The use of topical corneal anaesthetics for pain relief after corneal abrasion also seems to have limited use [24]; Bisla and Tanelian examined epithelial regeneration in the presence of lidocaine 100–1000 µg/ml, and observed a dose-dependent impairment of epithelial wound healing with concentrations higher than 250 µg/ml, which would also demonstrate the negative

effect of LA [24]. All these studies demonstrated potential harm using local anaesthetics, but did not specify the exact impairment mechanism. Results from our study confirm other experimental findings, demonstrating that bupivacaine has a higher toxicity potential compared to lidocaine and ropivacaine [25,26]. In addition, it corroborates the results from Sturrock and Nunn, demonstrating compromised

cell survival in hamster lung fibroblasts with an effective dose (ED50) of 0·06% for bupivacaine compared to 0·09% for lidocaine [27]. The present study suggests that the learn more observed cell death is not BMS-777607 purchase due mainly to increased apoptosis rate, as activity of caspase-3 was correlated significantly with the amount of living cells. An exception was observed for the short stimulation period of 3 days for bupivacaine and ropivacaine. Caspase-independent mechanisms of cell death have been described in LA-induced cytotoxicity due to a change in intracellular Ca2+ homeostasis [28–33]. It is postulated in myocytes that LA induce Ca2+ release from the sarcoplasmic reticulum by interaction with ryanodine receptors [34,35]. Other studies have suggested an inhibition of Ca2+ reuptake into the sarcoplasmic reticulum, possibly regulated by Ca2+ ATPase activity [34,36]. Besides dysregulated intracellular Ca2+, the involvement

of ROS production is another possible mechanism of LA-induced cell death [37,38]. As described for cocaine, LA and/or its oxidative metabolites might trigger ROS release, which has a toxic effect on hepatocytes [37,38]. Other authors claimed a correlation between the dysregulation of mitochondrial Ca2+ and ROS production, therefore reflecting a possible combination of the two proposed insult pathways [39]. A trigger such as LA or, as O-methylated flavonoid described by Brookes et al., ischaemia/reperfusion, might lead to a mitochondrial Ca2+ overload, mitochondrial dysfunction and ROS production which exacerbates mitochondrial damage [39]. However, cytotoxic effects of LA have been described in several studies without elucidation of the underlying mechanism [10,40,41]. Park et al. have shown increased ROS concentration correlating with cell death of Schwann cells after incubation with bupivacaine [42]. The authors thereby suggested a ROS-triggered caspase-3-activated apoptosis in neuronal cells. These conclusions were supported by results from Perez-Castro, which showed caspase-3/-7 activation in human neuroblastoma cells after 10 min incubation with lidocaine, ropivacaine and bupivacaine [43].

This might support an early, efficient elimination of bacteria while reducing inflammation-associated tissue damage. Secondly, ARA290 directly reduces cellular infection due to interference with bacterial invasion. Because the intracellular niche is regarded as a relevant reservoir for E. coli, this may confer protection against recurrence of the infection. Taken together, the combination of these effects

makes ARA290 a promising substance both to boost the immune response during acute UTI and to prevent recurrence of the infection. This work was supported by grants from the Swedish Research Council (56X-20356) and ALF Project Funding and Karolinska Institutet. “
“In the present study, we have found that intestinal flora strongly influence peritoneal neutrophilic inflammatory responses selleck to diverse stimuli, including pathogen-derived particles like zymosan and sterile irritant particles like crystals. When germ-free and flora-deficient (antibiotic-treated) mice are challenged with zymosan intraperitoneally, neutrophils are markedly impaired in their ability to extravasate from blood into the peritoneum. In contrast,

in these animals, neutrophils can extravasate in response to an intraperitoneal injection of the chemokine, macrophage inflammatory protein 2. Neutrophil recruitment upon inflammatory challenge requires stimulation by microbiota through a myeloid differentiation primary response gene (88) (MyD88) -dependent pathway. MyD88 signalling is crucial during the development of the immune system but depending upon the ligand it may be dispensable at the time of the actual inflammatory challenge. Furthermore, www.selleckchem.com/products/Adriamycin.html pre-treatment of flora-deficient mice with a purified MyD88-pathway agonist is sufficient to restore neutrophil migration. In summary, this study provides insight into the role of gut microbiota in influencing acute inflammation at sites outside the gastrointestinal tract. Rucaparib The large intestinal tract of humans and other vertebrates is inhabited by numerous and diverse bacterial populations. The extent of microbial colonization is such that the number of microbial cells outnumbers the total number of cells in the human body 10-fold.

