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J Cooper

Publications and source records attributed to J Cooper.

At least 19 recordsLinked to original sources
PubMed2007

Common adiponectin gene variants show different effects on risk of cardiovascular disease and type 2 diabetes in European subjects.

Alterations in the secretion of adipokines may explain the link between obesity, type 2 diabetes (T2DM) and coronary artery disease (CAD). These conditions have been associated with variation in the adiponectin gene, although evidence for this relationship has been variable, with differences found even in similar samples. This study aims to clarify these inconsistencies by determining the impact of identified adiponectin gene (ADIPOQ) variants (-11391G>A,-1377C>G[promoter] and +45T>G[exon 2] and +276G>T[intron 2]) on the prospective risk of CAD and T2DM in healthy men, and on adverse metabolic markers, in myocardial infarct survivors and controls from different parts of Europe. The hazard ratio for cardiovascular disease varied across the -11391GG/GA/AA(p = 0.03) and -11371CC/CG/GG(p = 0.05) genotypes only. In contrast, only the +45T>G variant (3.80[1.76-8.24]) was associated with T2DM, while two haplotypes GCTT/GCGG (p < 0.05) and +276G>T(p = 0.01) increased risk in interaction with obesity. The variants were associated with a number of biomarkers in Southern but not Northern Europe (p = 0.01), despite no significant differences in allele or haplotype frequencies (p > 0.44). A risk haplotype could not be identified in either sample. Adiponectin gene variants are hence currently poor markers for the development of T2DM and CAD. Their influence on risk depends significantly on interactions that are not currently understood with either genetic variation elsewhere or the environment of the sample studied.

Adiponectin↗
PubMed2007

The impact of ACE genotype on serum ACE activity in a black South African male population.

The strong association between the angiotensin I-converting enzyme (ACE) gene I/D polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans, but has not previously been well assessed in others of African origin. This study addressed this issue in an ethnically well defined black South African population. A putative association for the A22982G ACE gene variant, a QTL likely to impact on serum ACE activity, was also sought. Subjects were 200 healthy male black South African volunteers from the Xhosa ethnic group. Venous blood was obtained from all subjects for DNA extraction. ACE I/D and A22982G genotypes were determined and serum ACE activity measured. Age and blood pressure were recorded. For the group as a whole (mean +/- SD age 38.5 +/- 9.8 years, SBP 119.6 +/- 14.1 mmHg, DBP 78.2 +/- 10.1 mmHg) serum ACE activity was 38.2 +/- 11.2 nmol ml(-1)min(-1). ACE I/D genotype was not significantly associated with serum ACE activity. In contrast, the A22982G variant was significantly associated with serum ACE activity, being 35.9 +/- 9.6, 38.1 +/- 10.6 and 42.4 +/- 15.3 nmol ml(-1)min(-1) for AA, AG and GG genotypes respectively; p = 0.03 by ANOVA and p = 0.01 by linear trend. In keeping with the findings in some other African populations, the ACE I/D polymorphism is not strongly associated with serum ACE activity in Xhosa South Africans. As such, it cannot be used as a marker of ACE activity in these subjects. In this regard the use of the A22982G gene variant may be more appropriate.

Black People↗
PubMed2006

Minimally invasive locking plate osteosynthesis for fractures of the distal tibia--results in 20 patients.

