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Biomedical subjects

Amanda J Lee

Publications and source records attributed to Amanda J Lee.

At least 19 recordsLinked to original sources

Inflammatory, haemostatic, and rheological markers for incident peripheral arterial disease: Edinburgh Artery Study.

AIMS: Recently, markers of inflammation, haemostasis, and blood rheology have received much attention as risk factors for coronary heart disease and stroke. However, their role in peripheral arterial disease (PAD) is not well established and some of them, including the pro-inflammatory cytokine interleukin-6 (IL-6), have not been examined before in prospective epidemiological studies. METHODS AND RESULTS: In the Edinburgh Artery Study, we studied the development of PAD in the general population and evaluated 17 potential blood markers as predictors of incident PAD. At baseline (1987), 1519 men and women free of PAD aged 55-74 were recruited. After 17 years, 208 subjects had developed symptomatic PAD. In analysis adjusted for cardiovascular risk factors and baseline cardiovascular disease (CVD), only C-reactive protein, fibrinogen, lipoprotein (a), and haematocrit [hazard ratio (95% CI) corresponding to an increase equal to the inter-tertile range 1.30 (1.08, 1.56), 1.16 (1.05, 1.17), 1.22 (1.04, 1.44), 1.22 (1.08, 1.38)] were significantly (P < 0.01) associated with PAD. However, these markers provided very little prognostic information for incident PAD to that obtained by cardiovascular risk factors and the ankle brachial index. Other markers including IL-6, intracellular adhesion molecule 1, d-dimer, tissue plasminogen activator antigen, and plasma and blood viscosities showed weak associations, which were considerably attenuated when CVD risk factors were accounted for. CONCLUSIONS: Our prospective data showed that several inflammatory, haemostatic, and rheological markers are associated with incident PAD; however, their clinical utility is likely to be limited. Future research is necessary to validate the importance of these biomarkers explicitly on PAD and to address the causality of the reported associations.

Aged↗

The increasing cost of the basic foods required to promote health in Queensland.

OBJECTIVE: To assess changes in the cost and availability of a standard basket of healthy food items (the Healthy Food Access Basket [HFAB]) in Queensland over time. DESIGN AND PARTICIPANTS: A series of four cross-sectional surveys (in 1998, 2000, 2001 and 2004) describing the cost and availability of foods in the HFAB over time. In the latest survey, 97 Queensland food stores across the five Australian Bureau of Statistics remoteness categories were compared. MAIN OUTCOME MEASURES: Cost comparisons for HFAB items by remoteness category for the 97 stores surveyed in 2004; changes in cost and availability of foods in the 81 stores surveyed since 2000; comparisons of food prices in the 56 stores surveyed in 1998, 2000, 2001 and 2004. RESULTS: In 2004, the Queensland mean cost of the HFAB was $395.28 a fortnight. The cost of the HFAB was 29.6% ($113.89) higher in "very remote" areas than in "major cities" (P < 0.001). Between 2001 and 2004, the Queensland mean cost of the HFAB increased by 14.0% ($48.45), while in very remote areas the cost increased by 18.0% ($76.93) (P < 0.001). Since 2000, the annualised per cent increase in cost of the HFAB has been higher than the increase in Consumer Price Index for food in Brisbane. The cost of healthy foods has risen more than the cost of some less nutritious foods, so that the latter are now relatively more affordable. CONCLUSIONS: Consumers, particularly those in very remote locations, need to pay substantially more for basic healthy foods than they did a few years ago. Higher prices are likely to be a barrier to good health among people of low socioeconomic status and other vulnerable groups. Interventions to make basic healthy food affordable and accessible to all would help reduce the high burden of chronic disease.

Costs and Cost Analysis↗

A hydroxyapatite graft substitute reduces subsidence in a femoral impaction grafting model.