The combined microbial gene set similarly exceeds the human gene complement about 150-fold.[1, 2] The intestinal flora plays a vital role in gut physiology. The mammalian digestive system is limited in its ability to produce all the enzymes that are required to metabolize the vast repertoire of energy substrates that are consumed and the gut flora complements the host’s digestive system in maximizing their utilization. The nutritive benefits of gut flora extend to carbohydrate fermentation and absorption, lipid storage and secretion of vitamins and amino acids and absorption of minerals.[3] Besides their role in digestion, intestinal flora contributes to intestinal epithelial cell growth and proliferation and development of mucosal immunity.

In vivo, its effects are varied and have been shown to play important roles in inflammatory conditions [31]. CD30 has been reported to function in regulating autoimmune diseases [32,33]. CD30

signalling protected against autoimmunity by preventing extensive expansion of autoreactive CD8+ effector T cells during secondary encounters with antigen in parenchymal tissues [32,33]. Also, elevated LY2109761 concentrations of the soluble form of CD153 were observed in the sera of RA patients together with increased levels of CD30 and CD153 in biopsies [34]. There is also evidence that expression of CD153 in RA synovia contributes to mast cell activation [34]. Savolainen et al. [35] and Okamoto et al. [36] have observed elevated concentrations of the soluble form of CD30 in RA patients, thus underlining the importance of this molecule in the development of RA. Okamoto et al. [36] have noted further that although CD4+ T cells from peripheral blood and synovial tissue expressed CD30 and produced interleukin (IL)-4 after in vitro stimulation,

they underwent CD30-mediated cell death. In an analogous study, Gerli et al. [37] found that, in addition to IL-4 and IFN-γ, CD30+ T cells produced large amounts of inflammatory IL-10, and they suggested that synovial CD30+ T cells may play a role in the control of RA-induced inflammatory responses. Soluble forms of CD30 were found to be elevated in the sera PD0325901 purchase and cerebrospinal fluids of multiple sclerosis (MS) patients, particularly during remission [38,39]. In addition, soluble forms of CD30 were elevated in patients with systemic lupus erythematosus and Sjögren’s syndrome [40,41]. In non-obese diabetic (NOD) mice, expression of

both CD30 and CD30L was elevated on peripheral lymph node CD4+ and CD8+ T cells [42]. As a result, treatment of NOD mice with neutralizing almost anti-CD30L monoclonal antibodies (mAb) prevented the development of diabetes [42]. Taken together, these observations underscore the importance of CD30/CD153 signalling in the development of autoimmune diseases (Table 1, Fig. 1b). CD40 is the most extensively studied member of the TNF superfamily. First identified on B cells [43], it is present on a variety of cells including DCs, follicular DCs, monocytes, macrophages, mast cells, fibroblasts, vascular smooth muscle cells and endothelial cells [44], and as a functional molecule on CD4+ T cells [45]. CD4–CD154 interactions generate one of the most effective APC-activating signals. Signalling via dendritic cell CD40 up-regulates expression of CD80 and CD86 and induces IL-12 secretion [46–48], and signalling via CD40 activates nuclear factor (NF)-κB [49,50] and rescues B cell receptor (BCR)-induced cell death [51]. Moreover, studies using CD40−/− mice have shown that the CD40–CD154 pathway is central to germinal centre formation and immunoglobulin (Ig) isotype-switching [52].

After 30 min, the blocking solution was discarded, and cell suspensions at various

dilutions were added to wells and incubated at 37 °C for 4 h under 5% CO2 in moist air. The cells were washed and then incubated with horseradish peroxidase-conjugated goat anti-mouse heavy chain α-specific antibodies (Southern Biotechnology Associates) at 4 °C for 20 h. Following incubation, the plates were washed with PBS and developed adding 3-amino-9-ethylcarbazole dissolved in 0.1 M sodium acetate buffer containing H2O2 to each well (Moss, Inc.). Plates were incubated at room temperature for 30 min and washed with distilled water, and AFCs were then counted with the aid of a stereomicroscope (Olympus, Tokyo, Japan). Mononuclear cells were isolated 7 days after the final immunization from submandibular lymph nodes (SMLs) of the immunized mice, adjusted high throughput screening to a concentration of 5 × 106 cells mL−1, and cultured with 5 μg mL−1 of 25k-hagA-MBP in RPMI-1640 medium containing 10% fetal bovine serum, 50 μM 2-mercaptoethanol, 15 mM HEPES, 2 mM l-glutamine, 100 U mL−1 penicillin, 100 μg mL−1

