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)

Recent studies have shown elevated inorganic pyrophosphate (PPi) levels in most knee joint fluid supernates from patients with pseudogout (PG) or osteoarthritis (OA) and more modestly elevated levels in some supernates from patients with gout or rheumatoid arthritis (RA) relative to PPi levels found in the venous blood plasma of normal or arthritic subjects. We measured the intraarticular PPi pool and its rate of turnover to better understand the significance of the joint fluid-plasma PPi gradient. Preliminary studies in rabbits showed that (32-P)PPi passed from joint space to blood and vice versa without detectable hydrolysis. Incubation of natural or synthetic calcium pyrophosphate dihydrate (CPPD) microcrystals with synovial fluid in vitro in the presence of (32P)PPi tracer showed no change in PPi specific activity in the supernate over a 19-h period so that exchange of PPi in solution with that in CPPD microcrystals could be ignored. Clearance rates of (32P)PPi and of (33P)Pi, as determined by serially sampling the catheterized knee joints of volunteers with various types of arthritis over a 3-h period, were nearly identical. The (32P)PPi/(32P)Pi was determined in each sample. A mixture of a large excess of cold PPi did not influence the clearance rate of either nuclide. The quantity of PPi turned over per hous was calculated from the pool size as determined by isotope dilution and the turnover rate. The residual joint fluid nuclide was shown to be (32P)PPi. The PPi pool was generally smaller and the rate of turnover was greater in clinically inflamed joints. The mean plus or minus SEM pool size (mu-moles) and turnover rate (percent/hour) in PG knees was 0.23 plus or minus 0.07 and 117 plus or minus 11.9, hydrolysis rate (%/h) to Pi was 27.7 plus or minus 13.2; in OA knees: 0.45 plus or minus 0.26 and 72 plus or minus 9.2, hydrolysis 6.9 plus or minus 0.9; in gouty knees: 0.8 plus or minus 0.41 and 50 plus or minus 11.6, hydrolysis 9.8 plus or minus 2.8; and in RA knees: 0.14 plus or minus 0.14 and 114 plus or minus 35.8, hydrolysis 236 plus or minus 116. PPi turnover (mumoles/hour) correlated with the degree of OA change present in the joint as graded by radiologic criteria irrespective of the clinical diagnosis. Mean PPi turnover in joints with advanced OA was greater than in those with mild or moderate changes (P smaller than 0.001), but the mild and moderate groups showed no significant difference. We conclude that synovial PPi turnover and elevated PPi fluid concentrations are not specific for PG patients, and that these factors alone cannot be the only determinants of CPPD crystal deposition.
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PMID:Inorganic pyrophosphate pool size and turnover rate in arthritic joints. 16 95

A randomized, double-blind, parallel treatment trial was carried out in 24 patients with moderate to severe hypertension to compare the effectiveness and tolerance of two treatment regimens in reducing and maintaining supine diastolic blood pressure below 90 mmHg. Patients in Group I received 10 to 40 mg enalapril maleate per day with the addition of 50 mg hydrochlorothiazide per day and then 250 to 1000 mg alpha-methyldopa per day, if necessary. Patients in Group II received 50 mg hydrochlorothiazide per day with the addition of 80 to 240 mg propranolol and then 100 to 200 mg hydralazine per day, if necessary. Apart from the hydrochlorothiazide dosage which was fixed, the dosage of the other active drugs was titrated incrementally until the target blood pressure level was achieved. Blood pressures, heart rate and body weight were monitored at 2-weekly intervals during 26 weeks of active therapy. In Group I, blood pressure control was achieved and maintained with enalapril alone in 9 patients, 2 patients required double therapy and 1 patient triple therapy. In Group II, 9 patients required double therapy, 2 triple therapy, and only 1 patient received monotherapy. Supine and erect blood pressure control was comparable in both groups. There was, however, a significant decrease in supine heart rate in patients in Group II. More importantly, 8 of the 12 patients in Group II experienced non-life threatening adverse reactions (4 were hypokalaemic and required supplementary potassium, 2 had cold hands and feet, 1 man had sexual dysfunction and 1 acute gout) and no adverse reactions were reported by Group I patients.
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PMID:An appraisal of antihypertensive efficacy and adverse reactions with two drug regimens: enalapril maleate as part of triple therapy compared to conventional triple therapy in moderate to severe hypertension. 632 7

