• 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 adrenal failure: A potentially fatal consequence of an adulterated herbal remedy

      Sensi, H; Buch, H; Ford, L; Gama, R; Chemical Pathology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK. (BMJ, 2019-02-19)
      © 2019 BMJ Publishing Group Limited. Herbal remedies adulterated with glucocorticoids can cause Cushing's syndrome. We report a severe presentation of a 'herbal remedy' adulterated with glucocorticoids; causing a potentially fatal adrenal crisis precipitated by acute illness. Investigations were consistent with adrenal suppression and confirmed, after tablet analysis, to be due to a 'herbal remedy' containing synthetic betamethasone/dexamethasone. This case highlights the need for clinical vigilance and patient education about the potential risks associated with the use of unlicensed treatments and the role of tablet analysis in routine biochemistry.
    • 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-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome.

      Hamid, Colleen G.; Norgate, K.; D'Cruz, D.P.; Khamashta, M.A.; Arno, M.; Pearson, J.D.; Frampton, Geoffrey; Murphy, John J. (BMJ Publishing & European League Against Rheumatism, 2007)
      OBJECTIVE: To determine the effects of primary antiphospholipid syndrome (PAPS)-derived anti-beta(2)GPI antibodies on gene expression in human umbilical vein endothelial cells (HUVEC) by gene profiling using microarrays. METHODS: Anti-beta(2)GPI antibodies purified from sera of patients with PAPS or control IgG isolated from normal subjects were incubated with HUVEC for 4 h before isolation of RNA and processing for hybridisation to Affymetrix Human Genome U133A-2.0 arrays. Data were analysed using a combination of the MAS 5.0 (Affymetrix) and GeneSpring (Agilent) software programmes. For selected genes microarray data were confirmed by real-time PCR analysis or at the protein level by ELISA. RESULTS: A total of 101 genes were found to be upregulated and 14 genes were downregulated twofold or more in response to anti-beta(2)GPI antibodies. A number of novel genes not previously associated with APS were induced, including chemokines CCL20, CXCL3, CX3CL1, CXCL5, CXCL2 and CXCL1, the receptors Tenascin C, OLR1, IL-18 receptor 1, and growth factors CSF2, CSF3 IL-6, IL1beta and FGF18. The majority of downregulated genes were transcription factors/signalling molecules including ID2. Quantitative real-time RT-PCR analysis confirmed the microarray results for selected genes (CSF3, CX3CL1, FGF18, ID2, SOD2, Tenascin C). CONCLUSIONS: This study reveals a complex gene expression response in HUVEC to anti-beta(2)GPI antibodies with multiple chemokines, pro-inflammatory cytokines, pro-thrombotic and pro-adhesive genes regulated by these antibodies in vitro. Some of these newly identified anti-beta(2)GPI antibody-regulated genes could contribute to the vasculopathy associated with this disease.
    • 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.
    • Association of air pollution with the risk of initial outpatient visits for tuberculosis in Wuhan, China

      Xu, Man; Lao, Jiaqiang; Yin, Ping; Hou, Jiang; Zhou, Yun; Huang, Jiao; Liu, Bing; Chen, Ruoling; Ke, Li; Chen, Hongying; et al. (BMJ, 2019-07-12)
      © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Objectives Previous studies suggested the association of air pollution with initial Mycobacterium tuberculosis infection and the disease development. However, few studies have been conducted on air pollution and initial tuberculosis (TB) consults using short-interval data. We investigated the weekly association between air pollution and initial TB outpatient visits. Methods We used a Poisson regression model combined with a distributed lag non-linear model to conduct a time-series study with weekly air pollution data and TB cases during 2014-2017 in Wuhan, China. Results A 10 μg/m 3 increase in NO 2 (nitrogen dioxide) was associated with 11.74% (95% CI: 0.70 to 23.98, lag 0-1 weeks), 21.45% (95% CI: 1.44 to 45.41, lag 0-2 weeks) and 12.8% (95% CI: 0.97 to 26.02, lag 0-1 weeks) increase in initial TB consults among all patients with TB, old patients (≥60 years old) and male ones, respectively. A 10 μg/m 3 increase in SO 2 (sulfur dioxide) was associated with -22.23% (95% CI: -39.23 to -0.49, lag 0-16 weeks), -28.65% (95% CI: -44.3 to -8.58, lag 0-16 weeks), -23.85 (95% CI: -41.79 to -0.37, lag 0-8 weeks) and -23.82% (95% CI: -41.31 to -1.11, lag 0-16 weeks) increase in initial TB consults among the total, young (aged 15-59 years old), old and male patients, respectively. In old patients, a 0.1 mg/m 3 increase in CO (carbon monoxide) and a 10 μg/m 3 increase in PM 2.5 (particulate matter) were separately associated with 42.32% (95% CI: 1.16 to 100.22, lag 0-16 weeks) and 17.38% (95% CI: 0.28 to 37.38, lag 0-16 weeks) increases in TB consults. Conclusion Our study first highlighted the importance of weekly association between air pollution and the risk of initial TB consults, which is helpful for the arrangements of TB screening and medical assistance.
    • 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.
    • Cardiovascular disease risk factors in habitual exercisers, lean sedentary men and abdominally obese sedentary men.

