• A pilot study to determine the effectiveness of garlic oil capsules in the treatment of dyspeptic patients with Helicobacter pylori.

      McNulty, Cliodna A. M.; Wilson, Melanie P.; Havinga, Wouter; Johnston, Belinda; O'Gara, Elizabeth A.; Maslin, David J. (Wiley InterScience, 2001)
      BACKGROUND: Resistance of Helicobacter pylori to clarithromycin and metronidazole is now found worldwide. Steam-distilled garlic oil has in vitro activity against H. pylori and may be a useful alternative treatment strategy. MATERIALS AND METHODS: In this pilot study dyspeptic patients with positive serology for H. pylori confirmed by 13C urea breath test (UBT), at 0 and 2 weeks, were enrolled. Treatment consisted of one 4 mg garlic oil capsule with a meal four times per day for 14 days. H. pylori eradication was defined as a negative UBT at both follow-up appointments. Suppression was defined as a 50% fall in 13C excess between baseline and follow-up 1. RESULTS: Five patients completed the study. There was no evidence of either eradication or suppression of H. pylori or symptom improvement whilst taking garlic oil. CONCLUSION: These negative results show that, within the gastric milieu, garlic oil at this dose does not inhibit H. pylori. A higher dose administered for a longer time-period may be effective. Antibiotics are usually combined with a proton-pump inhibitor or bismuth salt, as the only antibiotic with any in vivo activity against H. pylori in monotherapy is clarithromycin. A proton pump inhibitor raises gastric pH and, by increasing bacterial division, may increase the in vivo activity of garlic oil. This may be worth pursuing in a future trial.
    • A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.

      Freimanis, Graham L.; Hooley, Paul; Ejtehadi, H Dava; Ali, H.A.; Veitch, A.; Rylance, P.; Alawi, A.; Axford, John; Nevill, Alan M.; Murray, Paul G.; et al. (Wiley-Blackwell, 2010)
      Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.
    • Acute rise of circulating vascular endothelial growth factor-A in patients with coronary artery disease following cardiothoracic surgery.

      Cotton, James M.; Mathur, A.; Hong, Ying; Brown, Angie S.; Martin, John F.; Erusalimsky, Jorge D.
      AIMS: Vascular endothelial growth factor-A (VEGF-A) is an angiogenic and vasoprotective molecule whose expression is modulated by hypoxia and inflammatory mediators. Here we have tested the hypothesis that plasma levels of VEGF-A are influenced by pre-existing coronary artery disease and by changes in circulating interleukin-6 (IL-6). METHODS AND RESULTS: Plasma VEGF-A and IL-6 were measured prior to and at various time intervals following surgery in individuals with angiographically normal coronary arteries requiring cardiac valve replacement (N group) and in patients with coronary artery disease and stable angina undergoing coronary artery bypass grafting (CAD group). Baseline VEGF-A levels were not significantly different in CAD (22.3+/-2.6 pg x ml(-1)) compared to the N group (14.9+/-2.9 pg x ml(-1)). Following cardiac surgery there was a significant rise of VEGF-A in CAD (P<0.0005 vs baseline), but not in the N group, reaching a maximum (approximately 2 fold increase) after 24 h. Surgery caused a rapid increase of plasma IL-6 in both groups, but the rise was significantly larger in CAD patients (P<0.0005 vs N) where it preceded the increase in VEGF-A. Furthermore, in patients with CAD there was a significant correlation between the change in VEGF-A and the change in IL-6 (P<0.04). CONCLUSION: These findings demonstrate that in patients with coronary artery disease cardiothoracic surgery leads to an acute rise in VEGF-A. We suggest that this rise may result from an interaction between the pre-existing atheromatous process and a systemic increase of inflammatory mediators.
    • Anti-tumour necrosis factor alpha therapy improves insulin sensitivity in normal-weight but not in obese patients with rheumatoid arthritis

