Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003090 (arthrodesis)
 8,374 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Five different subtypes of spondyloarthropathy (SpA) are now recognized. Clinical and radiologic involvement of the sacroiliac joint is an outstanding feature of the SpA, especially ankylosing spondylitis (AS). In this partly debilitating form of SpA a unique type of inflammatory axial involvement is observed which is characterized by inflammation and new bone formation at different spinal sites. In longstanding disease sacroiliitis, spondylitis and spondylodiscitis are easily recognized by conventional radiography and even better by computed tomography--especially when bony changes have already taken place. The advantage of dynamic magnetic resonance imaging (MRI) is to visualize morphologic changes and inflammation at the same time. This facilitates detection of sacroiliitis and spondylitis/spondylodiscitis at early time points. Hopefully, this will lead to other forms of therapy to prevent ankylosis of the spine. The origin of the granulation tissue infiltrating cartilage and bone in AS might be the synovium, the subchondrium or the bone marrow itself. T cells and macrophages seem to play an important role in this inflammatory process in which TNF-alpha is present in severe cases. The mechanisms responsible for the increased bone formation observed in the course of AS are unknown.
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PMID:Radiologic diagnosis and pathology of the spondyloarthropathies. 989 7

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-alpha agents currently available, infliximab (Remicade(R)) and etanercept (Enbrel(R)), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.
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PMID:Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches. 1222 5

The therapeutic options for patients suffering from the more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-tumour necrosis factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on more than 200 AS patients, and more than 100 PsA patients, this treatment seems to be even more effective than it is in rheumatoid arthritis (RA). The two major anti-TNF-alpha agents currently available, infliximab (Remicade) and etanercept (Enbrel), are approved for the treatment of RA in Europe and in the USA. The situation in SpA is different from RA because there is an unmet medical need, especially in AS, because disease-modifying anti-rheumatic therapy is not available for severely affected patients. Thus, TNF blockers might even be considered first-line immunosuppressive treatment in patients with active AS who are not sufficiently treated with non-steroidal anti-inflammatory drugs (NSAIDs). For infliximab, a dose of 5mg/kg was required, and intervals between 6 and 12 weeks were necessary for constant suppression of disease activity - a major aim also for long-term treatment. However, it remains to be shown whether patients benefit from long-term therapy and whether radiological progression and ankylosis can be stopped. The optimal doses of infliximab might well be determined individually. Allergic reactions and increased susceptibility to tuberculosis are rare side-effects which need to be recognized early. As it stands now, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings. The efficacy of etanercept was first demonstrated in PsA. A double-blind study has now been performed in AS - with similar results. There is preliminary evidence that both agents also work in other SpA such as undifferentiated SpA. Hopefully, both agents will be approved soon for the short-term treatment of severe SpA. In parallel, studies should be performed to document the long-term efficacy and safety of this treatment.
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PMID:Therapy for ankylosing spondylitis: new treatment modalities. 1240 31

The therapeutic options for patients suffering from severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-TNF therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on what is now several hundred AS and PsA patients, this treatment seems to be even more effective than the same therapy in rheumatoid arthritis (RA). The anti-TNF-alpha agents currently available, infliximab (Remicade); Centocor), etanercept (Enbrel); Amgen) and adalimumab (Humira; Abbott), are approved for the treatment of RA in the US; infliximab and etanercept are approved in Europe. The situation in SpA is different to RA because there is an unmet medical need, especially in AS, since no therapies with disease-controlling antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, TNF blockers might even be considered as first-line immunosuppressive agents in patients with active AS and PsA who are not sufficiently treated by non-steroidal anti-inflammatory drugs and sulfasalazine, if peripheral arthritis is present. For infliximab, a dosage of 5 mg/kg at intervals between 6 and 12 weeks was necessary to constantly suppress disease activity; this is also a major aim of long-term treatment. No dose-finding studies have yet been performed. The standard dose of etanercept is 25 mg s.c. twice-weekly. No studies on adalimumab (standard RA dose 20 - 40 mg s.c. every 2 weeks) have yet been conducted in SpA. The efficacy of etanercept was first demonstrated in PsA and etanercept is now approved for this indication. A double-blind study has also been performed in AS, with similarly clearcut efficacy. There is preliminary evidence that both agents do also work in other SpA such as undifferentiated SpA. Infliximab has recently been approved for short-term treatment of severe uncontrolled AS; the approval for etanercept is pending. Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis might be preventable but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. Tuberculosis can be mostly prevented if patients are checked for previous contact with tuberculosis. Currently, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.
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PMID:Novel approaches in the treatment of ankylosing spondylitis and other spondyloarthritides. 1283 46

