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ABSTRACT: Aim: Diabetes mellitus associated hyperglycemia and oxidative stress has been shown to have detrimental effects on the brain and may lead to impairment of cognitive functions. Resveratrol (Rsv), a polyphenolic antioxidant, has been shown to have moderate hypoglycemic and prominent hypolipidemic effects in diabetic rats. In the present study, we examined if Rsv improves the diabetic encephalopathy and explored its possible underlying mechanisms. Methods: Male SD rats were treated with streptozotocin (STZ, 65 mg/kg), and the diabetic rats were orally fed with Rsv (0.75 mg/kg, every 8 h) or normal saline for 4 weeks. Animals were then sacrificed and the brain tissues (hippocampus) processed for biochemical and histological studies. Results: Neurodegeneration and astrocytic activation were noted in the hippocampus of the diabetic rats. TNF-α, IL-6 transcripts and the nuclear NF-κB expression were increased in the brain. In addition, neuropathic alterations in the hippocampus were evident in diabetic rats, including increased blood vessel permeability and VEGF expression, decreased mitochondrial number and AMPK activity. In Rsv-treated diabetic rats, the aforementioned abnormalities were all attenuated. Conclusion: These observations suggest that Rsv significantly attenuated neurodegeneration and astrocytic activation in the hippocampus of diabetic rats. Our results suggested that Rsv could potentially be a new therapeutic agent for diabetic encephalopathy and neurodegeneration.
Neuroendocrinology 03/2013; · 2.38 Impact Factor
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ABSTRACT: Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600 μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80 μ g) and low-normal BLB (<80 μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100 μ g increment in BLB and each 10 μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.
BioMed research international. 01/2013; 2013:742545.
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ABSTRACT: Hyponatremia is the most common electrolyte disorder in hospitalized patients, and is frequently a marker of a significant underlying disease. The prognostic value of hyponatremia in patients with acute first-ever ischemic stroke is not known. We aimed to analyze whether hyponatremia in the acute stroke stage contributed to the risk of mortality or recurrent stroke in these patients.
We studied 925 patients presenting with acute first-ever ischemic stroke between 2002 and 2004. Sodium levels were obtained on arrival at the emergency room within 3 days of acute stroke onset. Hyponatremia was defined as a serum sodium concentration of 134 mmol/l or less. Clinical presentation, stroke risk factors, associated medical disease, and outcome were recorded. All patients were followed for 3 years for survival analysis. A multivariate Cox proportional hazards model was used to identify risk factors for 3-year mortality in these patients. We also constructed Kaplan-Meier survival curves, and compared groups with hyponatremia and normonatremia by means of log rank tests for significant differences.
Among the patients with acute first-ever ischemic stroke, 107 (11.6%) were hyponatremic. Among stroke risk factors, the prevalence of diabetes mellitus was significantly higher among hyponatremic patients (p < 0.001). Prevalence of chronic renal insufficiency was also higher in the hyponatremic group (p = 0.002). Clinical presentations, such as the length of acute ward stay, initial impaired consciousness, and clinical course in acute stroke were similar among normo- and hyponatremic patients. Among the complications, pneumonia and urinary tract infection were significantly higher in hyponatremic than in normonatremic patients. After multivariate logistic regression analysis, diabetes mellitus and chronic renal insufficiency were associated with hyponatremia in these patients. Kaplan-Meier analysis indicated that the survival rate was significantly lower in hyponatremic patients than in normonatremic patients (log rank test; p value <0.001). After multivariate Cox proportional hazards model analysis, hyponatremia was a significant predictor of 3-year mortality in these patients after adjustment for related variables (p value = 0.003, hazard ratio = 2.23, 95% confidence interval: 1.30-3.82).
Hyponatremia in the acute stroke stage is a predictor of 3-year mortality in patients with acute first-ever ischemic stroke that is independent of other clinical predictors of adverse outcome.
