Michael Doherty

Publications (10)54.95 Total impact

• Source

  Available from: Tim L Jansen

  Article: Gout: why is this curable disease so seldom cured?

  Michael Doherty, Tim L Jansen, George Nuki, Eliseo Pascual, Fernando Perez-Ruiz, Leonardo Punzi, Alexander K So, Thomas Bardin
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  ABSTRACT: Gout is the most common inflammatory arthritis and one in which pathogenesis and risk factors are best understood. One of the treatment objectives in current guidelines is 'cure'. However, audits show that only a minority of patients with gout receive adequate advice and treatment. Suboptimal care and outcomes reflect inappropriately negative perceptions of the disease, both in patients and providers. Historically, gout has been portrayed as a benign and even comical condition that is self-inflicted through overeating and alcohol excess. Doctors often focus on managing acute attacks rather than viewing gout as a chronic progressive crystal deposition disease. Urate-lowering treatment is underprescribed and often underdosed. Appropriate education of patients and doctors, catalysed by recent introduction of new urate-lowering treatments after many years with no drug development in the field, may help to overcome these barriers and improve management of this easily diagnosed and curable form of potentially severe arthritis.
  Annals of the rheumatic diseases 08/2012; 71(11):1765-70. · 8.11 Impact Factor
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  Available from: Martha Castano Betancourt

  Article: Genome-wide association and functional studies identify the DOT1L gene to be involved in cartilage thickness and hip osteoarthritis.

  Martha C Castaño Betancourt, Frederic Cailotto, Hanneke J Kerkhof, Frederique M F Cornelis, Sally A Doherty, Deborah J Hart, Albert Hofman, Frank P Luyten, Rose A Maciewicz, Massimo Mangino, [......], Fernando Rivadeneira, Maggie Wheeler, Weiya Zhang, Nigel Arden, Tim D Spector, Andre G Uitterlinden, Michael Doherty, Rik J U Lories, Ana M Valdes, Joyce B J van Meurs
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  ABSTRACT: Hip osteoarthritis (HOA) is one of the most disabling and common joint disorders with a large genetic component that is, however, still ill-defined. To date, genome-wide association studies (GWAS) in osteoarthritis (OA) and specifically in HOA have yielded only few loci, which is partly explained by heterogeneity in the OA definition. Therefore, we here focused on radiographically measured joint-space width (JSW), a proxy for cartilage thickness and an important underlying intermediate trait for HOA. In a GWAS of 6,523 individuals on hip-JSW, we identified the G allele of rs12982744 on chromosome 19p13.3 to be associated with a 5% larger JSW (P = 4.8 × 10(-10)). The association was replicated in 4,442 individuals from three United Kingdom cohorts with an overall meta-analysis P value of 1.1 × 10(-11). The SNP was also strongly associated with a 12% reduced risk for HOA (P = 1 × 10(-4)). The SNP is located in the DOT1L gene, which is an evolutionarily conserved histone methyltransferase, recently identified as a potentially dedicated enzyme for Wnt target-gene activation in leukemia. Immunohistochemical staining of the DOT1L protein in mouse limbs supports a role for DOT1L in chondrogenic differentiation and adult articular cartilage. DOT1L is also expressed in OA articular chondrocytes. Silencing of Dot1l inhibited chondrogenesis in vitro. Dot1l knockdown reduces proteoglycan and collagen content, and mineralization during chondrogenesis. In the ATDC5 chondrogenesis model system, DOT1L interacts with TCF and Wnt signaling. These data are a further step to better understand the role of Wnt-signaling during chondrogenesis and cartilage homeostasis. DOT1L may represent a therapeutic target for OA.
  Proceedings of the National Academy of Sciences 05/2012; 109(21):8218-23. · 9.68 Impact Factor
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  Available from: Sandie Reader

  Article: A randomised controlled trial of ibuprofen, paracetamol or a combination tablet of ibuprofen/paracetamol in community-derived people with knee pain.