streptomycin, and 10 U mL−1 of recombinant IL-2 (Genzyme, Cambridge, MA). Cultures were incubated for 4 days at 37 °C under 5% CO2 in air. To measure the 25k-hagA-MBP-specific cell proliferation, 1.0 μCi of [3H]thymidine was Selleck Acalabrutinib added to the culture 18 h before harvesting, and the incorporated radioactivity was measured by scintillation counting. Four-day culture supernatants were also collected and centrifuged to remove cell debris. The IL-4, IFN-γ, and TGF-β cytokine levels of the culture supernatants were then determined by cytokine-specific ELISA kit (Pierce Endogen; Pierce Biotechnology, Rockford, IL) as described previously (Hashizume et al., 2008). Mice were orally infected

with P. gingivalis as described previously (Du et al., 2011), with minor modifications. Briefly, mice were given ad libitum access to ionized water containing sulfamethoxazole/trimethoprim (Sulfatrim; Goldline Laboratories, Fort Lauderdale, FL) at 10 mL per pint for 10 days. This was followed by a 3-day antibiotic-free period. Mice were then administered 109 CFU of P. gingivalis suspended in 100 μL of PBS with 2% carboxymethylcellulose Exoribonuclease via oral topical application. Mice were inoculated five times a week (from Monday to Friday) for 3 weeks, for a total of 15 inoculations. Control groups included sham-infected mice, which received antibiotic pretreatment and carboxymethylcellulose without P. gingivalis. Horizontal bone loss around the maxillary molars was assessed by the morphometric method as described previously (Klausen et al., 1989). The distance from the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) was measured at a total of 14 buccal sites per mouse.

Based on the lack of bactericidal activity of the opacity proteins and the similar Omp85 levels in the two wt OMVs, no distinction will be made below between

the wt 1 and wt 2 control learn more OMVs. The mice were immunized with the Omp85+ and control wt vaccines as described in Table 1, and their specific Omp85 antibody levels measured by scanning of the Omp85 band intensities on immunoblots (Fig. 2A). The Omp85+ vaccine induced significantly higher Omp85 antibody levels in C57BL/6 (P = 0.023) and OFI mice (P = 0.008) than in Balb/c mice. Whereas all C57BL/6 and OFI mice showed high levels, only half of the Balb/c mice had corresponding responses. Compared with the Omp85+ vaccine, the wt vaccine induced significantly lower Omp85 antibody levels in Balb/c mice (P = 0.035) and C57BL/6 mice (P = 0.001). However, NMRI mice responded to the wt vaccine with antibody levels that were significantly higher than in Balb/c (P = 0.001) and C57BL/6 mice (P = 0.001)

and not significantly different from those in C57BL/6 and OFI mice receiving the Omp85+ vaccine (Fig. 2A). The wt vaccine did not induce significant differences in antibody levels between the Balb/c and C57BL/6 mice, nor did Balb/c MI-503 price mice, immunized with the two wt vaccines, show significant differences (data not shown) in support of their similar Omp85 content. Similar results but with lower Omp85 antibody levels were obtained when wt 1 OMVs were used as immunoblotting antigen. The mouse strains displayed no significant differences in PorA antibody levels, Baricitinib determined on the same blots, after immunization with the Omp85+ and wt vaccines (Fig. 2B), indicating that the vaccines expressed the same amount of PorA. However, some C57BL/6 mice showed low or no PorA responses with both vaccines. Taken

together, the blotting results indicated that the mice showed distinct strain-dependent antibody responses to Omp85 and PorA. Serum bactericidal assay was performed with strain 44/76 and its derived PorA-negative strain (B1723) as targets (Fig. 3). With strain 44/76, the bactericidal titres induced in Balb/c mice by the Omp85+ and wt vaccines were not significantly different. The same was observed for C57BL/6 mice, implying that the increased Omp85 level, induced by the Omp85+ vaccine, did not contribute to the bactericidal antibodies. However, titres in Balb/c mice, given the Omp85+ vaccine, were slightly higher (P = 0.047) than in C57BL/6 mice. The same trend was also observed with the wt vaccine, but this difference was not significant. The lack of PorA antibody activity in some sera from the C57BL/6 mice, as shown in Fig. 2B, may explain the titre differences. This was supported by the high Spearman’s correlation coefficients between the bactericidal titres and PorA antibody levels for C57BL/6 mice immunized with the Omp85+ (0.734; P = 0.005) and wt vaccine (0.615; P = 0.031).