      Stavropoulos-Kalinoglou, A; Metsios, GS; Panoulas, VF; Nightingale, P; Koutedakis, Y; Kitas, GD (Springer Science and Business Media LLC, 2012-07-05)
      Introduction: Insulin resistance (IR), a risk factor for the development of cardiovascular disease, is common among patients with rheumatoid arthritis (RA). Inflammation, and especially tumour necrosis factor alpha (TNFα), has been associated with IR, and the administration of anti-TNFα agents is suggested to improve insulin sensitivity. However obesity, a potent contributor to IR, may limit the beneficial effects of anti-TNFα medication on IR. The aim of this study is to compare the effects of anti-TNFα therapy on IR between normal-weight and obese patients with RA.Methods: Patients who were normal-weight with IR (N+IR) or obese with IR (O+IR) and had embarked on anti-TNFα treatment, participated. Assessments included body mass index (BMI), insulin sensitivity (Homeostasis Model Assessment of insulin resistance, HOMA and the Quantitative Insulin sensitivity Check Index, QUICKI), and RA disease characteristics before and following six months of anti-TNFα treatment. Their results were compared to matched (for age, gender, BMI, disease duration and smoking status) normal-weight patients without IR (N-IR) and obese without IR (N-IR), respectively. In total, 32 patients were assessed for this study, with 8 in each group.Results: Following six months of treatment, disease activity was significantly reduced in all groups (P < 0.05) to a similar extent (P for differences between groups > 0.05 in all cases). In the total population, changes in HOMA (mean reduction at 6 m = -0.2 ± 0.1; P = 0.088) and QUICKI (mean increase at 6 m = 0.03 ± 0.022; P = 0.092) after treatment were not statistically significant, though a trend towards improvement was observed. However, N+IR patients showed a significant decrease in HOMA (mean reduction at 6 m = -0.54 ± 0.2; P = 0.002) and increase in QUICKI (mean increase at 6 m = 0.046 ± 0.02; P = 0.011). These changes were significantly different compared to the other groups (P < 0.05 in all cases). Multivariable analyses showed that the change in Erythrocyte Sedimentation Rate (ESR), and the change in C-Reactive Protein (CRP) associated with the improvement in HOMA (ESR: F 1-7 = 5.143, P = 0.019; CRP: F 1-7 = 3.122, P = 0.022) and QUICKI (ESR: F 1-7 = 3.814, P = 0.021; CRP: F 1-7 = 2.67; P = 0.041) only in the N+IR group.Conclusions: Anti-TNFα therapy, through controlling inflammation, seems to improve insulin sensitivity in normal-weight RA patients with insulin resistance, but is not sufficient to achieving the same beneficial effect in obese RA patients with insulin resistance. © 2012 Stavropoulos-Kalinoglou et al.; licensee BioMed Central Ltd.
    • Association between environmental tobacco smoke exposure and dementia syndromes

      Chen, Ruoling; Wilson, Kenneth; Chen, Yang; Zhang, Dongmei; Qin, Xia; He, M; Hu, Zhi; Ma, Ying; Copeland, John R; School of Health Administration, Anhui Medical University, Hefei, China. ruoling.chen@kcl.ac.uk (BMJ, 2013-01-01)
      Objectives: Environmental tobacco smoke (ETS) has a range of adverse health effects, but its association with dementia remains unclear and with dementia syndromes unknown. We examined the dose-response relationship between ETS exposure and dementia syndromes. Methods: Using a standard method of GMS, we interviewed 5921 people aged ≥60 years in five provinces in China in 2007-2009 and characterised their ETS exposure. Five levels of dementia syndrome were diagnosed using the Automated Geriatric Examination for Computer Assisted Taxonomy instrument. The relative risk (RR) of moderate (levels 1-2) and severe (levels 3-5) dementia syndromes among participants exposed to ETS was calculated in multivariate adjusted regression models. Results: 626 participants (10.6%) had severe dementia syndromes and 869 (14.7%) moderate syndromes. Participants exposed to ETS had a significantly increased risk of severe syndromes (adjusted RR 1.29, 95% CI 1.05 to 1.59). This was dose-dependently related to exposure level and duration. The cumulative exposure dose data showed an adjusted RR of 0.99 (95% CI 0.76 to 1.28) for >0-24 level years of exposure, 1.15 (95% CI 0.93 to 1.42) for 25-49 level years, 1.18 (95% CI 0.87 to 1.59) for 59-74 level years, 1.39 (95% CI 1.03 to 1.84) for 75-99 level years and 1.95 (95% CI 1.34 to 2.83) for ≥100 level years. Significant associations with severe syndromes were found in never smokers and in former/current smokers. There were no positive associations between ETS and moderate dementia syndromes. Conclusions: ETS should be considered an important risk factor for severe dementia syndromes. Avoidance of ETS may reduce the rates of severe dementia syndromes worldwide.
    • Associations between static and dynamic field balance tests in assessing postural stability of female undergraduate dancers

