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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recognition of tissue deposits of crystalline material in a variety of organs, including the kidney, predated the association of crystals and arthritic disease. Because of this, the pathophysiology of crystal formation and its resultant inflammation is based in part on studies of renal stones. A number of disease states involving renal and articular crystallization exist. The most common of these, uric acid precipitation, or gout, and calcium phosphate precipitation were not reviewed in this discussion. This review described a variety of less common disease states involving articular and renal crystal deposition. The renal diseases discussed included both parenchymal or ectopic crystal deposition, as seen in nephrocalcinosis or cystinosis, and ductal crystallization as seen in renal calculus disease. The crystals involved included not only calcium oxalate, but also aluminum, amino acids and proteins (cystine, hemoglobin, cryoglobulins, and immunoglobulins), purine metabolites (xanthine, hypoxanthine), and even lipids and their degradative enzymes (cholesterol, phospholipids, phospholipase, and fatty acids). The simultaneous occurrence of crystals in both kidneys and joints was found in some cases to result from the systemic deposition of an excess of a particular biological compound. However, of more interest, some renal deposits were shown to more selectively reflect the normal or abnormal function of the kidney in its secretory and excretory roles. This is particularly evident in the variety of arthritic states described in end-stage renal disease.
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PMID:Calcium oxalate and other crystals associated with kidney diseases and arthritis. 264 79

The calcium antagonists are effective and safe agents for the treatment of arterial hypertension. They are well tolerated by the patients. In contrast to other types of antihypertensive agents, they cause few metabolic disturbances. They can be combined with diuretics, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors. They can be safely prescribed to patients with hypertension and concomitant diseases such as diabetes mellitus, chronic obstructive lung disease, congestive heart failure, gout, renal failure, peripheral atherosclerotic disease, or Raynaud's phenomenon. Dietary sodium restriction during antihypertensive therapy with calcium antagonists is not required for optimal antihypertensive efficacy. The second generation of calcium antagonists especially the dihydropyridine analogues that have greater potency and vascular selectivity, and a longer duration of action, will optimize the treatment of hypertension. Their antiatherosclerotic, antiplatelet, and "antitrophic" effects in experimental models for atherogenesis and hypertension hold great promise for the future since, so far, there has been no major success in reducing the incidence of coronary death by the treatment of hypertension.
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PMID:Calcium antagonists in hypertension. 265 29

The kinetics of calcium pyrophosphate dihydrate (CPPD) crystal growth was studied by allowing calcium and pyrophosphate (PPi-4) ions to diffuse through a denatured collagen matrix (biological grade gelatin) in the presence of either monosodium urate monohydrate (MSU) or hydroxyapatite (HA) crystals. In this in vitro model system, MSU crystals significantly altered the kinetics of PPi-4 ionic diffusion through the gelatin matrix by allowing the [PPi-4] gradient to fall off much more rapidly, suggesting an increased level of scavenging of PPi-4 ions into crystalline materials. Even more significantly, the presence of MSU crystals markedly influenced the crystal growth morphology of triclinic CPPD, producing that observed in vivo. A large number of epitaxially dimensional matches between MSU and triclinic (t) and monoclinic (m) CPPD were identified, suggesting that MSU crystals can epitaxially induce CPPD crystal growth. This finding supports the hypothesis that the association of urate gout and CPPD crystal deposition disease is based on the nucleating potential of MSU crystals for CPPD crystal growth. In contrast, the HA crystal structure did not appear to serve as a nucleating agent for CPPD crystals. However, HA crystals did serve as effective traps for PPi-4 ions and their presence led to more stable CPPD crystal growth.
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PMID:Calcium pyrophosphate crystal deposition: the effect of monosodium urate and apatite crystals in a kinetic study using a gelatin matrix model. 284 Jul 35

Less than 30 years ago, McCarty and others first described a syndrome which presented with gout-like attacks of arthritis but was due to CPPD crystals instead of urate crystals. They termed the condition "pseudogout." It was noted that this was often associated with chondrocalcinosis and it was commonly held that cartilage calcification had to be present if the diagnosis was to be suggested on the basis of the radiographic findings. Subsequently, a clinical and radiographic pattern has emerged in which the diagnosis of CPPD deposition disease can be suggested in the absence of chondrocalcinosis. This condition is termed pyrophosphate arthropathy and is differentiated from degenerative disease by the pattern and distribution of the joint disease. It is important to recognize CPPD deposition disease because of its association with other diseases, such as hemochromatosis and hyperparathyroidism. Although painful periarticular tendinous calcification (peritendinitis calcarea) resulting from the deposition of calcium HA crystals has long been recognized, it has only recently been discovered that intra-articular HA can be associated with an acute inflammatory synovitis. Additionally, patients are now being identified who have CPPD deposition at one anatomic location and HA deposition at another. Differentiation of these various types of crystal-induced arthropathies should lead to more effective therapy in the future.
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PMID:Chondrocalcinosis and other calcifications. 284 68