Synthetic bone graft substitutes have been developed for impaction grafting revision hip surgery in response to concerns about the availability and potential infection risk of allograft. We performed an in vitro experiment to determine whether a synthetic porous hydroxyapatite material might improve resistance to cumulative subsidence and cyclic (elastic) movement on loading. We impacted different ratios of hydroxyapatite and allograft (0%, 50%, 70%, and 90% hydroxyapatite) into composite femoral models (eight per group) and implanted tapered, polished stems with cement. Models were loaded for 18,000 cycles on a servohydraulic materials testing machine. Migration of the femoral prostheses and the distal cement was determined using radiostereometric analysis, and cyclic movement was measured mechanically by the testing machine. Hydroxyapatite decreased overall subsidence and subsidence at the prosthesis-cement interface, but there was no difference at the cement-femur interface. This decrease may have occurred because the hydroxyapatite-containing graft was more rigid, or because it resulted in a thicker cement mantle. Cyclic prosthesis movement also was lower with hydroxyapatite. While the biologic response to porous hydroxyapatite remains to be determined, its mechanical properties appear promising.

Arthroplasty, Replacement, Hip↗

Short-course montelukast for intermittent asthma in children: a randomized controlled trial.

RATIONALE: In children, intermittent asthma is the most common pattern and is responsible for the majority of exacerbations. Montelukast has a rapid onset of action and may be effective if used intermittently. OBJECTIVES: To determine whether a short course of montelukast in children with intermittent asthma would modify the severity of an asthma episode. METHODS: Children, aged 2-14 years with intermittent asthma participated in this multicenter, randomized, double-blind, placebo-controlled clinical trial over a 12-month period. Treatment with montelukast or placebo was initiated by parents at the onset of each upper respiratory tract infection or asthma symptoms and continued for a minimum of 7 days or until symptoms had resolved for 48 hours. MEASUREMENTS AND MAIN RESULTS: A total of 220 children were randomized, 107 to montelukast and 113 to placebo. There were 681 treated episodes (345 montelukast, 336 placebo) provided by 202 patients. The montelukast group had 163 unscheduled health care resource utilizations for asthma compared with 228 in the placebo group (odds ratio, 0.65; 95% confidence interval, 0.47-0.89). There was a nonsignificant reduction in specialist attendances and hospitalizations, duration of episode, and beta-agonist and prednisolone use. Symptoms were reduced by 14% and nights awakened by 8.6% (p = 0.043), and days off from school or childcare by 37% and parent time off from work by 33% (p < 0.0001 for both). CONCLUSIONS: A short course of montelukast, introduced at the first signs of an asthma episode, results in a modest reduction in acute health care resource utilization, symptoms, time off from school, and parental time off from work in children with intermittent asthma.

Absenteeism↗

A self-rating scale for patient-perceived side effects of inhaled corticosteroids.

BACKGROUND: Patient-reported side effect questionnaires offer a simple method for the systematic measurement of drug-related side effects. In order to measure patients' inhaled corticosteroids (ICS) related side effect perceptions the 14-day retrospective Inhaled Corticosteroid Questionnaire (ICQ) was developed. In this research we aim to assess the construct validity and reliability of the ICQ and test its responsiveness to dose changes in adult asthma patients. METHODS: In a cross-sectional study, current inhaler users with asthma completed the ICQ (27 with non ICS inhaler; 61 BDP equivalent daily ICS low dose < or =400 microg; 62 mid dose 401-800 microg; and 105 with high dose >800 microg). We generated 3 construct validity hypotheses: 1) a hierarchical dose-response pattern for scoring of the individual items on the ICQ, and statistically significant differences in the scores of each of the 15 ICQ domains by ICS dose group 2) an association between ICS dose and ICQ scoring after adjusting for appropriate confounders in multiple regression; 3) greater convergence between local side effect domains than between systemic and local domains of the scale. Test-retest reliability was assessed on a randomly selected subgroup of patients (n = 73) who also completed the ICQ a second time after 7 days. In a separate longitudinal study, 61 patients with asthma completed the ICQ at baseline and after changing their daily ICS dose, at 2- and 6- months, in order to test the ICQ's responsiveness. RESULTS: All three construct validity hypotheses were well supported: 1) a statistically significant difference existed in scores for 14 domains, the high ICS dose group scoring highest; 2) ICS dose independently predicted ICQ scoring after adjusting for confounders; 3) greater convergence existed between local ICQ domains than between local and systemic domains. The ICQ had good reproducibility: test-retest intraclass correlation coefficients were > or =0.69 for all but the 'Facial Oedema' domain. In the longitudinal study, ICQ scores for 'Voice Problems' changed significantly at 2- and 6-months from baseline and other ICQ domains displayed trends in scoring change accordant with dose modulation at 6-months. CONCLUSION: The ICQ has good dose-related discriminative properties, is valid, reliable, and shows potential responsiveness to ICS dose change.