Cerebrovascular Diseases 06/2012; 34(1):55-62. · 2.72 Impact Factor
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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
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ABSTRACT: Leukocyte count predicted the risk of first-time myocardial infarction and ischemic stroke. The aim of this study was to determine the role of elevated leukocyte count in non-diabetic patients admitted for acute first-ever ischemic stroke on clinical presentation and 3-year mortality. We studied 462 patients with acute first-ever ischemic stroke without diabetes mellitus or active infection at admission. Patients were classified into 2 groups according to their leukocyte count. A white blood cell (WBC) count ≥ 10,000/μL was defined as an elevated leukocyte count, otherwise as normal. Clinical presentation, risk factors for stroke, laboratory data, co-morbidities, and outcomes were recorded. 64 patients (13.9%) had elevated leukocytes. Multivariate logistic regression showed that an elevated platelet count was positively associated with the elevated leukocyte count, while a low serum sodium level was negatively associated with an elevated leukocyte count (P=0.008, P=0.003, respectively). An elevated leukocyte count was associated with a higher risk of a stroke in evolution (P=0.021). Multivariate Cox regression analysis revealed that an elevated leukocyte count is a significant predictor of 3-year mortality [P=0.010, HR=3.26 (1.33-7.98)]. In conclusion, higher leukocyte counts during the acute stroke stage are associated with increased risk of 3-year mortality in patients with acute, first-ever ischemic stroke.
Journal of the neurological sciences 02/2012; 316(1-2):93-8. · 2.32 Impact Factor
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ABSTRACT: BACKGROUND: Thousands of paraquat (PQ)-poisoned patients continue to die, particularly in developing countries. Although animal studies indicate that hemoperfusion (HP) within 2-4 h after intoxication effectively reduces mortality, the effect of early HP in humans remains unknown. METHODS: We analyzed the records of all PQ-poisoned patients admitted to 2 hospitals between 2000 and 2009. Patients were grouped according to early or late HP and high-dose (oral cyclophosphamide [CP] and intravenous dexamethasone [DX]) or repeated pulse (intravenous methylprednisolone [MP] and CP, followed by DX and repeated MP and/or CP) PQ therapy. Early HP was defined as HP <4 h, and late HP, as HP ≥4 h after PQ ingestion. We evaluated the associations between HP <4 h, <5 h, <6 h, and <7 h after PQ ingestion and the outcomes. Demographic, clinical, laboratory, and mortality data were analyzed. RESULTS: The study included 207 severely PQ-poisoned patients. Forward stepwise multivariate Cox hazard regression analysis showed that early HP <4 h (hazard ratio [HR] = 0.38, 95% confidence interval (CI) 0.16-0.86; P = 0.020) or HP <5 h (HR = 0.60, 95% CI: 0.39-0.92; P = 0.019) significantly decreased the mortality risk. Further analysis showed that early HP reduced the mortality risk only in patients treated with repeated pulse therapy (n = 136), but not high-dose therapy (n = 71). Forward stepwise multivariate Cox hazard regression analysis showed that HP <4.0 h (HR = 0.19, 95% CI: 0.05-0.79; P = 0.022) or <5.0 h (HR = 0.49, 95% CI: 0.24-0.98; P = 0.043) after PQ ingestion significantly decreased the mortality risk in repeated pulse therapy patients, after adjustment for relevant variables. CONCLUSION: The results showed that early HP after PQ exposure might be effective in reducing mortality in severely poisoned patients, particularly in those treated with repeated pulse therapy.
PLoS ONE 01/2012; 7(10):e48397. · 4.09 Impact Factor
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ABSTRACT: In this study, we investigated the outcomes for patients with intentional organophosphate poisoning. Previous reports indicate that in contrast to normal heart rate-corrected QT intervals (QTc), QTc prolongation might be indicative of a poor prognosis for patients exposed to organophosphates.
We analyzed the records of 118 patients who were referred to Chang Gung Memorial Hospital for management of organophosphate poisoning between 2000 and 2011. Patients were grouped according to their initial QTc interval, i.e., normal (<0.44 s) or prolonged (>0.44 s). Demographic, clinical, laboratory, and mortality data were obtained for analysis.