      Clarke, Frances; Koutedakis, Yiannis; Wilson, Margaret; Wyon, Matthew; Faculty of Dance, Trinity Laban Conservatoire of Music and Dance, London, and National Institute of Dance Medicine and Science, United Kingdom;, Email: f.clarke@trinitylaban.ac.uk. (J. Michael Ryan Publishing, 2021-06-03)
      Balance testing on dancers has used a wide variety of assessment tools. However, as most field balance tests have been developed for either sport or elderly populations, the evidence of associations between tests and their functional relevance to dance is inconclusive. We assessed possible associations between five such field balance tests . A total of 83 female undergraduate dance students (20 ± 1.5 years; 163 ± 6.6 cm; 61 ± 10.8 kg) volunteered for the tests. They executed the Star Excursion Balance Test (SEBT), the modified Romberg test, the Airplane test, the BioSway Balance System (Biodex, Shirley, New York, USA), and a dance-specific pirouette test. Spearman's correlation coefficients examined relationships between the measures of the balance tests. Results showed strongest relationships between some SEBT reach directions (p < 0.01) and very weak to moderate relationships between some balance tests, including some SEBT directions, Romberg, Airplane, Biosway, and pirouette (p < 0.01 and p < 0.05). Our findings suggest that current tests used to assess dancers' postural stability need further investigation to ensure functionality and relevance.
    • B-type natriuretic peptide in reversible myocardial ischaemia.

      Chatha, K.; Alsoud, M.; Griffiths, M.J.; Elfatih, A.; Abozguia, K.; Horton, R.C.; Dunmore, Simon J.; Gama, R. (BMJ Publishing, 2006)
      BACKGROUND: Coronary heart disease is associated with increased B-type natriuretic peptides (BNPs), and, although controversial, may cause exaggerated exercise-induced BNP secretion. We investigated BNP in relation to reversible myocardial ischaemia. Materials and methods: Serum N-terminal proBNP (NT-proBNP) was measured before and after an exercise electrocardiogram test (ETT) in 14 patients with and 45 patients without exercise-induced myocardial ischaemia. Statistical analysis was carried out on logarithmically transformed data. Results, however, are pre-transformed data. RESULTS: NT-proBNP increased with exercise both in ETT-positive patients (mean (SD) 71.4 (41.2) v 76.8 (44.0) ng/l; p<0.001) and ETT-negative patients (54.0 (61.2) v 60.1 (69.0) ng/l; p<0.001). Pre-exercise and post-exercise NT-proBNP were higher (p<0.05) in ETT-positive than in ETT-negative patients. Incremental NT-proBNP was similar in ETT-positive (4.7 (4.2) ng/l) and ETT-negative (6.2 (8.6) ng/l) patients. CONCLUSION: Serum NT-proBNP concentrations are higher in patients with exercise-induced myocardial ischaemia than in those without. Exercise-induced electrocardiographic myocardial ischaemia, however, is not associated with exaggerated BNP secretion.
    • Beliefs about medicines and non-adherence in patients with stroke, diabetes mellitus and rheumatoid arthritis: A cross-sectional study in China

      Wei, Li; Champman, Sarah; Li, Xiaomei; Li, Xin; Li, Sumei; Chen, Ruoling; Bo, Nie; Chater, Angel; Horne, Robert; Department of Practice and Policy, University College London School of Pharmacy, London, UK. (BMJ, 2017-10-05)
      © 2017 author(s). Objectives To investigate beliefs about medicines and their association with medicine adherence in patients with chronic diseases in China. Design A cross-sectional questionnaire-based study Setting Two large urban hospitals in Hefei and Tianjin, China Participants Hospital inpatients (313 stroke patients) and outpatients (315 diabetic patients and 339 rheumatoid arthritis (RA) patients) were recruited between January 2014 and September 2014. Outcome measures The Beliefs about Medicines Questionnaire (BMQ), assessing patients' beliefs about the specific medicine (Specific-Necessity and Specific-Concerns) prescribed for their conditions (stroke/diabetes/RA) and more general background beliefs about pharmaceuticals as a class of treatment (BMQ-General Benefit, Harm and Overuse); the Perceived Sensitivity to Medicines scale (PSM) assessed patients' beliefs about how sensitive they were to the effects of medicines and the Medication Adherence Report Scale. The association between non-adherence and beliefs about medicines was assessed using a logistic regression model. Results Patients with diabetes mellitus had a stronger perceived need for treatment (mean (SD) Specific-Necessity score, 3.75 (0.40)) than patients with stroke (3.69 (0.53)) and RA (3.66 (0.44)) (p=0.049). Moderate correlations were observed between Specific-Concerns and General-Overuse, General-Harm and PSM (Pearson correlation coefficients, 0.39, 0.49 and 0.49, respectively, p<0.01). Three hundred and eleven patients were non-adherent to their medicine (159 (51.0%) in the stroke group, 60 (26.7%) in the diabetes mellitus group and 62 (19.8%) in the RA group, p<0.01). Across the whole sample, after adjusting for demographic characteristics, non-adherence was associated with patients who had higher concerns about their medicines (OR, 1.35, 95% CI 1.07 to 1.71) and patients who believed that they were personally sensitive to the effects of medications (OR 1.44, 95% CI 1.16 to 1.85). Conclusion The BMQ is a useful tool to identify patients at risk of non-adherence. In the future, adherence intervention studies may use the BMQ to screen for patients who are at risk of non-adherence and to map interventional support.
    • Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial

