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Showing papers by "St Thomas' Hospital published in 2006"


Journal ArticleDOI
TL;DR: The EPIC study is the largest population-based survey to assess prevalence rates of OAB, UI, and other LUTS in five countries and is the first study to evaluate these symptoms simultaneously using the 2002 ICS definitions.

2,275 citations


Journal ArticleDOI
TL;DR: An international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest) found NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease.
Abstract: Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.

874 citations


Journal ArticleDOI
TL;DR: Concomitant supplementation with vitamin C and vitamin E does not prevent pre-eclampsia in women at risk, but does increase the rate of babies born with a low birthweight, and use of these high-dose antioxidants is not justified in pregnancy.

694 citations


Journal ArticleDOI
TL;DR: It is proposed that an inappropriate activation and positioning of neutrophils within the microvasculature contributes to the pathological manifestations of multiple organ failure and it is suggested that targeting neutrophil and their interactions with blood vessel walls could be a worthwhile therapeutic strategy for sepsis.

591 citations


Journal ArticleDOI
TL;DR: The general principles of infection control should be adopted for patients with MRSA, including patient isolation and the appropriate cleaning and decontamination of clinical areas, and the inappropriate or unnecessary use of antibiotics should be avoided.

563 citations


Journal ArticleDOI
TL;DR: Benefits of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed.
Abstract: Rheumatic diseases in women of childbearing years may necessitate drug treatment during a pregnancy, to control maternal disease activity and to ensure a successful pregnancy outcome. This survey is based on a consensus workshop of international experts discussing effects of anti-inflammatory, immunosuppressive and biological drugs during pregnancy and lactation. In addition, effects of these drugs on male and female fertility and possible long-term effects on infants exposed to drugs antenatally are discussed where data were available. Recommendations for drug treatment during pregnancy and lactation are given.

506 citations


Journal ArticleDOI
TL;DR: The increasing use in the literature of unvalidated cut-off scores on the Edinburgh Depression Scale (EDS/EPDS), as well as different wording and formatting in the scale, is highlighted to highlight possible reasons for these ‘errors’.
Abstract: Objectives: i) To highlight the increasing use in the literature of unvalidated cut-off scores on the Edinburgh Depression Scale (EDS/EPDS), as well as different wording and formatting in the scale; ii) to investigate and discuss the possible impact of using an unvalidated cut-off score; iii) to highlight possible reasons for these ‘errors’; and iv) to make recommendations to clinicians and researchers who use the EDS/EPDS. Method: A convenience sample of studies that have used unvalidated cut-off scores, or different formatting, are cited as evidence that these types of ‘errors’ are occurring fairly frequently. Examination of previous data from one of the authors is undertaken to determine the effect of using an unvalidated cut-off score. Summary: Many studies report rates of high scorers on the EDS/EPDS using different cut-off scores to the validated ones. The effect of doing this on the overall rate can be substantial. The effect of using different formatting is not known, though excluding items from the EDS/EPDS must also make a substantial difference. Recommendations: We recommend that i) the validated score of 13 or more is used when reporting on probable major depression in postnatal English-speaking women, and 15 or more when reporting on antenatal English-speaking women; ii) that the wording used is “13 or more” (or equivalent), and not other terms that may cause confusion (e.g., ‘>12’; ‘more than 12’; ‘13’ etc), iii) if a different cut-off score to the validated one is used, a clear explanation is given as to why this has been done; and iv) that the scale should be worded and formatted as originally described by its authors.

492 citations


Journal ArticleDOI
TL;DR: The most practical approach to risk prediction is based on a simple model incorporating renal function and diabetes mellitus, using data from large databases of percutaneous coronary intervention patients.
Abstract: In order to make appropriate decisions about clinical management, it is important for physicians to be able to stratify patients according to their risk for contrast-induced nephropathy (CIN). The most important risk marker for nephropathy after exposure to iodinated contrast media is preexisting renal impairment. The risk of CIN is elevated and becomes clinically important in patients with chronic kidney disease characterized by an estimated glomerular filtration rate <60 mL/min per 1.73 m(2). In patients with renal impairment, diabetes mellitus amplifies the risk of CIN and complicates postprocedure management. Other markers associated with an increased risk of CIN include cardiovascular disease, periprocedural hemodynamic instability, use of nephrotoxic drugs, and anemia. The effect of risk factors is additive, and the presence of multiple risk factors in the same patient can create a very high risk for CIN and acute renal failure requiring dialysis. Risk models incorporating baseline and periprocedural characteristics have been developed using data from large databases of percutaneous coronary intervention patients. These schemes are potentially valuable, but at present the most practical approach to risk prediction is based on a simple model incorporating renal function and diabetes mellitus.

