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Biomedical subjects

A Cooper

Publications and source records attributed to A Cooper.

At least 19 recordsLinked to original sources
PubMed2007

Biochemical monitoring after haemopoietic stem cell transplant for Hurler syndrome (MPSIH): implications for functional outcome after transplant in metabolic disease.

Hurler Syndrome is corrected by allogeneic BMT by the action of donor enzyme on recipient tissue. In this paper, we describe monitoring of 39 patients transplanted in two centres to determine donor chimerism, enzyme level and residual substrate - expressed as dermatan sulphate to chondroitin sulphate ratio. We show that in fully engrafted recipients, the enzyme level, expressed as mumol/g total protein/h, post-transplant is 24.2 from an unrelated donor and 10.2 from a heterozygote family donor (P<0.0001). There is a tight relationship between mean post-transplant enzyme level and residual substrate - Spearman's rank correlation coefficient (Rho) was -0.76 and -0.80 at 12 and 24 months, respectively (P<0.0001). We propose that these differences affect patient outcome. As unrelated donor transplant outcomes improve and especially given the higher levels of donor cell engraftment following cord transplants, our data might influence donor selection where only heterozygote-matched family members are available.

Chimerism↗
PubMed2006

A novel use of a unilateral hinged partial denture.

This report describes a unilateral removable partial denture with a hinged arm with magnetic retention and a prosthetic flange component that was provided for a patient with localised periodontal tissue loss. While a unilateral partial denture is not generally advocated because of the risk of swallowing or aspiration, this case illustrates the effective use of such a design.

Adult↗
PubMed2006

Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study.

Osteoporosis is a common and debilitating condition associated with significant morbidity and mortality. The efficacy and safety of oral bisphosphonates for the treatment of osteoporosis are well established. However, patient adherence and persistence on treatment are suboptimal. This randomised open-label multi-centre study of 6-months' duration compared persistence on treatment in postmenopausal women with osteoporosis receiving either once-monthly ibandronate plus a patient support programme (PSP), or once-weekly alendronate. To avoid falsely elevated persistence rates often associated with clinical trials, the study was designed to reflect everyday clinical practice in the UK and follow-up visits were limited to be consistent with the primary care setting. Analysis of the primary endpoint showed that persistence was significantly higher in the ibandronate/PSP group compared with the alendronate group (p < 0.0001). The estimated proportion of patients persisting with treatment at 6 months was 56.6% (306/541) and 38.6% (198/513) in the ibandronate/PSP and alendronate groups, respectively. Therefore, compared with alendronate, there was a 47% relative improvement in the proportion of patients persisting with treatment in the ibandronate/PSP group. Secondary endpoint measurements of adherence (e.g. proportion of patients remaining on treatment at study end; proportion of patients discontinuing from the study) were also significantly different in favour of ibandronate plus patient support. In summary, the PERSIST study demonstrated that persistence on treatment was increased in patients receiving once-monthly ibandronate plus patient support compared with once-weekly alendronate. Increased persistence on bisphosphonate treatment is expected to improve patient outcomes and decrease the social and economic burden of osteoporosis.

Aged↗
PubMed2006

Histological correlates of post mortem mitochondrial DNA damage in degraded hair.

We have assessed the histological preservation of naturally degraded human hair shafts, and then assayed each for levels of amplifiable mitochondrial DNA and damage-associated DNA miscoding lesions. The results indicate that as sample histology is altered (i.e. as hairs degrade) levels of amplifiable mitochondrial DNA decrease, but no correlation is seen between histology and absolute levels of mitochondrial DNA miscoding lesions. Nevertheless, amplifiable mitochondrial DNA could be recovered across the complete range of the histological preservation spectrum. However, when template copy number is taken into consideration, a correlation of miscoding lesions with histology is again apparent. These relationships indicate that a potential route for the generation of misleading mitochondrial sequence data exists in samples of poor histology. Therefore, we argue that in the absence of molecular cloning, the histological screening of hair may be necessary in order to confirm the reliability of mitochondrial DNA sequences amplified from hair, and thus represents a useful tool in forensic mitochondrial DNA analyses.

Animals↗
PubMed2005

Seminal tissue factor revisited.

