Tumor lysis syndrome (TLS) is a potentially lifethreating metabolic abnormality resulting from the rapid turnover of tumor cells. In the treatment of hematological malignancies (especially rapidly proliferating neoplasams such as acute lymphoblastic leukemia and high-grade non-Hodgkin's lymphoma), prevention of TLS is crucial to improve therapeutic efficacy of cytoreductive chemotherapy. Rasburicase is a recombinant urate oxidase enzyme and used as a supportive drug in cancers patients. Results of previous clinical trials have shown that rasburicase affords early control of hyperuricemia in patients with hyperuricemia prior to dosing and minimizes the risk of hyperuricemia following cytoreductive chemotherapy. In Japan, to evaluate the safety, especially hypersensitivity reaction and long-term follow-up of antirasburicase antibodies, and efficacy, a Phase II study was conducted. Fifty adults with leukemia or lymphoma were randomly assigned to rasburicase 0.15 mg/kg/d or 0.20 mg/kg/d for 5 days. The overall response rate was 98%. Both rasburicase doses Provided equal efficacy. Seven drug related adverse events, hypersensitivity, rash, anorexia, application site pain and pyrexia, were reported prior to chemotherapy. Only 5 patients had anti-rasburicase antibodies by day 29. Rasburicase is well tolerated both prior to and during chemotherapy. However, futher studies are needed to definitively identify the optimal dose for patients in different risk categories.
It is well known that patients with gout frequently have acidic urine, a major risk factor for urolithiasis. However, the underlying mechanism of acidic urine in patients with gout remains unclear. Recently, uric acid nephrolithiasis has been reported to be a factor contributing to of renal manifestation of metabolic syndrome. Therefore, to clarify the mechanism of acidic urine in patients with gout, we investigated the relationships between urinary pH and other components of metabolic syndrome. Patients with a 24-hour urinary pH below 5.5 showed higher or greater levels of blood pressure, serum triglyceride, blood sugar, plasma insulin, and visceral fat area, compared with those with a 24-hour urinary pH above 5.5. In addition, there were negative relationships between 24-hour urinary pH and serum triglyceride, visceral fat area, and HOMA index. PPAR a agonist, bezafibrate, significantly raised the 24-hour urinary pH in gout patients in accordance with a reduction in serum triglyceride concentration and HOMA-R, probably through improvement of insulin resistance. These findings suggest that insulin resistance plays at least a partial role in the development of acidic urine in patients with gout.
The increase in serum uric acid (UA) after smoking cessation was evaluated. Materials and methods: Annual health check-up data for 7805 males obtained in the years 1996 and 2000 were analyzed longitudinally. Result: Among those who were smokers in 1996 (n=4836,62%) but had quit smoking by 2000 (n=369; annual quitting rate 1.2%), serum uric acid increased by 0.68 mg/dl. This increase of 0.68 mg/dl (SE=0.055) over the baseline was much greater than the increase of 0.31 mg/dl (SE=0.026) in nonsmokers (P<0.001). Although quitters showed an increase in body weight of 1.67 kg (SD=3.92), the increase in UA was suggested to be much greater than that expected from the increase in body weight gain alone (P<0.001). Conclusion: Weight gain after smoking cessation was considered to regress towards normal and/or regular weight in this cohort. The increase in UA was greater than that expected from weight gain, suggesting the presence of a factor that suppresses UA levels in smokers. Smokers with smoking UA levels around 6 mg/dl can expect an increase in UA by 1-2 mg after smoking cessation. This suggests the relative importance of weight gain over that assumed as well as life style factors such as alcohol consumption in supporting the continuation of smoking cessation.
Although gout has been recognized as a disorder with a high incidence of comorbid renal insufficiency, the causal relationship uric acid and renal insufficiency remains controversial. To examine whether the serum urate level and other aspects of gouty arthritis are independently associated with renal insufficiency, a cross-sectional study of 26,753 gouty patients from the Hoping Gout Database was performed. Renal insufficiency was defined according to the serum creatinine level (male>1.4 mg/dL and female>1.2 mg/dL) at the initial clinical examination. The serum urate level and the other clinical variables indicating the severity of gouty arthritis were tested for their independent association with renal insufficiency by logistic regression analysis controlling for known risk factors. In a total of 26,753 gouty cases in the database,7,245 (27.1%) were classified as having renal insufficiency. Increased duration of disease, number of joint involved by gout, frequency of flares in the last year, and tophus formation were all independently associated with renal insufficiency after controlling for covariates and serum urate level. The odds ratio for comorbid renal insufficiency by tophus formation was significantly higher than that for other clinical variables of gouty arthritis. Among the covariates, age, history of hypertension and nephrolithiasis were significantly associated with renal insufficiency, while body mass index, history of smoking and drinking, and family history of gout were significantly associated with the absence of renal insufficiency. In conclusion, this study demonstrates that the duration and severity of gouty arthritis is associated with renal insufficiency and uric acid may play an important part in the pathogenesis.