The results also showed that the proliferation of B6 spleen cells with IL-2 pre-incubation was significantly weaker than that of the controls

without IL-2 pre-incubation (P = 0·0025, Fig. 2b). SOCS-3 can inhibit the Th1-type polarization which plays a critical role in the pathophysiology of aGVHD [21,22,35,36]; therefore, we explored whether high SOCS-3 mRNA expression induced by IL-2 pre-incubation can inhibit Th1-type polarization in B6 naive CD4+ lymphocytes. According to the regularity of expression of SOCS-3 mRNA, we pre-incubated B6 naive CD4+ lymphocytes and B6 spleen cells, respectively, with IL-2 for 4 h before stimulation of allogeneic antigen-BALB/c spleen cells inactivated by mitomycin for 48 h. We then collected the supernatants to detect the levels of IFN-γ and IL-4. The results showed that expression of IFN-γ and learn more IL-4 of B6 naive CD4+ lymphocytes was different between pre-incubation of the two groups with or without IL-2. The IFN-γ level in group pre-incubation with IL-2 was lower than that in group pre-incubation without IL-2 (P = 0·000, Fig. 3a). The IL-4 level in group pre-incubation with IL-2 was higher than that in group pre-incubation without IL-2 (P = 0·000, Fig. 3a). The expression Buparlisib datasheet of IFN-γ and IL-4 of B6 spleen cells was similar to that of B6 naive CD4+ lymphocytes (P = 0·002, and 0·000, respectively, Fig. 3b) We assessed suppressive function in vivo in an aGVHD mice model.

We used female BALB/C recipients and male B6 donors. All recipients received 5 Gy TBI as conditioning regimen. In group A (n = 9), B6 spleen cells (3 × 107 cells) were injected intraperitoneally into recipients as control. We first explored whether aGVHD was inhibited in the recipients (group B, n = 9) which received Branched chain aminotransferase 3 × 107 B6 spleen cells pre-incubated with IL-2 before intraperitoneal injection. We found that the mean survival time of group B (14·4 ± 1·5 days) was not statistically different from that of group A (12·2 ± 3·1 days) (P = 0·3090, Fig. 4a). The scores of aGVHD symptoms between the two groups were

also not different (P = 0·7851). These findings suggest that IL-2 pre-incubation can up-regulate the expression of SOCS-3, but it was a short-lived gene product induced by IL-2 in lymphocytes. If the spleen cells with short-lived SOCS-3 did not receive allogeneic antigen in time, aGVHD could also not be inhibited; therefore, we projected another group (group D, n = 9) in which recipients received 3 × 107 B6 spleen cells which were presented with host-allogeneic antigen-inactivated BALB/C spleen cells for 72 h after IL-2 pre-incubation for 4 h. The results showed that aGVHD was inhibited significantly in group D. The mean survival time of group D was 44·1 ± 23·8 days, which was longer than that of group A (P = 0·0042, Fig. 4b). The score of aGVHD in group D was lower than that in group A (P = 0·0046).

Thus by exclusion, there is some support for the proposal that these massively calcified LGGs are distinct from other paediatric LGGs. In conclusion, our findings suggest that massively calcified LGGs of childhood could represent a distinct entity with characteristic radiological and pathological features and a lack of genetic alterations to align them readily with other paediatric LGGs. Study concept and design: D.W.E. Data

collection and interpretation: K.G., J.H.H., N.D.S., I.Q., K.K., D.W.E. Manuscript writing: K.G., D.W.E. Manuscript editing: K.G., J.H.H., N.D.S., I.Q., K.K., D.W.E. All authors have read the final version of the manuscript. “
“World Health Organization (WHO) grade III meningiomas are subclassified on the basis of their DAPT research buy architectural

pattern into papillary and rhabdoid subtypes. Some meningiomas even combine papillary architecture with rhabdoid cytology. Additionally, they always show malignant histological features, follow an aggressive clinical course and tend to spread through the CSF after frequent local recurrence. We render the first series of rhabdoid papillary meningioma with review of the literature to further elucidate its biological behavior. From six patients (three male, three female), nine specimens of rhabdoid papillary meningioma were obtained between 1994 and 2010. Correlations of histologic parameters, immunohistochemical study, and clinical features were assessed. The small molecule library screening mean age of patients was 44.7 years at their first operation. The mean postoperative follow-up period was 63.2 months. Five