Since the advent of highly effective TNF-alpha inhibitors for treating spondyloarthritides, referring rheumatologists have been requesting the sensitive visualization of inflammatory changes not only of the sacroiliac joints but of the entire spine. Given that changes in spondyloarthritis may be very subtle, their visualization by means of magnetic resonance (MR) imaging relies critically on selecting the proper imaging protocol. Spinal changes associated with spondyloarthritis are florid anterior spondylitis (or Romanus lesion), florid diskitis (or Andersson lesion), ankylosis, insufficiency fractures of the ankylosed spine, syndesmophytes, arthritis of the apophyseal and costovertebral joints, and enthesitis of the interspinal ligaments. A comparison of MR imaging findings with those of conventional radiography in individual patients reveals strengths and weaknesses of both modalities. Results of this comparison suggest that syndesmophytes are depicted better with radiography; ankylosis, equally well with both imaging techniques; and all other lesions, better with MR imaging. Classification of the different findings based on the typical signal-intensity changes seen on MR images enables standardized reporting, and scoring the lesions may be helpful in clinical trials.
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PMID:Spinal changes in patients with spondyloarthritis: comparison of MR imaging and radiographic appearances. 1588 8

Otosclerosis is an inflammatory disease associated with persistent measles virus (MV) infection of the otic capsule. The nature of sensorineural hearing loss (SNHL) related to otosclerosis can be due to the chronic TNF-alpha release from the foci. TNF-alpha enters the inner ear fluid spaces in histologically active stages of otosclerosis and may cause outer hair cell functional disorder and subsequent SNHL without morphological changes of the organ of Corti. On the contrary, non-otosclerotic stapes ankylosis being a non-inflammatory disease is not harmful for hair cells. Theoretically, SNHL should not associate to this type of stapes fixation. Stapes footplates (N = 248) were examined by hematoxylin-eosin staining and corresponding MV-, OPG- and TNF-alpha-specific RT-PCR. Anti-measles IgG levels of serum specimens were measured by ELISA. Preoperative audiological results were correlated with otosclerotic and non-otosclerotic histopathologies. Among patients with stapes fixation, we found 93 active and 67 inactive otosclerosis, and 88 non-otosclerotic stapes ankylosis. MV could only be detected in otosclerotic stapes footplates. Audiometry revealed bone conduction threshold elevation toward the high frequencies in otosclerotic patients, which was associated to the duration of hearing loss. OPG mRNA expression was significantly lower in the TNF-alpha positive specimens, which was independent from virus positivity. In about one-third of stapes fixations, the etiology is non-otosclerotic stapes ankylosis. Histologic otosclerosis exhibits a strong correlation with MV presence in the bone as a sign of persistent MV infection and related inflammation with TNF-alpha release. This causes SNHL in the function of time. Non-otosclerotic stapes fixations do not cause high-frequency SNHL.
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PMID:Otosclerosis: an organ-specific inflammatory disease with sensorineural hearing loss. 1934 Apr 43

