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

The authors described the results of an immunohistochemical, electron microscopic and morphometric study of the kidney bioptates of 45 patients with latent glomerulonephritis with hyperuricemia, 8 patients with primary gout and 12 patients with latent glomerulonephritis without hyperuricemia. Two possible variants of the involvement of the renal glomerula were revealed against a background of purine metabolism: typical immunocomplex glomerulonephritis and the so called "reactive" mesangial changes. The expression of interstitial changes (by the results of histometric investigation) was maximum in gout, slightly less in latent nephritis with hyperuricemia and minimum in nephritis without hyperuricemia. The authors emphasized the possibility of immunocomplex nephritis as one of the variants of renal lesion in gout and hyperuricemia and the necessity of specifying therapeutic modalities to be used in this condition including general nephrological approaches to the treatment of latent nephropathies.
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PMID:[Immune complex hyperuricemic nephritis: aspects of its morphology and pathogenesis]. 294 81

Superactive phosphoribosylpyrophosphate (PRPP) synthetases were characterized in fibroblasts and erythrocytes from 5 unrelated men with gout and/or hyperuricemia and uric acid overproduction. The kinetic basis of enzyme superactivity in all patients was increased maximal reaction velocity. Affinities of the enzymes for substrates and activators and responsiveness to inhibitors were normal, and levels of immunoreactive enzyme in patient and control fibroblast and erythrocyte extracts were comparable. Enzymes purified to homogeneity from 2 patients confirmed the presence of isolated catalytic defects. Altered physical properties of certain of the superactive enzymes suggested the presence of several distinctive structural defects among the aberrant forms. Fibroblasts from each affected patient showed increased PRPP concentration and generation, as well as accelerated rates of all PRPP-requiring purine nucleotide synthetic pathways. These findings support the concept that enzyme superactivity results in uric acid overproduction as a consequence of increased rates of PRPP and purine nucleotide synthesis. Cultured cells from female relatives of 2 patients showed evidence for the heterozygous carrier state, as measured both by enzyme activities and by rates of PRPP and purine synthesis. The clinical phenotype in 4 patients was limited to early adult-onset gout and its consequences, whereas the fifth patient expressed a familial constellation of hyperuricemia, sensorineural deafness, ataxia, and renal insufficiency. The severity of the derangements in PRPP synthetase and in PRPP and purine synthesis in cells from the 5 patients, however, was comparable. The neurologic accompaniments of enzyme superactivity found in 1 family described here, and in 2 others described previously, thus may not necessarily be consequences of primary defects in PRPP synthetase.
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PMID:Phosphoribosylpyrophosphate synthetase superactivity. A study of five patients with catalytic defects in the enzyme. 301 68

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

Gout is a clinical syndrome with a limited range of manifestations arising as a result of the deposition of crystals of monosodium urate, the final product of purine metabolism in humans. Hyperuricemia is a common chemical aberration that is most often mild and remains asymptomatic. Thus, hyperuricemia should be distinguished from gout, even though urate supersaturation is necessary for the expression of gout. Uric acid overproduction and diminished renal uric acid excretion are the major mechanisms resulting in hyperuricemia, and an understanding of the basis of hyperuricemia in individual gout patients is an important step in determining appropriate treatment and in identifying underlying disorders, offending drugs and toxins, and inherited enzyme defects, all of which can result in hyperuricemia and gout. A scheme is presented for the evaluation of patients with new-onset gout, along with a discussion of the relationships between gout/hyperuricemia and a variety of metabolic disorders that are unusually prevalent in gouty populations.
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PMID:Clinical aspects of monosodium urate monohydrate crystal deposition disease (gout). 305 Nov 56

Hyperuricemia is common in cyclosporine-treated renal allograft recipients. An increased incidence of gout in patients receiving both diuretics and cyclosporine has been reported, but the effect of hyperuricemia on renal allograft function has not been studied. In a prospective, randomized trial of cyclosporine and prednisone versus azathioprine, prednisone, and antilymphocyte globulin for immunosuppression in renal allograft recipients, 105 of 131 cyclosporine and prednisone-treated patients (80 percent) experienced hyperuricemia (serum uric acid level above 8 mg/dl) and 13 of 131 (10 percent) were severely hyperuricemic (serum uric acid level above 14 mg/dl). In contrast, hyperuricemia developed in 63 of 115 patients (55 percent) treated with azathioprine, prednisone, and antilymphocyte globulin (p less than 0.002). Despite the frequent occurrence of hyperuricemia, gout was rare. Clinical gout developed in six patients in the cyclosporine and prednisone group and in 0 patients in the azathioprine, prednisone, and antilymphocyte globulin group between 1 and 43 months (median 22.5 months) after transplantation. Neither severe hyperuricemia nor diuretic therapy were associated with a significantly increased incidence of gout. The mean serum creatinine concentration of severely hyperuricemic patients (all on cyclosporine and prednisone) was similar to that of normouricemic cyclosporine and prednisone patients (1.8 mg/dl versus 1.6 mg/dl, p greater than 0.2), and the severely hyperuricemic patients had a 4-year graft survival rate of 90 percent. Asymptomatic hyperuricemia after renal transplantation does not adversely affect allograft function, requires no specific therapy, and is not a contraindication to use of diuretics.
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PMID:Hyperuricemia after renal transplantation. 305 57