      Bahlis, Nizar; Corso, A; Mugge, LO; Shen, ZX; Desjardins, P; Stoppa, AM; Decaux, O; De Revel, T; Granell, M; Marit, G; et al. (Springer Science and Business Media LLC, 2017-11-01)
      © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ≥ very good partial response (VGPR; n=679), ≥ partial response (PR; n=1 225) or ≤ stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ≥ VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ≥ VGPR and ≥ PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ≥ VGPR and ≥ PR, respectively. In patients with CR, ≥ VGPR or ≥ PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.
    • Cardiorespiratory fitness levels and their association with cardiovascular profile in patients with rheumatoid arthritis: a cross-sectional study

      Koutedakis, Yiannis; Metsios, George S; Veldhuijzen van Zanten, Jet J C S; Stavropoulos-Kalinoglou, Antonis; Vitalis, Panagiotis; Duda, Joan L; Ntoumanis, Nikos; Rouse, Peter C; Kitas, George D (Oxford Journals (OUP), 2015-07-25)
      The aim of this study was to investigate the association of different physical fitness levels [assessed by the maximal oxygen uptake (VO2max) test] with cardiovascular disease (CVD) risk factors in patients with RA.A total of 150 RA patients were assessed for cardiorespiratory fitness with a VO2max test and, based on this, were split in three groups using the 33rd (18.1 ml/kg/min) and 66th (22.4 ml/kg/min) centiles. Classical and novel CVD risk factors [blood pressure, body fat, insulin resistance, cholesterol, triglycerides, high-density lipoprotein (HDL), physical activity, CRP, fibrinogen and white cell count], 10-year CVD risk, disease activity (DAS28) and severity (HAQ) were assessed in all cases.Mean VO2max for all RA patients was 20.9 (s.d. 5.7) ml/kg/min. The 10-year CVD risk (P = 0.003), systolic blood pressure (P = 0.039), HDL (P = 0.017), insulin resistance and body fat (both at P < 0.001), CRP (P = 0.005), white blood cell count (P = 0.015) and fibrinogen (P < 0.001) were significantly different between the VO2max tertiles favouring the group with the higher VO2max levels. In multivariate analyses of variance, VO2max was significantly associated with body fat (P < 0.001), HDL (P = 0.007), insulin resistance (P < 0.003) and 10-year CVD risk (P < 0.001), even after adjustment for DAS28, HAQ and physical activity.VO2max levels are alarmingly low in RA patients. Higher levels of VO2max are associated with a better cardiovascular profile in this population. Future studies need to focus on developing effective behavioural interventions to improve cardiorespiratory fitness in RA.
    • Comparative assessment of predictive performance of PRECISE-DAPT, CRUSADE, and ACUITY scores in risk stratifying 30-day bleeding events

