Tzung-Hai Yen

Publications (83) View all

• Article: Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

  T-H Yen, H-Y Yang, Y-H Yeh, P-H Chu, C-J Wen, J-F Fu, I-K Wang, C-C Liang, C-T Chang, K-H Chen, Y-C Tian, C-C Hung, J-L Lin, C-W Yang
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  ABSTRACT: This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).
  Lupus 12/2012; · 2.34 Impact Factor
• Article: Effect of chelation therapy on progressive diabetic nephropathy in patients with type 2 diabetes and high-normal body lead burdens.

  Kuan-Hsing Chen, Ja-Liang Lin, Dan-Tzu Lin-Tan, Hsiang-Hao Hsu, Ching-Wei Hsu, Kuang-Hung Hsu, Tzung-Hai Yen
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  ABSTRACT: A previous study in type 2 diabetic patients with high-normal body lead burdens showed that EDTA chelation therapy for 3 months slows progressive diabetic nephropathy during a 12-month follow-up. The effect of a longer course of therapy on kidney function decrease over a longer follow-up is not known. A 12-month run-in phase, then a randomized single-blind study with a 27-month intervention. University medical center; 50 patients (serum creatinine, 1.5-3.9 mg/dL) with high-normal body lead burden (≥80-<600 μg) were randomly assigned to the treatment and control groups. The treatment group received weekly chelation therapy for 3 months to reduce their body lead burden to <60 μg and then as needed for 24 months to maintain this level. The control group received placebo for 3 months and then weekly for 5 weeks at 6-month intervals for 24 months. The primary end point was change in estimated glomerular filtration rate (eGFR) over time. A secondary end point was a 2-fold increase in baseline serum creatinine level or the requirement for renal replacement therapy. Body lead burdens were assessed by EDTA mobilization tests and eGFR was calculated using the equation for Chinese patients with type 2 diabetes. Mean baseline eGFRs in the treatment and control groups were similar. After 3 months of chelation therapy, the change in eGFR in the treatment group (+1.0±4.8 mL/min/1.73 m(2)) differed significantly from that in the control group (-1.5±4.8 mL/min/1.73 m(2); P = 0.04). In the subsequent 24-month intervention, the yearly rate of decrease in eGFR (5.6±5.0 mL/min/1.73 m(2) per year) in the treatment group was slower than that (9.2±3.6 mL/min/1.73 m(2) per year; P = 0.04) in the control group. 17 (68%) control-group patients and 9 (36%) treatment-group patients achieved the secondary end point. Small sample size, not double blind. A 27-month course of EDTA chelation therapy retards the progression of diabetic nephropathy in type 2 diabetic patients with high-normal body lead burdens.
  American Journal of Kidney Diseases 06/2012; 60(4):530-8. · 5.43 Impact Factor
• Article: Spectrum of toxic hepatitis following intentional paraquat ingestion: analysis of 187 cases.

  Chin-Jung Yang, Ja-Liang Lin, Dan-Tzu Lin-Tan, Cheng-Hao Weng, Ching-Wei Hsu, Shen-Yang Lee, Shwu-Hua Lee, Chia-Ming Chang, Wey-Ran Lin, Tzung-Hai Yen
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  ABSTRACT: This retrospective observational study examined the clinical features, the degrees of toxic hepatitis, physiological markers and clinical outcomes after intentional paraquat poisoning and sought to determine what association, if any, might exist between these findings. A total of 187 patients were referred for management of intentional paraquat ingestion between 2000 and 2010. Patients were categorized into two groups according to their hepatic complication, i.e. with (N = 87) or without (N = 100) toxic hepatitis. Demographic, clinical and laboratory data were obtained for analysis. Mortality rates were also analysed. It was found that patients with toxic hepatitis were younger (39.7 ± 13.7 vs 44.2 ± 16.6 year old, P = 0.046), and suffered from greater incidences of acute respiratory failure (63.2 vs 48.0%, P = 0.037) and acute renal failure (75.9 vs 56.0%, P = 0.004) than patients without hepatitis. The hospitalization period was longer in patients with hepatitis than without hepatitis (16.2 ± 14.6 vs 11.2 ± 12.1 days, P = 0.012), even though there was no difference in mortality rate between both groups (56.3 vs 53.0%, P = 0.649). Notably, the symptoms of toxic hepatitis developed within 6.7 ± 6.3 days of exposure to paraquat with aspartate aminotransferase (AST) 138 ± 156 U/L, alanine aminotransferase (ALT) 127 ± 114 U/L and total bilirubin 2.7 ± 2.6 mg/dL. The hepatitis peaked at 9.5 ± 8.8 days with AST 125 ± 139 U/L, ALT 183 ± 181 U/L and total bilirubin 3.2 ± 3.6 mg/dL. Nevertheless, the symptoms resolved within 17.3 ± 9.8 days of paraquat exposure, and none of the patients died of hepatic complication. A substantial proportion of paraquat patients suffered from hepatic complication (46.52%), but the spectrum of hepatitis in these patients seemed mild and transient.
  Liver international: official journal of the International Association for the Study of the Liver 06/2012; 32(9):1400-6. · 3.82 Impact Factor
• Article: Early Identification of Leptospirosis as an Ignored Cause of Multiple Organ Dysfunction Syndrome.