Administration, Inhalation↗

In a randomized study of envelope and ink color, colored ink was found to increase the response rate to a postal questionnaire.

OBJECTIVE: To assess the effect of the colors of the envelope and ink on the response rate to a postal questionnaire in a study screening for undiagnosed parkinsonism in people aged 65 years and over in the community. STUDY DESIGN AND SETTING: A total of 2,524 people aged 65 years and over from five general practices in Aberdeen were randomized to receive a questionnaire about the symptoms of parkinsonism printed in either colored (green) or black ink, and sent out in either a brown or white envelope. RESULTS: The overall response rate was 63.5%. There was no significant interaction between envelope and ink color. The use of green ink compared to black significantly increased the response rate from 61.4% to 65.7% (OR 1.20, 95% confidence interval 1.02, 1.41). There was no overall effect of envelope color on response rate (62.3% brown and 64.8% white, OR 0.90, 95% confidence interval 0.76, 1.06) but there was significant heterogeneity between the general practices. When this general practice-envelope interaction was accounted for, brown envelopes had a significantly lower response rate than white ones (OR 0.49). CONCLUSION: This study, along with existing evidence, has shown that the use of certain ink colors in postal questionnaires is likely to increase response rates relative to black ink. The effect of envelope color was inconsistent both within this study and between previous studies.

Aged↗

Can pain can be more or less neuropathic? Comparison of symptom assessment tools with ratings of certainty by clinicians.

Chronic pain is generally regarded as being divided into two mutually exclusive pain mechanisms: nociceptive and neuropathic. Recently, this dichotomous approach has been questioned and a model of chronic pain being 'more or less neuropathic' has been suggested. To test whether such a spectrum exists, we examined responses by patients with chronic pain to validated neuropathic pain assessment tools and compared these with ratings of certainty about the neuropathic origin of pain by their specialist pain physicians. We examined 200 patients (100 each with nociceptive and neuropathic pain) and administered the self-complete Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS score) and the Neuropathic Pain Scale (NPS). Clinicians were asked to rate their certainty of the presence of neuropathic pain mechanisms on a 100 mm visual analogue scale (VAS) (0='not at all neuropathic in origin' to 100='completely neuropathic in origin'). The whole sample was divided into tertiles based on ascending ratings of diagnostic certainty by clinicians using the VAS and labelled 'unlikely', 'possible' and 'definite' neuropathic pain. There were significant differences in median S-LANSS and NPS composite scores between all tertile groups. There were also significant differences between many S-LANSS and NPS item scores between groups. We have shown that higher scores on both the S-LANSS and the NPS are indicative of greater clinician certainty of neuropathic pain mechanisms being present. These data support the theoretical construct that pain can be more or less neuropathic and that pain of predominantly neuropathic origin may be a useful clinical concept.

Chronic Disease↗

The epidemiology of chronic pain of predominantly neuropathic origin. Results from a general population survey.

