect on the histological outcome, whereas CP130 significantly reduced interstitial oedema (at 5 min reperfusion compared to the DFX-treated group), intracellular oedema (at 60 min reperfusion compared to the DFX-treated group) and congestion (at 5 min reperfusion compared with a control group not given any agent). It is concluded that while CP130 and DFX exhibited similar antioxidant properties, CP130 provided better protection from ischaemia/reperfusion injury at the histological level. Synthetic iron chelators may therefore be of benefit in clinical organ transplantation by protecting against tissue damage caused by prolonged ischaemia.

Animals↗