Angiotensin II receptor blocker prevents upper gastrointestinal bleeding in hypertensive patients with chronic kidney disease not on dialysis.

AIMS: Investigate if angiotensin II receptor blocker (ARB) decreases risk of upper gastrointestinal bleeding (UGIB) in hypertensive patients with chronic kidney disease (CKD) not on dialysis. METHODS: All hypertensive patients with CKD not on dialysis in outpatient department of China Medical University Hospital from 2003 to May 2013 were enrolled. The risk of UGIB was analysed using Cox proportional hazard regression. RESULTS: A total of 2744 hypertensive CKD patients including 1515 male and 1229 female, aged 64.9 ± 13.8 years old in a median of 1.9 (0.9-3.9) years were analysed. The incidence of UGIB was 4.5 per 100 patient-years. ARB was associated with a decreased risk of UGIB (p < 0.001) with an adjusted hazard ratio (HR) of 0.533 [95% confidence interval (CI) 0.404-0.703]. A history of UGIB, Helicobacter pylori infection, diabetes, lower estimated glomerular filtration rate, elevated blood urea nitrogen and decreased serum albumin were independently associated with an increased risk of UGIB. CONCLUSIONS: Angiotensin II receptor blocker is associated with a decreased risk of UGIB in hypertensive CKD patients not on dialysis, independent of their renal function, history of gastrointestinal bleeding and nutrition status.

Subdural hematoma in patients with end-stage renal disease receiving hemodialysis.

BACKGROUND AND PURPOSE: Hemodialysis (HD) may increase the risk of acute subdural hematoma (SDH) with high fatality, but the extent of this disease in non-western populations is unclear. The incidence of and fatality from SDH in patients with end-stage renal disease (ESRD) on HD were examined for an Asian population. METHODS: A cohort of 4709 newly diagnosed ESRD patients on HD from 1998 to 2010 and a control cohort of 18 663 subjects without any kidney disease were identified from a universal insurance claims database in Taiwan. The incidence and hazard of SDH for the two cohorts and 30-day mortality from SDH were measured by the end of 2010. RESULTS: The incidence of SDH was 4.47-fold higher in the HD cohort than in the control cohort (56.3 vs. 12.6 per 10 000 person-years) with an adjusted hazard ratio (HR) of 3.81 (95% CI 2.77-5.25). HD patients with SDH had a high odds of 30-day mortality with an adjusted odds ratio of 6.34 (95% CI 2.37-16.9). CONCLUSIONS: ESRD patients with HD were demonstrated to be at high risk of subsequent SDH and to have a high mortality risk from SDH. Proper care for HD patients is necessary to prevent the devastating disorder.

Influence of predialysis comorbidity and damage accrual on mortality in lupus patients treated with peritoneal dialysis.

OBJECTIVE: Although there have been many studies on systemic lupus erythematosus (SLE) patients, there are few data about survival analysis of lupus patients receiving dialysis. Therefore, the objective of this study is to analyze risk factors predicting mortality in lupus patients treated with peritoneal dialysis (PD). In addition, we also delineate the relationship between predialysis comorbid illnesses, damage accrual, and mortality in lupus patients undergoing PD. METHODS: This longitudinal cohort study included 38 lupus patients undergoing PD between 1990 and 2008. The clinical parameters, disease activity (non-renal SLEDAI, nrSLEDAI), comorbid illnesses, and damage accrual were collected. We applied the Charlson Comorbidity Index (CCI), Khan Index, and Davies Index to elucidate the impact of predialysis comorbidity on mortality. Moreover, we examined prognostic value of predialysis SDI (Systemic Lupus International Collaborating Clinics Disease Damage Index) for lupus PD patients. RESULTS: There were 33 women and five men included for analysis. The mean age at PD entry was 32.2 +/- 10.4 years and mean duration of PD was 39.7 +/- 22.4 months. The nrSLEDAI score during PD significantly decreased, compared to the predialysis one (2.13 +/- 2.09 vs. 4.00 +/- 3.08, p < 0.001). All comorbidity indices and SDI scores were significantly and positively correlated with each other (p < 0.001). Univariate Cox regression analysis showed that serum creatinine level, date at PD entry, and the CCI were predictors for mortality. The predialysis nrSLEDAI and SDI scores did not have roles in predicting mortality of lupus PD patients. CONCLUSIONS: The predialysis CCI, instead of SDI, determines an increased risk for mortality in lupus patients treated with PD. The prognosis of lupus patients treated with PD largely depends on the severity of predialysis comorbidity, especially cardiovascular diseases.