UNLABELLED: Progress in the understanding of chronic pain with neuropathic features has been hindered by a lack of epidemiologic research in the general population. The Leeds Assessment of Neuropathic Symptoms and Signs score (S-LANSS) was recently validated for use in postal surveys, making the identification of pain of predominantly neuropathic origin possible. Six family practices in 3 UK cities (Aberdeen, Leeds, and London) generated a total random sample of 6,000 adults. The mailed questionnaire included demographic items, chronic pain identification, and intensity questions, the S-LANSS, the Level of Expressed Needs questionnaire, and the Neuropathic Pain Scale. With a corrected response rate of 52%, the prevalence of any chronic pain was 48% and the prevalence of pain of predominantly neuropathic origin was 8%. Respondents with this chronic neuropathic pain were significantly more likely to be female, slightly older, no longer married, living in council rented accommodation, unable to work, have no educational qualifications, and be smokers than all other respondents. Multiple logistic regression modeling found that pain of predominantly neuropathic origin was independently associated with older age, gender, employment (being unable to work), and lower educational attainment. Respondents with this pain type also reported significantly greater pain intensity, higher scores on the NPS, higher levels of expressed need, and longer duration of pain. This is the first estimate of the prevalence and distribution of pain of predominantly neuropathic origin in the general population, using a previously validated and reliable data collection instrument. PERSPECTIVE: Chronic pain with neuropathic features appears to be more common in the general population than previously suggested. This type of pain is more severe than other chronic pain but distributed similarly throughout sociodemographic groups.

Adolescent↗

Reduced lung function in patients with abdominal aortic aneurysm is associated with activation of inflammation and hemostasis, not smoking or cardiovascular disease.

OBJECTIVE: Abdominal aortic aneurysms often coexist with reduced lung function and chronic obstructive pulmonary disease (COPD). These conditions are each associated with cigarette smoking, cardiovascular disease, and evidence of increased inflammatory and hemostatic activity. The aim of this study was to determine if these factors accounted for the link between aneurysms and pulmonary disease. METHODS: The design was a case-control study comparing patients with an asymptomatic abdominal aortic aneurysm with population-based controls without an aneurysm. Aneurysms were diagnosed by ultrasound scan, and pulmonary function was measured by respiratory questionnaire and spirometry. Activation of inflammation and hemostasis was measured by assay of plasma interleukin-6 (IL-6), fibrinogen, von Willebrand factor (vWF), tissue plasminogen activator (tPA) antigen, fibrin D-dimer, and plasmin antiplasmin complexes. RESULTS: Cases with an abdominal aortic aneurysm (n = 89) had more COPD and worse expiratory lung function as measured by forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) than controls (n = 98) (FEV1, 1.9 vs 2.2 L, P < .01; FEV1/FVC, 0.67 vs 0.75, P < .001) and did not differ in restrictive function (FVC, 2.9 vs 3.0 L, P = .33). Cases also had higher levels of lifetime cigarette smoking (30 vs 24 pack-years, P < 0.01), cardiovascular disease (35% vs 18%, P = .01), plasma fibrinogen (3.5 vs 3.1 g/L, P = .02), IL-6 (2.8 vs 1.8, pg/mL, P < .001), plasmin antiplasmin complexes (596 vs 384 microg/L, P = .01), and D-dimer (442 vs 93 ng/mL, P < .001). On multiple logistic regression analysis of lung function and COPD on the risk of aneurysm, both cigarette smoking and cardiovascular disease had little effect on the relationships. For the markers of activated inflammation and hemostasis, plasmin antiplasmin complexes and D-dimer had the most important confounding effect on the odds ratios. All markers combined had a substantial effect: odds ratio of aneurysm for a one standard deviation decrease in FEV1 fell from 2.3 (95% confidence interval [CI], 1.5 to 3.5) (P < .01) to 1.3 (95% CI, 0.55 to 2.4) (P > or = .05). CONCLUSION: The association between reduced respiratory function and abdominal aortic aneurysm was not accounted for by cigarette smoking or cardiovascular disease. We hypothesize that activation of inflammation and hemostasis in response to injury may be an important explanation of the association between aneurysm formation and reduced respiratory function. Further studies are required to test this hypothesis.

Aged↗

A future career in general practice? A longitudinal study of medical students and pre-registration house officers.