Hyperuricaemia carries with it a high risk of tophi development affecting connective tissue in kidney, skin and joints, its overt clinical expression being gout. Diuretics, which are invariably prescribed in congestive heart failure and widely used for the treatment of essential hypertension, may cause hyperuricaemia and predispose to gout by inducing renal retention of urate. The angiotensin I converting enzyme inhibitors captopril and enalapril have been found to augment renal urate excretion both in normal volunteers and in hypertensive patients. Current evidence appears to indicate that the uricosuric effect of captopril and enalapril could be due to the rises in renin and angiotensin I these drugs elicit by angiotensin I converting enzyme inhibition, and/or to pharmacological actions not related, at least directly, to the renin-angiotensin-aldosterone system. Serum urate levels have been significantly reduced by monotherapy with captopril in hypertensive patients suffering from hyperuricaemia. Diuretic-induced hyperuricaemia in hypertensive patients can be prevented or counteracted by the administration of captopril and enalapril. Available clinical data support the argument that captopril and enalapril should be used as first choice drugs for the treatment of hyperuricaemic hypertensive patients. When diuretic-induced hyperuricaemia develops in patients suffering from congestive heart failure, captopril or enalapril should be added to the therapeutic regime in doses capable of countering the shift in plasma urate concentration, provided the clinical condition of the patients permits such additional pharmacological treatment. Therapy with captopril and enalapril should preferably be instituted in a gradual manner, especially in patients with hyperuricaemia, in order to prevent the precipitation of urate in the kidney and in the urinary tract.
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PMID:Angiotensin I converting enzyme inhibitors and the renal excretion of urate. 315 8

The study of a hyperuricemic variant of chronic latent glomerulonephritis in asymptomatic hyperuricemia and gout suggested that relevant pathologic lesion can be morphologically represented by immune-complex glomerulonephritis and reactive mesangial changes as well as secondary tubulointerstitial nephritis. The underlying pathogenetic mechanism in the development of immune-complex glomerulonephritis and secondary tubulointerstitial nephritis is formation of antibodies to antigens of basal glomerular membrane and to alkaline edge of the proximal nephron, respectively. Reactive mesangial changes of the glomeruli reflect mesangiocyte sensitization to the antigens.
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PMID:[Morphological characteristics of hyperuricemic variant of chronic latent glomerulonephritis]. 317 17

We recently conducted a cross-sectional survey of the prescribing practices of rheumatologists and a random sample of family physicians. While in general there was agreement as to the preferred management of gout, family physicians were (a) more likely to use phenylbutazone, (b) more liberal in their use of allopurinol, (c) less likely to cover the introduction of allopurinol with antiinflammatory agents or to titrate the dose against the serum uric acid, or to adjust the dose according to the serum creatinine. A small number of physicians continued to routinely use urate lowering drugs in the treatment of entirely asymptomatic hyperuricemia.
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PMID:A survey of current prescribing practices of antiinflammatory and urate lowering drugs in gouty arthritis in the province of Ontario. 818 60

The effects of bezafibrate and fenofibrate on serum lipoproteins and serum urinary uric acid were compared. In a double-blind, placebo-controlled, cross-over study, each drug was administered in random order for 6 weeks followed by a 3-week drug-free phase to ten men with primary hypertriglyceridemia. Serum triglyceride and cholesterol concentrations decreased significantly with both fenofibrate and bezafibrate, although no significant change in serum apolipoprotein B, serum low density lipoprotein (LDL) cholesterol or serum high density lipoprotein (HDL) cholesterol concentrations was apparent. Serum uric acid levels, which were elevated on placebo and bezafibrate, were significantly reduced by 20% by fenofibrate. This was associated with an increase in renal uric acid clearance of 30% during fenofibrate therapy. Because it seems likely that hypertriglyceridemia and hyperuricemia are linked by a common carbohydrate inducibility, we studied the acute hyperuricemic response to orally administered fructose. Fructose (50 g) caused the anticipated rise in serum urate reaching a peak between 60 and 90 minutes, which was quantitatively greater in the men with hypertriglyceridemia than in healthy controls. The serum uric response to fructose was unaffected by bezafibrate, but was converted to normal by fenofibrate. The hyperuricemic action of fenofibrate is of sufficient magnitude to be of therapeutic value in the management of patients whose hypertriglyceridemia is associated with gout.
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PMID:Hypertriglyceridemia and hyperuricemia: effects of two fibric acid derivatives (bezafibrate and fenofibrate) in a double-blind, placebo-controlled trial. 327 90

To determine the frequency of gout in our renal transplant population and to identify any predisposing factors, we retrospectively examined the outpatient records of all patients transplanted between January 1980 and July 1984 in whom the allograft functioned for at least 1 year. Two hundred forty-three charts were sufficiently complete to be evaluated. Of the 211 patients receiving corticosteroids and cyclosporine (CyA) as immunosuppression, 25 had at least one documented episode of gout (9.7% of total, 11.8% of CyA patients); no episodes occurred in the 32 patients receiving azathioprine and corticosteroid therapy (P = .05). The time from transplantation to the first episode of gout ranged from 4 months to 4 years. Of the patients without gout, 103 of the 186 receiving CyA (55.5%) and eight of 32 receiving azathioprine (25%) had asymptomatic hyperuricemia (serum uric acid greater than 8.5 mg/dL for men, greater than 7.0 mg/dL for women, P less than .01). The number of patients receiving diuretics in the CyA treated group was 142 of 211 (67%) v 12 of 32 (37.5%) in the azathioprine group. However, the increased incidence of gout or hyperuricemia in patients receiving CyA was not due to the effect of the diuretic alone. There was no correlation between the serum creatinine and uric acid in either the CyA or azathioprine group (r value for CyA group = -.06 and for the azathioprine group = -.26). Compared with patients receiving azathioprine, we conclude that there is an increased incidence of gout and/or hyperuricemia in renal transplant patients treated with CyA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The incidence of gout in renal transplant recipients. 331 90


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