Association of calcium urolithiasis with urokinase P141L and 3′-UTR C>T polymorphisms in a Japanese population

This was a case–control study to analyze the associations between calcium urolithiasis and the urokinase polymorphisms, P141L (rs2227564) and 3′-UTR C>T (rs4065), in a Japanese population. Cases consisted of 232 patients with urinary calcium stones (174 men and 58 women) who presented to a general hospital between April 2009 and June 2011. Among these cases, 115 (49.6 %) patients had calcium oxalate stones alone, and 113 (48.7 %) patients had calcium oxalate stones mixed with calcium phosphate stones. Controls consisted of 454 subjects who had a routine health check-up in the same prefecture. The two polymorphisms were genotyped via polymerase chain reaction with confronting two-pair primers. In the control group, the genotype frequencies of P141L were 0.573 for PP, 0.375 for PL, and 0.052 for LL, and those of 3′-UTR C>T were 0.835 for CC, 0.165 for CT, and TT was not identified. Neither of the polymorphisms was significantly associated with urolithiasis. The age- and sex-adjusted odds ratios of urolithiasis were 0.96 [95 % confidence interval (CI), 0.66–1.41] for PL and 1.22 (0.58–2.57) for LL as compared with PP genotype of P141L, and 1.01 (0.62–1.64) for CT as compared with CC genotype of 3′-UTR C>T. When compared with the PP genotype of P141L, the frequency of PL was significantly lower in female cases with a family history of urolithiasis than in females without such family history (p = 0.028). P141L and 3′-UTR polymorphisms of the urokinase gene are not associated with urolithiasis in a Japanese population.     

Population pharmacokinetics of mizoribine in pediatric patients with kidney disease

Background

The present study aimed to obtain information enabling optimisation of the clinical effect of mizoribine (MZR) in pediatric patients with kidney disease.

Methods

A total of 105 pediatric patients with kidney disease treated at our institutions were enrolled. Kidney transplant patients were excluded. Population pharmacokinetic analysis of MZR was performed based on serum concentration data. Area under the curve from time zero to infinity (AUC_∞) and maximal concentration (C _max) were calculated by Bayesian analysis.

Results

In children, the appearance of MZR in the blood tended to be slower and the subsequent rise in blood concentration tended to be more sluggish, compared to healthy adults. Apparent volume of distribution and oral clearance were also higher in children compared to adults. A significant positive correlation was observed between patient age and AUC_∞. There were significant differences of AUC_∞ and C _max by age group. No relationship was observed between the administration method of MZR and serum concentration.

Conclusion

The pharmacokinetics of MZR was different in children compared to adults. To obtain the expected clinical efficacy, the regular MZR dosage schedule (2–3 mg/kg/day) might be insufficient for pediatric patients. In particular, younger patients might require a higher dosage of MZR per unit body weight.

     

Predicting sustained virological response in chronic hepatitis C patients treated with pegylated interferon and ribavirin using a novel highly sensitive Real-time detection PCR assay

The Abbott Real Time HCV assay (lower limit of detection 12 IU/ml) was developed as a highly sensitive HCV RNA quantitative assay using real-time detection PCR(RTD-PCR). We assessed whether the new assay more effectively predicts sustained virological response (SVR) than conventional PCR (PCR) in 38 chronic hepatitis patients infected with HCV genotype 1b and treated with pegylated interferon alpha2b plus ribavirin. Sixteen patients reached SVR, 10 patients relapsed, 9 patients did not respond, 3 patients discontinued treatment. Positive predictive value (PPV) for SVR of undetectable HCV RNA at W4, 8, 12 by RTD-PCR and PCR was (100% vs. 100% at W4), (100% vs. 100% at W8), (83.3% vs. 72.7% at W12). HCV RNA undetectable at W12 had a higher PPV for SVR when measured by RTD-PCR than by conventional PCR.     

ASO Visual Abstract: Preoperative FDG Positive Lymph Nodes Predict the Postoperative Prognosis in Resectable Biliary Tract Cancers

Annals of Surgical Oncology -