  Michael Doherty, Chris Hawkey, Michael Goulder, Iain Gibb, Nicola Hill, Sue Aspley, Sandie Reader
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  ABSTRACT: To compare the efficacy and safety of single versus combination non-prescription oral analgesics in community-derived people aged 40 years and older with chronic knee pain. A randomised, double-blind, four-arm, parallel-group, active controlled trial investigating short-term (day 10) and long-term (week 13) benefits and side-effects of four regimens, each taken three times a day: ibuprofen (400 mg); paracetamol (1000 mg); one fixed-dose combination tablet (ibuprofen 200 mg/paracetamol 500 mg); two fixed-dose combination tablets (ibuprofen 400 mg/paracetamol 1000 mg). There were 892 participants (mean age 60.6, range 40-84 years); 63% had radiographic knee osteoarthritis and 85% fulfilled American College of Rheumatology criteria for osteoarthritis. At day 10, two combination tablets were superior to paracetamol (p<0.01) for pain relief (determined by mean change from baseline in WOMAC pain; n=786). At 13 weeks, significantly more participants taking one or two combination tablets rated their treatment as excellent/good compared with paracetamol (p=0.015, p=0.0002, respectively; n=615). The frequency of adverse events was comparable between groups. However, by 13 weeks, decreases in haemoglobin (≥1 g/dl) were observed in some participants in all groups. Twice as many participants taking two combination tablets had this decrease compared with those on monotherapy (p<0.001; paracetamol, 20.3%; ibuprofen, 19.6%; one or two combination tablets, 24.1%, 38.4%, respectively). Ibuprofen/paracetamol combination analgesia, at non-prescription doses, confers modest short-term benefits for knee pain/osteoarthritis. However, in this population, paracetamol 3 g/day may cause similar degrees of blood loss as ibuprofen 1200 mg/day, and the combination of the two appears to be additive. Study no ISRCTN77199439.
  Annals of the rheumatic diseases 09/2011; 70(9):1534-41. · 8.11 Impact Factor
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  Available from: Tim L Jansen

  Article: International position paper on febuxostat.

  Tim L Jansen, Pascal Richette, Fernando Perez-Ruiz, Anne-Kathrin Tausche, Philip-André Guerne, Leonardo Punzi, Burkhard Leeb, Victoria Barskova, Till Uhlig, José Pimentão, Irena Zimmermann-Górska, Elisio Pascual, Thomas Bardin, Michael Doherty
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  ABSTRACT: This position paper aims to clarify the presumed place of febuxostat in the management of gout patients. Since this novel xanthine oxidase inhibitor is now available, an international group of gout experts decided to formulate an international consensus statement. This statement presents the place for this new xanthine oxidase inhibitor in the treatment of gout which may contribute to optimize treatment of gout patients in Europe and worldwide.
  Clinical Rheumatology 08/2010; 29(8):835-40. · 2.00 Impact Factor
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  Available from: Tim L Jansen

  Article: International position paper on febuxostat.

  Tim L Jansen, Pascal Richette, Fernando Perez-Ruiz, Anne-Kathrin Tausche, Philip-André Guerne, Leonardo Punzi, Burkhard Leeb, Victoria Barskova, Till Uhlig, José Pimentão, Irena Zimmermann-Górska, Eliseo Pascual, Thomas Bardin, Michael Doherty
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  ABSTRACT: This position paper aims to clarify the place of febuxostat in the management of gout patients. Since this novel xanthine oxidase inhibitor is now available, an international group of gout experts decided to formulate an international consensus statement based on the pivotal trials in which febuxostat was compared with allopurinol and recent randomized controlled trials with allopurinol targeting for a specific biochemical serum urate target. Treating to target has become important in gout as can be deduced from the European guidelines that were recently developed. This review presents the place for this new xanthine oxidase inhibitor in the treatment of gout, i.e., placing febuxostat in gout patients after proven intolerance or failing on allopurinol, dosed individually and optimally. This positioning of febuxostat after allopurinol (with or without uricosuric) failure contributes to optimize treatment of gout patients in Europe and worldwide.
  Clinical Rheumatology 04/2010; · 2.00 Impact Factor
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  Available from: oxfordjournals.org

  Article: Comment on: New insights into the epidemiology of gout: reply.