AIMS: We report our experiences with minimally invasive locking plate osteosynthesis (MILPO), for distal tibia fractures, with specific reference to fracture union and complications encountered. PATIENTS AND METHODS: Twenty patients underwent MILPO for open and closed distal tibia fractures between March 2003 and December 2004. Fractures were classified according to the AO system. Open fractures were graded using the Gustilo and Anderson classification and closed fractures via the Tscherne classification system. RESULTS: There were 16 males and 4 females of mean age 44.7 years (range 19-69 years). Thirteen patients had temporary external fixation, prior to definitive fracture fixation. Minimum follow-up was 12 months and average time to full weight bearing in the closed fracture group (12 patients) was 18.1 weeks (range 8-32 weeks) and 19.3 weeks in the open fracture group (8 patients, range 8-44 weeks). Fracture healing was defined as radiological evidence of bridging mature callus combined with pain-free full weight bearing. In the open fracture group, four fractures united within 6 months, one within 6-12 months and one united 12 months after surgery; there were two cases of non-union. In the closed fracture group, seven fractures united within 6 months, three fractures between 6 and 12 months and two after 12 months from surgery. Two of the 20 patients required additional procedures to aid bone healing in the post-operative period. Three of the 20 patients required metalwork removal, for delayed wound breakdown in two cases and wound infection in one case. An uneventful recovery was made following this, in all three cases. There was one case of implant failure due to plate breakage at 32 weeks post-op. The fracture site was opened and re-plated at 32 weeks with a DCP. There were no complications following this. CONCLUSION: MILPO was used for definitive fixation of high energy, open and closed, peri-articular distal tibia fractures. This approach aims to preserve bone biology and minimise surgical soft tissue trauma. This surgical approach may provide an answer to treating a challenging group of fractures and further research is warranted.

Adult↗
PubMed2006

The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to cerebral aneurysms.

BACKGROUND AND AIMS: An important part is played by inflammation in intracranial aneurysm formation. The hypothesis that there is an association of the proinflammatory cytokine interleukin-6 (IL-6) genotypes (-572G>C and -174G>C) with intracranial aneurysms was tested. METHODS: IL-6 genotypes were determined in 91 Caucasian patients with aneurysms and compared with 2720 healthy UK controls. RESULTS: For both polymorphisms, the distribution of the genotypes and estimated allele frequency were different between the control group and the aneurysm group. For -572G>C, a higher frequency of the C allele (p = 0.001) and more people homozygous for the C allele were found among those with aneurysms than among the controls (4.4% v 0.3%, p = 0.001). For -174G>C, more people homozygous for the C allele were found among the controls than among those with aneurysm (18% v 7%, p = 0.007). The 572C/174G haplotype was associated with an increased risk of aneurysms, with the relative risk compared with the common haplotype being 1.89 and that for the -572G/174C haplotype being 0.58 (p<0.0005). CONCLUSION: This is the first study to show that IL-6 promoter polymorphisms are associated with intracranial aneurysmal disease. Whether this association is with the development, progression or rupture of such aneurysms, or represents survivor bias, is unclear.

Adult↗
PubMed2006

Lp-PLA2 activity and PLA2G7 A379V genotype in patients with diabetes mellitus.

Lipoprotein associated phospholipase A2 (Lp-PLA2) modulates low-density lipoprotein (LDL) oxidation by hydrolysing oxidised phospholipids present on particle surfaces. We investigated whether Lp-PLA2 activity and PLA2G7 A379V genotype were related to mediators of atherosclerosis in a diabetic study. Plasma Lp-PLA2 activity (taken in men only) and A379V genotype were investigated with regards to metabolic syndrome (MS), UKPDS risk score, and oxidised LDL (oxLDL/LDL), in a cohort of Caucasian men and women (n=783, age 62.5+/-13.7 years). After adjustment for type of diabetes, CHD status, and statin use, those individuals with features defining the MS (WHO guidelines) had higher Lp-PLA2 activity (35.6+/-11.9 nmol/min/ml) compared to those without (33.0+/-10.8 nmol/min/ml) (p=0.02). Quartiles of UKPDS coronary heart disease (CHD) risk score were also positively associated with Lp-PLA2 activity (p=0.006, p=0.004 linear trend). Those men in the highest quartile of oxLDL/LDL level had the lowest Lp-PLA2 activity (31.3+/-10.5 nmol/min/ml) when compared to the middle two (32.3+/-9.8 and 35.9+/-10.9 nmol/min/ml, respectively) and lowest quartile (35.6 +/-12.5 nmol/min/ml; p=0.03, p=0.004 linear trend). There was no significant association between A379V genotype and Lp-PLA2 enzyme activity (p=0.34) or oxLDL/LDL (p=0.32). Lp-PLA2 activity is an independent predictor of CHD risk and MS in a sample of subjects with diabetes mellitus. The association of Lp-PLA2 activity with oxLDL/LDL suggests that Lp-PLA2 may be a modulating factor in the process of atherosclerosis.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2006

Clinical effectiveness and cost-effectiveness of tests for the diagnosis and investigation of urinary tract infection in children: a systematic review and economic model.