453 citations


Journal ArticleDOI
TL;DR: Although risedronate did not improve signs or symptoms of OA, nor did it alter progression of Oa, a reduction in the level of a marker of cartilage degradation was observed and a sustained clinically relevant improvement in signs and symptoms was observed.
Abstract: Objective Bisphosphonates have slowed the progression of osteoarthritis (OA) in animal models and have decreased pain in states of high bone turnover. The Knee OA Structural Arthritis (KOSTAR) study, which is the largest study to date investigating a potential structure-modifying OA drug, tested the efficacy of risedronate in providing symptom relief and slowing disease progression in patients with knee OA. Methods The study group comprised 2,483 patients with medial compartment knee OA and 2–4 mm of joint space width (JSW), as determined using fluoroscopically positioned, semiflexed-view radiography. Patients were enrolled in 2 parallel 2-year studies in North America and the European Union. These studies evaluated the efficacy of risedronate at dosages of 5 mg/day, 15 mg/day, 35 mg/week (in Europe), and 50 mg/week (in North America) compared with placebo in reducing signs and symptoms, as measured by the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and patient global assessment (PGA) scores, and in slowing radiographic progression. Results A reduction of ∼20% in signs and symptoms, as measured by WOMAC subscales and PGA scores, was observed in all groups, with no treatment effect of risedronate demonstrated. Risedronate did not significantly reduce radiographic progression as measured by decreased JSW or using a dichotomous definition of progression (joint space loss of ≥0.6 mm). Thirteen percent of patients receiving placebo demonstrated significant disease progression over 2 years. A dose-dependent reduction in the level of C-terminal crosslinking telopeptide of type II collagen, a cartilage degradation marker associated with progressive OA, was seen in patients who received risedronate. No increase in the number of adverse events was demonstrated for risedronate compared with placebo. Conclusion Although risedronate (compared with placebo) did not improve signs or symptoms of OA, nor did it alter progression of OA, a reduction in the level of a marker of cartilage degradation was observed. A sustained clinically relevant improvement in signs and symptoms was observed in all treatment and placebo groups.

388 citations



Journal ArticleDOI
Gary French1
TL;DR: The methods by which bactericidal and bacteriostatic properties are defined and tested are outlined, the potential importance of bactericidal therapy in MRSA and other infections are discussed and the potential role of daptomycin in treatment is examined.
Abstract: Over the last decade, methicillin-resistant Staphylococcus aureus (MRSA) strains have emerged as serious pathogens. These strains are often multiresistant to several antibiotic classes and are a major cause of serious hospital- and now community-acquired infections and associated morbidity and mortality. As a result of increasing antimicrobial resistance, glycopeptides, such as vancomycin, are widely used as first-line therapy for serious MRSA infections. However, the emergence of glycopeptide tolerance and resistance has complicated treatment and there remains a clinical need for new antibiotics with suitable pharmacokinetic properties with activity against MRSA and other Gram-positive pathogens. Infections caused by MRSA and other bacteria usually respond as well to bacteriostatic agents as to bactericidal ones. Nevertheless, there is evidence that rapid bacterial killing has potential clinical advantages over bacteriostatic therapy in certain infections. Daptomycin, the first of the cyclic lipopeptides, shows rapid bactericidal activity against S. aureus, including strains tolerant or resistant to other agents. This review outlines the methods by which bactericidal and bacteriostatic properties are defined and tested, discusses the potential importance of bactericidal therapy in MRSA and other infections and examines the potential role of daptomycin in treatment.