Varying combinations of acute inflammatory and/or chronic degenerative arthritis have been found to be associated with crystals of calcium pyrophosphate dihydrate (CPPD) and/or basic calcium phosphates (BCPs). Since the arthropathies associated with CPPDs and/or BCPs occur in older individuals, while diagnosis and treatment for monosodium urate monohydrate crystal deposition disease (gout) have become extremely precise and effective, joint problems associated with calcium crystals have become more common than those associated with monosodium urate monohydrate crystals. The classification, pathogenesis, clinical manifestations, and treatment of CPPD and BCP crystal deposition are discussed.
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PMID:Arthritis associated with crystals containing calcium. 300 84

Monosodium urate crystals are clearly related to acute attacks of gout and to the hard tissue destruction of chronic tophaceous gout. Fortunately, the acute attacks are readily treated with anti-inflammatory drugs, and destructive changes due to tophi may be prevented or reversed, at least in part, by the intelligent control of serum urate levels. Control of gout is one of the premier success stories of modern medicine. In contrast, the number of patients who have arthritis associated with crystals that contain calcium appears to be rising--perhaps a function of better recognition, perhaps related to the aging of the population. CPPD and BCP crystals can be associated with acute or subacute inflammation, but as in acute gout, it is easily controlled with anti-inflammatory drugs or by local injections of corticosteroids. A direct relationship of BCP and CPPD crystals to the associated destructive arthropathies has been hypothesized and is supported by clinical observations, animal studies, and in vivo experiments. Unlike gout, which is usually associated with a systemic metabolic abnormality (i.e., hyperuricemia), calcium crystals deposition seem to be a localized phenomenon, although numerous local sites in several joints are often involved in a given patient. Tissue degeneration in gout clearly follows (tophaceous) crystal deposition. Calcium crystal deposition may follow, rather than precede, destructive joint changes. Alternatively, both destructive changes and crystal deposition may derive independently from a common, still obscure, biochemical abnormality of joint tissues. P. A. Dieppe and colleagues believe that calcium crystal deposition follows either primary or secondary tissue degeneration but that the crystals exert a positive feedback effect (amplification loop) that accelerates degeneration. Each of those formulations of a pathogenetic role for crystals may be true in a given case, analogous to the etiology of primary and secondary forms of hyperuricemia and to sodium urate crystal deposition coexistent with osteoarthritis (tophus formation in Heberden's nodes). Conclusive proof of a significant role for BCP or CPPD crystals in the pathogenesis of human joint tissue damage depends on interrupting the postulated disease mechanism and showing that this prevents joint deterioration and leads to significant repair of existing damage. Our current position is somewhat analogous to that of our colleagues who had to contend with management of gouty arthritis before the advent of effective drugs for control of hyperuricemia.
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PMID:Arthropathies associated with calcium-containing crystals. 302 71

Calcium pyrophosphate dihydrate crystal deposition disease is a clinical condition characterised by Gout-like synovitis (pseudogout), calcification on and around the joints and an arthropathy that is radiologically similar to osteoarthritis (chronic pyrophosphate arthropathy). Though all these radiological clinical aspects may coexist in the same patient this is often not the case. An examination of the X-ray data on the 68 cases studied which were diagnosed on the basis of the criteria proposed by McCarty, shows that the disease is relatively common especially in the over-fifties. When chronic pyrophosphate arthropathy is the only clinical manifestation of the disease differential diagnosis from the osteoarthrosis so common in the elderly is difficult and depends on the greater severity and progression of the joint damage that may often affect joints not subjected to weight such as the shoulder, unlike what happens in osteoarthritis.
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PMID:[Clinico-radiologic aspects of calcium pyrophosphate dihydrate deposition disease]. 302 32

We reported before that monosodium urate (MSU) crystals were potent stimulators of endogenous pyrogen (EP) production from human and rabbit mononuclear phagocytes, and proposed that this property of MSU crystals may be important in the pathogenesis of gout. EP activity is now attributed to interleukin 1 (IL 1) peptides but IL 1 is not the only pyrogenic monocyte-derived cytokine, since both interferon-alpha (alpha-IFN) and tumor necrosis factor (TNF) are also pyrogenic in rabbits. Using a T cell comitogenic assay based on a murine helper T cell clone that does not respond to IFN or TNF, we now report the release of IL 1 activity from human blood monocytes and synovial fluid mononuclear cells (MNC), following stimulation with MSU crystals. MSU-induced supernatants with IL 1 activity were neutralized with rabbit antiserum to human IL 1 and also stimulated the growth ([3H]thymidine incorporation) of long-term fibroblast-like cell lines derived from human synovial rheumatoid exudate. Two other crystals associated with articular inflammation were tested: hydroxyapatite was a much less potent stimulus compared with MSU crystals, and calcium pyrophosphate dihydrate did not stimulate IL 1 release from human monocytes or synovial fluid MNC. As a model for the inflammatory consequences of acute and chronic overproduction of IL 1, gout is the only sterile inflammatory disease where the local and systemic pathology is compatible with such overproduction; raised IL 1 levels have been found at the site of inflammation, and a necessary etiologic agent, crystalline urate, has been shown unequivocally to be a direct activator of mononuclear IL 1 release.
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PMID:Interleukin 1 (IL 1) as a mediator of crystal arthritis. Stimulation of T cell and synovial fibroblast mitogenesis by urate crystal-induced IL 1. 303 70