OBJECTIVES: To determine the diagnostic accuracy of tests for detecting urinary tract infection (UTI) in children under 5 years of age and to evaluate the effectiveness of tests used to investigate further children with confirmed UTI. Also, to evaluate the effectiveness of following up children with UTI and the cost-effectiveness of diagnostic and imaging tests for the diagnosis and follow-up of UTI in children under 5. An additional objective was to develop a preliminary diagnostic algorithm for healthcare professionals. DATA SOURCES: Electronic databases were searched up to the end of 2002/early 2003. Consultation with experts in the field. REVIEW METHODS: A systematic review was undertaken using published guidelines and results were analysed according to test grouping: diagnosis of UTI and further investigation of UTI. The cost-effectiveness results from existing evaluations were synthesised. A separate cost-effectiveness model was developed using the best available evidence, in part derived from the results of the systematic review, to illustrate the potential cost-effectiveness of some alternative management strategies in a UK setting. The results of the systematic review were used to propose diagnostic algorithms for the diagnosis and further investigation of UTI in children. Economic analyses did not contribute directly to the development of these algorithms. RESULTS: The studies included in the review provided very little data on the accuracy of clinical investigations for the diagnosis of UTI, and criteria for clinical suspicion of UTI were not further defined. The majority of studies included in the review found that clean voided midstream urine (CVU) samples had similar accuracy to suprapubic aspiration (SPA) samples when cultured with the advantage of being a non-invasive collection method that can be used in the GP's surgery. Pad, nappy or bag specimens may be appropriate methods for obtaining a urine sample in non-toilet-trained children, although only limited data were available. Although the glucose test was reported to have the highest accuracy in terms of both ruling in and ruling out disease, only a limited number of studies of this test were included and these were conducted over 30 years ago. Dipstick tests are easy to perform in the GP's surgery, give an immediate result and are relatively cheap. The results of the systematic review showed that a dipstick for leucocyte esterase (LE) and nitrite, where both test results are interpreted in combination, was a good test both for ruling in (both positive) and ruling out (both negative) a UTI. A dipstick positive for either LE or nitrite and negative for the other provides inconclusive diagnostic information and further testing is therefore required in these patients. Microscopy is more time consuming and expensive to perform than a dipstick test, but potentially quicker and cheaper than culture. As with dipstick tests, a combination of microscopy for pyuria and bacteriuria can be used accurately to rule in and rule out a UTI. An indeterminate test result is again obtained if microscopy is positive for either pyuria or bacteriuria, and negative for the other. Confirmatory culture is required in these patients. In patients considered to have a UTI, further culture to determine antibiotic sensitivities may be an option to inform treatment decisions. Only one study satisfied the inclusion criteria of the economic review and the review highlighted a number of potential limitations of this study for NHS decision-making. A separate decision-analytic model was therefore developed to provide a more reliable estimate of the optimal strategy regarding the diagnosis and further investigation of children under 5 with suspected UTI from the perspective of the NHS. The economic model found that the optimal diagnostic strategy for children presenting with symptoms suggestive of UTI depends on a number of key factors. These included the relevant subgroup of children concerned, in terms of gender and age, and the health service's maximum willingness to pay for an additional quality-adjusted life-year. CONCLUSIONS: The results of the systematic review were used to derive an algorithm for the diagnosis of UTI in children under 5. This algorithm represents the conclusions of the review in terms of effective practice. There were insufficient data to propose an algorithm for the further investigation of UTI in children under 5. The quality assessment highlighted several areas that could be improved upon in future diagnostic accuracy studies.

Algorithms↗
PubMed2005

Declining case fatality rates for acute myocardial infarction in South Asian and white patients in the past 15 years.