OBJECTIVE: To monitor the future career preferences of medical students throughout their undergraduate years and into their postgraduate career, and to evaluate which factors may influence career choice intentions, and when this happens, over time. DESIGN: Longitudinal study. METHODS: Questionnaire to all Aberdeen, United Kingdom, Medical School entrants in 1996, and five annual follow-ups (four undergraduate, one postgraduate). RESULTS: Response rates: year 1, 100%; year 2, 78%; year 3, 70%; year 4, 64%; year 5, 65%; pre-registration house officer (PRHO), 60%. Throughout the study, females were more positive about a career in general practice. General practice was the first choice for 13% of students in year 1; year 2, 9%; year 3, 22%; year 4, 24%; year 5, 27%; PRHO, 29%. Those choosing general practice were more likely than those choosing other specialties to be female, have their family home in Scotland, rate their academic abilities lower and their non-academic abilities as average, and have decided on their future career earlier. Reasons for general practice included: working in and being part of a community; continuity of patient contact; variety of illnesses and people encountered; undergraduate teaching experiences; dislike of or disillusionment with hospital medicine; and an increasing awareness of part-time opportunities. CONCLUSION: As medical undergraduates progressed through the curriculum and became PRHOs, general practice became more popular as a career choice, particularly with females. This may be partly explained by the increased exposure to general practitioners and patients in the new community-based teaching programme and the increasing awareness of lifestyle advantages with the particular benefits of more regular hours and working part time.

Adolescent↗

Effectiveness of a breastfeeding peer coaching intervention in rural Scotland.

BACKGROUND: Breastfeeding initiation in Scotland in 2000 was 63 percent, compared with over 90 percent in Norway and Sweden. Although peer support is effective in improving exclusivity of breastfeeding in countries where over 80 percent of women initiate breastfeeding, the evidence for effectiveness in countries with lower initiation is uncertain. Our primary aim was to assess whether group-based and one-to-one peer breastfeeding coaching improves breastfeeding initiation and duration. METHODS: Action research methodology was used to conduct an intervention study in 4 geographical postcode areas in rural northeast Scotland. Infant feeding outcomes at birth and hospital discharge; at 1, 2, and 6 weeks; and at 4 and 8 months were collected for 598 of 626 women with live births during a 9-month baseline period and for 557 of 592 women with live births during a 9-month intervention period. Groups met in 5 locations, with 266 groups meeting in the period when intervention women were eligible to attend. Data on place of birth and length of postnatal hospital stay were also collected. Control data from 10 other Health Board areas in Scotland were compared. An intention-to participate survey about coaching participation was completed by 206 of 345 women initiating breastfeeding. Group attendance data were collected by means of 266 group diaries. RESULTS: There was a significant increase in any breastfeeding of 6.8 percent from 34.3 to 41.1 percent (95% CI 1.2, 12.4) in the study population at 2 weeks after birth compared with a decline in any breastfeeding in the rest of Scotland of 0.4 percent from 44 to 43.6 percent (95% CI -1.2, 0.4). Breastfeeding rates increased compared with baseline rates at all time points until 8 months. However, the effect was not uniform across the 4 postcode areas and was not related to level of deprivation. Little difference was seen in receipt of information and knowledge about the availability of coaching among areas. All breastfeeding groups were well attended, popular, and considered helpful by participants. A minority of women (n = 14/206) participated in formal one-to-one coaching. Women who received antenatal, birth, and postnatal care from community midwife-led units were more likely to be breastfeeding at 2 weeks (p = 0.007) than women who received some or all care in district maternity units. CONCLUSIONS: Group-based and one-to-one peer coaching for pregnant women and breastfeeding mothers increased breastfeeding initiation and duration in an area with below average breastfeeding rates.

Adult↗

Low ankle-brachial pressure index predicts increased risk of cardiovascular disease independent of the metabolic syndrome and conventional cardiovascular risk factors in the Edinburgh Artery Study.

