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The influence of allopurinol on renal function in gout.

Our data demonstrate that adequate control of uric acid production and serum acid concentration in primary gout arrests further deterioration of renal function and in some instances permits subsequent improvement in renal hemodynamic function even when renal impairment is clearly established. In considering the nature of the lesions of urate nephropathy, our study suggests that control of serum uric acid with drug therapy before renal involvement is apparent might prevent or significantly delay the morbidity and mortality of this complication of primary gout.

Allopurinol↗

Plasma follicle-stimulating hormone, luteinizing hormone, and sex hormones in patients with gout.

Plasma levels of follicle-stimulating hormone, luteinizing hormone, testosterone, progesterone, 17 beta-estradiol, and cortisol were examined in normal subjects and gout patients under baseline conditions and after clomiphene stimulation. A significant decrease in follicle-stimulating hormone, luteinizing hormone, and 17 beta-estradiol was observed both in male and female gout patients; in the same patients, the plasma testosterone: 17 beta-estradiol ratio was found to be significantly higher than in control subjects. The changes observed suggest a possible role played by 17 beta-estradiol in the regulation of purine biosynthesis and uric acid metabolism.

Adult↗

Persistence of monosodium urate crystals and low-grade inflammation in the synovial fluid of patients with untreated gout.

Synovial fluid (SF) from 74 asymptomatic knees of patients with gout was analyzed. These patients had never been treated with serum uric acid-lowering agents. SF samples were analyzed for the presence of crystals and for cell counts, using undiluted SF directly in a Niebauer cell counting chamber. Thirty-seven of the aspirated knees had previously been inflamed, and monosodium urate (MSU) crystals were seen in SF aspirates from 36 of them (97%). Of the 37 knees that had never been inflamed, only 8 contained MSU crystals (P less than 0.00001). After reaching the joint, MSU crystals will persist in the SF as long as the serum uric acid level has not been lowered by appropriate treatment. In this situation, analysis of SF is an excellent diagnostic test for the intercritical gout. The mean cell count in the 44 SF samples that contained MSU crystals was 449/mm3 (95% confidence interval 310-589); the mean cell count in the 30 SF without MSU crystals was 64/mm3 (95% confidence interval 34-95) (P less than 0.00002). The SF samples that contained MSU crystals also had a higher percentage of polymorphonuclear leukocytes than those without MSU crystals (P less than 0.002). These data suggest that there is a low-grade inflammation present in the knees of patients with MSU crystals, the consequences of which should be investigated.

Adult↗

Allopurinol sensitivity in a patient with chronic tophaceous gout: success of intravenous desensitization after failure of oral desensitization.

Sensitivity to allopurinol, which occurs in 10-15% of patients, can seriously limit the drug's use in chronic tophaceous gout. Oral allopurinol desensitization has been advocated for sensitive patients in whom use of the drug is warranted. We report the successful use of intravenous allopurinol desensitization in a patient with chronic tophaceous gout in whom oral desensitization had previously failed.

Administration, Oral↗

Spinal involvement in gout.

A 45-year-old man with severe gout was admitted to the hospital because of Staphylococcus aureus septicemia. He had also a biclonal dysglobulinemia, without signs of myeloma. An asymptomatic lytic lesion of the left pedicle of L5 was discovered on radiographs. Histologic examination of the biopsied lesion showed typical tophaceous gout.

Gout↗

Multi-centre trial of naproxen and phenylbutazone in acute gout.

Naproxen 750 mg as a single dose followed by 250 mg three times daily has been compared with phenylbutazone 200 mg four times daily for 48 hours followed by 200 mg three times daily for the treatment of acute gout in an open study on 41 patients. The drugs were equally effective with few and relatively mild side effects. Naproxen is a useful alternative agent for the treatment of acute gout.

Adult↗

Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: identification of point mutations in Japanese patients with Lesch-Nyhan syndrome and hereditary gout and their permanent expression in an HPRT-deficient mouse cell line.