64±10.87×106 and WT: 31.54±15.52×106 for B220+; Hax1−/−: 3.71±0.77×106 and WT: 2.55±1.05×106 for T1; Hax1−/−: 6.91±3.61×106 and WT: 4.73±2.23×106 for T2; Hax1−/−: 5.89±2.89×106 and WT: 4.53±2.39×106 for mature B cells; Hax1−/−: 2.92±1.84×106 and WT: 2.34±1.16×106 for MZ B cells). Our data clearly demonstrate that Hax1−/− LSK cells in a Hax1+/+ environment were able to fully reconstitute the lethally irradiated hosts. To further investigate the reason for the massive B lymphocyte deficiency, we investigated selleckchem the expression of CXCR4 and BAFFR on splenic B cells. CXCR4 is expressed on hematopoietic precursors 22 as well as on centroblasts within the germinal centre

18. CXCR4-expressing cells migrate towards CXCL12, expressed by stromal cells and germinal center dark zone compartments. Thus, an impaired CXCR4 expression would severely impede normal B-cell development. Alternatively, signals through the BAFFR have a significant role in promoting B-cell survival and homeostatic proliferation 23. For real time analysis, we isolated total splenocytes of four 10-wk-old WT and Hax1−/− mice and enriched for B lymphocytes using magnetic cell sorting. Both the CXCR4 and the BAFFR Erlotinib amplification showed prominent amplification products. Most interestingly, CXCR4 expression

in HAX1-deficient B cells was decreased by around 70% compared to WT cells. BAFFR expression was slightly, but not significantly, decreased in HAX1-deficient B cells (Fig. 7A). However, the decreased expression had no effect on the formation of follicular structures. No differences in the distribution of B- L-gulonolactone oxidase and T-cell areas, as stained by CD3 and B220, were detectable (Fig. 7B). Because of the fact that the transfer of Hax1−/− bone marrow cells into a HAX1+ environment gave rise to normal levels of B220+ cells and functional B-cell subsets, we conclude that the severely decreased

CXCR4 expression on HAX1-deficient B cells is not solely responsible for the described B-cell loss in Hax−/− mice. Previously, we described HAX1 as interaction partner of membrane bound IgE (mIgE) 24. From that point of view, it would have been of most interest to analyse IgE responses on a Hax1-deficient background. However, the short lifespan of Hax1−/− mice impeded a direct analysis. Therefore, we focused on the detailed investigation of the biological function of HAX1 during lymphocyte development. Hax1−/− mice are characterized by a severely diminished cellularity of lymphoid tissues accompanied by a significant reduction of B and Tlymphocytes. Recently, Chao et al. 25 reported on the role of HAX1 with a similar approach. Our results demonstrate that the developmental impairment is not restricted to specific developmental stages. We observed reduced numbers of B cells from the pro-pre B-cell stage in the bone marrow to mature stages in the spleen. The analysis of splenic subpopulations clearly demonstrated a continuation of the developmental defects for T1 and T2 B cells 26, 27.

In this case, it has not been established whether the long-term residence of the T cells in the sensory ganglion is dependent on prolonged antigen exposure due to continued viral gene expression; however, when we consider the initial site of HSV-1 infection in the skin, it appears that prolonged

antigen exposure is unnecessary to keep memory T cells on site. Scarification of flank skin and infection with HSV-1 is followed buy Buparlisib by viral replication in epidermal cells and latent infection of neurons in the local dorsal root ganglia. After the skin lesions heal and virus is no longer detectable, CD8+ T cells specific for HSV-1 remain behind in the epidermis. Subsequent ipsilateral versus contralateral flank rechallenge small molecule library screening with virus reveals that the ipsilateral side is much more resistant to viral replication in the epidermis and this protection is T-cell mediated 14. In this case, it is unlikely that memory T cells are retained in skin due to prolonged antigen presentation

because infectious virus is not produced in the infected neurons to traffic back to the original site of infection. Furthermore, when previously infected skin is grafted to a naïve animal and nerve endings are severed, the HSV-specific T cells remain in the graft 14. Skin-resident CD8+ T cells, unlike memory cells in the spleen, express high levels of integrins CD103 and VLA-1. The known ligand for CD103 is E-cadherin which is expressed at high levels by the epithelial cells. Although HSV-1 does not recrudesce in mice and spread from the latently infected ganglia back to the skin, this model system provides a wonderful example of how adaptive immune memory attempts

