Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output.

OBJECTIVE: To compare renal handling of uric acid in patients with primary gout with that of a control group. METHODS: A case-control study of 100 patients with primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, urinary uric acid to creatinine ratio, and glomerular uric acid filtered load were calculated using 24-hour urine samples. After treatment with allopurinol to achieve similar glomerular filtered load of uric acid, patients were again compared with controls. RESULTS: Patients with gout showed lower uric acid clearance, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to creatinine ratio than controls at baseline, when patients showed hyperuricemia. Although the glomerular uric acid filtered load was much higher in patients with gout than controls, 24-hour uric acid excretion was not statistically different. After treatment with allopurinol, and achieving similar uric acid filtered loads, patients still showed lower figures than controls. When patients with 24-hour urinary uric acids levels >700 mg/day were compared with controls, they had lower uric acid clearance and fractional excretion of uric acid than controls, both at baseline and after achieving similar filtered loads with allopurinol therapy. CONCLUSIONS: Renal underexcretion is the main mechanism for the development of primary hyperuricemia in gout, but even patients showing apparent high 24-hour uric acid output show lower uric acid clearance than controls, indicating that relative, low-grade underexcretion of uric acid is at work.

Improvement of renal function in patients with chronic gout after proper control of hyperuricemia and gouty bouts.

AIM: To evaluate the effect of nonsteroidal anti-inflammatory drug (NSAID) withdrawal on renal function in patients with chronic gout after proper control of hyperuricemia and gouty symptoms. METHODS: Patients with chronic gout, who regularly used NSAIDs to control gouty symptoms prior to urate-lowering therapy, were prospectively followed up in an observational study. Risk factors for renal function impairment were recorded, and the clearance of creatinine (Ccr) was initially measured while on colchinine therapy to prevent gouty bouts. Therapy with urate-lowering drugs was started in order to keep serum urate levels under 6.0 mg/dl (275 micromol/l), and the Ccr was monitored during the follow-up period. Final assessment of the renal function was made after 1 year free from gouty bouts and without NSAID therapy during this period. RESULTS: 87 patients completed a 1-year period of NSAID withdrawal. Low initial Ccr was related to age, hypertension, hypertriglyceridemia and the presence of previous renal diseases. After proper control of gout and NSAID withdrawal during 1 year, the mean Ccr significantly raised from 94 to 104 ml/min. The improvement was especially significant in patients whose initial Ccr was under 80 ml/min. Their mean Ccr rose from 60 to 78 ml/min, and 12 of 29 patients achieved normal Ccr at the end of the study. No risk factor correlated with improvement of the renal function. CONCLUSIONS: Renal function impairment in patients with chronic gout is mainly related to vascular risk factors, but improvement of the renal function was observed after proper control of hyperuricemia and NSAID withdrawal. Optimal control of hyperuricemia and, therefore, of symptoms of gout should be especially considered in patients with vascular risk factors in order to avoid renal function loss due to NSAID use.

Treatment of chronic gout in patients with renal function impairment: an open, randomized, actively controlled study.

Treatment of gout and hyperuricemia can be difficult in patients with chronic renal failure. At present, there is no study available comparing the efficacy of the most widely used agent, allopurinol, and the uricosuric benzbromarone for the control of hyperuricemia in patients with renal insufficiency. We describe an open, randomized, actively controlled, comparative trial in patients with clearance of creatinine from 20 to 80 mL/ min/1.73 m(2). Patients were randomized to take benzbromarone (100-200 mg/day) or allopurinol (100-300 mg/day). Outcome variables were the following: reduction of serum urate (Sur), Sur & tl; 6 mg/dL (357 micromol/L), reduction of gouty bouts and reduction of tophi. During 9-24 months of follow-up 36 patients were studied.The reduction of Sur was higher with benzbromarone, and only 1 of 17 patients taking benzbromarone did not achieve Sur < 6 mg/dL versus 7 of 19 taking allopurinol. Patients who did not reach optimal Sur levels with allopurinol were more frequently taking diuretics and showed lower fractional excretion of urate and higher initial Sur levels than patients with proper control of Sur. Seven patients with suboptimal control of serum urate were changed to benzbromarone 100 mg/day, which showed efficacy similar in those who were initially randomized to benzbromarone. A reduction of gouty bouts and size of tophi was observed after proper control of Sur. Allopurinol is effective in controlling hyperuricemia, but patients with higher initial Sur levels or taking concomitant diuretic therapy are less prone to reach therapeutic goals.Benzbromarone is useful for the control of hyperuricemia in patients with renal insufficiency even with concomitant diuretic administration; patients benefited include those who previously had no improvement by taking allopurinol.

Efficacy of allopurinol and benzbromarone for the control of hyperuricaemia. A pathogenic approach to the treatment of primary chronic gout.