patients experienced tumor recurrence, and one of them died from the disease after diffuse leptomeningeal dissemination. The mean time to first recurrence was 28 months. Only one patient was free of tumoral recurrence after an 8-year follow-up. Immunohistochemically, all tumors were positive for vimentin and epithelial membrane antigen. MIB-1 labeling indices were higher following tumor recurrence. The present study expands the clinicopathologic horizon of rhabdoid papillary meningioma and suggests that it will behave aggressively based on its histology and concomitant features of atypia or malignancy or high MIB-1 labeling indices. Close follow-up and aggressive treatments of these tumors are warranted. “
“To assess the sensitivity of the FTDC Mannose-binding protein-associated serine protease revised criteria of behavioral variant frontotemporal dementia (bvFTD) in a pathological cohort and to determine their predictive values in a clinical context suggestive of bvFTD. To assess the influence of the age at onset and underlying pathology in the clinico-pathological correlations. Retrospective, blinded review of the clinical and neuropathological data from the Neurological Tissue Bank (NTB) of the Biobank-Hospital Clinic-IDIBAPS, Barcelona (Spain) assessing the fulfillment of the diagnostic criteria on a case-by-case basis.

51 The current study reveals one more link between the immune and neuroendocrine systems in which the neuroendocrine AMP catestatin activates human mast cells, and may exert immunomodulatory effects on the cutaneous immune system. Further studies are needed for investigation of the pathophysiological roles of catestatin peptides in tissues where mast cells are abundantly CT99021 in vivo present. Our sincere thanks go to Dr Arnold Kirshenbaum (National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, MD) for kindly providing the LAD2 cell line. We thank the members of the Atopy (Allergy) Research Center and the Department of Immunology of Juntendo

University School of Medicine for their encouragement and critical comments, and Ms Michiyo Matsumoto for secretarial Obeticholic Acid molecular weight assistance. We are also deeply indebted to Dr Mukesh Pasupuleti (University of British Columbia, Vancouver, Canada)

for his contribution in designing the catestatin scrambled peptide. This work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan; Atopy (Allergy) Research Center, Juntendo University, Tokyo, Japan; and Japan International Cooperation Agency (JICA). The authors have no conflicts of interest to declare. “
“Several epidemiological studies have demonstrated that patients with primary biliary cirrhosis (PBC) have a higher incidence of urinary tract infections (UTI) and there is significant homology of the immunodominant mitochondrial autoantigen, the E2 component of the pyruvate dehydrogenase complex (PDC-E2), between mammals and bacteria. Previous work

has demonstrated that non-obese diabetic (NOD).B6 Idd10/Idd18 infected with Novosphingobium aromaticivorans developed liver lesions similar to human PBC. It was postulated Digestive enzyme that the biliary disease was dependent upon the presence of the unique N. aro glycosphingolipids in activating natural killer T (NK T) cells. To address this issue, we infected NOD.B6 Idd10/Idd18 mice with either Escherichia coli, N. aro or use of a phosphate-buffered saline (PBS) vehicle control and serially followed animals for the appearance of liver pathology and anti-mitochondrial autoantibodies (AMA). Of striking importance, the biliary disease of E. coli-infected mice was more severe than N. Aro-infected mice and the titre of AMA was higher in E. coli-infected mice. Furthermore, the immunopathology did not correlate with the ability of bacterial extracts to produce antigen-dependent activation of NK T cells. Our data suggest that the unique glycosphingolipids of N. aro are not required for the development of autoimmune cholangitis. Importantly, the data highlight the clinical significance of E.

Increasing evidence now supports the case for a regulatory role for CD8+CD28−

T cells in immune suppression in cancer [5], transplantation [6] and autoimmune disease, such as systemic lupus erythematosus (SLE) [7]. As an alternative regulatory link in the immune network, these cells may prove as important as CD4+CD25hiFoxP3+ Treg in controlling immune homeostasis in a disease where accelerated immune ageing enhances the loss of CD28 [8]. This study investigated the ex vivo phenotypic and functional characteristics of the CD8+CD28− Treg in RA. CD8+CD28− Treg were more abundant in RA patients treated with methotrexate [RA(MTX)], https://www.selleckchem.com/products/azd9291.html although fewer cells expressed inducible co-stimulator (ICOS) and programmed death (PD)-1 when compared with healthy controls. CD8+CD28− Treg from RA(MTX) failed to mediate suppression in the presence of a blocking transforming growth factor (TGF)-β antibody and produced

