Effects of the N/L-type calcium channel blocker cilnidipine on nephropathy and uric acid metabolism in hypertensive patients with chronic kidney disease (J-CIRCLE study).

This study assessed the urinary albumin/creatinine ratio (ACR) and uric acid metabolism in 70 hypertensive patients with chronic kidney disease in whom urinary ACR had remained ≥30 mg/g under the treatment of the L-type calcium channel blocker amlodipine. Three months after switching to the N/L-type calcium channel blocker cilnidipine, blood pressure (BP) did not change; however, urinary ACR significantly decreased with cilnidipine. Serum uric acid levels showed no significant change. In cases where uric acid production had been high (urinary uric acid/creatinine ratio ≥0.5), the urinary uric acid/creatinine ratio decreased significantly after cilnidipine treatment, suggesting that cilnidipine can suppress excessive uric acid formation. These results suggest that switching from amlodipine to cilnidipine results in a significant reduction in urinary ACR as well as significant reduction in uric acid production. Thus, cilnidipine is more useful than amlodipine in improving albuminuria and uric acid metabolism in hypertensive patients with chronic kidney disease.

A case of eosinophilic cholangitis: imaging findings of contrast-enhanced ultrasonography, cholangioscopy, and intraductal ultrasonography.

A 38-year-old woman was referred to our institution due to epigastralgia. She presented with obstructive jaundice and eosinophilia. Endoscopic retrograde cholangiopancreatography showed diffuse narrowing from the distal common bile duct to the bifurcation of the hepatic ducts. An endoscopic plastic biliary stent was inserted; the specimen obtained from the common bile duct wall revealed dense infiltration by eosinophils. Treatment was started with prednisolone 60 mg daily. The patient's biliary stenosis and eosinophilia gradually improved. Eosinophilic infiltration in the lungs or stomach is relatively common, but it is rare in the common bile duct. Most of the reported cases of eosinophilic cholangitis presented with eosinophilia; our patient's eosinophil count was over 1000/mm(3). Since our patient had allergies to pollen and house dust, a relationship between the allergies and the eosinophilic cholangitis was suspected, but no cause was identified.

Histologic assessment of right atrial appendage myocardium in patients with atrial fibrillation after coronary artery bypass graft surgery.

Atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Despite the prevalence of AF occurring after cardiac surgery, its pathophysiology is incompletely understood. Our previous study demonstrated that age and left atrial enlargement were independent predictors of postoperative AF. Accordingly, the purpose of this study was to determine whether cellular changes such as fibrosis and/or hypertrophy occurred in the atrium in patients who subsequently developed postoperative AF. Right atrial appendage tissue was obtained during atriotomy in patients undergoing elective CABG surgery. Quantitative assessment of atrial fibrosis was performed with Sirius red stain, and atrial cell diameter was measured with the HE stain. Linear regression, t test, chi2 test or Fisher exact test were used for statistical analysis. Sixty-one patients (mean age 71 +/- 8 years) were studied. Increasing age was significantly associated with fibrosis (beta 0.3, 95% CI: 0.06-0.55, p = 0.017). The amount of right atrial fibrosis tended to correlate with the incidence of postoperative AF (p = 0.08). Cell diameter was not significantly different between patients with versus without postoperative AF (p = 0.85). These results suggest that the age-related atrial fibrosis rather than cellular hypertrophy may be important in the pathogenesis of AF after CABG surgery and should be further investigated.

Evaluation of serum concentrations of human hepatocyte growth factor during interferon therapy for chronic hepatitis C.