      O'Donovan, G.; Owen, A.; Kearney, E. M.; Jones, D. W.; Nevill, Alan M.; Woolf-May, K.; Bird, Steve (nature.com, 2005)
      OBJECTIVE: To investigate whether the favourable cardiovascular disease (CVD) risk factor profile of habitual exercisers is attributable to exercise or leanness. DESIGN: Cross-sectional study of 113 nonsmoking men aged 30-45 y. CVD risk factors were compared in exercisers (n=39) and sedentary men (n=74), and in subgroups of lean exercisers (n=37), lean sedentary men (n=46) and obese sedentary men (n=28). Waist girth was used to identify lean (<100 cm) and abdominally obese (> or =100 cm) subgroups. MEASUREMENTS: Blood pressure, physical activity (7-day recall), physical fitness (maximum oxygen consumption) and fasted lipoproteins, apolipoprotein (apo) B, triglycerides, glucose and fibrinogen. RESULTS: Exercisers were fitter and leaner than sedentary men and had a better CVD risk factor profile. Total cholesterol, LDL-cholesterol and apo B concentrations were lower in lean exercisers than in lean sedentary men, suggesting that exercise influences these risk factors. Indeed, time spent in vigorous activity was the only significant predictor of total cholesterol and LDL-cholesterol in multiple linear regression models. Exercise status had little influence on triglycerides and HDL-cholesterol (HDL-C), and unfavourable levels were only evident among obese sedentary men. Waist girth was the sole predictor of triglycerides and HDL-C, explaining 44 and 31% of the variance, respectively. CONCLUSIONS: These findings suggest that the CVD risk factor profile of habitual exercisers is attributable to leanness and exercise. Leanness is associated with favourable levels of HDL-C and triglycerides, while exercise is associated with lower levels of total cholesterol, LDL-cholesterol and apo B.
    • Clinical characteristics and outcomes of IgD myeloma: experience across UK national trials

      Agbuduwe, Charles; Iqbal, Gulnaz; Cairns, David; Menzies, Tom; Dunn, Janet; Gregory, Walter; Kaiser, Martin; Owen, Roger; Pawlyn, Charlotte; Child, J. Anthony; et al. (American Society of Hematology, 2022-07-05)
      Immunoglobulin D (IgD) myeloma is a subtype often considered to have adverse features and inferior survival, but there is a paucity of data from large clinical studies. We compare the clinical characteristics and outcomes of patients with IgD myeloma from UK phase 3 myeloma trials analyzed in 2 groups: old (1980-2002) and recent (2002-2016) clinical trials, based on the time of adoption of novel myeloma therapies. Patients with IgD myeloma comprised 44 of 2789 (1.6%) and 70 of 5773 (1.2%) of the old and recent trials, respectively. Overall, IgD myeloma was associated with male predominance, low-level paraproteinemia (,10g/L), and l light chain preference. The frequency of ultra-high-risk cytogenetics was similar in IgD myeloma compared with other subtypes (4.3% vs 5.3%, P . .99). Despite the old trial series being a younger group (median age: 59 vs 63 years, P 5 .015), there was a higher frequency of bone lesions, advanced stage at diagnosis, worse performance status, and severe renal impairment compared with the recent trials. Furthermore, the early mortality rate was significantly higher for the old trial series (20% vs 4%, P 5 .01). The overall response rate following induction therapy was significantly higher in the recent trials (89% vs 43%, P, .0001), and this was consistent with improved median overall survival (48 months; 95% confidence interval [CI] 35-67 months vs 22 months; 95% CI, 16-29 months). Survival outcomes for IgD myeloma have significantly improved and are now comparable to other myeloma types because of earlier diagnosis, novel therapies, and improved supportive care.
    • 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.
    • 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.