In William Harvey's day almost any or every arthropathy was termed gout. This is evident in the case histories of some of his patients and in his own case, where his own cold water therapy would suggest the correct diagnosis was not gout but erythromelalgia (Weir Mitchell's disease).
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PMID:William Harvey and his gout. 637 Jan 46

A 33-yr-old male ran 10 miles, drank some beer, and developed pain in his left knee and ankle. He took some leftover antibiotics but was no better after 6 d, when a heart murmur and an aortic valve nodule were discovered. He was presumed to have endocarditis with septic arthritis and was started on intravenous antibiotics. On the second hospital day, synovial fluid analysis revealed acute gout, and the patient improved very rapidly on anti-gout therapy. The valvular nodule remained unexplained, but one very rare cause of valvular heart nodules is visceral gout. An unsuccessful attempt to resorb the nodule was made by using allopurinol. This patient demonstrates several points about gout in endurance athletes: 1) acute gout can mimic infectious endocarditis, 2) misdiagnosed or undertreated gout often leads to multiple joint involvement and sometimes to visceral tophi, and 3) athletes who exercise in warm weather and quench their thirst with cold beer are at risk for acute gout.
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PMID:Runner with gout and an aortic valve nodule. 767 64

Characteristic feature of pathogenesis, epidemiology and laboratory findings in hyperuricemia of gouty patients are studied and reasonable treatments of gout in clinical medicine are discussed. Gout is characterized by repeated arthritis attacks on the metacarpophalangeal joint of the first toe or other small joints, especially overworked joints or those exposed to cold. The arthritis attack lasts for 3.5 days and then diminishes gradually. The intervals are shortened in patients under poor hyperuricemic control but tophi formation is less frequent. Complications in combination with hyperlipidemia, diabetes mellitus, obesity and hypertension, which are compatible to syndrome X, are frequent in gouty patients and are suspected of rapidly progressing to arteriosclerosis, such as ischemic heart diseases. Hyperuricemia consists of over-production and underexcretion, which can be diagnosed by the urate clearance test. Classification is valuable for surveying the underlying diseases of secondary hyperuricemia and treating gouty patients. Underexcretion was observed in 85% of gouty patients with hyperuricemia and even the mean urate clearance in the overproduction type was significantly lower than that of normal controls, suggesting that underexcretion is a fundamental phenomenon in all gouty patients. Treatments of complications as well as those of hyperuricemia with uricosuric agents are required for clinical treatment of gouty patients.
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PMID:[Characteristic features of gouty patients]. 897

Before the Song-Yuan dynasties, it was claimed that "gout" is the result of heat in the blood plus invasion of wind, cold, or dampness, leading to coagulation of turbid dampness in the channel-collaterals, characterized by arthralgia, exacerbated in the nighttime. "Gout" was first seen in the Ming yi bie lu (Other Records of Famous Physicians) of the Liang dynasty. Before that, it was categorized under "bi" syndrome. No detailed description was given to "gout" during the period from the first appearance of the title "gout" to the Yuan dynasty. In fact, it was vaguely mentioned in "bi", "li jie", and "bai hu (white tiger)" disorders. The title of "gout" was named by Zhu Danxi, and appeared alternately with gouty arthritis. "li jie" and "bai hu" are titles of two different diseases which were jointly called "lijiebaihu" in the Song dynasty, both similar to gouty arthritis. The TCM title of gout was based on this condition which is specific and very proximate to gouty arthritis.
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PMID:[Investigation on "gout" and comparison of disorder between Chinese and Western medicine in pre-Song-yuan dynasty]. 1573 Jul 59