high levels of interleukin (IL)-10. Concomitantly, RA T cell cultures expressed fewer cell surface IL-10 receptors (IL-10R) which may account, in part, for the relative selleck insensitivity of the RA responder cells. CD8+CD28− Treg function, but not the reduced expression of ICOS and PD-1, was improved following TNF inhibitor therapy. This study identifies CD8+ Treg as a potential immunosuppressive force that is compromised in RA. Donors provided informed written consent in the Academic Department of Rheumatology out-patient clinic at Guy’s Hospital and King’s College Hospital London UK. Ethical approval for the study was obtained from Bromley Hospital and Guy’s and St Thomas’s Hospital Local Research Ethical Committees. Heparinized peripheral blood (PB) samples were

collected from healthy controls (HC), osteoarthritis (OA) patients used as disease controls, RA patients treated with MTX only, RA(MTX) and RA patients treated with TNF-α inhibitors (adalimumab, infliximab or etanercept in combination with MTX only) RA(TNFi). Paired PB and synovial fluid (SF) samples were obtained from RA(MTX) and RA(TNFi). All donors were age- and sex-matched. No patients on steroids Clostridium perfringens alpha toxin or alternative disease modifying anti-rheumatic drugs were used. Patient demographics are shown in Table 1. Antibodies conjugated directly to fluorescein isothiocyanate (FITC), phycoerythrin (PE), peridinium chlorophyll cyanin 5·5 (PerCP.Cy5·5) or allophycocyanin (APC) were used for flow cytometric analysis: CD3, CD8, CD28, CD56, CD94, CD137/4-1BB, CD152/cytotoxic T lymphocyte antigen-4 (CTLA-4), CD210/IL-10R, CD278/ICOS, CD279/PD-1, isotype mouse immunoglobulin (Ig)G or rat IgG controls [Becton Dickinson (BD), Oxford, UK] were used as required.

Heligmosomoides polygyrus bakeri is a fascinating intestinal parasitic nematode of mice that was isolated in the 1950s by Ehrenford [1] and since then has attracted increasing attention from researchers, particularly in the last two decades and especially from parasite immunologists. H. p. bakeri represents an important model of chronic helminth infection and is phylogenetically related to the ruminant parasites Haemonchus contortus AZD2014 supplier and Teladorsagia circumcincta and the human hookworms Ancylostoma duodenale and Nector americanus

[2]. The parasite has played an important role in helping us to explore and understand many different aspects of infection with helminths, but its pre-eminence is its capacity to cause long-lasting chronic infections in its murine host [3, 4]. Unlike other rodent

intestinal nematodes that became popular laboratory models in the 1960s (e.g. Nippostrongylus brasiliensis, Trichuris muris, Trichinella spiralis, Strongyloides ratti [5, 6]) and which cause limited infections (although note that in some mouse strains, T. muris may develop to patency and cause chronic infections [7, 8]), often restricted Y-27632 mw to 2–3 weeks, and induce strong acquired immunity in their hosts, H. p. bakeri is able to survive for up to 10 months in many commonly used laboratory mouse strains [3, 4]. It is this capacity to cause long-lasting chronic infections

in mice that distinguishes H. p. bakeri from other intestinal nematodes and which makes it a convenient model of chronic nematode infections in humans and our domestic animals [9-12]. This capacity of H. p. bakeri to survive for so long, without inducing rapid expulsion, is facilitated by the mechanisms that this species uses to downregulate local intestinal immune responses primarily in its immediate vicinity, but also in more distant host tissues [13-15]. H. p. bakeri is known to secrete immunomodulatory factors BCKDHA (IMF) that interfere with both the induction and expression of mucosal immune responses [12, 16-18], and one consequence of this is that other parasites residing in the intestinal tract (and elsewhere in host tissues) of concurrently infected animals can benefit by sustaining longer infections than would otherwise be the case. The prolongation of infections with other species has been demonstrated in the laboratory [19-22] and has been detected in the field in wild rodent populations naturally infected with the close relative H. p. polygyrus [23, 24]. The literature on H. p. bakeri is large and has been complicated by taxonomic problems centring on the relationships of H. p. bakeri with another closely related parasite of wild rodents in Europe, which is now more correctly referred to as H. p. polygyrus.