The relationship between chronic hepatitis B infection and bone mineral, metabolism in peritoneal dialysis patients.

OBJECTIVE: Abnormality of bone mineral metabolism is a common complication in chronic liver disease and/or chronic renal disease patients. We designed this study to evaluate the relationship between chronic hepatitis B infection and bone mineral metabolism in peritoneal dialysis patients. PATIENTS AND METHODS: Serum calcium[adj], phosphorus, calcium and phosphorus product (Ca x P), along with intact parathyroid hormone (iPTH) levels were compared in peritoneal dialysis patients with and without chronic hepatitis B infection. RESULTS: A total of 220 patients (142 female, 78 male) with a mean age of 56.30 +/- 14.28 (range 19 - 86) years old were recruited, 23 showed chronic hepatitis B infection and 197 showed none. No statistically significant difference in serum calcium[adj] levels (9.90 +/- 0.85 mg/dl vs. 10.08 +/- 0.80 mg/dl, p = 0.354), phosphorus levels (5.26 +/- 1.58 mg/dl vs. 5.21 +/- 1.35 mg/dl, p = 0.879) and calcium and phosphorus product (Ca x P) (52.23 +/- 17.54 mg(2)/dl(2) vs. 52.42 +/- 14.16 mg(2)/dl(2), p = 0.960) between groups with and without chronic hepatitis B infection was observed. Serum iPTH levels were significantly lower in chronic hepatitis B patients (median 143 pg/ml, range 3.42 - 889) than in the control group (median 235 pg/ml, range 3 - 2381) (p = 0.035). As analyzed by multi-variable linear regression, chronic hepatitis B was a predictor of lower serum iPTH levels (beta = -0.271; p = 0.030) after adjustments for age, gender, serum calcium and phosphorus levels and diabetes. CONCLUSION: No significant difference in serum calcium[adj]), phosphorus and calcium and phosphorus product (Ca x P) levels appeared between peritoneal dialysis patients with and without chronic hepatitis B infection. Serum iPTH levels proved to be definitely lower in chronic hepatitis B infection patients.

C-reactive protein predicts ischaemic stroke in haemodialysis patients.

Dialysis patients have a higher incidence of cerebrovascular events compared with the general population. However, the value of C-reactive protein (CRP) in predicting stroke in chronic haemodialysis patients is unknown. The aim of this study was to determine the association between serum CRP levels and ischaemic stoke in chronic haemodialysis patients. We retrospectively reviewed 391 chronic haemodialysis patients between November 2001 and November 2004. Patients who developed acute ischaemic stroke within 36-month were recorded. Patients who had lacunar infarction discovered accidentally during brain computed tomography or magnetic resonance imaging scans were recorded for subgroup analysis. The relation of predialysis serum CRP levels, measured via the nephelometric method, to the development of acute ischaemic stroke was analysed using Kaplan-Meier analysis. Factors related to lacunar infarctions were analysed by multivariate logistic regression. Of the 391 patients, 21 developed acute stroke and 24 had lacunar infarction. Kaplan-Meier analysis showed that patients with a serum CRP > 0.8 mg/dl were at risk of developing acute infarction (p = 0.002). In the Cox regression model adjusted for age, cardiovascular disease, hypertension and diabetes, patients with serum CRP > 0.8 mg/dl are at risk of developing acute ischaemic stroke (p = 0.03). In multivariate logistic regression with adjusted for age, hypertension and diabetes, serum CRP levels significantly associated with lacunar infarction (p = 0.05). Serum CRP levels, independent of cardiovascular disease, age, hypertension and diabetes, are associated with the development of acute ischaemic stroke and lacunar infarct in chronic haemodialysis patients.