Two different single nucleotide transitions of hypoxanthine-guanine phosphoribosyltransferase (HPRT) were identified in a Japanese patient with Lesch-Nyhan syndrome (LNS) and a patient with hereditary gout. HPRT enzyme activities in the two patients were severely deficient, but the size and amount of mRNA were normal according to Northern analysis. Entire coding regions of HPRT cDNAs were amplified by PCR and sequenced. A G-to-A substitution at base 208 in exon 3, which predicted glycine 70 to arginine, was detected in the LNS patient (identical mutation with HPRT Utrecht). A C-to-A substitution at base 73 in exon 2, which predicted proline 25 to threonine, was detected in the gout patient (designated HPRT Yonago). We transfected normal HPRT cDNA, mutant cDNA with HRPT Utrecht or mutant cDNA with HPRT Yonago, respectively, to HPRT-deficient mouse cells and isolated permanent expression cell lines. The HPRT-deficient mouse cells had no detectable HPRT activity and a very low amount of HPRT mRNA. When the HPRT-deficient mouse cells were transfected with normal human cDNA, HPRT enzyme activity increased to 21.8% that of normal mouse cells. The mouse cells transfected with HPRT Utrecht showed no increase in HPRT activity; however, when the mouse cells were transfected with HPRT Yonago, the activity increased to 2.4% that of normal activity. The proliferative phenotypes of these cells in HAT medium and in medium containing 6-thioguanine were similar to those of skin fibroblasts from the patients. This series of studies confirmed that each of the two point mutations was responsible for the decreases in HPRT enzyme activity, and the proliferative phenotypes in HAT medium and medium containing 6-thioguanine.

Adolescent↗

Gout in the spine and sacro-iliac joints: radiological manifestations.

It is well known that deposits of urates in soft tissues occur commonly in gout, particularly in para-articular areas and in articular cartilages of the limbs. Involvement of the spine and sacro-iliac joints by such deposits, however, has been regarded as being relatively unusual and has attracted little attention in the literature. As we were impressed by the frequency of episodes of acute back pain in our patients with gouty arthritis, established definitely on clinical and biochemical grounds, we undertook a radiological investigation of the spine and sacro-iliac joints in a series of 54 subjects. It was suspected that their episodes of pain were clinical manifestations of gout, and 12 of the group had suffered one or more attacks. Of these 12 subjects, eight were found to have radiological abnormalities. In six subjects, evidence of sacro-iliitis was demonstrated, which is comparable to the report of Resnick and Reinke [8], and in two patients vertebral lesions corresponded to those describe by Jaffe [5]. Hyperostotic spondylosis was present in no fewer than 29 of the series. Although lacking histological confirmation of the lesions demonstrated radiologically, we believe that our suspicions have been confirmed.

Adult↗

Isolated or dominant lesions of the patella in gout: a report of seven patients.

Isolated or dominant osteolytic lesions of the patella are an unusual manifestation of gout. We present seven patients who had such patellar lesions unilaterally (six patients) or bilaterally (one patient) and analyze the radiologic characteristics to determine whether they can be differentiated from those of other osteolytic lesions of the patella. The lesions were uniformly characterized by a geographic pattern of bone destruction in the superolateral aspect of the patella. Five lesions were each accompanied by a peripatellar soft tissue mass, four of which contained calcification. It therefore appears that an osteolytic lesion of the superolateral portion of the patella, especially when associated with a peripatellar calcified soft tissue mass, should alert one to the possible diagnosis of gout. Awareness of this possibility may obviate the need for invasive diagnostic procedures.

Adult↗

Gout and uric acid nephropathy: some new aspects in diagnosis and treatment.