OBJECTIVES: To determine whether case fatality rates in South Asian (Bangladeshi, Indian and Pakistani) patients with acute myocardial infarction have shown similar declines to those reported for white patients during the past 15 years. DESIGN: Cross-sectional, observational study. SETTING: Coronary care unit in east London. PATIENTS: 2640 patients-29% South Asian-admitted with acute myocardial infarction between January 1988 and December 2002. MAIN OUTCOME MEASURES: Differences over time in rates of in-hospital death, ventricular fibrillation and left ventricular failure. RESULTS: The proportion of South Asians increased from 22% in 1988-92 to 37% in 1998-2002. Indices of infarct severity were similar in South Asian and white patients, with declining frequencies of ST elevation infarction (88.2% to 77.5%, p < 0.0001), Q wave development (78.1% to 56.9%, p < 0.0001) and mean (interquartile range) peak serum creatine kinase concentrations (1250 (567-2078) to 1007 (538-1758) IU/l, p < 0.0001) between 1988-92 and 1998-2002. Rates of in-hospital death (13.0% to 9.4%, p < 0.01), ventricular fibrillation (9.2% to 6.0%, p < 0.001) and left ventricular failure (33.2% to 26.5%, p < 0.0001) all declined; these changes did not interact significantly with ethnicity. Odds ratios for the effect of time on risk of death increased from 0.81 (95% CI 0.70 to 0.93) to 1.02 (95% CI 0.87 to 1.21) after adjustment for ethnicity and indices of infarct severity (ST elevation, peak creatine kinase, Q wave development and treatment with a thrombolytic). CONCLUSIONS: In the past 15 years, death from acute myocardial infarction among South Asians has declined at a rate similar to that seen in white patients. This is largely caused by reductions in indices of infarct severity.

Asian People↗
PubMed2005

Physiological responses to hyper-saline waters in sailfin mollies (Poecilia latipinna).

We examined the ionoregulatory physiology and biochemistry of the teleost sailfin molly (Poecilia latipinna), an inhabitant of salt marshes along the gulf coast, during exposure to hyper-saline waters (salinity range 35-95 ppt). Mollies were able to tightly control plasma Na(+) and Cl(-) concentrations and tissue water levels up to 65 ppt, but at higher salinities plasma ion levels began to rise and muscle water content dropped. Still, even at the highest salinity (90 ppt) plasma Na(+) and Cl(-) levels were only 32% and 39%, respectively, above levels at 35 ppt. Drinking rates at 60 ppt climbed 35%, while gut Na(+)/K(+)-ATPase (NAK) activity rose 70% and branchial NAK activity jumped 200%. The relatively small rise in drinking rate, in the face of a more than doubling of the osmotic gradient, suggests that a reduction in branchial water permeability significantly limited water loss and associated salt load. At 80 ppt, a salinity where plasma ion levels just begin to rise, drinking rate rose more rapidly, but gut and gill NAK activity did not, suggesting that mollies employed other pathways (perhaps renal) of salt excretion. At higher salinities, plasma ion levels continued to rise and muscle water content fell slightly indicating the beginnings of internal osmotic disturbances. To evaluate the energetic costs of hyper-salinity on mollies we measured the rate of O(2) consumption and found it rose with salinity, in sharp contrast to virtually all species previously examined. Interestingly, despite higher metabolism, growth was unaffected by hyper-salinity.

Animals↗
PubMed2005

Nicotine acts as a pharmacological chaperone to up-regulate human alpha4beta2 acetylcholine receptors.

Human neuronal nicotinic acetylcholine receptor (AChR) alpha4 subunits and an alpha4 mutant (S247Falpha4) found in autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) were expressed along with beta2 in permanently transfected tsA201 human embryonic kidney cell lines. Their sensitivity to activation, desensitization, and up-regulation by cholinergic ligands was investigated. Up-regulation after 3 to 24 h resulted primarily from an increase in assembly of AChRs from large pools of unassembled subunits, but up-regulation also resulted from a 5-fold increase in the lifetime of AChRs in the surface membrane. Up-regulation does not require current flow through surface membrane AChRs, because up-regulation occurs in the presence of the channel blocker mecamylamine and with the alpha4 mutant, which prevents nearly all AChR function. Both membrane-permeable ligands like nicotine and much less permeable quaternary amine cholinergic ligands can act as pharmacological chaperones within the endoplasmatic reticulum to promote the assembly of AChRs. Agonists are more potent pharmacological chaperones than antagonists, presumably because activated or desensitized conformations assemble more efficiently. Assembly intermediates are disrupted by solubilization in Triton X-100, but chemical cross-linking stabilizes a putative assembly intermediate approximately the size of an alpha4beta2alpha4beta2 tetramer.