  Huang-Yu Yang, Tzung-Hai Yen, Chan-Yu Lin, Yung-Chang Chen, Min-Jeng Pan, Chih-Hsiung Lee, Chun-Chen Yu, Mai-Szu Wu, Shin-Shu Wu, Cheng-Hao Weng, Kwan-Hsing Chen, Cheng-Chieh Hung, Chih-Wei Yang
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  ABSTRACT: Leptospirosis is the most common zoonosis in the world but remains underreported, owing to protean manifestations and ignorance about the disease among healthcare providers in Taiwan. From September 2000 to March 2006, surveillance of 455 multiple organ dysfunction syndrome patients with unclear cause or clinical suspicion of leptospirosis was performed. Diagnosis was further confirmed by microscopic agglutination test or isolation of leptospira. Cases were classified as excluded based on confirmed etiology other than leptospirosis or negative paired serologic test. Forty-two patients were confirmed as leptospirosis, which accounted for 9.2% of total patients with multiple organ dysfunction syndrome. Forty-nine excluded cases were identified for a case-control analysis for clinical distinction. The most common presentations of leptospirosis were fever (97.6%), acute kidney injury (85.7%), and jaundice (61.9%). The leptospirosis group showed lower urine specific gravity (cutoff value: 1.0145) and enlarged kidney size (cutoff value: 11.05 cm) as compared with the excluded cases by multivariate logistics regression. Delayed antibiotics administration prolongs the duration of hospitalization (R Square: .486, P< .01). No mortality has been found in the leptospirosis group after initiation in 2003 of rapid IgM serology assay that showed considerably high sensitivity and specificity. Leptospirosis accounts for a salient cause of multiple organ dysfunctions in Taiwan. Early awareness of leptospirosis by distinct presentations, followed by prompt antibiotics therapy can dramatically save the patients. The easy-performed rapid IgM serology assay is suitable as a rapid screening test for the diagnosis of leptospirosis.
  Shock (Augusta, Ga.) 05/2012; · 2.87 Impact Factor
• Article: Bacteremia in hemodialysis and peritoneal dialysis patients.

  I-Kuan Wang, Yi-Chih Chang, Chih-Chia Liang, Feng-Rong Chuang, Chiz-Tzung Chang, Hsin-Hung Lin, Chung-Chih Lin, Tzung-Hai Yen, Po-Chang Lin, Che-Yi Chou, Chiu-Ching Huang, Wen-Chen Tsai, Jin-Hua Chen
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  ABSTRACT: To analyze the incidence rates and risk factors for bacteremia in patients undergoing hemodialysis (HD) and peritoneal dialysis (PD). The records of 898 consecutive patients undergoing dialysis from January 2003 to December 2008 were reviewed retrospectively. Episodes of bacteremia were recorded. China Medical University (Taichung, Taiwan). The overall incidence rate of bacteremia was 7.63 per 100 patient-years in HD patients and 3.56 per 100 patient-years in PD patients and it was higher in HD patients each year from 2003 to 2008. S. aureus (27.53%) was the most common pathogen in HD patients, whereas Coagulase-negative Staphylococcus (21.3%) was the most common pathogen in PD patients. Vascular access infection was the most common etiology in HD patients, whereas peritonitis was the most common etiology in PD patients. Older age, shorter dialysis vintage, use of HD rather than PD, current smoker, use of a venous dialysis catheter, presence of diabetes mellitus, higher comorbidity score, and lower serum albumin were significant risk factors for bacteremia. Diabetes mellitus and lower serum albumin were significant risk factors for bacteremia-associated mortality. Placement of a permanent access (fistula, graft, or PD catheter) prior to initiation of dialysis, smoking cessation, and better nutritional status (i.e. higher serum albumin) were associated with a reduced risk of bacteremia in dialysis patients. Higher serum albumin was also associated with a reduced bacteremia-associated mortality.
  Internal Medicine 01/2012; 51(9):1015-21. · 0.94 Impact Factor