  Michael Doherty
  Rheumatology (Oxford, England) 01/2010; · 4.24 Impact Factor
• Article: Can we make gout crystal clear? Introduction.

  Thomas Bardin, Michael Doherty
  Rheumatology (Oxford, England) 05/2009; 48 Suppl 2:ii1. · 4.24 Impact Factor
• Article: New insights into the epidemiology of gout.

  Michael Doherty
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  ABSTRACT: Gout is a true crystal deposition disease caused by formation of monosodium urate crystals in joints and other tissues. It is a common inflammatory arthritis that has increased in prevalence in recent decades. Gout normally results from the interaction of genetic, constitutional and environmental risk factors. It is more common in men and strongly age related. A major determinant is the degree of elevation of uric acid levels above the saturation point for urate crystal formation, principally caused by inefficient renal urate excretion. Local joint tissue factors may influence the topography and extent of crystal deposition. Recent studies have provided information on dietary risk factors for gout: higher intakes of red meat, fructose and beer are independently associated with increased risk, whereas higher intakes of coffee, low-fat dairy products and vitamin C are associated with lower risk. Several renal urate transporters have been identified including URAT1 and SLC2A9 (GLUT9) and polymorphisms in these genes are associated with an increased risk of hyperuricaemia and gout. Many drugs influence serum uric acid levels through an effect on renal urate transport. Comorbidities, including the metabolic syndrome and impaired renal function are common in gout patients. The usual initial presentation of gout is with rapidly developing acute inflammatory monoarthritis, typically affecting the first MTP joint. If left untreated it may progress with recurrent acute attacks and eventual development of chronic symptoms and joint damage. New knowledge of the modifiable risk factors for gout can be integrated into the management strategy to optimize long-term patient outcomes.
  Rheumatology (Oxford, England) 05/2009; 48 Suppl 2:ii2-ii8. · 4.24 Impact Factor
• Article: An update on the epidemiology of calcium pyrophosphate dihydrate crystal deposition disease.

  Pascal Richette, Thomas Bardin, Michael Doherty
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  ABSTRACT: The aim of this review is to summarize recent research relating to the epidemiology of chondrocalcinosis (CC), including prevalence of CC, the association between CC and OA, familial forms of CC and diseases associated with CC. We searched MEDLINE for articles published in English from 1998 to 2008 using MEsH terms covering all aspects of the epidemiology of CC. Aging is the main risk factor for the occurrence of sporadic CC. Prevalence of CC varies from 7 to 10% in people aged approximately 60 years and shows equal sex distribution. There is a positive association between CC and OA, but CC does not appear to be a risk factor for subsequent structural progression in terms of cartilage loss. Mutations in the ankylosis human (ANKH) gene have been identified as a cause of familial CC in some kindreds. There is good evidence that hereditary haemochromatosis, hyperparathyroidism and hypomagnesaemia are metabolic disorders that predispose to secondary CC. In conclusion, sporadic CC is a common condition in the elderly and frequently associates with OA. Primary metabolic disorders or familial predisposition are uncommon but should be considered if CC occurs before 55 years of age or if there is florid polyarticular CC. After the age of 55 years, hyperparathyroidism should be considered in all patients.
  Rheumatology (Oxford, England) 05/2009; 48(7):711-5. · 4.24 Impact Factor
• Article: Aspiration of normal or asymptomatic pathological joints for diagnosis and research: indications, technique and success rate.

  E Pascual, M Doherty
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  ABSTRACT: Although joint aspiration is a basic clinical skill, aspiration of normal joints, or asymptomatic clinically quiescent joints, is only rarely undertaken. There are two main indications for this procedure. Firstly, for definitive diagnosis of crystal-associated arthritis (gout and pseudogout) during the intercritical period and for subsequent monitoring of treatment success of gout; and secondly, to obtain normal synovial fluid for biomarker research. The justification for these indications, the success rate and the technical aspects related to this procedure are presented in this article.
  Annals of the rheumatic diseases 05/2008; 68(1):3-7. · 8.11 Impact Factor