Studies of seminal tissue factor (TF) are few and mostly based on small numbers. Due to the reported lack of factor (F) X in semen, it has been suggested that TF may not have a role in seminal coagulum formation. However, recent identification of a number of haemostatic factors in semen justifies a re-evaluation of its occurrence. Semen specimens were collected from sub-fertile (n = 19), normally fertile (n = 33), semen donors (n = 30) and vasectomized subjects (n = 62), some fractionated into sperm, a prostasome-rich fraction and seminal plasma. Functional and antigenic TF levels were measured and related to conventional fertility parameters. Semen contains high concentration of functional and antigenic TF. Most TF was found in seminal plasma prepared by low-speed centrifugation. When further fractionated by ultracentrifugation much of this may reside in the pellet (prostasomal fraction). It was also detectable on sperm. TF antigen levels were higher in vasectomized subjects than sub-fertile, normally fertile, donor (p = 0.02) and a 'pooled normal semen parameters' (PNSP) stratification (derived from a combination of measurements) (p = 0.06). The sub-fertile group showed a wider variation than normal, donor or the PNSP subjects. Seminal TF antigen levels correlated significantly with sperm agglutination (p = 0.03) and abnormal sperm morphology (p = 0.04). Subjects with anti-sperm antibodies also showed high TF antigen levels. In conclusion, semen contains functional and antigenic TF at high concentrations. A full complement of clotting factors probably exists in semen, so some pro-coagulant role for TF should not be excluded. Decreased seminal TF levels appear to be associated with seminal parameters that are known to favour male fertility.

Adult↗
PubMed2005

Heparan sulfate levels in mucopolysaccharidoses and mucolipidoses.

Glycosaminoglycans are accumulated in both mucopolysaccharidoses (MPS) and mucolipidoses (ML). MPS I, II, III and VII and ML II and ML III patients cannot properly degrade heparan sulphate (HS). In spite of the importance of HS storage in the metabolic pathway in these diseases, blood and urine HS levels have not been determined systematically using a simple and economical method. Using a new ELISA method using anti-HS antibodies, HS concentrations in blood and urine were determined in MPS and ML II and ML III patients. HS concentrations were determined in 156 plasma samples from MPS I (n = 23), MPS II (n = 26), MPS III (n = 24), MPS IV (n = 62), MPS VI (n = 5), MPS VII (n = 5), ML II (n = 8) and ML III (n = 3), and 205 urine samples from MPS I (n = 33), MPS II (n = 33), MPS III (n = 30), MPS IV (n = 82), MPS VI (n = 7), MPS VII (n = 9), ML II (n = 8) and ML III (n = 3). The ELISA method used monoclonal antibodies against HS. MPS I, II, III and VII and ML II and III patients had significant elevation in plasma HS, compared to the age-matched controls (p < 0.0001). Eighty-three out of 89 (93.3%) of individual values in the above MPS types and ML were above the mean +2SD of the controls. In urine samples, 75% of individual values in patients with those types were above the mean +2SD of the controls. In contrast to the previous understanding of the HS metabolic pathway, plasma HS levels in all five MPS VI and 15% of MPS IV patients were elevated above the mean +2SD of the controls. These findings suggest that HS concentration determined by ELISA, especially in plasma, could be a helpful marker for detection of the most severe MPS I, II, III, VI and VII and ML II, distinguishing them from normal populations.

Adolescent↗
PubMed2005

Keratan sulphate levels in mucopolysaccharidoses and mucolipidoses.

The mucopolysaccharidoses (MPS) is characterized by accumulation of glycosaminoglycans (GAGs), and mucolipidosis (ML) by accumulation of GAGs and sphingolipids. Each type of MPS accumulates specific GAGs. The lysosomal enzymes N-acetylgalactosamine-6-sulphate sulphatase and beta-galactosidase involve the stepwise degradation of keratan sulphate (KS). Deficiency of these enzymes results in elevation of KS levels in the body fluids and in tissues, leading to MPS IV disease. In this study, we evaluated blood and urine KS levels in types of MPS and ML other than MPS IV. Eighty-five plasma samples came from MPS I (n = 18), MPS II (n = 28), MPS III (n = 20), MPS VI (n = 3), MPS VII (n = 5) and ML (n = 11) patients while 127 urine samples came from MPS I (n = 34), MPS II (n = 34), MPS III (n = 32), MPS VI (n = 7), MPS VII (n = 9) and ML (n = 11) patients. KS levels were determined using the ELISA method. Plasma KS levels varied with age in both control and patient populations. In all age groups, the mean values of plasma KS in MPS and ML patients were significantly higher than those in the age-matched controls. Plasma KS values in four newborn patients were above the mean + 2SD of the age-matched controls (mean, 41 ng/ml). Overall, 85.9% of individual values in non-type IV MPS and ML patients were above the mean + 2SD of the age-matched controls. For urine KS levels, 24.4% of individual values in patients were above the mean + 2SD of the age-matched controls. In conclusion, KS in blood is elevated in each type of non-type IV MPS examined, in contrast to the conventional understanding. This finding suggests that measurement of KS level provides a new diagnostic biomarker in a wide variety of mucopolysaccharidoses and mucolipidoses in addition to MPS IV.