These changes were suppressed by blood pressure non-dependent in the WT-Aldo+Eple.

Furthermore, caspase-1-positive cells in the kidney were merged with the immunofluorescent staining AZD2281 manufacturer for the macrophage marker F4/80. Therefore, inflammasomes were mainly activated in the infiltrating macrophages. Tubulointerstitial injuries were significantly attenuated in the ASCKO-Aldo. Increased Caspase-1 activity and expressions of IL-1β and IL-18 were also attenuated in ASCKO-Aldo. The production of IL-1β and IL-18 were detectable in the supernatant of macrophages by Aldo stimulation. These changes were suppressed by eplerenone. Conclusion: Our results indicate that Aldo induced interstitial fibrosis via activation of inflammasomes in infiltrated macrophages. Thus, inflammasome activation in macrophages could be a new therapeutic target for CKD. TAKAORI KOJI1, selleck kinase inhibitor NAKAMURA JIN1, YAMAMOTO TADASHI2, YANAGITA MOTOKO1 1Department of Nephrology, Kyoto University; 2Department of Structural Pathology, Niigata University Introduction: Recently we clarified that renal fibroblasts including erythropoietin (Epo) producing cells transdifferentiate into myofibroblasts and predominantly contribute to fibrosis, with concomitant loss

of Epo production in the diseased kidney. It remains unclear, however, what triggers the transdifferentiation of fibroblasts to myofibroblasts and how proximal tubule injury affects other segment of

the nephron. Methods: For in vitro analysis, we utilized co-culture of renal fibroblasts and tubular epithelial cells. For in vivo analysis, we utilized N-myc downstream-regulated gene-1 (Ndrg1)CreERT2 inducible simian diphtheria toxin receptor (DTR) transgenic mice (Ndrg1CreERT2:iDTR mice) in which Cre-mediated excision of a STOP cassette is achieved after the administration of tamoxifen, and renders proximal tubules sensitive to diphtheria toxin (DT). Furthermore, we utilized Uterine sensitization-associated gene-1 (USAG1)-LacZ mice in which LacZ is expressed in Cell press distal tubules and examined the expression profile of LacZ-positive distal tubule cells after the administration of DT. Results: First, we confirmed that DTR is expressed in almost all proximal tubules and a part of collecting duct in the kidney of Ndrg1-CreERT2:iDTR mice. A single DT injection to these mice causes proximal tubule injury and interstitial fibrosis accompanied with the proliferation of proximal tubules and fibroblasts. While electric microscopy examinations reveal the normal glomerular structure, massive proteinuria was observed after the injection of DT. We also confirmed the induction of collagen expression in fibroblasts when co-cultured with damaged tubular epithelial cells. We further demonstrated the induction of distal tubule injury after the administration of DT to Ndrg1-CreERT2:iDTR:USAG1-LacZ mice.

46 There are a large number of risk factors for the development of NODAT. These include standard risk factors such as increasing age, male gender, non-white ethnicity and BMI. Substantial weight gain occurs in the first 1–2 years post transplantation47 and this has been shown to be associated with an increased

risk of NODAT. There are, however, a number of additional risk factors more specific to transplantation. These include Hepatitis C with a recent48 meta-analysis showing OR 3.97 for the development of NODAT with Hepatitis C infection and the use of a number of immunosuppressive agents. click here The use of corticosteroids49 and calcineurin inhibitors, in particular tacrolimus,50 has been shown to increase the incidence of NODAT. The DIRECT

trial51 randomized patients to tacrolimus or cyclosporine after renal transplantation and found a significantly higher incidence of NODAT and a nearly twofold risk of insulin requirement with tacrolimus compared with cyclosporine. Additionally, the use of sirolimus appears to be implicated in the development of NODAT resulting in reductions in insulin sensitivity, beta cell function and overall glucose tolerance.52 The development of diabetes after renal transplantation has a significant impact on outcomes after transplantation. There is a marked increased risk of cardiovascular events in patients both with impaired glucose tolerance and with