Journal ArticleDOI
TL;DR: Contrast-induced nephropathy (CIN) as discussed by the authors is a potentially serious complication of the use of iodinated contrast media in patients at risk of acute renal injury.
Abstract: Contrast-induced nephropathy (CIN), usually defined as an increase in serum creatinine of 0.5 mg/dL (44.2 μmol/L), or a 25% increase from the baseline value 48 hours after the procedure, is a common and potentially serious complication of the use of iodinated contrast media in patients at risk of acute renal injury. It is an important cause of hospital-acquired renal failure, responsible for approximately 11% of cases. CIN may be difficult to distinguish from cholesterol embolization, another cause of postprocedure renal impairment. The reported incidence of CIN varies depending on the patient population studied. The impact of postprocedural renal impairment on clinical outcomes has been evaluated most extensively in patients undergoing percutaneous coronary intervention. CIN is associated with increased mortality both in hospital and at 1 year. A higher incidence of in-hospital and late cardiovascular events, as well as longer hospital stays, has been reported in patients developing CIN. In a small proportion of patients, CIN is severe enough to require dialysis, and these patients have a particularly poor prognosis. Many of the risk markers for CIN are also predictive of a worse prognosis.

Journal ArticleDOI
TL;DR: It is demonstrated for the first time in a prospective study that synovial membrane cytokine mRNA expression is predictive of joint damage progression in RA.
Abstract: OBJECTIVE The primary aim of this prospective 2-year study was to explain the wide variability in joint damage progression in patients with rheumatoid arthritis (RA) from measures of pathologic changes in the synovial membrane. METHODS Patients underwent clinical measurements and joint damage assessments by magnetic resonance imaging (MRI) and radiography at enrollment and at year 2. Synovial membrane was obtained by knee biopsy and assessed histologically by hematoxylin and eosin staining. Interleukin-1beta (IL-1beta), IL-10, IL-16, IL-17, RANKL, tumor necrosis factor alpha (TNFalpha), and interferon-gamma (IFNgamma) messenger RNA (mRNA) expression was determined by quantitative reverse transcription-polymerase chain reaction. The relationship of synovial measurements to joint damage progression was determined by multivariate analysis. RESULTS Sixty patients were enrolled. Histologic features had no relationship to damage progression. Multivariate analysis by several different methods consistently demonstrated that synovial membrane mRNA levels of IL-1beta, TNFalpha, IL-17, and IL-10 were predictive of damage progression. IL-17 was synergistic with TNFalpha. TNFalpha and IL-17 effects were most pronounced with shorter disease duration, and IL-1beta effects were most pronounced with longer disease duration. IFNgamma was protective. These factors explained 57% of the MRI joint damage progression over 2 years. CONCLUSION We have demonstrated for the first time in a prospective study that synovial membrane cytokine mRNA expression is predictive of joint damage progression in RA. The findings for IL-1beta and TNFalpha are consistent with results of previous clinical research, but the protective role of IFNgamma, the differing effects of disease duration, and IL-17-cytokine interactions had only been demonstrated previously by animal and in vitro research. These findings explain some of the variability of joint damage in RA and identify new targets for therapy.

Journal ArticleDOI
TL;DR: High-osmolar dyes directly impair the autoregulatory capacity of the kidney through a loss of nitric oxide production and lead to overt acute tubular necrosis and the syndrome of CIN.
Abstract: Contrast-induced nephropathy (CIN) is the third leading cause of acute kidney injury in hospitalized patients and is associated with significant patient morbidity. The pathogenesis of CIN is complex and not fully understood, but iodinated contrast agents induce intense and prolonged vasoconstriction at the corticomedullary junction of the kidney. Moreover, high-osmolar dyes directly impair the autoregulatory capacity of the kidney through a loss of nitric oxide production. These effects, coupled with direct tubular toxicity of contrast media, lead to overt acute tubular necrosis and the syndrome of CIN.