Skeletal muscle atrophy is a serious concern for patients afflicted by limb restriction due to surgery (e.g., arthrodesis), several articular pathologies (e.g., arthralgia), or simply following cast immobilization. To study the molecular events involved in this immobilization-induced debilitating condition, a convenient mouse model for atrophy is lacking. Here we provide a new immobilization procedure exploiting the normal flexion of the mouse hindlimb using a surgical staple to fix the ventral part of the foot to the distal part of the calf. Histological analysis revealed that our approach induced significant skeletal muscle atrophy by reducing the myofiber size of the tibialis anterior (TA) muscle by 36% compared with the untreated contralateral TA within a few days postimmobilization. Two molecular markers for atrophy, atrogin-1/muscle atrophy F-box (atrogin-1/MAFbx) and muscle ring finger 1 (MuRF-1) mRNAs, were significantly upregulated by 1.9- and 5.9-fold, respectively. Interestingly, our model also revealed the presence of an early inflammatory process during atrophy, characterized by the mRNA upregulation of TNF-alpha, IL-1, and IL-6 (1.9-, 2.4-, and 3.4-fold, respectively) simultaneously with the upregulation of the common leukocyte marker CD45 (6.1-fold). Moreover, muscle rapidly recovered on remobilization, an event associated with significantly increased levels of uncoupling protein-3 and peroxisome proliferator-activated receptor gamma coactivator-1alpha mRNA, key components of prooxidative muscle metabolism. This model offers unexpected new insights into the molecular events involved in immobilization atrophy.
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PMID:A novel hindlimb immobilization procedure for studying skeletal muscle atrophy and recovery in mouse. 1934 35

Ankylosing spondylitis is a chronic inflammatory condition which preferentially affects the axial skeleton, often beginning in the sacroiliac joints. The etiology of the pathologic lesions of this condition including enthesitis, erosive articular changes, osteitis, and fibrous ankylosis, as well as changes which occur in the eye, gastrointestinal tract, cardiovascular system, and lungs is unknown; however, there is a strong association with HLA-B27, which indicates altered immunity. One of the major mediators of the immune response is TNF-alpha, which functions as a pleiotrophic soluble messenger primarily from macrophages. TNF-alpha is principally involved with activation of both normal and transformed cells, including endothelium, synoviocytes, osteoclasts, chondrocytes, and fibroblasts. The cornerstone of medical management of ankylosing spondylitis includes intensive physical therapy and nonsteroidal anti-inflammatories for symptomatic relief. However, it is becoming increasingly recognized that TNF-alpha blockade has an important role in the reduction of spine and joint inflammation. This review discusses the data that supports use of etanercept in the treatment of ankylosing spondylitis.
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PMID:Treatment of ankylosing spondylitis: focus on etanercept. 1970 47

The treatment of the two most frequent inflammatory rheumatic diseases rheumatoid arthritis (RA) and ankylosing spondylitis (AS) has some similarities but in total more differences. Thus, therapy with non-steroidal anti-inflammatory agents (NSAIDs), conventional disease modifying anti-rheumatic drugs (DMARDs) and biologic agents has a different role in the management and different efficacy in AS and RA. This implies signs and symptoms, function, and structural damage. This is in part due to the different pathogenesis: (i) while the synovium is an important target in RA it is rather the bone in AS and (ii) while the pathology in RA is rather osteodestructive to cartilage and bone presenting with erosions, it is predominantly osteoproliferative in AS as indicated by syndesmophytes and ankylosis. Biologic agents targeting tumor necrosis factor (TNF-alpha) work clinically well in both diseases but, while they clearly inhibit structural damage in RA, they do not seem to have much influence on new bone formation in AS. DMARDs are efficacious in RA but less so in AS. NSAIDs are efficacious in both RA and AS, but they are considered first line of therapy in AS while they are rather adjunctive agents in RA. In AS, NSAIDs, potentially especially coxibs, may even prevent new bone formation due to their inhibitory effect on cyclooxygenase-2.
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PMID:Treatment of rheumatoid arthritis and ankylosing spondylitis. 1982 62