      Kawashima, H; Gao, C; Takahashi, K; Tomaniak, M; Ono, M; Hara, H; Wang, R; Chichareon, P; Suryapranata, H; Walsh, S; et al. (Georg Thieme Verlag, 2020-06-22)
      Background The utility of the PRECISE-DAPT score in predicting short-term major bleeding, either alone, or in comparison with the CRUSADE and ACUITY scores, has not been investigated. This analysis compared the predictive performances of the three bleeding scores in stratifying the risk of 30-day major bleeding postpercutaneous coronary intervention in patients with dual-antiplatelet therapy. Methods In this post hoc subanalysis of the GLOBAL LEADERS trial, the primary safety objective (bleeding according to the Bleeding Academic Research Consortium [BARC] criteria [type 3 or 5]) was assessed at 30 days according to the three scores in the overall population, and in patients with acute (ACS) and chronic coronary syndrome (CCS). Results In a total of 15,968 patients, we calculated all three scores in 14,709 (92.1%). Irrespective of clinical presentation, the PRECISE-DAPT (c-statistics: 0.648, 0.653, and 0.641, respectively), CRUSADE (c-statistics: 0.641, 0.639, and 0.644, respectively), and ACUITY (c-statistics: 0.633, 0.638, and 0.623, respectively) scores were no significant between-score differences in discriminatory performance for BARC 3 or 5 bleeding up to 30 days, and similarly the PRECISE-DAPT score had a comparable discriminative capacity according to the integrated discrimination improvement when compared with the other scores. In ACS, the CRUSADE score had a poor calibration ability (Hosmer-Lemeshow goodness-of-fit [GOF] chi-square = 15.561, p = 0.049), whereas in CCS, the PRECISE-DAPT score had poor calibration (GOF chi-square = 15.758, p = 0.046). Conclusion The PRECISE-DAPT score might be clinically useful in the overall population and ACS patients for the prediction of short-term major bleeding considering its discriminative and calibration abilities.
    • CpG methylation profiling in VHL related and VHL unrelated renal cell carcinoma

      McRonald, FE; Morris, MR; Gentle, D; Winchester, L; Baban, D; Ragoussis, J; Clarke, NW; Brown, MD; Kishida, T; Yao, M; et al. (Springer Nature, 2009-06-03)
      Background: Renal cell carcinoma (RCC) is histopathologically heterogeneous with clear cell and papillary the most common subtypes. The most frequent molecular abnormality in clear cell RCC is VHL inactivation but promoter methylation of tumour suppressor genes is common in both subtypes of RCC. To investigate whether RCC CpG methylation status was influenced by histopathology and VHL status we performed high-throughput epigenetic profiling using the Illumina Goldengate Methylation Array in 62 RCC (29 RCC from von Hippel-Lindau (VHL) disease patients, 20 sporadic clear cell RCC with wild type VHL and 13 sporadic papillary RCC). Results: 43 genes were methylated in >20% of primary RCC (range 20-45%) and most (37/43) of these had not been reported previously to be methylated in RCC. The distribution of the number of methylated CpGs in individual tumours differed from the expected Poisson distribution (p < 0.00001; log-likelihood G test) suggesting that a subset of RCC displayed a CpG Island Methylator Phenotype. Comparison of RCC subtypes revealed that, on average, tumour specific CpG methylation was most prevalent in papillary RCC and least in VHL RCC. Many of the genes preferentially methylated in pRCC were linked to TGFβ or ERK/Akt signalling. Conclusion: These findings demonstrate differing patterns of tumour-specific CpG methylation in VHL and non VHL clear cell RCC and papillary RCC, and identify multiple novel potential CpG methylation biomarkers for RCC. © 2009 McRonald et al; licensee BioMed Central Ltd.
    • Cyclodiode photocoagulation for refractory glaucoma after penetrating keratoplasty.