It has been recognized that primary disorders of uric acid metabolism result from impaired renal excretion or increased endogenous production of uric acid. It has also been found that these two mechanisms do not comprise two distinct syndromes, but may each constitute a group of syndromes. Contrary to earlier as well as currently published reports we conclude from our clinical and experimental experience that the fraction of so-called over-producers is less than 1% of all patients with primary hyperuricaemia and gout. A procedure for the diagnosis of uric acid overproduction is suggested. The manifestation of hyperuricaemia and gout mainly depends on renal uric acid clearance and is greatly influenced by dietary habits in most of the patients. An impaired renal uric acid excretion results in an increased intestinal excretion; this partly compensates for the defect. Normalization of serum uric acid should be achieved by dietary regimens with or without additional drug treatment, but not by drug treatment alone. With drug treatment xanthine oxidase inhibitors are preferable to uricosurics; no other xanthine oxidase inhibitor besides Allopurinol has been in clinical trial, however. Due to the enhancement of uric acid clearance with uricosurics, there are groups of patients who should not be treated with these drugs. Fixed combinations of Allopurinol and uricosurics should not be used. Drugs which have uricosuric as well as other pharmacologic properties are under investigation. So far they have not reached general clinical application.

Adult↗

Juvenile gout with typical radiographic findings.

Gout, a common disorder in adults is exceedingly rare in the first decade of life and uncommon in teenagers. A recent book on bone diseases in childhood does not even mention gout [7]. Childhood podagra with a radiographic findings is a very unusual finding indeed.

Adolescent↗

Uric acid metabolism in two patients with coexistent Down's syndrome and gout.

Two patients with coexistent Down's syndrome and gout are described. Although increased serum urate levels are frequently reported in Down's syndrome, only a few such patients have been described with concomitant gout. In our patients no significant alterations of the purine salvage pathway were found, and the turnover parameters of uric acid, determined by means of a 14C-labeled uric acid study, were consistent with the metabolic findings observed in normoexcretor gouty patients.

Adult↗

Juvenile intraosseous gout of the calcaneus.

Gout presenting as an osteolytic lesion is exceedingly rare in children with asymptomatic hyperuricemia. We report the clinical and radiological presentation of intraosseous gout in a 13-year-old boy.

Adolescent↗

Tophaceous gout in an amputation stump in a patient with chronic myelogenous leukemia.

Gout is a common rheumatologic disorder that can have an unusual clinical presentation. This case report describes the development of a gouty tophus at a site of remote traumatic forearm amputation in a patient with chronic myelogenous leukemia (CML). It further addresses the imaging characteristics of tophaceous gout as well as the differential diagnostic considerations as regards both the imaging findings and the clinical presentation.

Aged↗

Tophaceous gout in the cervical spine.

Gout is a common metabolic disorder typically affecting the distal joints of the appendicular skeleton. Involvement of the axial skeleton, particularly the facet joints and posterior column of the cervical spine, is rare. This case report highlights such a presentation in a 76-year old female who presented with cervical spine pain following a fall. Her radiological findings were suggestive of a destructive metastatic process. Histological diagnosis confirmed tophaceous gout.

Aged↗

Hyperuricemia and gout following pediatric renal transplantation.

Hyperuricemia and gout are common complications in adult renal transplant recipients. In pediatric recipients, however, hyperuricemia seems to be rare, but data are scarce. Thirty-two children (21 males, 11 females) were investigated for a median time of 4.8 years (range: 0.4-11.2 years) following renal transplantation. The median age of this pediatric study group was 13.9 years (range: 5.7-20.3 years), and the calculated glomerular filtration rate (GFR) was 61 ml/min per 1.73 m(2) (range:12-88 ml/min per 1.73 m(2)). All patients were given calcineurin inhibitors, with 22 and ten children receiving cyclosporine A (CSA) and tacrolimus (TAC), respectively. The median plasma uric acid was 385 micromol/l (range: 62-929 micromol/l); 15 children (47%) were above the age-related normal range. Only one patient experienced gouty arthritis. There was a significant correlation between plasma uric acid concentration and both time span after transplantation and plasma creatinine, and an inverse correlation to GFR (p<0.05). No significant correlation was found between plasma uric acid and body mass index (BMI). Plasma uric acid concentrations were neither different among CSA- and TAC-treated children, nor did they correlate with drug exposure or blood trough levels of CSA or TAC. Plasma uric acid concentration was not different when compared to children with chronic renal failure (CRF) of a similar degree in native kidneys. We conclude that hyperuricemia is common among pediatric renal transplant recipients and rather a consequence of chronic renal transplant dysfunction than the use of calcineurin inhibitors. Gout, however, is rare.

Adolescent↗