Adolescent↗
PubMed2005

Development and testing of a computerised 24-h recall questionnaire measuring fruit and snack consumption among 9-11 year olds.

OBJECTIVE: To evaluate the validity, reliability and sensitivity of a computerised single day 24-h recall questionnaire designed for the comparison of children's fruit and snack consumption at the group (school) level. DESIGN: Relative validity and reliability were assessed in relation to (i) intake at school and (ii) intake throughout the whole day, using diary-assisted 24-h recall interviews and a 7-day test-retest procedure. Sensitivity was assessed in relation to intake by comparing results from schools with differing food policies, and by sex. SUBJECTS AND SETTING: Eight schools took part in the validity and reliability assessments, with 78 children completing the 24-h recall interviews and 195 children completing the test-retest procedure. A total of 43 schools (1890 children) took part in the sensitivity analysis. All children were aged 9-11 y. All schools were in South Wales and South-west England. RESULTS: For fruit intake at school, the questionnaire showed fair levels of validity at the individual level (kappa = 0.29). At the group level, there were little or no differences in fruit intake at school between the two measures and two occasions. The questionnaire was sufficiently sensitive to identify statistically significant differences between girls and boys, and between schools with different food policies. For snack intake at school, validity at the individual level was slightly lower (kappa = 0.220.25), but the data remained of value in analyses at the group level. For fruit and snack intake throughout the whole day there was little agreement at the individual level (kappa = 0.00-0.06), and at the group level there tended to be substantial differences between the two measures and two occasions. CONCLUSIONS: The computerised questionnaire is a quick and cost-effective means of assessing children's consumption of fruit at school. While further development is required to improve validity and reliability, it has the potential to be particularly useful in randomised controlled trials of school-based dietary interventions.

Candy↗
PubMed2005

The launch of MCBEND 10.

MCBEND 10 is the latest release of the general radiation transport Monte Carlo code from the ANSWERS Software Service of Serco Assurance. MCBEND is developed within a Nuclear Code Development (NCD) partnership between Serco Assurance and BNFL. The ANSWERS vision is 'to provide easy-to-use software that meets the current and emerging needs of the user community'. In the case of MCBEND, this vision focuses on the key areas of accuracy, understanding of uncertainties, efficiency and user-friendliness. MCBEND 10 is a major launch of the code with many new and enhanced features. New developments in MCBEND 10 include automatic splitting mesh generation, point energy adjoint for neutrons, calculation of uncertainty in the results due to material cross section uncertainties and a unified source facility. Enhanced features include improved temperature treatment, extended scoring of sensitivity to geometry perturbations, geometry improvements, extensions to formulae and improved user guide image. The user-friendliness of the MCBEND code has been further enhanced by recent developments to the visualisation tools, VISAGE and VISTA-RAY. Developments have been made to the three-dimensional visualisation tool, VISTA-RAY, to simplify the detailed checking of a model, with the option to use a mouse-pointer to select regions of interest for further detail and to visually highlight incorrectly defined areas. A further development to VISTA-RAY is the inclusion of the capability to overlay a representation of a user-designated set of results from a MCBEND analysis on the model. Improvements have also been made to the graphical user interface LaunchPad for submitting and controlling calculation submission, with a common user-image across all the systems. Recent enhancements to LaunchPad include a job-scheduler to simplify processing multiple tasks. A selection of the new developments in MCBEND 10, VISTA-RAY and LaunchPad will be described in this paper.

Algorithms↗
PubMed2005

Electromyography characterization of stretch responses in hemiparetic stroke patients and their relationship with the Modified Ashworth scale.