The incidence of hypotension in patients with prolonged QTc intervals was higher than that in the patients with normal QTc intervals (P = 0.019). By the end of the study, 18 of 118 (15.2%) patients had died, including 3 of 75 (4.0%) patients with normal QTc intervals and 15 of 43 (34.9%) patients with prolonged QTc intervals. Using multivariate-Cox-regression analysis, we found that hypotension (OR = 10.930, 95% CI = 2.961-40.345, P = 0.000), respiratory failure (OR = 4.867, 95% CI = 1.062-22.301, P = 0.042), coma (OR = 3.482, 95% CI = 1.184-10.238, P = 0.023), and QTc prolongation (OR = 7.459, 95% CI = 2.053-27.099, P = 0.002) were significant risk factors for mortality. Furthermore, it was revealed that non-survivors not only had longer QTc interval (503.00±41.56 versus 432.71±51.21 ms, P = 0.002), but also suffered higher incidences of hypotension (83.3 versus 12.0%, P = 0.000), shortness of breath (64 versus 94.4%, P = 0.010), bronchorrhea (55 versus 94.4%, P = 0.002), bronchospasm (50.0 versus 94.4%, P = 0.000), respiratory failure (94.4 versus 43.0%, P = 0.000) and coma (66.7 versus 11.0%, P = 0.000) than survivors. Finally, Kaplan-Meier analysis demonstrated that cumulative mortality was higher among patients with prolonged QTc intervals than among those with normal QTc intervals (Log-rank test, Chi-square test = 20.36, P<0.001).
QTc interval helps predict mortality after intentional organophosphate poisoning.
PLoS ONE 01/2012; 7(5):e36576. · 4.09 Impact Factor
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ABSTRACT: Hemoglobin variability in hemodialysis patients treated with erythropoiesis-stimulating agents has been used to evaluate mortality and comorbidity. Different outcomes have been reported in American and European hemodialysis patients. There are, however, few studies of the effects of hemoglobin variability in peritoneal dialysis patients.
We investigated hemoglobin variability in 363 peritoneal dialysis patients over 2 years to evaluate mortality and the association with comorbidity, peritonitis, and hospitalization. The hemoglobin of all patients selected for the study had been monitored for at least 6 months (April 2008 to September 2008). We assessed hemoglobin variability as fluctuations from the target hemoglobin level (11-12.5 g/dL). We defined the following 6 patient groups on the basis of hemoglobin patterns: consistently low (< 11 g/dL), consistently target range (11-12.5 g/dL), consistently high (> 12.5 g/dL), low-amplitude fluctuation with low hemoglobin levels, low-amplitude fluctuation with high hemoglobin levels, and high amplitude fluctuation.
Only 2% of patients maintained a stable hemoglobin level within the target range and 46.8% of patients exhibited consistently low hemoglobin levels. After 2 years of observation, there was no difference in mortality as assessed by Kaplan-Meier analysis. There were also no differences in peritonitis and hospitalization between the 6 groups. However, the length of hospital stay was longer in the high amplitude fluctuation group (p = 0.008).
Hemoglobin variability does not predict mortality in peritoneal dialysis patients.
Chang Gung medical journal 01/2012; 35(1):79-87.
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ABSTRACT: Diabetes mellitus (DM) is characterized by dysregulated energy metabolism. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in diabetic animals. However, its overall in vivo effects on energy metabolism and the underlying mechanism require further investigation. In the present study, electrospray ionization-tandem mass spectrometry was employed to characterize the urine and plasma metabolomes of control, streptozotocin-induced DM and RSV-treated DM rats. Using principal component analysis (PCA) and heat map analysis, we discovered significant differences among control and experimental groups. RSV treatment significantly reduced the metabolic abnormalities in DM rats. Compared with the age-matched control rats, the level of carnitine was lower, and the levels of acetylcarnitine and butyrylcarnitine were higher in the urine and plasma of DM rats. RSV treatment ameliorated the deranged carnitine metabolism in DM rats. In addition, RSV treatment attenuated the diabetic ketoacidosis and muscle protein degradation, as evidenced from the attenuation of elevated urinary methyl-histidine and plasma branched-chain amino acids levels in DM rats. The beneficial effects of RSV in DM rats were correlated with activation of hepatic AMP-activated protein kinase and SIRT1 expression, increase of hepatic and muscular mitochondrial biogenesis and inhibition of muscle NF-κB activities. We concluded that RSV possesses multiple beneficial metabolic effects in insulin-deficient DM rats, particularly in improving energy metabolism and reducing protein wasting.
AJP Endocrinology and Metabolism 07/2011; 301(5):E853-63. · 4.75 Impact Factor
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ABSTRACT: The association between blood lead levels and mortality in patients on maintenance hemodialysis remains unclear.