NODAT53 selleck screening library while Tolmetin both pre-existing diabetes and NODAT are associated with reductions in long-term patient survival.2 There has also been an increased risk of acute rejection reported in those with poor glycaemic control after transplantation.54 Despite this, there are very few trials examining prevention and treatment of patients with diabetes after kidney transplantation. One study55 examined the effects of lifestyle modification (dietician referral, exercise, weight loss advice) in patients with impaired glucose tolerance (IGT) or NODAT demonstrating a 15% improvement in 2 h postprandial glucose in this group. Thiazolidinediones have been used after transplantation but not in clinical trials. While they appear to be safe in case reports, troglitazone induces P450 and lowers cyclosporine levels.56 After renal transplantation, there has been one retrospective review of patients with either NODAT or pre-existing diabetes being treated with metformin.57 A total of 32 patients had been treated with metformin with a mean GFR of 74 mL/min at the start of treatment. In those patients with pre-existing diabetes, there was a reduction in the GFR at a mean of 16 months follow up; however, the mean GFR remained relatively high at 60 mL/min. Five patients, however, discontinued metformin because of an increase in the serum creatinine with a cut-off of 1.6 mg/dL (142 µmol/L).

Among several HSPs, gp96 was determined as a potent adjuvant for eliciting immune responses in vaccine development against different diseases [37–41]. It was reported that gp96 and its N-terminal domain can elicit bystander activation of CD4+ T cell Th1 cytokine production [42]. In our previous study,

the adjuvant activity of the gp96 along with HPV16 E7 was determined and proved in different formulations including DNA/DNA and DNA/protein immunization strategies [27]. In the current study, to evaluate the adjuvant potential of NT-gp96 in protein vaccine strategy, the immunogenicity of PLX3397 order the recombinant fusion protein (HPV16 E7-NT-gp96) as well as its potential for inducing anti-tumour immune responses was analysed. The source of gp96 in our study is from Xenopous laevis. Gp96 elicits T cell responses against antigenic peptides that it chaperones in vertebrates from man to frogs [43]. It was demonstrated that the ability of gp96 to facilitate cross-presentation of chaperoned antigens by interacting with CD91 which leads to specific potent T cell response has been conserved between the amphibian Xenopus and mammals [44]. Clearly, generation of humoral and cellular immune responses is influential parameters for designing ideal protein vaccine. In our present study, the rE7- as well as rE7-NT-gp96-immunized mice secrete the mixture of IgG1 and IgG2a isotypes. The rE7 immunization

induce significantly higher amount of IgG1 find more than IgG2a after challenge, while rE7-NT-gp96-immunized mice secrete the same levels of IgG1 and IgG2a at that time. Although both IgG1 and IgG2a isotype levels were lower in rE7-NT-gp96-immunized mice,

it is worthy to mention that IgG2a response is stable over times after challenge in this group. Totally, it can be concluded that the NT-gp96 fusion to E7 induces low-level specific antibody responses. Moreover, evaluation STAT inhibitor of cellular immune response displayed that E7 stimulated splenocytes derived from (E7-NT-gp96)-immunized mice produced significantly high level of IFN-γ as compared to E7-immunized mice. Furthermore, the high level of IFN-γ in rE7-NT-gp96-immunized mice is E7-specific and is not due to NT-gp96 stimulation (Fig. 4A). The amount of IL-5 is low and nearly at the same level after E7 or NT-gp96 in vitro stimulation (Fig. 4B). Consistent with Chu et al. [45] studies, immunization of mice with E7 protein resulted in IL-5 production. Indeed, E7 fused Hsp65 considerably alters the E7 recall response from IL-5 to IFN-γ secretion. In the current study, linkage between E7 and NT-gp96 also caused this immune response alteration. In addition, IFN-γ/IL-5 ratio confirmed that the N-terminal fragment of gp96 drives T cell responses towards a Th1-type manner. Our observation that the antigen-HSP fusion protein potentiated the Th1 immune response is similar to other reports.

Further research is encouraged to confirm these findings. Although we examined an average of 41 observations for each dyad and the study lasted 14 months,

the low number (10) of dyads involved in the study, owing to the difficulties of collecting data so frequently and over a long period of time, unfortunately reduced the power of the statistical test we used. Moreover, limiting data collection to only one instrument did not permit us to explore possible relationships between coregulation development and other measures, and confined the analysis of individual differences to the information provided by our coding system. A research design which includes other individual and environmental variables is needed to identify those factors which may account for variability in development.