OBJECTIVES: To study the efficacy of allopurinol and benzbromarone to reduce serum urate concentrations in patients with primary chronic gout. METHODS: Prospective, parallel, open study of 86 consecutive male patients with primary chronic gout. Forty nine patients (26 normal excretors and 23 under excretors) were given allopurinol 300 mg/day and 37 under excretors benzbromarone 100 mg/day. After achieving steady plasma urate concentrations with such doses, treatment was then adjusted to obtain optimal plasmatic urate concentrations (under 6 mg/dl). RESULTS: Patients receiving allopurinol 300 mg/day showed a mean reduction of plasmatic urate of 2.75 mg/dl (from 8.60 to 5.85 mg/dl) and 3.34 mg/dl (from 9.10 to 5.76 mg/dl) in normal excretors and under excretors respectively. Patients receiving benzbromarone 100 mg/day achieved a reduction of plasmatic urate of 5.04 mg/dl (from 8.58 to 3.54 mg/dl). Fifty three per cent of patients receiving allopurinol and 100% receiving benzbromarone achieved optimal plasma urate concentrations at such doses. The patients with poor results with allopurinol 300 mg/day achieved a proper plasma urate concentration with allopurinol 450 to 600 mg/day, the mean final dose being 372 mg/day. Renal function improved and no case of renal lithiasis was observed among benzbromarone treated patients, whose mean final dose was 76 mg/day. CONCLUSION: Benzbromarone is very effective to control plasma urate concentrations at doses ranging from 50 to 100 mg/day. Uricosuric treatment is a suitable approach to the treatment of patients with gout who show underexcretion of urate.

Efficacy of radiosynovectomy of the knee in rheumatoid arthritis: evaluation with magnetic resonance imaging.

The intra-articular injection of a radiopharmaceutical agent (radiosynovectomy) produces a reduction of the synovial inflammatory process. The inflammed synovial membrane can be identified with magnetic resonance imaging after the intravenous administration of gadolinium (MRI-Gd). A 6-month prospective study was carried out in 10 patients with rheumatoid arthritis after radiosynovectomy of the knee. The efficacy was evaluated with clinical parameters and MRI-Gd. A progressive amelioration of synovial effusion, pain, articular range of mobility, total leucocytes count in synovial fluid and synovial membrane thickness through MRI-Gd was observed. The global efficacy was considered to be good in six patients, fair in three and bad in one. The study shows for the first time that MRI-Gd allows the evaluation of the response of the synovial membrane to radiosynovectomy.

High prevalence of undetected carpal tunnel syndrome in patients with fibromyalgia syndrome.

OBJECTIVE: To assess the prevalence of carpal tunnel syndrome (CTS) in patients with fibromyalgia syndrome (FM). METHODS: A series of 206 consecutive patients with FM was evaluated for CTS in an unblinded, uncontrolled study. Sixty patients with dermatomal paresthesia in the fingers enervated by the median nerve were evaluated with electromyogram and nerve conduction velocity studies (EMG/NCV). RESULTS: Thirty-three patients showed EMG/NCV findings diagnostic for CTS (16% of the 206 cases, 55% of the 60 EMG studies). Only 2 of the 33 patients with CTS had been diagnosed before rheumatologic evaluation. We compared our results with those reported for women in the general population. The overall prevalence of CTS in women was higher (16 vs 10.2%), but not statistically different. However, in our series, there was a clear difference in the higher rate of undetected CTS in women with FM compared to that of the general population (14.1 vs 6.7%) (p < 0.01). CONCLUSION: (1) CTS is at least as common in patients with FM as in the general population, contrary to that reported in retrospective studies; (2) the rate of underdiagnosed CTS in women with FM is much higher than the rate reported in the general population; (3) NCV studies may be necessary to evaluate underdiagnosed CTS in patients with FM and dermatomal paresthesia in their hands.

[Multicenter comparative study of synthetic salmon calcitonin administered nasally in the treatment of established postmenopausal osteoporosis]. / Estudio comparativo multicéntrico de la calcitonina sintética de salmón, administrada por vía nasal en el tratamiento de la osteoporosis postmenopáusica establecida.

We study the effectivity and tolerance of synthetic salmon calcitonin nasally administered (Miacalcic) in the treatment of established postmenopausic osteoporosis. During one year, two randomized groups of postmenopausic women diagnosed of osteoporosis were treated in an outpatient service either with 1 gr of calcium element per day during the whole study or with 100 daily I.U. of salmon synthetic calcitonin nasally administered in patterns of 14 days and the same period of rest, plus a supplement of 500 mgr of calcium element per day. Globally, 43 patients were assessed at the end of the study in the calcitonin plus calcium group and 45 in the group receiving only calcium. The main evaluation parameters were pain and presence of new fractures. At the beginning and at the end of the study, complementary tests of blood biochemistry were conducted, including alkalin phosphatase, calcium, phosphorus and uric acid, as well as calcium, hydroxiprolin and creatinini in the urine. The results showed a significant improvement of pain (p < 0.001) in the group treated with calcitonin, supported by a lower consumption of analgesics. The rate of vertebral fractures determined according to the Meunier's index, was also significantly lower (p < 0.001) in the group treated with calcitonin at the end of the study period. These results suggest that, compared to only calcium, nasally administered calcitonin precludes the formation of new vertebral fractures during one year of treatment and it is effective in terms of pain reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Toxic oil syndrome. A long-term follow-up of a cohort of 332 patients.