A cross-sectional and 18-month prospective study included 927 patients on maintenance hemodialysis. Baseline variables and blood lead levels were measured before hemodialysis and categorized as 3 equal groups: high (>12.64 μg/dL), middle (8.51-12.64 μg/dL), and low (<8.51 μg/dL). Mortality and cause of death were recoded for longitudinal analyses.
At baseline, after related variables were adjusted, logarithmic transformation of blood lead level was negatively related to log ferritin and positively related to the vintage of hemodialysis and the percentage of urban area patients. By the end of the follow-up, 59 patients had died. Kaplan-Meier survival analysis showed that the high blood lead level group had greater mortality than the low blood lead level group (log-rank test, P<.001). After adjustment for potential variables, Cox multivariate analysis demonstrated that by using the low blood lead level as the reference, high blood lead levels were associated with increased hazard ratios (HRs) for all-cause (HR 4.70; 95% confidence interval [CI], 1.92-11.49; P=.003), cardiovascular-cause (HR 9.71; 95% CI, 2.11-23.26; P=.005), and infection-cause (HR 5.35; 95% CI, 1.38-20.83; P=.046) 18-month mortality in patients on maintenance hemodialysis. Moreover, there was a significant trend (P=.032) of HRs for all-cause mortality among the 3 study groups.
High blood lead level is associated with increased HRs for all-cause, cardiovascular-cause, and infection-cause 18-month mortality in patients on maintenance hemodialysis.
The American journal of medicine 04/2011; 124(4):350-8. · 4.47 Impact Factor
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ABSTRACT: Cadmium exposure is related to severity of diabetes and diabetes-related organ damage in diabetic patients. Elevated blood cadmium levels (BCLs) are well known in maintenance haemodialysis (MHD) patients but the clinical significance in diabetic MHD patients remains unknown.
A total of 212 diabetic MHD patients were enrolled in this 18-month prospective study and were categorized into three equal groups according to the basal BCL: high (> 0.889 μg/L; n = 71), middle (0.373-0.889 μg/L; n = 70) and low (< 0.373 μg/L; n = 71) BCL groups. The mortality and cause of death were recorded and analysed longitudinally.
Patients with high BCL had trends of higher white blood cell counts, glycosylated haemoglobin, phosphate and blood lead levels than other group patients. At the end of the follow-up, 31 patients had died. Kaplan-Meier analysis showed that the high BCL group patients had a higher mortality than other group patients (log-rank test, P = 0.036). Cox multivariate analysis demonstrated that logarithmic BCL was associated with increased hazard ratios (HR) for the all-cause mortality (HR = 2.336, 95% confidence intervals [CI] = 1.099-4.964, P = 0.027) in diabetic MHD patients. Similarly, if the low BCL group was the reference, the high BCL was associated with increased HR for all-cause mortality (HR = 2.865, 95% CI = 1.117-7.353, P = 0.043) in these patients.
The study results first demonstrated that BCL is associated with increased HR for 18-month all-cause mortality in diabetic MHD patients. Avoiding smoking and high cadmium-containing food may be important in these patients.
Nephrology Dialysis Transplantation 03/2011; 26(3):998-1005. · 3.40 Impact Factor
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ABSTRACT: Diabetic nephropathy (DN) is the major cause of end-stage renal disease. The early changes in DN are characterized by an increased in kidney size, glomerular volume, and kidney function, followed by the accumulation of glomerular extracellular matrix, increased urinary albumin excretion (UAE), glomerular sclerosis, and tubular fibrosis. Resveratrol (RSV) has been shown to ameliorate hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. In the present study, we examined the beneficial effects of RSV on DN and explored the possible mechanism of RSV action. Male Sprague-Dawley rats were injected with streptozotocin at 65mg/kg body weight. The induction of diabetes mellitus (DM) was confirmed by a fasting plasma glucose level ≥300mg/dL and symptoms of polyphagia and polydipsia. The DM rats were treated with or without RSV at 0.75mg/kg body weight 3 times a day for 8 weeks. Animals were sacrificed and kidney histology was examined by microscopy. Urinary albumin excretion, glomerular hypertrophy and expressions of fibronectin, collagen IV, and TGF-β in the glomeruli were alleviated in RSV-treated DM rats, but not in untreated DM rats. In addition, RSV treatment reduced the thickness of the glomerular basement membrane (GBM) to the original thickness and increased nephrin expressions to normal levels in DM rats. Moreover, RSV inhibited phosphorylation of smad2, smad3 and ERK1/2 in diabetic rat kidneys. This is the first report showing that RSV alleviates early glomerulosclerosis in DN through TGF-β/smad and ERK1/2 inhibition. In addition, podocyte injuries of diabetic kidneys are lessened by RSV.
