Osteoprotegerin, inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis.

BACKGROUND AND AIMS: Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients. METHODS AND RESULTS: AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥ 15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥ 15 were 3.46 (p = 0.043) for mortality and 1.90 (p = 0.007) for hospitalization. CONCLUSIONS: %AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.

Dipyridamole inhibits human peritoneal mesothelial cell proliferation in vitro and attenuates rat peritoneal fibrosis in vivo.

BACKGROUND: Peritoneal fibrosis (PF) is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Proliferation of human peritoneal mesothelial cells (HPMC) and matrix over-production are regarded as the main processes predisposing to PF. Dipyridamole (DP) has been reported to have potential as an antiproliferative and antifibrotic agent. We thus investigated the effect of DP in inhibiting proliferation and collagen synthesis of HPMC. A rat model of peritonitis-induced PF was also established to demonstrate the in vivo preventive effect of DP. METHODS: HPMC was cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay. Intracellular cAMP was measured using an enzyme immunoassay (EIA) kit. Total collagen synthesis was measured by (3)H-proline incorporation assay. Expression of collagen alpha1 (I) and collagen alpha 1 (III) mRNAs was determined by Northern blotting. The rat model of peritonitis-induced PF was developed by adding dextran microbeads (Cytodex, 8 mg/1 mL volume) to a standardized suspension (3 x 10(9)) of Staphylococcus aureus. DP was administrated via intravenous infusion (4 mg in 1 h) daily for seven days. Macroscopic grading of intraperitoneal adhesions and histological analyses of peritoneal thickness and collagen expression were performed. RESULTS: Addition of DP to HPMC cultures suppressed serum-stimulated cell proliferation and collagen synthesis. The antimitogenic and antifibrotic effects of DP appear to be predominantly mediated through the cAMP pathway, as DP increased intracellular cAMP in a dose-dependent manner. The macroscopic grade of intraperitoneal adhesion and peritoneal thickness were both significantly increased in animals treated with Cytodex plus S. aureus; on the other hand, DP attenuated these fibrotic changes with statistical significance (P < 0.01). Analysis of gene expression of collagen alpha 1 (I) and alpha1 (III) in the peritoneal tissue of experimental animals yielded similar results. CONCLUSIONS: This study suggests that dipyridamole may have therapeutic potential in treating peritoneal fibrosis.

Pentoxifylline inhibits human peritoneal mesothelial cell growth and collagen synthesis: effects on TGF-beta.

BACKGROUND: Prevention or treatment of peritoneal fibrosing syndrome has become an important issue in patients on continuous ambulatory peritoneal dialysis (CAPD). Recent evidence has suggested that mesothelial stem cell proliferation and matrix over-production predispose the development of peritoneal fibrosis. We investigated whether pentoxifylline (PTX) affects human peritoneal mesothelial cell (HPMC) growth and collagen synthesis. METHODS: HPMC was cultured from human omentum by an enzymic disaggregation method. Cell proliferation was assayed using a methyltetrazolium uptake method. Cell cycle analysis was performed by flow cytometry. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Prostaglandins and cAMP were determined by enzyme immunoassay. Northern blot analysis was used to determine mRNA expression. RESULTS: Our data show that PTX inhibited serum-stimulated HPMC growth and collagen synthesis in a dose-dependent manner. Cell cycle analysis showed that PTX arrested the HPMCs in the G1 phase. PTX decreased the procollagen alpha1 (I) mRNA expression either stimulated by serum or transforming growth factor-beta (TGF-beta). PTX did not alter prostaglandins synthesis but dose-dependently increased intracellular cAMP level. PTX, the same as 3-isobutyl-l-methylxanthine, could potentiate prostaglandin E1 (PGE1) increased cAMP levels of HPMC. The antimitogenic and antifibrogenic effects of PTX on HPMC were reversed by N-[2]-((p-Bromocinnamyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89). Therefore, the mechanism of these effects may be due to the phospodiesterase inhibitory property of PTX. CONCLUSIONS: These data suggest that PTX may have a role in treating peritoneal fibrosing syndrome.

ED overcrowding in Taiwan: facts and strategies.

The objective of this study was to quantity the extent of emergency department (ED) overcrowding in Taiwan and to identify possible solutions. The ED log was reviewed for all patients who presented to the National Taiwan University Hospital's ED from January 16, 1996 through February 15, 1996. Charts from patients held longer than 72 hours were reviewed. Among 5,810 patients, 213 (3.6%) were held in the ED for more than 72 hours (7.1 patients per day). In 149 (70.0%) of them, admission was indicated but delayed (42 because more than one subspecialty were involved, 57 because of unavailability of bed, and 50 because of the disparity in admission priority between the emergency physicians and house staffs). Eighteen (8.4%) patients did not meet admission criteria (13 could have been treated in outpatient clinics, 3 needed placement in nursing homes, 2 because of personal problems). The others (22%) recovered while waiting. Significant overcrowding exists in EDs in Taiwan. Four solutions are proposed: (1) creation of a holding unit; (2) flexible ward assignment; (3) pre-established rules for admission priority-setting; and (4) active interfacility transfer. Only through these efforts can EDs in Taiwan guarantee an optimal level of care in the face of a growing patient demand.