very to predict the site of re-entry or reactivation of an infectious agent. Fixed drug eruptions provide intriguing evidence from the clinic that the skin is a patchwork of fixed or sessile resident memory T cells. Observations in some patients show specific skin lesions at reproducible sites on their skin when administered a drug orally 15. The lesions have been described as classic delayed-type hypersensitivity reactions with CD8+ T cells as the mediators but in which the trigger is delivered systemically and the reactive T cells are local. Whether the drug or its metabolites cause the reaction is not known, nor is the identity of the original insult that generates such a fixed site of local memory. In addition to memory cells that remain for extended periods in the epidermis at sites of prior infection, a large fraction of circulating memory T cells expresses the adhesion molecule cutaneous lymphocyte antigen (CLA) which mediates preferential migration into and through the skin. Clark has estimated that 20 billion memory T cells are present in our skin, outnumbering those present in the entire circulation 6. Such tissue-selective homing may be imprinted on the responding T cells in skin-draining lymph nodes.

The phenotyping

of the circulating T cells detected initially in our patient at the age of 23 months and all the way to the point before we started him on ERT showed that they were mostly CD8+, although CD4+ T cells were also raising. Moreover, NK cells also increased and reached normal counts by 50 months of age, suggesting that a common T/NK committed lymphoid progenitor might have been affected by the partial reversal of the mutation and that the reversion might have taken place in NK cells as well [26]. However, we were only able to show that negatively enriched CD3+ T cells harboured the revertant nucleotide; therefore, we do not know in which T INCB024360 order cells (CD4+ and/or CD8+) and NK cells the reversion also took place. With respect to the circulating CD19+ B cells, we only phenotyped them at 35 months of age and found that similarly to what Liu et al. [13] found in their revertant patient, >80% of the B cells were also switched memory (IgD-CD27+) B cells (not shown). One intriguing aspect of our patient was that mostly during severe infectious episodes, his PBL cells expanded transiently (up to 6000 cells/ul, data not shown), still could not demonstrate that PBL proliferated in response to PHA before ERT; see more therefore, we assume that some undefined mechanism must have promoted these

transient expansions. It it has been shown in mice that in lymphopenic environments, T cells can proliferate in response to autologous antigens presented in the context of MHC-I and growth factors such as IL-7 and IL-15, a phenomenon known as homeostatic proliferation [27]. Whether a similar mechanism was responsible for promoting and maintaining a level of homeostatic proliferation in our patient could not be tested. In our patient, ERT with PEG-ADA resulted in long-term correction of the metabolic abnormalities, along with a transient expansion of PBL including CD4+ and CD8+ T cells and NK cells, followed by the stabilization of lymphocyte counts and mild lymphoproliferation. It has been reported that

in ADA-deficient patients, CD3dimCD4−CD8− T cells appear approximately between the 5th and 10th weeks of PEG-ADA treatment and CD3brightCD8+ and CD3brightCD4+ (mature T cells) after week 12 [17]. However, our ADA-deficient Inositol monophosphatase 1 patient was a revertant that had normal T- and NK-cell counts before starting ERT (Fig. 3). Therefore, it is likely that the transient expansion in all lymphocyte subsets observed during the first 2 weeks after ERT was partly due to a clonal expansion of pre-existing cells. Liu et al. reported that before ERT, their revertant patient had mostly circulating CD8+ T cells with a terminally differentiated phenotype [13]. Furthermore, over the course of 9 months of ERT, his patient steadily accumulated mature naïve CD4+ and CD8+ T cells [13].

The transcriptional networks that maintain oxidant balance in the mature kidney provide promising entry points for future therapeutic interventions, including for CKD. The use of anti-oxidants targeted to specific pathways that are altered in CKD may prove beneficial, but it is likely that several anti-oxidants will be needed as a multi-drug therapy to target oxidant modifying pathways during the development of CKD. These include lipid peroxidation, which can be improved by α-tocopherol; glutathione redox regulation, which can be restored by NAC; uremic

toxins, which can be reduced by allopurinol; inflammation, which can be attenuated by ω-3 polyunsaturated fatty acids; and finally, mitochondrial dysfunction, which may be improved by CoQ10. Mosca and colleagues86 PARP activity found that healthy individuals taking a combination of α-tocopherol, α-lipoic acid, CoQ10, carnitines