OBJECTIVE: To investigate whether a low ankle-brachial pressure index (ABI) predicts increased risk of cardiovascular disease (CVD) independent of the metabolic syndrome and conventional cardiovascular risk factors. RESEARCH DESIGN AND METHODS: The Edinburgh Artery Study is a population-based cohort study in which subjects were followed up until their death or for approximately 15 years. Low ABI at baseline was defined as <0.9; subjects with ABI >1.4 (n = 13) were excluded from the analyses. We used a modified version of the definition of the metabolic syndrome published in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, replacing waist circumference criteria with BMI criteria. Data on relevant parameters were available for 1,467 men and women ages 55-74 years at baseline. Cox proportional hazards models were used to study cardiovascular morbidity and mortality before and after adjusting for potential confounding factors. RESULTS: We determined that 25% of the study population had the metabolic syndrome and that a low ABI was more prevalent among people with than without the metabolic syndrome (24 vs. 15%; P < 0.001). During the follow-up period, there were 226 deaths from CVD and 462 nonfatal cardiovascular events. The hazard ratio (95% CI) for low ABI after adjusting for age, sex, baseline CVD, diabetes, smoking status, LDL cholesterol, and metabolic syndrome was 1.5 (1.1-2.1) for CVD mortality and 1.5 (1.2-1.8) for all CVD outcomes. CONCLUSIONS: Low ABI is associated with increased risk of CVD independent of the metabolic syndrome and other major CVD risk factors.

Aged↗

A pragmatic, three-arm randomised controlled trial of spiritual healing for asthma in primary care.

BACKGROUND: Well-designed trials are required to assess if complementary and alternative medicine (CAM) is effective. AIM: This study assessed the effectiveness of spiritual healing for asthma. DESIGN OF STUDY: Randomised, placebo-controlled trial. SETTING: Aberdeen, Scotland. METHOD: This was a single-blind, three-armed randomised, controlled trial of spiritual healing for asthma, comparing the effectiveness of five sessions of spiritual healing with placebo (delivered by an actor), and with a control group receiving normal care only. The primary outcome measure was the Juniper Asthma Quality of Life Questionnaire (AQLQ). Secondary outcomes were forced expiratory flow in one second (FEV1), peak expiratory flow (PEF), HADS (Hospital Anxiety Depression Scale), SF-36 and MYMOP (Measure Yourself Medical Outcome Profile). Baseline and follow-up data were collected. RESULTS: Eighty-eight adult patients receiving pharmacological treatment for asthma participated. AQLQ scores improved significantly from baseline and the end of treatment in all groups (spiritual healing P = 0.008; 'sham' healing P = 0.001 and control P = 0.01) but there was no significant difference between groups (P = 0.57). These improvements were maintained at follow-up 1 for two of the groups (spiritual healing P = 0.016; sham healing P = 0.001 and control P = 0.09) but none of the groups showed an improvement at follow-up 2 (spiritual healing P = 0.161; sham healing P = 0.016 and control P = 0.11). Similar proportions of patients in each group showed a clinically important improvement in AQLQ score. Analysis of AQLQ scores at end of treatment and both follow-up periods indicated no significance between group differences. No consistent changes were seen in secondary outcome measures, possibly due to the small sample size. CONCLUSION: Spiritual healing does not appear to have any specific affect on patient asthma related quality of life.

Adult↗

Hemostatic factors, inflammatory markers, and progressive peripheral atherosclerosis: the Edinburgh Artery Study.

