Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic crystal-associated arthropathies such as gout and pseudogout can lead to local bone destruction. Because osteoblasts, which orchestrate bone remodeling via soluble factors and cell-to-cell interactions, have been described in contact with microcrystals, particularly in uratic foci of gout, we hypothesized that microcrystals of monosodium urate monohydrate (MSUM) and of calcium pyrophosphate dihydrate (CPPD) could alter osteoblastic functions. MSUM and CPPD adhered to human osteoblastic cells (hOB) in vitro and were partly phagocytized as shown by scanning electron microscopy. MSUM and CPPD dose-dependently stimulated the production of PGE(2) in hOB as assessed by enzyme immunoassay, a response that was synergistically enhanced in the presence of IL-1. The mechanism of this synergism was, at least in part, at the level of the expression of cyclooxygenase-2 as evaluated by immunoblot analysis. MSUM and CPPD also stimulated the expression of IL-6 and IL-8 and reduced the 1,25-dihydroxyvitamin D(3)-induced activity of alkaline phosphatase and osteocalcin in hOB (with no synergism with IL-1). MSUM- or CPPD-stimulated expression of IL-6 in hOB pretreated with the selective cyclooxygenase-2 inhibitor NS-398 was increased, unlike that induced by IL-1 alone which was partially reduced. MSUM-, CPPD- or IL-1-induced expression of IL-8 was unchanged by pretreating hOB with NS-398. These results suggest that inflammatory microcrystals alter the normal phenotype of hOB, redirecting them toward reduced bone formation and amplified osteoblast-mediated bone resorption, abnormalities that could play a role in the bone destruction associated with chronic crystal-induced arthritis.
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PMID:Inflammatory microcrystals alter the functional phenotype of human osteoblast-like cells in vitro: synergism with IL-1 to overexpress cyclooxygenase-2. 1199 89

Acute monoarthritis can be the initial manifestation of many joint disorders. The first step in diagnosis is to verify that the source of pain is the joint, not the surrounding soft tissues. The most common causes of monoarthritis are crystals (i.e., gout and pseudogout), trauma, and infection. A careful history and physical examination are important because diagnostic studies frequently are only supportive. Examination of joint fluid often is essential in making a definitive diagnosis. Leukocyte counts vary widely in septic and sterile synovial fluids and should be interpreted cautiously. If the history and diagnostic studies suggest an infection, aggressive treatment can prevent rapid joint destruction. When an infection is suspected, culture and Gram staining should be performed and antibiotics should be started. Light microscopy may be useful to identify gout crystals, but polarized microscopy is preferred. Blood tests alone never confirm a diagnosis, and radiographic studies are diagnostic only in selected conditions. Referral is indicated when patients have septic arthritis or when the initial evaluation does not determine the etiology.
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PMID:Diagnosing acute monoarthritis in adults: a practical approach for the family physician. 1288 14

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is characterized by the accumulation of pyrophosphate dihydrate crystals in articular and periarticular tissues. Various terms have been utilized to describe this arthropathy, which has led to some confusion. CPPD crystal deposition disease is among many conditions that may result in crystal deposition within cartilage. Chondrocalcinosis is a pathologic and radiographic term denoting calcification of cartilage within joints including both hyaline articular cartilage and fibrocartilage. Pseudogout is a clinical term applied to an acute inflammatory process in a joint(s) mimicking a gout attack. Pseudogout is just one of the multiple clinical presentations for CPPD crystal deposition disease. Pyrophosphate arthropathy is a term that has been used to describe the peculiar pattern of joint destruction associated with CPPD crystal deposition disease. This article reviews the protean manifestations of CPPD crystal deposition disease with emphasis on diagnostic imaging.
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PMID:Calcium pyrophosphate dihydrate crystal deposition disease. 1459 59