Intravenous iron attenuates postvaccination anti-HBsAg titres after quadruple hepatitis B vaccination in dialysis patients with erythropoietin therapy.

BACKGROUND: Anaemia in patients with end-stage renal disease (ESRD) is commonly treated with recombinant human erythropoietin (rHuEPO), often in combination with an adjuvant iron supplement. There is much evidence that rHuEPO can influence the immune response by its effect on lymphocytes. Also, iron catalyses the formation of radicals and increases the risk of major infections by negatively affecting the immune system. The relationship between antibodies to hepatitis B surface antigen (anti-HBsAg) responsiveness after hepatitis B vaccination and rHuEPO/adjuvant iron supplementation has not been reported before. AIM: To determine the effects of subcutaneous erythropoietin and intravenous (i.v.) iron therapy on the responsiveness of anti-HBsAg after quadruple hepatitis B vaccination among ESRD patients. METHODS: Retrospective medical records were reviewed in a hospital with a tertiary teaching facility. Eighty-three ESRD patients, including 51 who underwent haemodialysis and 32 who underwent peritoneal dialysis therapy, received a quadruple recombinant hepatitis B vaccine. We investigated anti-HBsAg titres in those patients who either received rHuEPO alone (n = 50) or rHuEPO in combination with i.v. iron (n = 33). RESULTS: We found that the postvaccination anti-HBsAg titre was significantly lower in the rHuEPO plus i.v. iron group when compared with the group with rHuEPO alone (p < 0.05). The increment of anti-HBsAg between the initial month and the seventh month was positively correlated with therapeutic rHuEPO dosages in the group with rHuEPO alone (r = 0.303, p = 0.033). This relationship was not present in the rHuEPO with i.v. iron group (r = -0.289, p = 0.229). CONCLUSIONS: The levels of anti-HBsAg after hepatitis B vaccination are positively correlated with the dose of rHuEPO treatment during the vaccinated period among ESRD patients without i.v. iron supplementation. Also, i.v. iron negatively impacts the responsiveness of anti-HBsAg titre after hepatitis B vaccination in ESRD patients who have undergone rHuEPO therapy.

The highly specific platelet glycoprotein (GP) VI agonist trowaglerix impaired collagen-induced platelet aggregation ex vivo through matrix metalloproteinase-dependent GPVI shedding.

BACKGROUND: C-type lectin proteins (CLPs) have diverse targets including platelet GPIb, GPVI and integrin alpha(2)beta(1), and affect platelet function in a various way. In this study, we characterized a huge, heterodimeric venom protein, trowaglerix, which belongs to the CLP family. METHODS: We purified a potent platelet-aggregation inducer, trowaglerix, from the crude venom of Tropidolaemus wagleri. Biotinylated trowaglerix was used for binding assays, and immunoblotting was used to investigate the signal transduction involved. RESULTS: Two distinct subunits of trowaglerix with similar masses of around 16 kDa were eluted by high-performance liquid chromatography after reduction and alkylation. Trowaglerix induced platelet aggregation of washed human platelets and platelet-rich plasma (PRP) in a concentration-dependent manner. Biotinylated trowaglerix specifically bound to platelet membrane GPVI, but not to GPIb or alpha(2) integrin. Treatment with trowaglerix induced GPVI loss in human platelets in vitro and impaired the platelet aggregation of mouse PRP ex vivo in response to collagen but not in response to adenosine diphosphate (ADP). However, GM6001, a matrix metalloproteinase (MMP) inhibitor, inhibited trowaglerix-induced GPVI cleavage and restored the platelet responsiveness of PRP to collagen. CONCLUSIONS: Trowaglerix activates platelets through specific binding to GPVI, leading to kinases-dependent exposure of functional alpha(IIb)beta(3) and platelet aggregation, and also induces MMP-dependent GPVI shedding from platelets.

Bone mineral density in long-term Chinese heart transplant recipients: a cross-sectional study.