Journal ArticleDOI
TL;DR: The Age-Related Eye Disease Study (AREDS), a randomized clinical trial, showed a significantly lower incidence of late ARM in a cohort of patients with drusen maculopathy treated with high doses of antioxidants than in a placebo group, creating a platform for the search for new prophylactic and therapeutic measures to alleviate or prevent photoreceptor and RPE degeneration in ARM.
Abstract: The pathogenesis of age-related maculopathy (ARM), the most common cause of visual loss after the age of 60 years, is indeed a complicated scenario that involves a variety of hereditary and environmental factors The pathological cellular and molecular events underlying retinal photochemical light damage, including photoreceptor apoptosis, have been analysed in experimental animal models Studies of age-related alterations of the retina and photoreceptors, the accumulation of lipofuscin in retinal pigment epithelium (RPE) cells, and the formation of drusen have greatly contributed to our knowledge A new concept of an inflammatory response to drusen has emerged, suggesting immunogenic and systemic reactions in Bruch's membrane and the subretinal space Oxidative stress and free radical damage also impact on the photoreceptors and RPE cells in the ageing eye Based on the photoelectric effect, a fundamental concept in quantum physics, the consequences of high-energy irradiation have been analysed in animal models and cell culture Short-wavelength radiation (rhodopsin spectrum), and the blue light hazard (excitation peak 440 nm), have been shown to have a major impact on photoreceptor and RPE function, inducing photochemical damage and apoptotic cell death Following cataract surgery, there is a dramatic change in ocular transmittance In aphakic or pseudophakic eyes (with clear intraocular lenses), high-energy (blue) and ultraviolet-A radiation strikes the retina Epidemiological data indicate a significantly increased 5-year incidence of late ARM in non-phakic eyes compared with phakic eyes In recent years, putative prophylactic measures against ARM have emerged The implantation of 'yellow' intraocular lenses (IOLs) that absorb high-energy blue radiation is, from a theoretical point of view, the most rational approach, and, from a practical point of view, is easy to accomplish With increasing age, RPE cells accumulate lipofuscin (chromophore A2E) It is noteworthy that the yellow IOL not only protects A2E-laden human RPE cells from blue light (peak 430 nm) damage, but also alleviates the detrimental effects of green (peak 550 nm) and white light A prophylactic treatment using antioxidants is aimed at counteracting oxidative stress and free radical cellular damage The Age-Related Eye Disease Study (AREDS), a randomized clinical trial, showed a significantly lower incidence of late ARM in a cohort of patients with drusen maculopathy treated with high doses of antioxidants than in a placebo group In recent years, considerable progress in retinal research has been achieved, creating a platform for the search for new prophylactic and therapeutic measures to alleviate or prevent photoreceptor and RPE degeneration in ARM

Journal ArticleDOI
TL;DR: Recent multinational studies in safety and drug interaction data for three phosphodiesterase type 5 (PDE5) inhibitors are reviewed, with emphasis on the safety of these agents in men with ED and concomitant cardiovascular disease.

Journal ArticleDOI
TL;DR: Low SES, in addition to the harmful effects of smoking, obesity and lack of exercise, appears to have an impact on telomere length.
Abstract: Low socio-economic status (SES) is associated with a shortened life expectancy, but its effect on aging is unknown. The rate of white-blood-cell (WBC) telomere attrition may be a biological indicator of human aging. We tested the hypothesis that SES is associated with telomere attrition independent of known risk factors influencing the aging process. We studied 1552 female twins. A venous blood sample was taken from each twin and isolated WBCs used for extraction of DNA. Terminal restriction fragment length (TRFL) was measured. Questionnaire data were collected on occupation, education, income, smoking, exercise, height and weight. Standard multiple linear regression and multivariate analyses of variance tested for associations between SES and TRFL, adjusting for covariates. A discordant twin analysis was conducted on a subset to verify findings. WBC telomere length was highly variable but significantly shorter in lower SES groups. The mean difference in TRFL between nonmanual and manual SES groups was 163.2 base pairs (bp) of which 22.9 bp (approximately 14%) was accounted for by body mass index, smoking and exercise. Comparison of TRFL in the 17 most discordant SES twin pairs confirmed this difference. Low SES, in addition to the harmful effects of smoking, obesity and lack of exercise, appears to have an impact on telomere length.