The interplay between inflammatory and hemostatic mechanisms may play a crucial role in the development and progression of atherosclerosis. The authors evaluated the separate and joint associations of hemostatic and inflammatory variables on peripheral atherosclerotic progression in the Edinburgh Artery Study, a population cohort study of 1,592 men and women aged 55-74 years that started in 1987. Levels of fibrinogen, fibrin D-dimer, von Willebrand factor, tissue plasminogen activator antigen, factor VII, prothrombin fragment 1 + 2, urinary fibrinopeptide A, C-reactive protein, and interleukin-6 were measured at baseline. Arm and ankle blood pressures were measured, and atherosclerotic progression was assessed by computing ankle brachial index (ABI) at baseline (1,582 participants) and after 12 years of follow-up (813 participants). Fibrinogen (p = 0.05) and D-dimer (p < or = 0.05) were significantly associated with ABI change independently of baseline ABI and cardiovascular disease risk factors. However, these associations were no longer significant when analyses were adjusted for either C-reactive protein or interleukin-6. Moreover, subjects with higher levels of both D-dimer and interleukin-6 at baseline had the greatest ABI decline. In conclusion, fibrinogen and D-dimer, but not other hemostatic factors, were associated with progressive peripheral atherosclerosis. Since D-dimer and fibrinogen are acute phase reactants, these data support the hypothesis that inflammation is more related to atherosclerosis than is hypercoagulation.

Aged↗

C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study.

BACKGROUND: The relationship between levels of circulating inflammatory markers and risk of progressive atherosclerosis is relatively undetermined. We therefore studied inflammatory markers as predictors of peripheral atherosclerotic progression, measured by the ankle-brachial index (ABI) at 3 consecutive time points over 12 years. METHODS AND RESULTS: The Edinburgh Artery Study is a population cohort study of 1592 men and women aged 55 to 74 years. C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), and E-selectin were measured at baseline. Valid ABI measurements were obtained on 1582, 1081, and 813 participants at baseline and 5-year and 12-year follow-up examinations, respectively. At baseline, a significant trend was found between higher plasma levels of CRP (P< or =0.05) and increasing severity of peripheral arterial disease (PAD), after adjustment for baseline cardiovascular risk factors. IL-6 at baseline (P< or =0.001) was associated with progressive atherosclerosis at 5 years (ABI change from baseline), and CRP (P< or =0.01), IL-6 (P< or =0.001), and ICAM-1 (P< or =0.01) were associated with changes at 12 years, independently of baseline ABI, cardiovascular risk factors, and baseline cardiovascular disease. Only IL-6 independently predicted ABI change at 5 years (P< or =0.01) and 12 years (P< or =0.05) in analyses of all inflammatory markers simultaneously and adjusted for baseline ABI, cardiovascular risk factors, and cardiovascular disease at baseline. CONCLUSIONS: These findings suggest that CRP, IL-6, and ICAM-1 are molecular markers associated with atherosclerosis and its progression. IL-6 showed more consistent results and stronger independent predictive value than other inflammatory markers.

Aged↗

Long term effects of hysterectomy on mortality: nested cohort study.

OBJECTIVES: To investigate the long term risk (mean > 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy. DESIGN: Nested cohort study. SETTING: Royal College of General Practitioners' oral contraception study. PARTICIPANTS: 7410 women (3705 flagged at the NHS central registries for cancer and death who had a hysterectomy during the oral contraception study and 3705 who were flagged but did not have the operation). MAIN OUTCOME MEASURES: Mortality from all causes, cardiovascular disease, and cancer. RESULTS: 623 (8.4%) women had died by the end of follow-up (308 in the hysterectomy group and 315 in the non-hysterectomy group). Older women who had had a hysterectomy had a 6% reduced risk of death compared with women of a similar age who did not have the operation (adjusted hazard ratio 0.94, 95% confidence interval 0.75 to 1.18). Compared with young women who did not have a hysterectomy those who were younger at hysterectomy had an adjusted hazard ratio for all cause mortality of 0.82 (0.65 to 1.03). Hysterectomy was not associated with a significantly altered risk of mortality from cardiovascular disease or cancer regardless of age. CONCLUSION: Hysterectomy did not increase the risk of death in the medium to long term.

Adult↗

Interindividual variability in response to sodium dichromate-induced oxidative DNA damage: role of the Ser326Cys polymorphism in the DNA-repair protein of 8-oxo-7,8-dihydro-2'-deoxyguanosine DNA glycosylase 1.