Gout is largely solved, both from diagnostic and therapeutic standpoints. Acute gout is easily suppressed and joint destruction can be prevented and at least reversed by lowering the serum uric acid level with relatively safe and very effective drugs. But the arthritides associated with the calcium-containing crystals remain untreatable by other than symptomatic or surgical means. If we had a method or a drug to remove CPPD or BCP crystal deposits from joints, would it make any difference in the severity of the arthritis? Which of the paradigms shown in Figure 5 holds for these crystals? If joint damage directly follows crystal deposition as in gout, then crystal removal should prove prophylactic. The unusual pattern of joint degeneration associated with polyarticular CPPD crystal deposition and the initial appearance of CPPD crystals in radiographically normal cartilage favors this idea. But radiologic chondrocalcinosis appearing in knees subjected years before to meniscectomy but not in the contralateral knees suggests that crystal deposition, in these cases at least, is secondary to trauma or surgery. If degeneration of cartilage precedes crystal deposition, as it probably does in the case of BCP crystals, then crystal removal may not be particularly helpful. Dieppe and his colleagues proposed that the calcium crystals provide a positive feedback (amplification) loop. This represents the minimalistic view of their importance. The biologic consequences of the calcium crystal deposition diseases are now being explored at the molecular level. Much more data are needed before more than speculative answers to the questions posed here can be formulated. Calcium crystal deposition is more common in older persons. The degenerative and destructive arthropathies associated with them will predictably become increasingly common as our population ages.
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PMID:Crystal identification in human synovial fluids. Methods and interpretation. 305 Nov 51

Numerous trials have shown the efficacy of ACE-inhibitors in moderate and severe essential hypertension. Their use must be regarded as very promising. They lower peripheral vascular resistance without influencing cardiac index and heart rate. Additionally, they maintain serum potassium and do not effect plasma lipids or provoke diabetes mellitus or gout. In 20-30% of hypertensive patients ACE-inhibitors have to be combined with diuretics and/or calcium antagonists. The addition of beta-blockers is useful in patients with resting tachycardia. In mild hypertension the use of ACE-inhibitors as first-line drugs is indicated in patients with adverse reactions to beta-blockers or diuretics. In bilateral renovascular hypertension, ACE-inhibitors may induce a strong blood pressure fall; in bilateral stenosis they contribute to a deterioration of renal function with reversible renal insufficiency. In renoparenchymal hypertension, ACE-inhibitors may attenuate the progression of renal insufficiency; in addition, proteinuria is lowered. In systolic hypertension in the elderly, one must be aware of a marked first-dose hypotensive effect. ACE-inhibitors decrease exaggerated exercise-induced elevation of blood pressure and heart rate and therefore lower myocardial oxygen consumption. In patients with hypertension and diabetes mellitus, antihypertensive treatment should be initiated for blood pressure levels above 140/90 mmHg, to attenuate the progression of vascular damage in the kidney. In patients with severe left ventricular hypertrophy, ACE-inhibitors reduce left ventricular mass within three months by about 30%. In hypertension and coronary heart disease, recent studies report benefits of ACE-inhibitors on coronary circulation. Presently available ACE-inhibitors and those in preparation do not differ in pharmacodynamic, but in pharmacokinetic properties, concerning the beginning and duration of blood pressure lowering. A hypotensive first-dose effect can be observed in diuretic pretreated patients, in severe (malignant) and renovascular hypertension. ACE-inhibitors should not be used during pregnancy or in patients with autoimmune diseases or those undergoing treatment with immunosuppressive drugs, due to the side effects of neutropenia and proteinuria, which are more often seen under these conditions. Results from long-term studies on the influence of ACE-inhibitor treatment on cardiovascular risk in mild hypertension have not been available until now. In the decision to treat mild hypertension with ACE-inhibitors as first-line drug therapy, the costs of therapy in comparison to cheaper antihypertensives must be taken into account.
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PMID:[The value of angiotensin-converting enzyme inhibitors in the treatment of hypertension]. 306 60


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