      Shah, Peter; Lee, Graham A.; Kirwan, James K.; Bunce, Catey; Bloom, Philip A.; Ficker, Linda A.; Khaw, Peng T. (Elsevier Science Direct, 2001)
      OBJECTIVE: This study analyzes the results of intraocular pressure (IOP) reduction by contact diode cycloablation (cyclodiode) in cases of refractory glaucoma after penetrating keratoplasty. DESIGN: Retrospective noncomparative, interventional case series. PARTICIPANTS: Twenty-eight eyes in 28 patients attending the Moorfields Eye Hospital. INTERVENTION: Cyclodiode (40 applications x 1.5 W x 1.5 seconds over 270-300 degrees ) was used to control the IOP in refractory glaucoma after penetrating keratoplasty. MAIN OUTCOME MEASURES: Postoperative IOP, graft status, visual acuity, and number of antiglaucoma medications were recorded after cyclodiode treatment. RESULTS: Cyclodiode resulted in a reduction of IOP from a median of 33 mmHg (interquartile range [28, 40.5]) to a median of 15 mmHg (interquartile range [12, 20.5]). Most patients had a significant lowering in IOP with a median reduction of 16 mmHg (interquartile range [12, 25]; P < 0.0001). IOPs of 6 to 21 mmHg were achieved in 22 patients (79%). Sixteen patients (57%) required more than one treatment with cyclodiode to control the IOP, with three patients (11%) requiring three treatments and two patients (7%) requiring four treatments. Visual acuity improved (> two Snellen lines of acuity) in three patients (11%) and remained the same (+/- one Snellen line) in 17 patients (61%). The mean number of antiglaucoma medications before cycloablation was 2.6 and was 1.8 after treatment (P < 0.001). Of the 19 patients (68%) with originally clear grafts, three grafts (16%) developed opacification. One patient (4%), with a history of nanophthalmos and recurrent uveal effusion, had delayed hypotony (IOP < 6 mmHg) occurring 46 months after the diode treatment. All patients had at least 6 months follow-up. CONCLUSIONS: These patients have often undergone multiple previous complicated ocular interventions and are often not suitable for filtration surgery. Reduction of IOP with maintenance of visual acuity and a good safety profile was achieved in most patients in this study but may require multiple treatments. We propose cyclodiode as an effective treatment for many patients in the management of refractory glaucoma after penetrating keratoplasty.
    • Diagnostic power of circulatory metabolic biomarkers as metabolic syndrome risk predictors in community-dwelling older adults in Northwest of England (a feasibility study)

      Hassannejad, Razieh; Sharrouf, Hamsa; Haghighatdoost, Fahimeh; Kirk, Ben; Amirabdollahian, Farzad; Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan 8158388994, Iran. (MDPI, 2021-06-30)
      Metabolic Syndrome (MetS) is a cluster of risk factors for diabetes and cardiovascular diseases with pathophysiology strongly linked to aging. A range of circulatory metabolic biomarkers such as inflammatory adipokines have been associated with MetS; however, the diagnostic power of these markers as MetS risk correlates in elderly has yet to be elucidated. This cross-sectional study investigated the diagnostic power of circulatory metabolic biomarkers as MetS risk correlates in older adults. Hundred community dwelling older adults (mean age: 68.7 years) were recruited in a study, where their blood pressure, body composition and Pulse Wave Velocity (PWV) were measured; and their fasting capillary and venous blood were collected. The components of the MetS; and the serum concentrations of Interleukin-6 (IL-6), Tumor Necrosis Factor-α (TNF-α), Plasminogen Activator Inhibitor-I (PAI-I), Leptin, Adiponectin, Resistin, Cystatin-C, C-Reactive Protein (CRP), insulin and ferritin were measured within the laboratory, and the HOMA1-IR and Atherogenic Index of Plasma (AIP) were calculated. Apart from other markers which were related with some cardiometabolic (CM) risk, after Bonferroni correction insulin had significant association with all components of Mets and AIP. These associations also remained significant in multivariate regression. The multivariate odds ratio (OR with 95% confidence interval (CI)) showed a statistically significant association between IL-6 (OR: 1.32 (1.06-1.64)), TNF-α (OR: 1.37 (1.02-1.84)), Resistin (OR: 1.27 (1.04-1.54)) and CRP (OR: 1.29 (1.09-1.54)) with MetS risk; however, these associations were not found when the model was adjusted for age, dietary intake and adiposity. In unadjusted models, insulin was consistently statistically associated with at least two CM risk factors (OR: 1.33 (1.16-1.53)) and MetS risk (OR: 1.24 (1.12-1.37)) and in adjusted models it was found to be associated with at least two CM risk factors and MetS risk (OR: 1.87 (1.24-2.83) and OR: 1.25 (1.09-1.43)) respectively. Area under curve (AUC) for receiver operating characteristics (ROC) demonstrated a good discriminatory diagnostics power of insulin with AUC: 0.775 (0.683-0.866) and 0.785 by cross validation and bootstrapping samples for at least two CM risk factors and AUC: 0.773 (0.653-0.893) and 0.783 by cross validation and bootstrapping samples for MetS risk. This was superior to all other AUC reported from the ROC analysis of other biomarkers. Area under precision-recall curve for insulin was also superior to all other markers (0.839 and 0.586 for at least two CM risk factors and MetS, respectively). Fasting serum insulin concentration was statistically linked with MetS and its risk, and this link is stronger than all other biomarkers. Our ROC analysis confirmed the discriminatory diagnostic power of insulin as CM and MetS risk correlate in older adults.
    • Different patterns of brisk walking are equally effective in decreasing postprandial lipaemia.