In this study, the serum concentrations of human hepatocyte growth factor (HGF) were examined to clarify the relationship between HGF and interferon (IFN) therapy for hepatitis C. The subjects were 94 patients with chronic hepatitis C who underwent liver biopsy at our institution from 1994 through 1996. These patients were treated with natural IFN-alpha, IFNalpha(2a) and IFNalpha(2b) for periods varying from 12 to 26 weeks. Serum levels of HGF were determined in individual patients just before and after the administration of IFN and at 6 months and 1 year thereafter. The serum concentration of HGF was evaluated using enzyme-linked immunosorbent assay kits. The intra-hepatic location of HGF was explored using an immunoperoxidase-staining method. A positive correlation was found between the degree of HGF expression in the liver and the serum HGF concentrations. The degree of HGF expression in the liver decreased in the virologically sustained responders (SVRs) following IFN therapy. The serum HGF concentrations immediately after IFN therapy were lower than those before therapy in 83% of the patients. The concentrations gradually rose thereafter in about 45% of the non-responders, while it remained low or declined further in about half of the patients in this group. In the SVRs, the serum HGF concentrations declined in 88% of patients immediately after IFN therapy. Thereafter, it remained equally low or declined further in 60% of the SVRs. The serum HGF concentrations at 6 months and 1 year after IFN therapy were significantly lower in the SVRs than in the non-responders. In conclusions, serum HGF concentrations declined following IFN treatment regardless of the virological outcome of treatment. The decrease in serum HGF concentrations results from a decrease in the number of mesenchymal cells producing HGF. Consequently, evaluation of the serum HGF concentration is of clinical value for assessing changes in liver tissues after IFN therapy.

Long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C and liver cirrhosis after interferon therapy.

OBJECTIVE: Because the determination of the stage of fibrosis depends on rather subjective judgment, more objective parameters are needed. In this study, we followed the long-term outcome, with monitoring of platelet counts, in patients with chronic hepatitis C or liver cirrhosis (LC) who had undergone interferon (IFN) therapy. METHODS: 596 patients who were diagnosed at our institute from 1987 to 1998 with chronic hepatitis C and LC were treated with IFNs. A further 58 patients were not treated (NT). The annual rate of changes in platelet counts were calculated and compared for IFN-treated and NT patients. RESULTS: The relationship between the efficacy of IFN therapy and the incidence of hepatocellular carcinoma (HCC) showed that the patients who were virologic sustained responders (VSR) had a significantly lower incidence of HCC than the nonresponders (NR) and NT patients. The change in platelet counts was +4,350/microl/year in the VSR, +1,010/microl/year in the biochemical sustained responders (BSR), -4,540/microl/year in the NR and -6,180/microl/year in the NT patients, indicating a significant platelet increase in the VSR, a decrease of the same magnitude in the NR and NT patients, and no change in the BSR. The cumulative probability of developing HCC and liver failure was significantly higher in groups with decreased platelet counts than in groups with increased platelet counts among patients who had undergone IFN therapy. Multivariate analyses revealed that a decrease in platelet counts was the cardinal risk factor for development of HCC and liver failure in chronic hepatitis C or LC patients. CONCLUSION: Investigation of platelet counts was useful for determining the long-term outcome of patients who had undergone IFN therapy and for predicting the development of HCC.

TT virus infection does not affect the clinical profiles of patients with hepatitis B and C in Yanbian City, China.

China is an area of high endemicity for viral hepatitis, and the molecular epidemiological investigation of TT virus (TTV) infection is of interest. In the present study, we investigated the epidemiology, clinical significance and molecular characteristics of TTV infection in patients with chronic hepatitis B and C in Yanbian City, China. Serum samples obtained from 74 patients with hepatitis B and hepatitis C who visited Yanbian Hospital, located in northeast China, were analyzed in this study. The study group included 22 cases of chronic hepatitis B (B-CH), 17 cases of liver cirrhosis B (B-LC), 7 cases of hepatocellular carcinoma (B-HCC), 16 cases of chronic hepatitis C (C-CH), 11 cases of liver cirrhosis C (C-LC) and 1 case of hepatocellular carcinoma (C-HCC). Detection of TTV DNA was performed as described by Nishizawa et al. The second-round PCR products from 7 subjects were sequenced, followed by investigation of nucleotide homology and phylogenetic analysis. TTV DNA was present in 18.2, 5.9, 28.6, 6.3, 9.1 and 0% of the patients with B-CH, B-LC, B-HCC, C-CH, C-LC and C-HCC, respectively. The highest prevalence of TTV infection was seen in the groups aged 40-50 and over 60 years. There was no significant correlation between the presence of TTV DNA and the clinical parameters in patients with hepatitis B and C. The various isolates showed 97.9-100% with isolates reported previously from Japan and 98.4-100% with isolates reported previously from China. Nucleotide sequence analysis revealed that the Yanbian isolates could be classified in the same group as the Japan and China isolates. We concluded that chronic coinfection with TTV did not affect the serological features of chronic hepatitis B and C in China, as found in Tokyo, Japan.