Osteoporosis, which usually peaks during 6 to 12 months after transplantation, remains an important concern after heart transplantation. Immunosuppressants contribute to this phenomenon. Glucocorticoids are well documented to cause bone loss, but the role of cyclosporine (CsA) remains controversial, especially among long-term recipients on low doses of steroid. We herein report a cross-sectional study of bone mineral density (BMD) among long-term Chinese heart transplant recipients. We enrolled 41 patients of mean age 50.15 +/- 13.58 years with a mean follow-up of 57.02 months. Lumbar spine and femoral neck BMD were measured by dual energy x-ray absorptiometry. Trough CsA levels (C(0)) and markers of mineral metabolism, including bone-specific alkaline phosphatase and urinary N-telopeptide, were determined by immunoassay. Sixty six percent of subjects showed bone loss at the femoral neck, significantly more than those in the lumbar spine. Those receiving a higher CsA dosage (<2.5 mg/kg/d) showed greater femoral neck BMD, but lower serum creatinine values. Our results demonstrated that bone loss remains long after transplantation, though bone markers are within normal limits.

Extraintestinal manifestations of Edwardsiella tarda infection.

Summary Edwardsiella tarda, a member of the family Enterobacteriaceae, is a rare human pathogen. Gastroenteritis is the most frequently reported manifestation of E. tarda infection. In contrast, extraintestinal infection with E. tarda has rarely been reported. This study made a retrospective case and microbiological data review of patients with extraintestinal E. tarda infections to further understand this disease. This study retrospectively reviewed the charts of all isolates of E. tarda cultures from clinical specimens other than faeces at Chang Gung Memorial Hospital, Taoyuan, Taiwan from October 1998 through December 2001. Edwardsiella tarda was isolated from 22 clinical specimens from 22 hospitalised patients (13 females and nine males). The extraintestinal manifestations of E. tarda infection included biliary tract infection, bacteraemia, skin and soft tissue infection, liver abscess, peritonitis, intra-abdominal abscess, and tubo-ovarian abscess. The major underlying diseases predisposing to E. tarda extraintestinal infection were hepatobiliary diseases, malignancy and diabetes mellitus. The overall mortality rate of E. tarda extraintestinal infection in the present series was 22.7% (5/22), and four (40%) of 10 patients with bacteraemia expired. Although rare, human E. tarda extraintestinal infections can have diverse clinical manifestations and moreover may cause severe and life-threatening infections. Consequently, E. tarda should be considered a potentially important pathogen.

Effect of ingestion of cow's milk hydrolysed formulas on whey protein-specific Th2 immune responses in naïve and sensitized mice.

BACKGROUND: For genetically predisposed atopic infants, cow's milk protein hydrolysed formulas have been widely used. OBJECTIVE: Whether hydrolysed formulas can induce oral tolerance to whey proteins will be extensively studied in naïve and sensitized mice. METHODS: Antigenicity of hydrolysed formulas was first studied using immunoblotting. Naïve mice fed hydrolysed formulas for 1-4 weeks were sensitized with whey allergens. In contrast, mice sensitized with whey allergens were fed hydrolysed formulas continually for 12 weeks. RESULTS: Whey allergens were found in Nan and Neoangelac FL. Large whey peptides with antigenicity were found in Nan-HA. Profound suppression of IgE, IgG1 and IgG responses to whey allergens were induced in those fed Nan for 1 week, or Nan-HA for 4 weeks. IgE responses to whey allergens were suppressed in those fed Neoangelac FL for 4 weeks, or Nan-HA for 1-2 weeks. In contrast, those fed extensively hydrolysed formulas for 1-4 weeks failed to show decreased responses. On the other hand, IgE responses to beta-lactoglobulin, but not to bovine serum albumin or alpha-lactalbumin, were decreased in sensitized mice fed Nan for 12 weeks. There was no suppression in sensitized mice fed hydrolysed formulas. CONCLUSION: Suppression of IgE responses to whey proteins was readily induced in naïve mice fed Nan or Nan-HA for 1 week. In contrast, it was hardly induced in sensitized mice even after prolonged feeding of Nan for 12 weeks, let alone hydrolysed formulas.

Systematic variation of polymer jacketed fibres and the effects on tip etching dynamics.