OBJECTIVES: To determine the validity of the Modified Ashworth Scale as a measure of spasticity by determining its relationship to surface electromyography activity and contracture. DESIGN: A controlled study of hemiparetic stroke patients with spasticity. SETTING: A physiotherapy department in a secondary care hospital. SUBJECTS: Thirty-one stroke patients and 20 healthy volunteers. MAIN MEASURES: The resistance to passive movement around the knee and ankle of the affected and unaffected legs was rated using the Modified Ashworth Scale. Passive range of movement was measured with a goniometer. Surface electromyography recordings of four lower limb muscles were taken during passive stretches of the knee and ankle. RESULTS: Hemiparetic patients produced surface electromyography responses to stretch that were of greater amplitude (unaffected limbs: mean = 25.82 mV (43.85), affected limbs: mean = 24.77 mV (35.46)) than those of healthy volunteers (mean = 15.85 (29.96)). The affected muscles of hemiparetic patients were more likely to produce surface electromyography responses to stretch of a sustained duration (45% of cases) compared with unaffected limbs (24% of cases) and those of healthy volunteers (16% of cases). The Modified Ashworth Scale showed a positive correlation with the magnitude (p < 0.05) and duration (p < 0.001) of the surface electromyography response. High scores on the Modified Ashworth Scale were associated with contracture (p < 0.001). Contracted muscles produced significantly greater surface electromyography reflex responses compared with noncontracted muscles (p < 0.05). CONCLUSION: The Modified Ashworth Scale reflects spasticity in terms of surface electromyography stretch responses produced by passive movement, but the relationship of spasticity to contracture remains unclear.

Aged↗
PubMed2004

Juvenile Sandhoff disease--nine new cases and a review of the literature.

Juvenile Sandhoff disease (McKusick 268800) is a rare lysosomal storage disorder with only 12 cases recorded in the literature. This condition is also referred to as the subacute form of hexosaminidase deficiency. We describe 9 new cases of Pakistani origin and compare these with the other published cases. Ataxia and speech abnormalities were the commonest presentation. Constipation and urinary incontinence were frequent and may be due to autonomic neuropathy. Cherry-red spot was not noted in any of our cases. Increased lower limb reflexes were the commonest physical finding. Significant delay in diagnosis may be due to the nonspecific presentation of this condition. Diagnosis was on the basis of hexosaminidase deficiency. Residual enzyme activity did not correlate with the clinical picture. Emerging therapies make early diagnosis of this disorder important.

Child↗
PubMed2004

A comparative clarithromycin bioavailability study: determination of clarithromycin and 14-(R)-hydroxyclarithromycin under fasting and fed conditions.

OBJECTIVE: To report the first comprehensive analysis of clarithromycin (CLA) and 14-(R)-hydroxyclarithromcin (14R) bioequivalence metrics under both fasting and fed conditions when using a validated analytical method. METHODS AND MATERIALS: In separate, single dose bioequivalence studies, fasting (n = 40) and fed (n = 18) non-smoking subjects entered a 2-treatment, 2-period, 2-sequence, crossover trial to assess the comparative bioavailability of a 500 mg generic clarithromycin tablet (IVAX Pharmaceuticals, NJ, USA) relative to the reference product (Biaxin Filmtab, Abbott Laboratories, IL, USA). The validated assay employed an HPLC coupled to a triple stage quadrupole mass spectrometer. RESULTS: The analytics permitted plasma samples to be measured for both analytes with high precision and a lower limit ofquantitation (LLOQ) of 11 ng/ml. In both fasting and fed studies, and for both analytes, the IVAX product met the common mean geometric ratio and 90% confidence limits in order to be declared bioequivalent with Biaxin Filmtab. Furthermore, the intra-subject variabilities for the comparative AUC metrics in both studies and for both analytes were < or = 21% and < or = 26% for Cmax. CONCLUSIONS: The fasting and fed results present definitive evidence that 500 mg IVAX clarithromycin and Biaxin Filmtab are bioequivalent under both fasting and fed conditions, whether based on CLA or 14R. Furthermore, at a 500 mg dose, clarithromycin is not a highly variable drug.

Administration, Oral↗
PubMed2003

Overseas dentists.

Explore the source record for details and available documents.

Foreign Professional Personnel↗
PubMed2003

Can patients with osteoporosis, who should benefit from implementation of the national service framework for older people, be identified from general practice computer records? A pilot study that illustrates the variability of computerized medical records and problems with searching them.