Chemico-biological interactions 02/2011; 190(1):45-53. · 2.46 Impact Factor
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ABSTRACT: The cardiothoracic ratio (CTR) indicates the left ventricular size; however, the significance of the CTR in patients on maintenance peritoneal dialysis (PD) remains unclear. In this study, 335 PD patients were enrolled and demographic, biochemical, co-morbidity, and dialysis-related data were obtained. The factors determining CTR were further analyzed. All patients were followed up for two years to investigate the mortality risks. We defined a normal CTR as less than the mean CTR value, mild cardiomegaly as a CTR between the mean and mean + 1 SD, and moderate-to-severe cardiomegaly as more than the mean CTR + 1 SD. Among the 335 patients, 163 patients were classified as having a normal CTR (<49.2%), 112 patients as having mild cardiomegaly (CTR 49.2-55.7%), and 60 patients as having moderate-to-severe cardiomegaly (CTR > 55.7%). χ(2) -analysis showed that the incidences of malnutrition and anemia were significantly higher in patients with severe cardiomegaly than in patients of the other groups. The CTR was positively correlated with age, but negatively correlated with albumin and hemoglobin levels. Twenty-six patients (7.7%) had died by the end of the study. Cox multivariate analysis revealed that the CTR significantly predicts all-cause two-year mortality in PD patients on maintenance PD; therefore, the CTR correlates with the nutritional and anemic status of PD patients and is a reliable predictor for all-cause two-year mortality. The analytical results of this study support continued efforts to reduce the CTR and treat underlying causes in patients with cardiomegaly.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 02/2011; 15(1):81-8. · 1.39 Impact Factor
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ABSTRACT: The aim of this study was to investigate clinical significance of impaired fasting glucose (IFG) in nondiabetic patients on maintenance peritoneal dialysis (PD).
In total, 362 maintenance PD patients were enrolled and followed up for 2-years. According to 1997 definitions, patients were divided into 3 groups: diabetic (n = 85), nondiabetic with IFG (n = 62) and nondiabetic with normal fasting glucose levels (n = 215). After basal data were collected for cross-sectional analyses, mortality and cause of death were recorded for longitudinal analyses.
After adjusting for related variables by multivariate logistic regression analysis, IFG was found to be positively associated with age but negatively associated with normalized protein nitrogen appearance and transferrin saturation in nondiabetic maintenance PD patients. Thirty nondiabetic patients had died after the 2-year follow-up. Cox multivariate analysis showed that age (hazard ratio: 1.037; 95% confidence interval: 1.002-1.073; P = 0.036) and presence of IFG (hazard ratio: 2.719; 95% confidence interval: 1.082-6.833; P = 0.033) were significant risk factors for all-cause 2-year mortality in nondiabetic maintenance PD patients.
IFG, a preventable and treatable condition, was associated with all-cause 2-year mortality in nondiabetic maintenance PD patients.
The American Journal of the Medical Sciences 02/2011; 341(4):312-7. · 1.39 Impact Factor
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ABSTRACT: To clarify the efficacy of repeated methylprednisolone (MP) and cyclophosphamide (CP) pulse therapy and daily dexamethasone (DEX) therapy in patients with severe paraquat (PQ) poisoning.
A total of 111 patients with severe PQ poisoning and dark-blue color in urine tests within 24 h of intoxication were included prospectively. The control group consisted of 52 patients who were admitted between 1998 and 2001 and who received high doses of CP (2 mg/kg per day) and DEX (5 mg every 6 h) for 14 days. The study group consisted of 59 patients who were admitted from 2002 to 2007 and who received initial MP (1 g) for 3 days and CP (15 mg/kg per day) for 2 days, followed by DEX (5 mg every 6 h) until a PaO(2) of >80 mmHg had been achieved, or treated with repeated 1 g MP for 3 days and 1 g CP for 1 day if the PaO(2) was <60 mmHg.