Journal ArticleDOI
TL;DR: In this paper, the authors evaluated the frequency and clinical characteristics of pruritic dermatoses in pregnancy and to assess a rationalized classification, and proposed classifying the dermatoses of pregnancy as PG, PEP, AEP, and ICP.
Abstract: Objectives We sought to evaluate the frequency and clinical characteristics of pruritic dermatoses in pregnancy and to assess a rationalized classification. Methods Data of 505 pregnant patients seen at two university-based dermatologic hospitals (1994-2004) were retrospectively studied. Results Diagnoses included eczema in pregnancy (49.7%), polymorphic eruption of pregnancy (PEP) (21.6%), pemphigoid gestationis (PG) (4.2%), intrahepatic cholestasis of pregnancy (ICP) (3%), prurigo of pregnancy (0.8%), pruritic folliculitis of pregnancy (0.2%), and miscellaneous dermatoses (20.6%). Eczema in pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy showed considerable overlap and were summarized as atopic eruption of pregnancy (AEP). While PEP, PG, and ICP presented in late pregnancy, AEP started significantly earlier. Primigravidae and multiple gestations were characteristic for PEP, abdominal involvement for PEP and PG, and a history of affected pregnancies for ICP. Limitations This was a retrospective study. Conclusion We propose classifying the dermatoses of pregnancy as PG, PEP, AEP, and ICP. Stereotypic immunofluorescence and laboratory findings are diagnostic of PG and ICP, whereas distinct clinical characteristics facilitate discrimination between PEP and AEP.

Journal ArticleDOI
TL;DR: It is found that illness perceptions of AMI patients who view their condition as controllable, as symptomatic, and with severe consequences, and who feel that they understand their condition are more likely to attend cardiac rehabilitation.

Journal ArticleDOI
20 Dec 2006-PLOS ONE
TL;DR: Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality, according to this collaborative study.
Abstract: Background A sedentary lifestyle remains a major threat to health in contemporary societies. To get more insight in the relative contribution of genetic and environmental influences on individual differences in exercise participation, twin samples from seven countries participating in the GenomEUtwin project were used. Methodology Self-reported data on leisure time exercise behavior from Australia, Denmark, Finland, Norway, the Netherlands, Sweden and United Kingdom were used to create a comparable index of exercise participation in each country (60 minutes weekly at a minimum intensity of four metabolic equivalents). Principal Findings Modest geographical variation in exercise participation was revealed in 85,198 subjects, aged 19–40 years. Modeling of monozygotic and dizygotic twin resemblance showed that genetic effects play an important role in explaining individual differences in exercise participation in each country. Shared environmental effects played no role except for Norwegian males. Heritability of exercise participation in males and females was similar and ranged from 48% to 71% (excluding Norwegian males). Conclusions Genetic variation is important in individual exercise behavior and may involve genes influencing the acute mood effects of exercise, high exercise ability, high weight loss ability, and personality. This collaborative study suggests that attempts to find genes influencing exercise participation can pool exercise data across multiple countries and different instruments

Journal ArticleDOI
TL;DR: This is the first report of loci, mapped in a sample of healthy individuals, that influence mean telomere variation in humans, and significant linkage was observed on chromosome 14.
Abstract: Telomeres play a central role in cellular senescence and cancer pathobiology and are associated with age-related diseases such as atherosclerosis and dementia. Telomere length varies between individuals of the same age, is influenced by DNA-damaging factors such as oxidative stress, and is heritable. We performed a quantitative-trait linkage analysis using an ∼10-cM genomewide map for mean leukocyte terminal-restriction fragment (TRF) lengths measured by Southern blotting, in 2,050 unselected women aged 18–80 years, comprising 1,025 complete dizygotic twin pairs. Heritability of mean batch-adjusted TRF was 36% (95% confidence interval [CI] 18%–48%), with a large common environmental effect of 49% (95% CI 40%–58%). Significant linkage was observed on chromosome 14 (LOD 3.9) at 14q23.2, and suggestive linkage at 10q26.13 (LOD 2.4) and 3p26.1 (LOD 2.7). This is the first report of loci, mapped in a sample of healthy individuals, that influence mean telomere variation in humans.