      Murphy, Marie H.; Nevill, Alan M.; Hardman, Adrianne E. (MCB University Press (Emerald), 2000)
      OBJECTIVE: To compare the effects of different patterns of brisk walking on day-long plasma triacylglycerol concentrations in sedentary adults. DESIGN: A three-trial, repeated measures design in which subjects were studied in the fasted state and throughout a day during which they consumed three standardized, mixed meals. On different occasions, subjects undertook no exercise (control), walked briskly for 10 min before each meal (short walks) or walked briskly for 30min before breakfast (long walk). SUBJECTS: Seven postmenopausal sedentary women and three sedentary men aged between 34 and 66y, with body mass index between 24 and 35 kg/m2. MEASUREMENTS: Plasma concentrations of triacylglycerol, non-esterified fatty acids, glucose and insulin, metabolic rate and whole-body substrate oxidation in the fasted state and at hourly intervals for 3 h after each meal. RESULTS: Postprandial plasma triacylglycerol concentrations were lower (P= 0.009) during the walking trials than during the control trial (average values: control 2.08 +/- 0.28 mmol/l; short walks 1.83 +/- 0.22mmol/l; long walk 1.84 +/- 0.22mmol/l (mean+/-s.e.) but did not differ between the two patterns of walking. The difference between control and walking trials increased as successive meals were consumed (interaction of trial x meal P= 0.03). Plasma triacylglycerol concentration increased during the 3 h after breakfast, changed little after lunch and decreased after the evening meal (interaction of meal x time P=0.001). When both walking trials were treated as one condition, walking increased postprandial fat oxidation (average values: control, 0.066 +/- 0.009 g/min;walking 0.074 +/- 0.008 g/min; P < 0.01). CONCLUSIONS: Thirty minutes of brisk walking, undertaken in one session or accumulated throughout a day, reduces postprandial plasma triacylglycerol concentrations and increases fat oxidation.
    • Effect of material deprivation on Epstein-Barr virus infection in Hodgkin's disease in the West Midlands.

      Flavell, Joanne R.; Constandinou, C.; Lowe, D.; Scott, K.; Newey, C.; Evans, D.; Dutton, A.; Simmons, S.; Smith, Richard; Crocker, John; et al. (nature.com, 1999)
      We have used Townsend scores from postcode data to compare levels of material deprivation and Epstein-Barr virus (EBV)-positivity for 223 patients diagnosed with Hodgkin's disease (HD) in the period 1981-1997. The presence of EBV in HD tumours was determined using in situ hybridization to target the abundantly expressed EBV early RNAs. EBV was detected in the malignant Hodgkin and Reed-Sternberg cells in 47/223 HD cases (21%). There was found to be a tendency for higher Townsend scores (indicative of higher levels of material deprivation) in EBV-positive HD patients, but this association was not statistically significant. When various subgroups of patients from the study were examined separately the indication of higher Townsend scores in EBV-positive patients was found to be more marked for patients with mixed cellularity disease (P = 0.09) and for females (P = 0.03). The results of this study suggest that differences in the level of material deprivation are important in determining the likelihood of EBV-positive HD in the UK, particularly for certain subgroups of patients. It is not known what specific socioeconomic factors are responsible for these differences, although alterations in the timing or rate of primary EBV infection, or decline in the level of EBV-specific immunity, may be important. (Cancer Research UK)
    • Effects of nitric oxide synthase inhibition on Basal function and the force-frequency relationship in the normal and failing human heart in vivo.

      Cotton, James M.; Kearney, Mark T.; MacCarthy, Philip A.; Grocott-Mason, Richard M.; McClean, Dougal R.; Heymes, Christophe; Richardson, Peter J.; Shah, Ajay M. (American Heart Association Inc, 2001)
      BACKGROUND: Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. METHODS AND RESULTS: We compared the effects of intracoronary NO synthase inhibition with N(G)-monomethyl-L-arginine (L-NMMA; 25 micromol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (n=11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (n=7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt(max) (from 1826 to 1578 mm Hg/s; P<0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt(max) were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt(max) (from 1313 to 1337 mm Hg/s; P=NS). The blunted pacing-induced rise in LV dP/dt(max) in these patients was unaltered by L-NMMA. CONCLUSION: Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.
    • Factorial invariance for combined Wechsler Adult Intelligence Scale-Revised and Wechsler Memory Scale-Revised scores in a sample of clients with alcohol dependency.