There were no differences between the two groups with regard to baseline data and plasma PQ levels. The study group patients had a lower mortality rate (39/59, 66%) than the control group patients (48/52, 92%; P=0.003, log-rank test). Multivariate Cox regression analysis revealed that the repeated pulse therapy was correlated with decreased hazard ratios (HR) for all-cause mortality (HR=0.50, 95% CI 0.31-0.80; P=0.004) and death from lung fibrosis-related hypoxemia (HR=0.10, 95% CI 0.04-0.25; P<0.001) in severely PQ-intoxicated patients.
Repeated pulses of CP and MP, rather than high doses of CP and DEX, may result in a lower mortality rate in patients with severe PQ poisoning.
European Journal of Intensive Care Medicine 02/2011; 37(6):1006-13. · 5.17 Impact Factor
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ABSTRACT: Elevated white blood cell (WBC) counts predict coronary heart disease and all-cause mortality in the general population. Chronic inflammation and malnutrition are associated with increased risk of cardiovascular death in individuals with chronic kidney disease. In this study, we investigated the association between WBC count with inflammation, malnutrition, and mortality in maintenance hemodialysis (MHD) patients. A total of 959 MHD patients were stratified into four equal sized groups based on WBC count. Demographic, hematological, nutritional and inflammatory markers, and biochemical and dialysis-related data were obtained for cross-sectional analysis. All patients were followed for one year to investigate the risks for mortality. The mean WBC count was 6.4 ± 1.8 × 10(3)/µL (range: 2.3-16.3 × 10(3)/µL). Stepwise multiple linear regression analysis indicated a positive correlation between WBC count and inflammation (high-sensitivity C-reactive protein > 3 mg/L). Forty-five patients (4.7%) died within the 1-year study period. Cox multivariate regression analysis demonstrated that total WBC count significantly predicts 1-year mortality due to all-cause (hazard ratio (HR): 1.228, 95% confidence interval (CI): 1.095-1.378; P < 0.001), due to cardiovascular disease (HR: 1.242, 95% CI: 1.046-1.475; P = 0.013) and due to infection (HR: 1.252, 95% CI: 1.066-1.470; P = 0.006). These findings suggest that total WBC count should be measured in future studies that evaluate the clinical outcome of MHD patients and that dialysis patients with elevated WBC counts require further medical attention to reduce risks of mortality.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 12/2010; 14(6):552-9. · 1.39 Impact Factor
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ABSTRACT: patients with chronic peritoneal dialysis (CPD) use glucose-based dialysate to maintain their life; however, whether the glycemic status influences outcome of these patients without diabetes remains unknown.
we conducted a cross-sectional and 18-month prospective study, and 269 nondiabetic patients with CPD were enrolled in a medical center. Glycated hemoglobin (HbA1c) levels were measured at baseline and categorized in tertiles of HbA1c: high (>5.4%), middle (5.1-5.4%) and low normal (<5.1%). Mortality and cause of death were recorded for longitudinal analyses.
the study results showed high HbA1c group patients had a trend of being older and having higher body mass index (BMI) than other group patients. Stepwise multiple linear regression analysis showed HbA1c was positively related to age, BMI and the peritoneal solute transport rate. After 18 months of follow-up, Cox multivariate analysis showed that HbA1c (HR: 4.114; 95% CI: 1.426-11.872; p = 0.009) was the significant risk factor for all-cause mortality after relating variables were adjusted. Moreover, high HbA1c (HR: 3.892; 95% CI: 1.273-11.959; p = 0.026) and low HbA1c (HR: 1.179; 95% CI: 1.160-1.198; p = 0.039), with middle HbA1c group as the reference, also significantly predicted for mortality in these patients.
HbA1c levels, or presence of low or high HbA1c, are associated with 18-month all-cause mortality in nondiabetic patients with CPD.