Rheumatic diseases are among the most frequent causes of pain and disability. Effective management of rheumatic diseases including osteoarthritis (OA), ankylosing spondylitis (AS), and gouty arthritis requires an understanding of the underlying disease mechanisms.Symptoms of OA result from both mechanical factors and elements of inflammation. Current management strategies target both of these factors and generally consist of nonpharmacologic and pharmacologic interventions, including use of nonspecific nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2-specific inhibitors (coxibs), which have analgesic and antiinflammatory properties. Other approaches include intraarticular hyaluronate and the use of alternative therapies under investigation such as acupuncture or glucosamine.Disease mechanisms in AS involve enthesitis, an inflammation at the site of insertion of ligaments, tendons, or joint capsules to bone. Posture and exercise are important nonpharmacologic strategies that may be made easier with the use of NSAIDs or coxibs. Recently developed therapies, including tumor necrosis factor inhibitors, target the underlying disease mechanisms and have demonstrated dramatic symptomatic effects. Disease-modifying effects still need to be established.In gout, hyperuricemia leads to crystal-induced inflammation in some patients. Etoricoxib, one of the newer coxibs, has shown promise in treating acute gout, with efficacy similar to indomethacin, the current standard NSAID often used in these patients. Oral or intraarticular steroids can also be considered. For chronic care uricosurics can be beneficial if renal function is normal and excretion is not excessive, but allopurinol is used most often. Nonpharmacologic modalities, such as rest and cold applications, are useful for acute episodes, and lifestyle modification in the form of diet can also play a role in chronic disease management.
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PMID:Management strategies for osteoarthritis, ankylosing spondylitis, and gouty arthritis. 1704 96

Medicine of V and IV centuries B.C. attested in the Corpus Hippocraticum ascribes all diseases to the rheuma, i.e. the flux of humours into the body. This flux produces not only the rise of cold, hoarseness, cough, reddening, dropsy, but also arthritis, sciatica, gout.
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PMID:[Rheumatic diseases in the Corpus Hippocraticum]. 1743 35

Rilonacept (IL-1 Trap/Arcalyst) is a long-acting interleukin-1 (IL-1) blocker developed by Regeneron Pharmaceuticals. Initially, Regeneron entered into a joint development effort with Novartis to develop rilonacept for the treatment of rheumatoid arthritis (RA) but this was discontinued following the review of phase II clinical data showing that IL-1 blockade appeared to have limited benefit in RA. In February 2008, Regeneron received Orphan Drug approval from the Food and Drug Administration for rilonacept in the treatment of two cryopyrin-associated periodic syndromes (CAPS) disorders, namely, familial cold-induced autoinflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS), for children and adults 12 years and older. CAPS is a group of inherited inflammatory disorders consisting of FCAS, MWS, neonatal-onset multisystem inflammatory disease (NOMID), also known as chronic infantile neurologic, cutaneous and articular (CINCA) syndrome, all associated with heterozygous mutations in the NLRP3 (CIAS1) gene, which encodes the protein NLRP3 or cryopyrin. Prior to the discovery of the NLRP3 (CIAS1) mutations and the advent of IL-1-targeted therapy, treatment was aimed at suppressing inflammation but with limited success. The dramatic success of selective blockade of IL-1beta, initially with the IL-1 receptor antagonist (IL-1Ra; Kineret(R) or anakinra/ Amgen, Inc.), not only provided supportive evidence for the role of IL-1beta in CAPS but also demonstrated the efficacy of targeting IL-1beta for treatment of these conditions. A high-affinity protein called rilonacept has been produced by cytokine Trap technology and was developed by Regeneron. The desirable longer half-life of rilonacept offers potential alternatives to patients who do not tolerate daily injections very well or have difficulty with drug compliance. The initial evidence for the beneficial effects of rilonacept for MWS and FCAS suggests that it would also be a suitable treatment for CNICA/NOMID. It is yet to be determined whether rilonacept would be an effective treatment for other chronic inflammatory conditions such as gout, familial Mediterranean fever and systemic juvenile idiopathic arthritis.
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PMID:Rilonacept in the treatment of chronic inflammatory disorders. 1964 32

In the Traditional Chinese medical literature of ancient times, Bi referred to the pathogenesis, or the symptoms as well as the name of the disease. As the name of a disease, Bi has the different meanings of broad and narrow., joint-running, joint-running wind, white tiger joint-running, gout etc. referring to the narrow meaning of Bi disease. The theory of etiology and pathogenesis of the narrow meaning of Bi disease developed from damp-impediment, wind-cold-damp impediment to damp-hot impediment, stasis-hot impediment, which reflected the constant deepening of cognition.
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PMID:[The evolution of related names of Bi syndrome and the theory of etiology and pathogenesis]. 1993 Sep 37


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