The management of hip injuries in athletes has evolved significantly in the past few years with the advancement of arthroscopic techniques. The application of minimally invasive surgical techniques has facilitated relatively rapid returns to sporting activity in both recreational and elite athletes. Recent advancements in both hip arthroscopy and magnetic resonance imaging have elucidated several sources of intraarticular abnormalities that result in chronic and disabling hip symptoms. Many of these conditions were previously unrecognized and, thus, left untreated. Current indications for hip arthroscopy include the presence of symptomatic acetabular labral tears, hip capsule laxity and instability, chondral lesions, osteochondritis dissecans, ligamentum teres injuries, snapping hip syndrome, iliopsoas bursitis, and loose bodies (for example, synovial chondromatosis). Less common indications include management of osteonecrosis of the femoral head, bony impingment, synovial abnormalities, crystalline hip arthropathy (gout and pseudogout), infection, and posttraumatic intraarticular debris. In rare cases, hip arthroscopy can be used to temporize the symptoms of mild-to-moderate hip osteoarthritis with associated mechanical symptoms. This article discusses the current clinical and radiographic methods to detect early hip joint disease and the current indications and surgical techniques of hip arthroscopy.
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PMID:Hip arthroscopy: current indications, treatment options, and management issues. 1462 76

Gout and pseudogout are inflammatory arthritides due to monosodium urate and calcium pyrophosphate dihydrate crystal formation. Both are prevalent among geriatric patients, and can present as acute mono- or oligoarticular disease, or as a chronic polyarthropathy resembling osteoarthritis or rheumatoid arthritis. Gout in the geriatric patient is a disease affecting women, commonly associated with diuretic usage, often involves the fingers, may be complicated by the development of masses of uric acid crystals (tophi) in soft tissues, and is frequently polyarticular. Pseudogout in the geriatric patient has a variety of clinical presentations, may be acute or chronic, and should be considered in evaluating any patient with osteoarthritis occurring in an atypical distribution. Treatment includes the use of nonsteroidal anti-inflammatory drugs, colchicine, or corticosteroids. Gout may be impacted by dietary factors, weight reduction, and avoidance of certain forms of alcohol; uric acid-lowering agents are effective for refractory or chronic tophaceous disease.
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PMID:Crystal arthritis. Gout and pseudogout in the geriatric patient. 1546 Dec 35

Advancement in diagnostic and therapeutic applications for hip arthroscopy have dispelled previous myths about early hip disease. Arthroscopic findings have established the following facts: Acetabular labral tears do occur; acetabular chondral lesions do exist; tears are most frequently anterior and often associated with sudden twisting or pivoting motions; and labral tears often occur in association with articular cartilage lesions of the adjacent acetabulum or femoral head, and if present for years, contribute to the progression of delamination process of the chondral cartilage. Magnetic resonance arthrography represents an improvement over conventional magnetic resonance imaging, it does have limitations when compared with direct observation. Although indications for hip arthroscopy are constantly expanding, the most common indications include: labral tears, loose bodies, chondral flap lesions of the acetabular or femoral head, synovial chondromatosis, foreign body removal, and crystalline hip arthropathy (gout, pseudogout, and others). Contraindications include conditions that limit the potential for hip distraction such as joint ankylosis, dense heterotopic bone formation, considerable protrusio, or morbid obesity. Complication rates have been reported between 0.5 and 5%, most often related to distraction and include sciatic or femoral nerve palsy, avascular necrosis, and compartment syndrome. Transient peroneal or pudendal nerve effects and chondral scuffing have been associated with difficult or prolonged distraction. Meticulous consideration to patient positioning, distraction time and portal placement are essential. Judicious patient selection and diagnostic expertise are critical to successful outcomes. Candidates for hip arthroscopy should include only those patients with mechanical symptoms (catching, locking, or buckling) that have failed to respond to conservative therapy. The extent of articular cartilage involvement has the most direct relationship to surgical outcomes. Improvements in technique and instrumentation have made hip arthroscopy an efficacious way to diagnose and treat a variety of intra-articular problems.
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PMID:Arthroscopic intervention in early hip disease. 1557 81