Despite these limitations, our findings Akt inhibitor are fine grained and quite consistent; so, they can be reliably taken as further evidence of the infant’s entry into the realm of secondary intersubjectivity as a gradual and multidetermined process. “
“We explored the amount and timing of temporal synchrony necessary to facilitate prenatal perceptual learning selleck kinase inhibitor using an animal model, the bobwhite quail. Quail embryos were exposed to various audiovisual combinations of a bobwhite maternal call paired with patterned light during the late stages of prenatal development and were tested postnatally for evidence of prenatal auditory learning of the familiarized call. Results Chlormezanone revealed that a maternal call paired with a single pulse of light synchronized with one note of the five note call was sufficient to facilitate embryos’ prenatal perceptual learning of the entire call. A synchronous note occurring at the onset of the call burst was most effective at facilitating learning. These findings highlight quail embryos’ remarkable sensitivity to temporal synchrony and indicate its role in promoting learning of redundantly specified stimulus properties during prenatal development. “
“This study investigated prosodic and structural characteristics of infant-directed

speech to hearing-impaired infants as they gain hearing experience with a cochlear implant over a 12-month period of time. Mothers were recorded during a play interaction with their HI infants (N = 27, mean age 18.4 months) at 3, 6, and 12 months postimplantation. Two separate control groups of mothers with age-matched normal-hearing infants (NH-AM) (N = 21, mean age 18.1 months) and hearing experience-matched normal-hearing infants (NH-EM) (N = 24, mean age 3.1 months) were recorded at three testing sessions. Mothers produced less exaggerated pitch characteristics, a larger number of syllables per utterance, and faster speaking rate when interacting with NH-AM as compared to HI infants.

Methods: We investigated the expression of CRegs, CD46, CD55 and CD59 in peritoneal mesothelial cells and levels of the complement activation marker sC5b-9 in PD fluids (PDF) to clarify influence of complement activation and CRegs expression in PD patients. Primary cell cultures of mesothelial cells were obtained from PD fluid of 30 PD patients and from omentum of 3 non-chronic kidney disease patients under laparoscopic operations for analysis of expression CCI-779 of CRegs. sC5b-9 levels were measured in the PDF of the PD patients, and background history, including complications of diabetes and usage of icodextrin

as PDF, and dialysate-to-plasma creatinine concentration ratio (D/P Cre), an indicator of peritoneal function, were noted. Results: In PD patients, expression of CD55 but not CD46 and CD59 on mesothelial cells was significantly correlated to peritoneal MI-503 manufacturer function (D/P Cre; p < 0.05). Levels of sC5b-9

in the PDF showed weak inverse-correlation with expression levels of CRegs on mesothelial cells. Production of mRNA level of CD55 was also correlated to expression of CD55 (p < 0.0001). Usage of icodextrin, or background history did not affect CD46, CD55 and CD59 expressions. Conclusion: Our results show that PD therapy alters expression of CRegs and complement regulation in the peritoneum. These data suggest that current PD protocols might impair peritoneal function by modulating the activation and regulation of the complement system. SAKA YOSUKE1, IIDA YOSHIYASU2, NARUSE TOMOHIKO1, WATANABE YUZO1, ITO YASUHIKO3, MARUYAMA SHOICHI3, MATSUO SEIICHI3 1Department of Internal Medicine, Kasugai Municipal Hospital; 2Department of Nephrology, Yokkaichi Municipal Hospital, Japan; 3Department of Nephrology, Nagoya University Graduate School of Medicine, Japan Introduction: Catheter malposition is one of the reasons for outflow failure in peritoneal dialysis

(PD) patients. Fluoroscopic manipulation is a non-surgical treatment option for catheter malposition. We retrospectively analyzed the efficacy and safety of fluoroscopic manipulation using Progesterone an alpha-replacer guidewire. Methods: The alpha replacer (JMS Co. Ltd., Tokyo, Japan) is a guidewire for treatment of catheter malposition. We used the alpha-replacer in 23 PD cases at our hospital from January 2008 to December 2012. We evaluated body mass index, time interval between catheter placement and malposition and interval between catheter exteriorization and malposition. Primary failure was defined as malposition at the time of catheter exteriorization, and secondary failure as malposition after functional PD therapy (correct position at time of exteriorization). Results: Successful catheter replacement rate using the alpha-replacer was 60.8% (14 of 23 cases). This was similar to the rates in previous reports. Successful replacement was mostly observed in those with a long interval between catheter placement and malposition (p = 0.