Cell Line↗
PubMed2005

Impact of the National Service Framework for coronary heart disease on treatment and outcome of patients with acute coronary syndromes.

OBJECTIVES: To evaluate the impact the National Service Framework (NSF) for coronary heart disease has had on emergency treatment and outcomes in patients presenting with acute coronary syndromes. DESIGN: Retrospective cohort study. SETTING: Coronary care units of two district general hospitals. RESULTS: Data from 3371 patients were recorded, 1993 patients in the 27 months before the introduction of the NSF and 1378 patients in the 24 months afterwards. After the introduction of the NSF in-hospital mortality was significantly reduced (95 patients (4.8%) v 43 (3.2%), p = 0.02). This was associated with a reduction in the development of Q wave myocardial infarction (40.6% v 33.3%, p < 0.0001) and in the incidence of left ventricular failure (15.9% v 12.3%, p = 0.003). The proportion of patients receiving thrombolysis increased (69.4% v 84.7%, p < 0.0001) with a decrease in the time taken to receive it (proportion thrombolysed within 20 minutes 12.1% v 26.6%, p < 0.0001). The prescription of beta blockers (51.9% v 65.8%, p < 0.0001), angiotensin converting enzyme inhibitors (37% v 66.4%, p < 0.0001), and statins (55.2% v 72.7%, p < 0.0001) improved and the proportion of patients referred for invasive investigation increased (18.3% v 27.0%, p < 0.0001). Trend analysis showed that improvements in mortality and thrombolysis were directly associated with publication of the NSF, whereas the improvements seen in prescription of beta blockers and statins were the continuation of pre-existing trends. CONCLUSIONS: In the two years that followed publication of the NSF the initial treatment and outcome of patients presenting with acute coronary syndromes improved. Some of the improvements can be attributed to the NSF but others are continuations of pre-existing trends.

Adrenergic beta-Antagonists↗
PubMed2005

The genome of the social amoeba Dictyostelium discoideum.

The social amoebae are exceptional in their ability to alternate between unicellular and multicellular forms. Here we describe the genome of the best-studied member of this group, Dictyostelium discoideum. The gene-dense chromosomes of this organism encode approximately 12,500 predicted proteins, a high proportion of which have long, repetitive amino acid tracts. There are many genes for polyketide synthases and ABC transporters, suggesting an extensive secondary metabolism for producing and exporting small molecules. The genome is rich in complex repeats, one class of which is clustered and may serve as centromeres. Partial copies of the extrachromosomal ribosomal DNA (rDNA) element are found at the ends of each chromosome, suggesting a novel telomere structure and the use of a common mechanism to maintain both the rDNA and chromosomal termini. A proteome-based phylogeny shows that the amoebozoa diverged from the animal-fungal lineage after the plant-animal split, but Dictyostelium seems to have retained more of the diversity of the ancestral genome than have plants, animals or fungi.

ATP-Binding Cassette Transporters↗
PubMed2005

Structural parameters of the vastus medialis muscle.

This research was designed to evaluate musculoskeletal anatomy of the quadriceps region relative to the patellofemoral joint. The hypothesis for the study was that the oblique portion (VMO) of the vastus medialis muscle (VM) is anatomically positioned to function primarily as an active medial stabilizer of the patella. Because many clinicians believe that the VMO functions independently as an active medial stabilizer of the patellofemoral joint (PFJ), PFJ rehabilitation protocols commonly target the VMO in an attempt to restore normal joint mechanics. It is unclear whether this purported selective function is supported by the underlying anatomical structure. Through dissection of 32 limbs from 24 intact cadavers with normal patellar alignment, data were collected on VM fiber alignment and innervation, the presence of fascial plane, and the length of VM about the patella. Statistical analyses demonstrated that the oblique and long heads of the VM muscle had significantly different (P < 0.05) angles of fiber orientation, as expected. When measurements were taken relative to a vertical axis (standardizing limb alignment between cadavers), the difference in fiber angles between oblique and long heads of the VM was reduced significantly. Additionally, < 10% of the length of the VM muscle inserted directly on the medial aspect of the patella, and there was no anatomical evidence of a fascial plane or separate innervation for the oblique and long heads of the VM. The results of the study did not support the hypothesis that the VMO is anatomically positioned to function primarily as an active medial stabilizer of the patella.