Toxic oil syndrome is a multisystemic, epidemic disease that appeared in Spain in 1981, related to the intake of rapeseed cooking oil sold in bulk. It affected 19,748 people, of whom 457 died. The toxic substance was never identified. We report the 8-year follow-up of a cohort of 332 patients. The disease was usually severe and disabling during the first 2 years, but the clinical condition of most of the patients improved thereafter. The acute phase lasted 2 months, and was characterized by pulmonary edema, rash, eosinophilia, and myalgia. During the intermediate phase (second to fourth months), severe myalgia, skin tenderness, subcutaneous edema, altered liver function, and pulmonary hypertension developed. Later on, an early chronic phase developed, from the fourth month to the end of the second year. It was marked by scleroderma, sicca syndrome, polyneuropathy, joint contractures, weight loss, and functional limitations. The clinical manifestations improved during the late chronic phase. Its most prominent clinical features were muscle cramps, chronic musculoskeletal pain, chronic lung disease, Raynaud phenomenon, carpal tunnel syndrome, and psychologic disturbances. Only 9% of the patients achieved remission after the acute phase, the rest developing late clinical manifestations of the disease. The severity of the chronic manifestations was rather variable. At the end of the 8-year follow-up, there were 10 TOS-related deaths (3%), 47% of the patients had some kind of complaint, albeit subtle in most cases, and 16% showed organic involvement related to TOS. The most important pathologic features of TOS were widespread interstitial infiltrates, non-necrotizing angiitis, endothelial proliferation, and tissue fibrosis. Toxic oil syndrome is a dramatic example of an induced scleroderma-like syndrome, similar to the eosinophilia-myalgia syndrome. Patients with EMS may develop some of the late clinical features of TOS in the years to come.

[Multifocal encephalopathy as the principle manifestation of an occult cancer]. / Encefalopatía multifocal como principal manifestación de un cáncer oculto.

We present a patient with an occult adenocarcinoma which manifested clinically as a confusional syndrome due to multiple cerebral infarctions associated to pericarditis and immunological abnormalities. Neurological involvement was secondary to nonbacterial thromboembolic endocarditis (NBTE) which did not provoke cardiac murmurs nor was detected in type B echocardiogram. Malignant cells were not observed in the pericardial effusion or in the pericardial biopsy (1.5 x 1 cm). The clinical picture mimicked an atypical lupous syndrome. The positive diagnosis was established on necropsy. The cardiovascular complications are not frequent in cancer. NBTE usually shows up clinically as a neurologic syndrome due to multiple cerebral infarctions: the normality of complementary exams and the lack of demonstration of an underlying disease do not rule out its diagnosis. When suspecting an NBTE treatment with heparin should be promptly started.

Spermatozoal density, motility and morphology in fertile and in infertile couples: a mathematical correlation.

Spermatozoal density, motility and morphology were mathematically correlated in a series of 167 fertile and 198 infertile male patients in the hope that should a high correlation between these parameters exist, a study of spermatozoal morphology might be indicated mainly in patients with low density and motility. Density, motility and morphology in the fertile series were lower than in the potentially fertile one. Partial correlation coefficients between density-morphology and between motility-morphology were lower in the fertile series than in the infertile one. Higher correlation coefficients were found between density-motility and morphology both in fertile and infertile series. Only slight differences were found between non-lineal and lineal coefficients for the pair motility-morphology. The best adjustment between motility and morphology was achieved by means of a logarithmic function. The low correlation coefficients found between density-morphology and between motility-morphology lead us to the conclusion that a study of the morphology of spermatozoa cannot be avoided in any semen sample no matter how normal the density and motility may be.

Morphology of spermatozoa in infertile men with and without varicocele.

This study was carried out to evaluate the morphology of spermatozoa in infertile men with and without varicocele. A series of 285 ejaculates were fully evaluated for seminal volume, sperm count, motility, and morphology, and classified into fertile (165 subjects), infertile without varicocele (93 subjects) and infertile with varicocele (27 subjects). Sperm morphology was classified by multiple entry criteria and recorded as normal, abnormal with head, midpiece, or tail single anomaly or abnormal with simultaneous multiple abnormalities. Semen volume was almost identical in the three groups. Among the infertile men, sperm count was lower in those having a varicocele, but conversely those with varicocele had a higher percentage of motile spermatozoa, higher percentage of spermatozoa with forward movement and higher sperm velocity. There were higher proportions of spermatozoa with abnormal morphology, total number of anomalies, and multiple anomalies in infertile men, both with and without varicocele, than in fertile men. The percentage of abnormal spermatozoa was higher in infertile men with varicocele than in those without varicocele. The pattern of sperm morphology differed between the infertile and the fertile group, and with the presence or absence of varicocele. In the presence of varicocele, only the incidence of elongated (tapered) forms was significantly increased.