Pharmacologic agents inhibit rat mesangial cell proliferation and collagen synthesis.

Prevention of the development of end-stage renal disease is one of the most promising areas of research in nephrology. Because mesangial cell proliferation and extracellular matrix accumulation have been regarded as antecedents of glomerulosclerosis, agents that can inhibit mesangial cell proliferation may have a potential to retard the progression of renal diseases. Therefore, we investigated several clinically available agents that might affect mesangial cell proliferation and collagen synthesis in male Sprague-Dawley rats. Cell proliferation was measured by the tetrazolium dye uptake method. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Intracellular cAMP levels were measured by enzyme immunoassay. Our results showed that hydralazine (82% inhibition at 10 micrograms/mL), ticlopidine (61% inhibition at 30 micrograms/mL), aminophylline (66% inhibition at 200 micrograms/mL), and nicametate (91% inhibition at 1 mg/mL) inhibited serum-stimulated rat mesangial cell (RMC) growth in a dose-dependent manner. Ticlopidine (43% inhibition at 30 mg/mL), aminophylline (52% inhibition at 200 mg/mL), and nicametate (35% inhibition at 1 mg/mL) inhibited collagen synthesis in confluent RMCs. Aminophylline may act through increasing intracellular cAMP levels (9.7 +/- 0.7 pmol/mg protein at 200 micrograms/mL of aminophylline vs 4.2 +/- 0.6 pmol/mg protein at control). These data suggest that aminophylline, ticlopidine, hydralazine, and nicametate can inhibit RMC proliferation and collagen synthesis.

Viral hepatitis infection should be considered for evaluating uremic pruritus in continuous ambulatory peritoneal dialysis patients.

Determining the possible association of viral hepatitis infection and degree of pruritus is the primary concern of this study. Ninety-six adequately dialyzed CAPD patients (47 male and 49 female) and 526 normal controls (266 male and 260 female) were enrolled. Blood hemoglobin, ferritin, electrolytes, calcium, phosphate, albumin, urea, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, and bilirubin were analyzed by routine methods. Serum HBsAg was examined, using a radioimmunoassay method and the anti-HCV, an enzyme immunoassay method. All cases were interviewed with a standardized questionnaire. The highest possible pruritus score (PS) was 22. The prevalences of HBsAg(+) and anti-HCV(+) were 14.6% and 17.7%, respectively. The mean PS in all 96 CAPD patients was 11.6 (range 7-22). The mean PS were 11.8 +/- 0.6 and 12.5 +/- 1.0 for patients infected with HBV and HCV, respectively. Both were significantly higher than that (10 +/- 0.9) of patients without hepatitis infection. AST and ALT were significantly higher in patients infected with viral hepatitis than those without. The other biochemical parameters were not significant. Thirty-seven (38.5%) of our 96 patients had mild pruritus (PS < or = 7) and 11 (15.9%) had severe pruritus (PS > or = 15). Of the 83.9% (26/31) patients with viral hepatitis, the grades of skin itching were moderate to severe; whereas those of the patients without viral hepatitis, 53.6% (37/69) belonged to the group of moderate to severe pruritus (p = 0.003, chi 2 test with Yates' correction). The authors recommended screening of viral hepatitis infection to be undertaken for uremic patients with unexplained skin itching.

Viral hepatitis in continuous ambulatory peritoneal dialysis patients in an endemic area for hepatitis B and C infection: the Taiwan experience.

The prevalence of hepatitis B virus (HBV), hepatitis C virus (HCV), and their associations in 64 continuous ambulatory peritoneal dialysis (CAPD) patients (30 males and 34 females) were evaluated. A comparison was also made with 526 normal controls (266 males and 260 females). Forty-seven (75%) CAPD patients were anti-HBc positive, with no significant difference to the control group (81.9%). This probably reflects acquisition of HBV infection by CAPD patients before initiation of chronic dialysis therapy in a region hyperendemic for HBV. On the contrary, 11 (17.2%) CAPD patients were anti-HCV positive and 8 (15.2%) were seropositive for both anti-HBc and anti-HCV-much greater prevalence rates compared to those of the control group. The prevalence of anti-HCV correlated with the history and numbers of blood transfusion, and the length of time on previous hemodialysis. A similar correlation occurred in patients with both anti-HBc(+) and anti-HCV(+). In conclusion, in an HBV endemic area such as Taiwan, the prevalence of coexisting HBV and HCV infection in CAPD patients depends on the latter.

Simultaneous determination of refractive indices and angles of prisms.

By using the Fraunhofer diffraction on a fine slit and the statistic models of the least-squares error plus the normal error distribution, the refractive indices and the angles of prisms can be determined simultaneously with a simple experimental setup. The accuracy is of the order of 10(-4) for refractive indices and of the order of minutes for angles. The computer algorithms to apply the statistical models are explained.