and selenomethionine increased plasma anti-oxidant status, decreased lymphocyte find more apoptosis and decreased mitochondrial-derived ROS. In the CKD population, identification of patients who would benefit from anti-oxidant therapy is first needed, and then a multifaceted anti-oxidant approach may be necessary for successful treatment of CKD. “
“Aim:  There is little data on the prevalence and severity of dyslipidaemia in Asian patients with lupus nephritis (LN). Whether the dyslipidaemia in LN patients differs from subjects with comparable levels of renal impairment also remains undefined. Methods:  Lipid profiles of 100 Chinese patients with quiescent LN (age 46.3 ± 9.3 years, 83% female, maintenance prednisolone dose 5.80 ± 2.43 mg/day) were studied and compared with 100 controls who had non-lupus non-diabetic chronic kidney diseases (CKD), matched for sex, age and renal function. Results:  LN patients and CKD controls

had Ribonucleotide reductase similar renal function and proteinuria, while blood pressure was higher in controls. Twenty-five percent of LN patients and 17% of controls were receiving statin treatment. Despite this, 59% of LN patients and 46% CKD controls showed abnormal lipid parameters (P = 0.066). LN patients showed higher levels of total cholesterol (TC) and triglycerides (TG) than controls (5.28 ± 0.12 vs 4.86 ± 0.08 mmol/L, P = 0.004; and 1.62 ± 0.12 vs 1.20 ± 0.07 mmol/L, P = 0.002, respectively). More LN patients had abnormal TC, TG or low-density lipoprotein cholesterol (LDL-C) (54%, 16% and 38%; P = 0.016, = 0.005 and = 0.021, respectively). Hydroxychloroquine (HCQ) treatment was associated with lower TC, LDL-C and HDL-cholesterol. Conclusion:  Dyslipidaemia is prevalent in LN patients and is more severe than controls with a similar degree of CKD despite disease quiescence, low steroid dose and low level of proteinuria. Concomitant corticosteroid and renal impairment are likely contributing factors. HCQ treatment is associated with reduced severity of dyslipidaemia in LN patients.

Results: The average thiamine level was 50.1 ng/mL (normal range, 24–66 ng/mL). Of the 100 patients included in the analysis, 15 were found to have reduced serum thiamine levels (<24 ng/mL). The patients were dichotomized according to the median serum thiamine level into a high-thiamine group (≥35.5 ng/mL) and a low-thiamine group (<35.4 ng/mL), and the clinical characteristics were compared between the two groups. The former group exhibited higher serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and exhibited selleckchem lower C-reactive protein (CRP) than the latter group. We found a significant correlation

between the serum thiamin levels and the serum levels of AST and ALT (p < 0.0001, r = 0.44, p = 0.0002, r = 0.63). In addition, 18 patients showed a decrease from the baseline of the serum thiamine level post

hemodialysis. We divided these 18 patients into two groups, namely, the decrease group (n = 18) and the increase group (n = 82), and compared the clinical characteristics between the two groups. The comparison, however, revealed no significant difference in the Kt/V or type of dialyzer between the two groups. Conclusion: We conclude that thiamine deficiency did not occur in our regular dialysis patients, with the exception CT99021 price of a few cases. The serum AST or ALT may be used as a marker of thiamine deficiency in dialysis patients. TONGPAE Phosphatidylinositol diacylglycerol-lyase PINCHART1, NONGNUCH ARKOM2 1M.D., Fellow Nephrology Division, Medicine Department,

Ramathibodi Hospital; 2M.D. Nephrology Division, Medicine Department, Ramathibodi Hospital Introduction: There are many techniques used in vascular access surveillance for hemodialysis with the goal to detect access stenosis before thrombosis occurs. The ideal technique is that easy to perform, cost-effective, widely available and highly accurate. The purpose of this study is to determine sensitivity and specificity of three diagnostic tests including Venous Static Pressure (VP), Ultrasound Dilution Test (UDT), Duplex Doppler Ultrasound (DDU) or combination tests. Method: Patients with chronic stable hemodialysis via permanent vascular access were recruited and measured static venous pressure, intra-access flow using UDT and DDU. All patients were confirmed by angiography which is the gold standard for diagnosis access stenosis. Each test was performed within two weeks apart. Results: All three tests were evaluated using Receiver Operating Characteristic curve and found that UDT had the AUC of 0.76 (95% CI 0.6 to 0.9), DDU 0.66 (95% CI 0.5 to 0.8) and VP 0.54 (95% CI 0.3 to 0.7). The cutoff value used to predict access stenosis was 750 ml/min for UDT, PSV 290 cm/sec for DDU, and ratio 0.2 for VP. When compared the results of combined VP and DDU to UDT using the same cutoff value as above, the sensitivity and specificity were similar.