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2.
Rheumatology (Oxford) ; 47(8): 1231-4, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18550639

ABSTRACT

OBJECTIVE: Intestinal Behçet's Syndrome (BS) is a difficult diagnosis to establish. We describe the use of wireless capsule endoscopy (WCE) in the investigation of 11 patients with suspected intestinal BS. METHODS: Out of 11 patients, 10 with suspected intestinal BS were found to have small intestinal ulcers on capsule endoscopy. Each case was retrospectively assessed for symptoms, signs, anaemia, other investigations, treatment and complications. RESULTS: All 11 patients had established diagnoses of BS as defined by the International Study Group criteria. Central abdominal pain and change in bowel habit were the predominant symptoms, both occurring in seven patients. Upper gastrointestinal (GI) endoscopy and colonoscopy identified duodenitis, ileitis and colitis in three patients. Barium studies and CT were normal in all cases. WCE revealed small intestinal ulcers throughout the ileum in five patients and ulcers located either in the proximal and/or distal ileum in five other patients. One patient had significant symptoms, signs and ulcers leading to a change in treatment to infliximab, and this resulted in resolution of symptoms and ulcers. Ten age- and sex-matched controls investigated for unexplained GI symptoms had no intestinal lesions on capsule endoscopy. CONCLUSION: WCE is useful in the investigation of GI symptoms in BS. It is particularly helpful in those patients in whom conventional investigations have been normal or fail to account for symptoms and signs. This technique may guide treatment and provide a better understanding of intestinal pathology in BS.


Subject(s)
Behcet Syndrome/diagnosis , Capsule Endoscopy , Intestinal Diseases/diagnosis , Adult , Behcet Syndrome/drug therapy , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Ulcer/diagnosis
3.
J Thromb Haemost ; 5(12): 2537-46, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17927807

ABSTRACT

BACKGROUND: Heme oxygenase-1 (HO-1), by exerting anti-inflammatory, antiproliferative, antiapoptotic and antioxidant effects in the vasculature, protects against atherosclerosis and post-transplant vasculopathy. We noted the overlap between the effects of HO-1 and those attributed to 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins). This led to an investigation of the role of HO-1 in statin-mediated cytoprotection in primary human endothelial cells (ECs), and the ability of Kruppel-like factor 2 (KLF2) to regulate HO-1 function. METHODS/RESULTS: Treatment of human umbilical vein and aortic ECs with atorvastatin significantly upregulated HO-1 promoter activity, mRNA expression and protein expression, increasing HO-1 enzymatic activity as shown by raised intracellular bilirubin IXalpha. This effect was indirect, dependent upon inhibition of HMG-CoA reductase and geranylgeranylation, and independent of nitric oxide or changes in mRNA stability. Atorvastatin protected ECs against the generation of reactive oxygen species and H(2)O(2)-induced injury. HO-1 inhibition, with small interfering RNA (siRNA) or zinc protoporphyrin IX, abrogated atorvastatin-mediated cytoprotection. Atorvastatin upregulated KLF2 expression, whereas KLF2 siRNA attenuated statin-induced HO-1 and its associated antioxidant cytoprotective effects. Iron chelation, adenoviral-mediated overexpression of ferritin or supplementation of culture media with biliverdin reversed the inhibitory effects of HO-1 and KLF2 siRNA, suggesting that bile pigments and ferritin mediate the antioxidant actions of statin-induced HO-1. CONCLUSIONS: We have identified a novel link between KLF2 and HO-1 in human vascular ECs, demonstrating that atorvastatin-mediated HO-1 upregulation, and its associated antioxidant effect, is KLF2-dependent. The relationship between KLF2 and HO-1 is likely to represent an important component of the vasculoprotective profile of statins.


Subject(s)
Antioxidants/pharmacology , Cytoprotection , Endothelial Cells/drug effects , Heme Oxygenase-1/biosynthesis , Heptanoic Acids/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Kruppel-Like Transcription Factors/metabolism , Oxidative Stress/drug effects , Pyrroles/pharmacology , Atorvastatin , Bilirubin/metabolism , Biliverdine/metabolism , Cell Survival/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Endothelial Cells/enzymology , Endothelial Cells/metabolism , Enzyme Induction , Enzyme Inhibitors/pharmacology , Ferritins/genetics , Ferritins/metabolism , Heme Oxygenase-1/antagonists & inhibitors , Heme Oxygenase-1/genetics , Humans , Hydrogen Peroxide/pharmacology , Iron Chelating Agents/pharmacology , Kruppel-Like Transcription Factors/genetics , Mevalonic Acid/pharmacology , Oxidants/pharmacology , Prenylation , Promoter Regions, Genetic/drug effects , Protoporphyrins/pharmacology , RNA Interference , RNA, Messenger/biosynthesis , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Terpenes/pharmacology
4.
Clin Rheumatol ; 26(4): 584-6, 2007 Apr.
Article in English | MEDLINE | ID: mdl-16416032

ABSTRACT

The presence of an acute phase response may pre-date the eventual diagnosis of malignant disease by months or even years. We describe two patients referred to the rheumatology clinic, in which extensive investigation failed to identify an underlying cause to account for the presenting symptoms and an associated acute phase response. Several months later, repeated abdominal CT scans revealed an abnormality and subsequent laparoscopic biopsy confirmed a diagnosis of peritoneal mesothelioma.


Subject(s)
Acute-Phase Reaction/etiology , Mesothelioma/pathology , Peritoneum/pathology , Female , Humans , Male , Mesothelioma/complications , Mesothelioma/diagnosis , Middle Aged
5.
Postgrad Med J ; 82(969): 446-53, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16822921

ABSTRACT

Reactive arthritis is an important cause of lower limb oligoarthritis, mainly in young adults. It is one of the spondyloarthropathy family; it is distinguishable from other forms of inflammatory arthritis by virtue of the distribution of affected sites and the high prevalence of characteristic extra-articular lesions. Many terms have been used to refer to this and related forms of arthritis leading to some confusion. Reactive arthritis is precipitated by an infection at a distant site and genetic susceptibility is marked by possession of the HLA-B27 gene, although the mechanism remains uncertain. Diagnosis is a two stage process and requires demonstration of a temporal link with a recognised "trigger" infection. The identification and management of "sexually acquired" and "enteric" forms of reactive arthritis are considered. Putative links with HIV infection are also discussed. The clinical features, approach to investigation, diagnosis, and management of reactive arthritis are reviewed.


Subject(s)
Arthritis, Reactive/diagnosis , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Arthritis, Reactive/etiology , Arthritis, Reactive/therapy , Diagnosis, Differential , Female , HIV Infections/complications , Humans , Male , Medical History Taking , Physical Examination , Physical Therapy Modalities , Spondylarthropathies/diagnosis , Spondylarthropathies/etiology , Spondylarthropathies/therapy
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