Journal ArticleDOI
TL;DR: The CIN Consensus Working Panel considered that, of the pharmacologic agents that have been evaluated, theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, ascorbic acid, and prostaglandin E(1) deserve further evaluation.
Abstract: In view of the clinical importance of contrast-induced nephropathy (CIN), numerous potential risk-reduction strategies have been evaluated. Adequate intravenous volume expansion with isotonic crystalloid (1.0-1.5 mL/kg per hr) for 3-12 hours before the procedure and continued for 6-24 hours afterward can lessen the probability of CIN in patients at risk. There are insufficient data on oral fluids (as opposed to intravenous volume expansion) as a CIN-prevention strategy. No adjunctive medical or mechanical treatment has been proved to be efficacious in reducing risk for CIN. Prophylactic hemodialysis and hemofiltration have not been validated as effective strategies. The CIN Consensus Working Panel considered that, of the pharmacologic agents that have been evaluated, theophylline, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), ascorbic acid, and prostaglandin E(1) deserve further evaluation. N-acetylcysteine is not consistently effective in reducing the risk for CIN. Fenoldopam, dopamine, calcium channel blockers, atrial natriuretic peptide, and l-arginine have not been shown to be effective. Use of furosemide, mannitol, or an endothelin receptor antagonist is potentially detrimental. Nephrotoxic drugs should be withdrawn before contrast administration in patients at risk for CIN.

Journal ArticleDOI
TL;DR: It is document successful reconstitution of immune function in a child with the adenosine deaminase (ADA)-deficient form of severe combined immunodeficiency (SCID) following hematopoietic stem cell (HSC) gene therapy.

Journal ArticleDOI
TL;DR: Attention at pubs/clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with increased risk for meningococcal carriage, but age, sex, social deprivation, home crowding, or school characteristics had little or no effect.
Abstract: Understanding predisposing factors for meningococcal carriage may identify targets for public health interventions. Before mass vaccination with meningococcal group C conjugate vaccine began in autumn 1999, we took pharyngeal swabs from ≈14,000 UK teenagers and collected information on potential risk factors. Neisseria meningitidis was cultured from 2,319 (16.7%) of 13,919 swabs. In multivariable analysis, attendance at pubs/clubs, intimate kissing, and cigarette smoking were each independently and strongly associated with increased risk for meningococcal carriage (p<0.001). Carriage in those with none of these risk factors was 7.8%, compared to 32.8% in those with all 3. Passive smoking was also linked to higher risk for carriage, but age, sex, social deprivation, home crowding, or school characteristics had little or no effect. Social behavior, rather than age or sex, can explain the higher frequency of meningococcal carriage among teenagers. A ban on smoking in public places may reduce risk for transmission.

Journal ArticleDOI
TL;DR: It is demonstrated that type I protein kinase A is redoxactive, forming an interprotein disulfide bond between its two regulatory RI subunits in response to cellular hydrogen peroxide, which causes a subcellular translocation and activation of the kinase, resulting in phosphorylation of established substrate proteins.

Journal ArticleDOI
David D'Cruz1
13 Apr 2006-BMJ
TL;DR: Advances in the epidemiology, genetics, cardiovascular risks, lupus nephritis, CNS disease, the antiphospholipid syndrome, assessment of disease activity and damage, and pregnancy related and quality of life issues are drawn attention.
Abstract: Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder with various clinical presentations. It is prevalent among young women with a peak age of onset between the late teens and early 40s and a female to male ratio of 9:1. It is more common in certain ethnic groups, such as people with African or Asian ancestry. One study estimated the prevalence of lupus as 27.7/100 000 and as high as 206/100 000 in Afro-Caribbean women.1 SLE is a chronic illness that may be life threatening when major organs are affected but more commonly results in chronic debilitating ill health. No single cause for SLE has been identified, though factors such as sunlight and drugs may precipitate the condition, and there is a complex genetic basis. Autoantibodies may be present for many years before the clinical onset of the disease, and there may be increasing numbers of antibodies just before symptoms develop, pointing to a multi-factorial pathogenesis.2 I used PubMed to identify references, supplemented by review articles and lectures from the American College of Rheumatology annual conference in 2005. Search terms included systemic lupus erythematosus, antiphospholipid syndrome, lupus nephritis, central nervous system disease in lupus, and fatigue. Articles were selected according to their impact on clinical practice. It is not possible to give a comprehensive guide to the management of all the possible complications of lupus so I have focused on areas where there is a consensus on management or where there have been major new developments. The widely recognised presentation of a young woman with inflammatory arthritis and a butterfly facial rash is uncommon. Non-specific symptoms of fatigue, malaise, oral ulcers, arthralgia, photosensitive skin rashes, lymphadenopathy, pleuritic chest pains, headache, paraesthesiae, symptoms of dry eyes and mouth, Raynaud's phenomenon, and mild hair loss are more likely …