Although the genotoxic mechanism(s) of hexavalent chromium (CrVI) carcinogenicity remain to be fully elucidated, intracellular reduction of CrVI and concomitant generation of reactive intermediates including reactive oxygen species and subsequent oxidative damage to DNA is believed to contribute to the process of carcinogenesis. In the current study, substantial interindividual variation (7.19-25.84% and 8.79-34.72% tail DNA as assessed by conventional and FPG-modified comet assay, respectively) in levels of DNA strand breaks after in vitro treatment of WBC with sodium dichromate (100 micromol/L, 1 hour) was shown within a group of healthy adult volunteers (n = 72) as assessed by both comet and formamidopyrimidine glycosylase-modified comet assays. No statistically significant correlation between glutathione S-transferases M1 or T1, NADPH quinone oxidoreductase 1 (codon 187) and X-ray repair cross complementation factor 1 (codon 194) genotypes and individual levels of DNA damage were observed. However, individuals homozygous for the Cys(326) 8-oxo 7,8-dihydro-2'-deoxyguanosine glycosylase 1 (OGG1) polymorphism had a statistically significant elevation of formamidopyrimidine glycosylase-dependent oxidative DNA damage after treatment with sodium dichromate when compared with either Ser(326)/Ser(326) or Ser(326)/Cys(326) individuals (P = 0.008 and P = 0.003, respectively). In contrast, no effect of OGG1 genotype on background levels of oxidative DNA damage was observed. When individuals were divided on the basis of OGG1 genotype, Cys(326)/Cys(326) individuals had a statistically significant (P < 0.05, one-way ANOVA followed by Tukey test) higher ratio of oxidative DNA damage to plasma antioxidant capacity than either Ser(326)/Ser(326) or Ser(326)/Cys(326) individuals. The results of this study suggest that the Cys(326)/Cys(326) OGG1 genotype may represent a phenotype that is deficient in the repair of 8-oxo-7,8-dihydro-2'-deoxyguanosine, but only under conditions of cellular oxidative stress. We hypothesize that this may be due to oxidation of the Cys(326) residue. In conclusion, the homozygous Cys(326) genotype may represent a biomarker of individual susceptibility of lung cancer risk in individuals that are occupationally exposed to CrVI.

8-Hydroxy-2'-Deoxyguanosine↗

Characterisation and comparison of health-related quality of life for patients with renal failure.

OBJECTIVE: The objective of this study was to assess the health related quality of life (HRQOL) in patients with kidney failure who had received renal transplants compared to those receiving haemodialysis, peritoneal dialysis or were waiting to start dialysis. RESEARCH DESIGN AND METHODS: The study was conducted at the University Hospital of Wales, Cardiff. HRQOL was measured using the EQ-5D, SF-36 and the Kidney Disease Quality of life questionnaire (KDQOL). Patients with kidney failure were identified from the renal unit departmental database and were surveyed by postal questionnaire or during their treatment. RESULTS: Of 1251 people surveyed, 416 valid returns were received, a response rate of 33%. For renal transplant patients the mean EQ-5Dindex was 0.712 (SD 0.272), significantly higher than those in the other treatment groups (haemodialysis mean = 0.443 (SD 317), p < 0.001; peritoneal dialysis mean = 0.569 (SD 329), p < 0.001). This difference remained after controlling for age and co-morbidity. With the exception of pain, the SF-36 showed significantly higher scores across all domains for transplant patients compared to both dialysis groups. From the KDQOL there were significantly lower scores compared with the transplant patients for both groups of dialysis patients for the effects and burden of kidney disease and general symptoms and problems. However, overall health scores were significantly higher for dialysis patients compared with transplant patients. CONCLUSION: Kidney failure has a high cost in terms of health related quality of life. There was a large difference between patients who have received a functioning graft following kidney transplant versus the alternative methods of renal replacement therapy, that is, peritoneal dialysis and haemodialysis. Kidney transplant should be the treatment of choice, and every effort should be made to increase the availability of kidneys for transplantation.

Adult↗