Using a chemically etched fibre probe through a plastic jacket provides a simple way to smooth a tip's surface. Convection flow in the plastic tube and lateral diffusion with fixed meniscus height has been proposed to explain such improvement. Fibres with additive thin polymer layers and bare fibres with thick untapered/tapered plastic layers have been prepared to verify the dominant mechanism. The additive layers greatly change the tip's geometry and bare-fibres with untapered plastics cannot form tips. This confirmed that lateral diffusion dominates the etching process. Based on our investigation, we propose a new non-meniscus end-etching method by using tapered plastics. Unlike etching methods with meniscus, the end-etching method can regularly form very smooth tips. It is insensitive to vibrations and temperature drifts and also suitable for most fibres.

Antioxidant administration inhibits exercise-induced thymocyte apoptosis in rats.

PURPOSE: The purpose of this study was to investigate the effect of antioxidant on exercise-induced apoptosis in rat thymocytes. METHODS: After exercise at 13.8 m x min(-1) for 60-90 min x d(-1) on a motor-driven drum exerciser for 2 consecutive days, rat thymocyte apoptosis was monitored by the feature of DNA fragmentation. To study the effect of antioxidant, rats were administered with butylated hydroxyanisole (BHA) for 7 d before exercise. RESULTS: Exercise could induce thymocyte DNA fragmentation as detected on electrophoretic gel and by cell death detection ELISA kit. Further studies indicated that pretreatment with antioxidant BHA to rats resulted in a blockage of exercise-induced DNA fragmentation. The concentrations of glutathione (GSH) were not significantly changed in rat thymocytes after exercise with or without BHA treatment. CONCLUSION: These results suggest that reactive oxygen species may play a role in thymocyte apoptosis induced by exercise. However, changes in GSH levels were not observed in this exercise model.

Immunostimulation by Alsophila spinulosa extract fraction VII of both humoral and cellular immune responses.

Alsophila spinulosa (Cyatheaceae) has been used in Asia as a herbal medicine. In this study, the immunomodulatory effects of Alsophila spinulosa dried stems water extract fraction VII (AS-VII) were studied in vitro using an animal model. The results showed that AS-VII stimulated splenocyte proliferation in both BALB/c and C3H/HeJ mice. By cell fractionation analysis, the results showed that the mitogenic effect of AS-VII was predominantly on B cell population. The antibody response was also augmented by AS-VII in BALB/c and C3H/HeJ mice. The augmentation of immune responses in C3H/HeJ, the lipopolysaccharide (LPS)-hyporesponsive mouse strain, indicated that the activity was not simply due to the LPS contamination which may be present in AS-VII preparation. Furthermore, AS-VII caused an increase in cytotoxic T cell activity in a mixed lymphocyte reaction culture. These data indicate that AS-VII possesses the capability of augmenting both humoral and cellular immune responses.

[The stress distribution of prefabricated screw posts. Part III: Techniques].

Some commonly used endodontic screw posts were analysed for various techniques of post insertion by photoelastic stress distribution. These endodontic dowels were installed in assumed clinical conditions. These conditions included: (1) no backing off during post installation, (2) the channelling of the post without cleaning, (3) a smaller drill was used prepare the post channel, and (4) an axis deviated contrangle was used to prepare the post channel. According to this photoelastic analysis, the techniques of post insertion may affect the stress distribution. Suggestions for post insertion are as follows: 1. The stress can be reduced by counterrotating the dowel one-fourth turn after resistance to installation has been detected. 2. The channel should be cleaned thoroughly before post insertion. 3. Because accurate post fit is important to maximize both retention and support, the screw post should be used with the matched post/reamer system; and accurate contrangle drilling should be maintained.

[Stress distribution of prefabricated screw posts. Part I: Post size].

A commonly used prefabricated screw post was analysed for its various lengths and diameters. When endodontic dowels were installed in standardized models, direct comparisons of stress distributing properties were analysed through photoelastic stress analysis. According to the analysis, installation of the post produced severe lateral stress. At shorter lengths, these stress concentrations were much more severe. However, increasing the diameter of the dowel may reduce the stress slightly. Under load conditions, the stress-producing characteristics of the dowel increased with shorter lengths and smaller diameters. It seems that increasing the surface area of insertion with the dentin improves the distribution of the load caused by the insertion of the post.