Journal ArticleDOI
TL;DR: The results suggest that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK-1/ERK proteins, and the p38 MAP kinase-dependent nuclear translocation and activation of NF-kappaB/Rel proteins.
Abstract: Objective Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL). In patients with primary APS, expression of tissue factor (TF) on the surface of monocytes is increased, which may contribute to thrombosis in these patients. However, the intracellular mechanisms involved in aPL-mediated up-regulation of TF on monocytic cells are not understood. This study was undertaken to investigate the intracellular signals induced by aPL that mediate TF activation in monocytes from APS patients. Methods We analyzed, both in vivo and in vitro, aPL interactions with proteins that have signaling functions, including mitogen-activated protein kinases (MAP kinases) and NF-κB/Rel proteins. Results In vivo studies demonstrated significantly higher levels of both TF messenger RNA and TF protein in monocytes from APS patients compared with controls. At the molecular level, increased proteolysis of IκBα and activation of NF-κB were observed. Constitutive activation of both p38 and ERK-1 MAP kinases was also found. Treatment of normal monocytes with aPL activated ERK-1 and p38 MAP kinases, as well as the IκB/NF-κB pathway, in a dose-dependent manner. NF-κB activation and IκBα degradation induced by aPL were inhibited by the NF-κB inhibitor SN50 and the p38 MAP kinase inhibitor SB203580, thus suggesting crosstalk between these pathways. However, the MEK-1/ERK inhibitor PD98059 did not affect aPL-induced NF-κB binding activity. TF expression induced by aPL was significantly inhibited by combined treatment with the 3 inhibitors. Conclusion Our results suggest that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK-1/ERK proteins, and the p38 MAP kinase–dependent nuclear translocation and activation of NF-κB/Rel proteins.

Journal ArticleDOI
TL;DR: In this paper, a reference gliadin was obtained from 28 wheat cultivars representative of the three main European wheat producing countries, France, UK and Germany, which were selected as a source for the preparation of a reference Gliadin.

Journal ArticleDOI
TL;DR: The use of gadolinium or CO(2) as alternative contrast media to avoid the risk of nephrotoxicity cannot be substantiated by clinical trials and therefore cannot be recommended.
Abstract: Various properties of iodinated contrast media (osmolality, ionic versus nonionic, and viscosity) may contribute to contrast-induced nephropathy (CIN). Therefore, the choice of contrast medium affects the risk for CIN. There is good evidence that low-osmolar contrast media are less nephrotoxic than high-osmolar contrast media in patients at increased risk for CIN who receive intra-arterial iodinated contrast. Current evidence suggests that nonionic isosmolar contrast presents the lowest risk for CIN in patients with chronic kidney disease (CKD), particularly in those patients with diabetes mellitus. Intra-arterial administration of contrast media may be associated with a greater risk for CIN above that observed with intravenous administration. The use of gadolinium or CO 2 as alternative contrast media to avoid the risk of nephrotoxicity cannot be substantiated by clinical trials and therefore cannot be recommended. Most studies show that, within a class, higher volumes (>100 mL) of iodinated contrast medium are associated with a higher risk for CIN. However, in patients at high risk, such as those with CKD and diabetes, even small volumes of contrast medium can have adverse effects on renal function.

Journal ArticleDOI
TL;DR: Covered CP stents may be used as the therapy of choice in patients with complications after CoA repairs, whereas they provide a safe alternative to conventional stenting in patientswith severe and complex CoA lesions or advanced age.