      Bowden, Stephen C.; Ritter, Alison J.; Carstairs, Jane R.; Shores, E. Arthur; Pead, J.; Greeley, Janet D.; Whelan, Gregory; Long, Caroline M.; Clifford, Christine C. (Psychology Press (Taylor & Francis), 2001)
      This study examined the joint factor structure of the WAIS-R and WMS-R in a sample of 289 participants (mostly males) with alcohol dependency. In a confirmatory phase we contrasted a range of factor models derived from previous analyses of the Wechsler scales. The best fitting model incorporated five factors representing Verbal Comprehension, Perceptual Organization, Attention-Concentration, Verbal Memory, and Visual Memory, with reassignment of factor loadings for two subtests. The invariance of the measurement model was then examined comparing data from a large sample of healthy participants (J. R. Carstairs & E. A. Shores, 1999). The results indicated that the number of factors was invariant across samples, and four of the factors satisfied the criterion of partial measurement invariance.
    • Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma

      Morris, MR; Ricketts, C; Gentle, D; Abdulrahman, M; Clarke, N; Brown, M; Kishida, T; Yao, M; Latif, F; Maher, ER; et al. (Springer Nature, 2010-02-15)
      Promoter region hyermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many types of human cancers. Functional epigenetic studies, in which gene expression is induced by treatment with demethylating agents, may identify novel genes with tumour-specific methylation. We used high-density gene expression microarrays in a functional epigenetic study of 11 renal cell carcinoma (RCC) cell lines. Twenty-eight genes were then selected for analysis of promoter methylation status in cell lines and primary RCC. Eight genes (BNC1, PDLIM4, RPRM, CST6, SFRP1, GREM1, COL14A1 and COL15A1) showed frequent (30% of RCC tested) tumour-specific promoter region methylation. Hypermethylation was associated with transcriptional silencing. Re-expression of BNC1, CST6, RPRM and SFRP1 suppressed the growth of RCC cell lines and RNA interference knock-down of BNC1, SFRP1 and COL14A1 increased the growth of RCC cell lines. Methylation of BNC1 or COL14A1 was associated with a poorer prognosis independent of tumour size, stage or grade. The identification of these epigenetically inactivated candidate RCC TSGs can provide insights into renal tumourigenesis and a basis for developing novel therapies and biomarkers for prognosis and detection. © 2010 Macmillan Publishers Limited.
    • Impact of air pollution on cognitive impairment in older people: A cohort study in rural and suburban China

      He, Fan; Tang, JJ; Zhang, Tao; Lin, J; Li, F; Gu, X; Chen, Ruoling; Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China. (IOS Press, 2020-10-13)
      Background: The impact of air pollution on cognitive impairment in older people has not been fully understood. It is unclear which air pollutants are the culprit. Objective: We assessed the associations of six air pollutants and air quality index (AQI) with cognitive impairment. Methods: We examined 7,311 participants aged ≥60 years from the ZJMPHS cohort in China. They were interviewed for baseline socio-demographic and disease risk factors in 2014, and re-interviewed in 2015 and 2016, respectively. The presence of cognitive impairment was determined by the Chinese version of the Mini-Mental State Examination. Daily area-level data monitored for air pollution during 2013-2015 was then examined for associations with cognitive impairment in logistic regression models. Results: Over the two years follow-up, 1,652 participants developed cognitive impairment, of which 917 were severe cases. Continuous air pollution data showed the risk of cognitive impairment increased with exposure to PM2.5 (fully adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.08), PM10 (1.03, 1.001-1.06), and SO2 (1.04, 1.01-1.08), but not with NO2, CO, O3, and AQI. Categorized data analysis for low, middle, and high level exposure demonstrated that the aOR increased with PM2.5 and AQI, somehow with PM10 and CO, but not significantly with SO2 and NO2, and decreased with O3. The patterns for these associations with severe cognitive impairment were stronger. Conclusion: Lowering PM2.5, PM10, SO2, and CO level could reduce the risk of cognitive impairment in older Chinese. Strategies to target most important air pollutants should be an integral component of cognitive interventions.