There have been very few reports in the literature of gout and pseudogout of the spine. We describe six patients who presented with acute sciatica attributable to spinal stenosis with cyst formation in the facet joints. Cytopathological studies confirmed the diagnosis of crystal arthropathy in each case. Specific formation of a synovial cyst was identified pre-operatively by MRI in five patients. In the sixth, the diagnosis was made incidentally during decompressive surgery. Surgical decompression alone was undertaken in four patients. In one with an associated degenerative spondylolisthesis, an additional intertransverse fusion was performed. Another patient had previously undergone a spinal fusion adjacent to the involved spinal segment, and spinal stabilisation was undertaken as well as a decompression. In addition to standard histological examination material was sent for examination under polarised light which revealed deposition of urate or calcium pyrophosphate dihydrate crystals in all cases. It is not possible to diagnose gout and pseudogout of the spine by standard examination of a fixed specimen. However, examining dry specimens under polarised light suggests that crystal arthropathy is a significant aetiological factor in the development of symptomatic spinal stenosis associated with cyst formation in a facet joint.
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PMID:Crystal arthropathy of the lumbar spine: a series of six cases and a review of the literature. 1579 2

Microcrystals of calcium pyrophosphate dihydrate (CPPD) and monosodium urate (MSU) deposited in synovium and articular cartilage initiate joint inflammation and cartilage degradation in large part by binding and directly activating resident cells. TLRs trigger innate host defense responses to infectious pathogens, and the expression of certain TLRs by synovial fibroblasts has revealed the potential for innate immune responses to be triggered by mesenchymally derived resident cells in the joint. In this study we tested the hypothesis that chondrocytes also express TLRs and that one or more TLRs centrally mediate chondrocyte responsiveness to CPPD and MSU crystals in vitro. We detected TLR2 expression in normal articular chondrocytes and up-regulation of TLR2 in osteoarthritic cartilage chondrocytes in situ. We demonstrated that transient transfection of TLR2 signaling-negative regulator Toll-interacting protein or treatment with TLR2-blocking Ab suppressed CPPD and MSU crystal-induced chondrocyte release of NO, an inflammatory mediator that promotes cartilage degeneration. Conversely, gain-of-function of TLR2 in normal chondrocytes via transfection was associated with increased CPPD and MSU crystal-induced NO release. Canonical TLR signaling by parallel pathways involving MyD88, IL-1R-associated kinase 1, TNF receptor-associated factor 6, and IkappaB kinase and Rac1, PI3K, and Akt critically mediated NO release in chondrocytes stimulated by both CPPD and MSU crystals. We conclude that CPPD and MSU crystals critically use TLR2-mediated signaling in chondrocytes to trigger NO generation. Our results indicate the potential for innate immunity at the level of the articular chondrocyte to directly contribute to inflammatory and degenerative tissue reactions associated with both gout and pseudogout.
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PMID:TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation. 1581 32

3 patients, 2 women aged 71 and 76 and a 55-year-old man, were originally diagnosed with rheumatoid arthritis (RA) and treated with disease-modifying antirheumatic drugs (DMARDs); two of these patients fulfilled the American College of Rheumatology criteria for RA. Because the symptoms persisted, the diagnosis was reconsidered. It turned out that they had pseudogout, which is an arthropathy caused by the deposition of calcium pyrophosphate crystals; the younger woman had no obvious metabolic disorder, the older woman had underlying hyperparathyroidism, and in the man the arthropathy was probably due to benign hypercalcaemia. DMARDs were replaced by NSAIDs. Varying degrees ofarthropathy persisted in the women, but in the man they were clearly decreased. In addition to resembling gout, the clinical manifestations of pseudogout can also mimic RA. It is important to distinguish pseudogout from RA because their treatment is completely different. Furthermore, pseudogout can be the first or sole symptom of a metabolic disorder.
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PMID:[Pseudogout in 3 patients with presumed therapy-resistant rheumatoid arthritis]. 1603 67

Since the original descriptions of the involvement of crystals in arthritis, our understanding of the clinical syndromes of gout and pseudogout, and the role of basic calcium crystals in arthritis has increased. Gout is usually considered an affliction confined to middle-aged men, but has an increasing prevalence in older populations, with unique and often atypical features. Calcium pyrophosphate dihydrate crystal deposition disease is common in elderly patients. The diagnosis of both of these common forms of arthritis and the need to individualize therapy in patients with other medical problems remain important clinical challenges to the practicing physician.
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PMID:Crystal-associated arthritis in the elderly. 1591 Dec 3


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