Aged↗
PubMed2005

Randomised clinical trial of the effectiveness of base-in prism reading glasses versus placebo reading glasses for symptomatic convergence insufficiency in children.

PURPOSE: To compare base-in prism reading glasses with placebo reading glasses for the treatment of symptomatic convergence insufficiency (CI) in children aged 9 to <18 years. METHODS: In a randomised clinical trial, 72 children aged 9 to <18 years with symptomatic CI were assigned to either base-in prism glasses or placebo reading glasses. Symptom level, measured with a quantitative symptom questionnaire (CI Symptom Survey-V15), was the primary outcome measure. Near point of convergence and positive fusional vergence at near were secondary outcomes. RESULTS: The mean (SD) CI Symptom Survey score decreased (that is, less symptomatic) in both groups (base-in prism glasses from 31.6 (10.4) to 16.5 (9.2); placebo glasses from 28.4 (8.8) to 17.5 (12.3)). The change in the CI Symptom Survey scores (p = 0.33), near point of convergence (p = 0.91), and positive fusional vergence (p = 0.59) were not significantly different between the two groups after 6 weeks of wearing glasses. CONCLUSIONS: Base-in prism reading glasses were found to be no more effective in alleviating symptoms, improving the near point of convergence, or improving positive fusional vergence at near than placebo reading glasses for the treatment of children aged 9 to <18 years with symptomatic CI.

Adolescent↗
PubMed2004

Three-dimensional optical trapping of partially silvered silica microparticles.

We demonstrate three-dimensional trapping of micrometer-diameter silica particles, partially coated with silver, within conventional optical tweezers. Although metallic particles are usually repelled from the beam focus by the scattering force, we show that transparent spheres partially coated with silver can be trapped with efficiencies comparable with dielectric particles. The trapping characteristics of these particles are examined as a function of metallic coverage, and the application of these particles to surface-enhanced resonance Raman scattering is investigated.

Coated Materials, Biocompatible↗
PubMed2004

The -344T>C promoter variant of the gene for aldosterone synthase (CYP11B2) is not associated with cardiovascular risk in a prospective study of UK healthy men.

INTRODUCTION: The tissue renin-angiotensin system is implicated in the pathogenesis of coronary artery disease (CAD). As locally synthesised aldosterone is a potential mediator of CAD, we have sought an association of the -344T>C variant of the aldosterone synthase (CYP11B2) gene with CAD events. METHODS: Subjects comprised of the Second Northwick Park Heart Study (NPHSII), a prospective study of unrelated, healthy middle-aged Caucasian males. CAD events were recorded in 2490 subjects, and defined as a sudden cardiac death, myocardial infarction or coronary artery revascularisation procedure. Mean follow-up was 10.8 years. Aldosterone synthase genotype was determined in 2490 subjects. Power calculation suggests that we have 80% power (at a significance level of 0.05) to detect a difference in hazard ratio (HR) between homozygote groups of 0.45. RESULTS: One hundred and eighty-seven CAD events were recorded in 2490 subjects. In the group overall, CAD events were independent of genotype with adjusted hazard ratios being 1.00 versus 1.25 versus 0.80 for TT versus TC versus CC genotypes, respectively, P = 0.07. Genotype interactions with smoking and blood pressure were sought. Whilst CAD events were independent of genotype amongst non-smokers, CC genotype in smokers was associated with a reduced risk HR 2.02 versus 2.28 versus 0.82 for TT versus TC versus CC genotypes, P = 0.05 (HR for TT + TC versus CC were 1.77 versus 0.67, P = 0.02). This apparent interaction remained after adjustment for conventional risk factors. No such interaction was found with blood pressure. CONCLUSIONS: Aldosterone synthase genotype is unrelated to overall CAD events risk. A possible interaction with smoking requires confirmation.

Analysis of Variance↗