Although UK general practice is highly computerized, comprehensive use of these computers is often limited to registration data and the issue of repeat prescriptions. The recording of diagnostic data is patchy. This study examines whether patients with, or at risk of, osteoporosis can be readily identified from general practice computer records. It reports the findings of a pilot study designed to show the variability of recording the diagnosis of osteoporosis and osteopenia, as well as how useful surrogate markers might be to identify these patients. The study also illustrates the difficulties that even skilled practitioners in a primary care research network experience in extracting clinical data from practice information systems. Computer searches were carried out across six practices in a general practice research network in the south-east of England. Two of these practices had previously undertaken research projects in osteoporosis and were consequently expected to have excellent data quality in osteoporosis. These two practices had a combined list size of 27,500 and the remaining practices had a combined practice population of 43,000 patients. The data were found to be variable with over 10-fold differences between practices in the recorded prevalence of osteoporosis diagnosis as well as its surrogate markers-such as fragility fractures, long-term steroid prescription, etc. There was no difference in data quality between the two practices that had conducted osteoporosis research and the rest of the group, other than in the areas of diagnostic recording and prescribing for osteoporosis and recording of fractures. Issues were raised by the practices that struggled to identify patients at risk of osteoporosis about the limitations of Read classification in this disease area. Practices need further assistance if the patients at risk are to be identified. Without urgent action, it will be difficult for practices to identify the patients who are likely to benefit from Standard 6-'Falls' of the National Service Framework for Older People. These findings also have broader implications as UK general practice moves towards the implementation of a quality-based contract.

Aged↗
PubMed2003

Sampling Broad Habitat change to assess biodiversity conservation action in Northern Ireland.

A habitat monitoring programme, the Northern Ireland Countryside Survey, carried out by the University of Ulster for the Department of the Environment for Northern Ireland, is described. It was based on a random sample of quarter kilometer grid squares, stratified by multivariate land classification. Estimates of change in habitat area between 1987-1992 and 1998 are presented and used to assess policy-related priorities for biodiversity conservation action in widespread habitats in Northern Ireland (NI). The basis of the assessment is Broad Habitats, a classification developed as part of the United Kingdom (UK) Biodiversity Action Plan. Improved Grassland, Neutral Grassland and Bog Broad Habitats occupy the largest area of NI, which holds a large proportion of the UK Neutral Grassland and Fen Marsh and Swamp Broad Habitat resource. The greatest net area increases with time were in Improved Grassland (33%), Coniferous Woodland (12%) and Broadleaved, Mixed and Yew Woodland (9%). The greatest net area decreases were in Neutral Grassland (-32%), Arable and Horticulture (-25%), Fen, Marsh and Swamp (-19%), Bog (-8%) and Calcareous Grassland (-7%). These changes are a function of agriculture, public and private forestry, building construction and peat cutting for fuel. The Key biodiversity issue is seminatural Broad Habitat loss, in particular, Neutral Grassland and Fen, Marsh and Swamp, highlighting the lack of effective action for protecting biodiversity in the countryside as a whole. The extent to which current land use is shown to be driving change, indicates that biodiversity conservation action through implementing landscape-scale agri-environment measures could deliver major biodiversity gains. The reliable information on recent changes, provided by the Northern Ireland Countryside Survey, has been used to guide conservation planning. Future re-survey will allow the effectiveness of the conservation strategy as it applies to the countryside as a whole, to be determined. As decisions on land use increasingly have a strong European dimension, concerted action for protecting biodiversity in the countryside as a whole is needed. This would be promoted by a structured sampling approach, based on standard habitat mapping procedures.

Agriculture↗
PubMed2003

Pharmacological prevention of cardiac risk in claudicants with ischaemic heart disease.

BACKGROUND: Claudicants rarely progress to critical limb ischaemia but have a threefold increase in mortality, mainly due to cardiac disease. Antithrombotic therapy, beta blockers, ACE inhibitors and statins have been shown to reduce mortality and cardiovascular morbidity in patients with ischaemic heart disease. AIM: To investigate secondary pharmacological prevention of ischaemic heart disease in claudicants. MATERIALS AND METHODS: We prospectively recorded comorbidity and drug treatment in 89 patients (67 men and 22 women) with a history of ischaemic heart disease recruited in a supervised exercise and lifestyle modification programme to improve claudication distance and prognosis. RESULTS: Of the 89 cases, 40 had a history of angina only and 49 of myocardial infarction. Sixteen (18%) had diabetes, 47 (53%) had hypercholesterolaemia and 52 (58%) were hypertensive. Antithrombotic therapy was prescribed to 61 patients (68.5%), 64 (72%) with a history of myocardial infarction and 27 (67.5%) with angina only (p = 1). Beta-blockers were prescribed to 12 (13.5%) patients only, seven (15%) with a history of myocardial infarction and five (12.5%) with angina only (p = 1). Of the 47 patients with hypercholesterolaemia, 29 (62%) were on a statin. CONCLUSION: Secondary pharmacological prevention of ischaemic heart disease in claudicants remains suboptimal, with only two thirds of patients receiving antithrombotic therapy and a small minority receiving beta blockers. Pharmacological prevention in claudicants should improve to reduce cardiac morbidity and mortality.

Adrenergic beta-Antagonists↗