American Journal of Nephrology 11/2010; 32(6):567-74. · 2.54 Impact Factor
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ABSTRACT: Background/Aims: Protein-energy wasting (PEW) is a well-known risk factor of long-term survival in peritoneal dialysis (PD) patients. Serum albumin is a measure of visceral protein, lean body mass is a measure of somatic protein stores and normalized protein nitrogen appearance is a measure of daily protein intake. A protein nutrition index (PNI) that combined these 3 factors was designed and tested as a function of survival in PD patients. Methods: We enrolled 552 PD patients for this study. Demographic, biochemical, nutritional markers, comorbidity and dialysis-related data were obtained. The PNI was calculated. All patients were followed up to investigate the risks for mortality. Results: Patients with probable PEW/low-average nutrition were older and had lower serum creatinine (Cr) and blood urea nitrogen, lower adequacy data and higher D4/P4 Cr compared with patients with high-average/good nutrition. 108 patients (19.6%) died during the observational period. By multivariate analysis, we found only age, comorbidity index and PNI (relative risk = 0.84, confidence interval: 0.76-0.93, p = 0.001) to be independent predictors of mortality. Conclusion: The PNI at the start of PD is associated with all-cause mortality, and each increase by a score of 1 in PNI leads to a 16% decrease in the risk of mortality. Predialysis evaluation of this scoring system is recommended for further research in order to improve outcomes in PD patients.
Kidney and Blood Pressure Research 06/2010; 33(3):174-180. · 1.46 Impact Factor
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ABSTRACT: The clinical significance of blood lead levels (BLLs) in chronic peritoneal dialysis (CPD) patients was undetermined prior to this study.
A total of 315 patients on CPD were included in this 18-month prospective study. BLLs measured at baseline were categorized according to a BLL tertile of high (>8.66 microg/dL), middle (5.62-8.66 microg/dL) and low (<5.62 microg/dL) for cross-sectional analyses. Mortality and cause of death were recorded for longitudinal analyses.
At baseline, patients with high BLLs had a trend of higher parathyroid hormone and lower residual renal function than patients in other groups. Stepwise multiple regression analysis found that parathyroid hormone positively correlated and residual renal function negatively correlated with logarithmic-transformed BLLs in CPD patients after other confounders were adjusted. At the end of follow-up, 37 (11.7%) patients had died. Kaplan-Meier analysis showed that patients with high BLLs had greater mortality than those with middle and low BLLs (P = 0.008). Cox multivariate analysis showed that, using the low BLL group as the reference, basal high BLLs (hazard ratio [HR] = 3.745, 95% confidence interval [95% CI] = 1.218-11.494, P = 0.001) and middle BLLs (HR = 1.867, 95% CI = 1.618-2.567, P = 0.001) were associated with increased HR for all-cause mortality for CPD patients. There is a significant trend (P < 0.001) of HR for mortality trend tests among the three study groups.
BLLs are associated with residual renal function and hyperparathyroidism and are related to increased HR for all-cause 18-month mortality in CPD patients.
Nephrology Dialysis Transplantation 05/2010; 25(5):1627-33. · 3.40 Impact Factor
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ABSTRACT: Chronic inflammation, which is common in dialysis patients, often causes malnutrition and even protein-energy wasting. However, the association of high-calcium dialysate with malnutrition and/or inflammation in non-diabetic maintenance haemodialysis patients remains unclear. This study investigated the possible adverse effects of high-calcium dialysate and mortality in this population.
A total of 717 non-diabetic haemodialysis patients participated in this 2 year prospective study. The subjects were categorized into three subgroups based on whether dialysate calcium concentrations were high (3.5 mEq/L), standard (3.0 mEq/L) or low (2.5 mEq/L). Demographic, haematological, nutritional and inflammatory markers, biochemical and dialysis-related data were obtained for cross-sectional analysis. Causes of death and mortality rates were also analyzed for each subgroup.
Patients with high-calcium dialysate (n = 82) had a higher incidence of malnutrition and inflammation (61.0% vs 44.1% and 43.9%, respectively) than those with standard- and low-calcium dialysate (n = 528 and 107). Backward stepwise multiple regression analysis revealed that high-calcium dialysate was negatively correlated with nutritional index, serum albumin levels, but positively associated with the inflammatory marker of serum ferritin levels. At the end of the 2 year follow up, 45 patients had died. Cox multivariate analysis demonstrated that high-calcium dialysate was a significant associated factor (relative risk 2.765; 95% confidence interval 1.429-5.352) for 2 year all-cause mortality in these patients.
The analytical results indicate that high-calcium dialysate is associated with malnutrition and inflammation as well as 2 year mortality in non-diabetic maintenance haemodialysis patients and the findings suggest that this population, even those with optimal mineral balance, should avoid high-calcium dialysate.
Nephrology 04/2010; 15(3):313-20. · 1.31 Impact Factor
