These data indicate that TINK cells exhibit a specific modulation of the expression of chemokine receptors involved in cell migration within the tumor microenvironment. The precise identification

of the molecular modulations in NK cells within the tumor microenvironment can help to understand how to control NK-cell antitumoral functions during tumor immunosurveillance [19]. The adoptive infusion of NK cells is a promising immunotherapy for patients with advanced malignancies [5]. Using gene and microRNA expression microarrays, Park et al. provided distinct expression profiles of ex vivo expanded NK cells and freshly isolated NK cells from cancer patients [17]. Among approximately 25 100 genes evaluated, the expanded NK cells overexpressed 1098 genes and 28 Carfilzomib ic50 microRNAs when compared with freshly

isolated human NK cells [17]. Genes related to crosstalk between DCs and NK cells as well as those for mitochondrial dysfunction were upregulated, while some genes related to immune function pathways were downregulated, including IFN, IL-10, and CXCR4 signaling. These differences may ultimately have an effect on the clinical outcomes when using adoptive transfer of NK cells as an immunotherapeutic strategy [17]. The outgrowth of CD3–CD56+CD16+ NK cells causes

NK-cell-type lymphoproliferative disease of granular lymphocytes www.selleckchem.com/products/epz015666.html (LDGLs), which can be further subdivided into two distinct categories: aggressive NK-cell leukemia and chronic NK lymphocytosis [16]. A comparison between purified pNK cells in healthy and chronic NK lymphocytosis individuals Liothyronine Sodium identified a total of 15 LDGL-associated genes, such as Bmi1, Zfr, and Optn, which may potentially serve as candidate genes for diagnosing NK-cell disorders; additionally, these data provided new insights into the molecular pathogenesis of NK-cell-type LDGLs [16]. Extranodal nasal-type NK/T-cell lymphoma (NKTL) is characterized by a clonal proliferation of NK or T cells with a cytotoxic phenotype [92]. Comprehensive genome-wide gene expression profiling revealed that human NKTL (including HANK-1) and NK-cell lines (including NK-92 and NK-YS) are enriched in several cell cycle related genes (including Plk1, Cdk1, and Myc) as compared with pNK cells from healthy donors. Almost all cases of NKTL expressed high p53 and survivin levels, which were not expressed in pNK cells from healthy humans. Thus, genomic profiling of NKTL provides further understanding into its pathogenesis and oncogenic pathways, and suggests that survivin is a potential novel therapeutic target for NKTL [92].

major infection changed

neither the cellular and humoral response to S. ratti nor the clearance of infection although 2 days of pre-existing L. major infection readily suppressed S. ratti-induced Th2 response (Figure 2b). We analysed the outcome of infection and the nature of immune response in mice co-infected with L. major and S. ratti, i.e. parasites that elicit and are efficiently cleared by Th1 and Th2 immune responses, respectively. We show that a pre-existing S. ratti infection did not interfere with the control of L. major high-dose or low-dose infections. Also, the generation of a protective memory response was not affected in co-infected mice. In line with these findings, neither the local L. major-specific Th1 response in the popLN

nor the systemic humoral response as indicated by L. major-specific Ig in the serum was suppressed by S. ratti co-infection. In contrast, we observed increased proliferation ��-catenin signaling and IFN-γ production in popLN of co-infected mice responding to anti-CD3 and SLA stimulation. signaling pathway We observed also spontaneous proliferation and cytokine secretion in the absence of stimulating agents in the popLN, thus reflecting a generalized activation of lymphocytes. As we set both experimental infections into the same footpad, the popLN that we investigated drained tissue containing both L. major and migrating S. ratti larvae. Therefore, we argue that we did not observe a compartmentalization of immune responses to parasites residing at distinct sites as was shown for L. sigmodontis and L. major co-infection (22). In our co-infection system,

the L. major-specific Th1 response apparently dominated the local lymphocyte differentiation. Infection with S. ratti is resolved within 3 to 4 weeks and displays a very short period, i.e. 3–5 days of maximal Th2 response and reciprocal suppression of Th1 response as we demonstrated by kinetic studies (10). It is conceivable that the transient nature of this nematode infection explained the missing impact on subsequent L. major infection. In line with our findings, efficient control of L. major infection was reported in C57BL/6 mice co-infected with Nippostrongylus brasiliensis that is expelled in the context of a Th2 response (23). Unchanged or even accelerated resolution of L. major of infection was reported in C57BL/6 mice with pre-existing L. sigmodontis infection (22). Furthermore, an increased IFN-γ production in response to L. major antigen and in the absence of stimulation was described in L. sigmodontis/L. major co-infected mice, strongly resembling the increased pro-inflammatory response we observed in the popLN in S. ratti/L. major co-infected mice. Although L. sigmodontis infection is long lasting in BALB/c mice, the larvae do not proceed beyond the fourth stage and never reach the patency in the C57BL6 mice used in the cited study (22,24,25).

We discuss the clinical and experimental evidence that supports the notion that the microcirculation, specifically cell-to-cell communication, likely contributes to the development of VaD. Through exploration of the concept of the NVU, we elucidate

the extensive cerebrovascular communication that exists and highlight models that may help test the contribution(s) of cell-to-cell communication at the microvascular level to the development and progression of VaD. Lastly, we explore the possibility that some dementia, generally considered to be MK-2206 datasheet purely neurodegenerative, may actually have a vascular component at the neurovascular level. Conclusion:  This latter recognition potentially broadens the critical involvement of microvascular events that contribute to the numerous dementias affecting an increasingly larger sector of the adult population. “
“Cell–cell adhesion complexes are increasingly recognized as an important cell-signaling site, similar to integrin-extracellular matrix FA. Furthermore, cell–cell adhesions are involved in the regulation

of multi-cellular/tissue organization and organ, tissue, and cellular level functional behavior. Although N-cadherin is the major cell–cell adhesion molecule in VSM, only limited studies have been undertaken to understand its function in VSM. Small molecule library In contrast, N-cadherin signaling and functions have been extensively studied in neurons, fibroblasts, and myocytes, as well as in the context

of epithelial-mesenchymal-transitions. Increasing evidence has indicated Isotretinoin that N-cadherin-mediated cell–cell adhesions are important for tissue integrity and cell proliferation. Relevant to VSM, N-cadherin’s role in actin cytoskeleton organization and contraction, as well as its role in regulation of Rho family GTPases are of particular interest. This article briefly reviews the fundamentals of N-cadherin biology that help shape our current understanding of its function and signaling mechanisms. In particular, attention is given to applications of this knowledge to VSM. The review points to the need for more research effort that is directed at understanding the role of N-cadherins in the regulation of vascular function. “
“Please cite this paper as: Wang, Hein, Zhang, Zawieja, Liao and Kuo (2011). Oxidized Low-Density Lipoprotein Inhibits Nitric Oxide-Mediated Coronary Arteriolar Dilation by Up-regulating Endothelial Arginase I. Microcirculation18(1), 36–45. Oxidized low-density lipoprotein (OxLDL) causes impairment of endothelium-dependent, nitric oxide (NO)-mediated vasodilation involving l-arginine deficiency. However, the underlying mechanism remains elusive. Since arginase and endothelial NO synthase (eNOS) share the substrate l-arginine, we hypothesized that OxLDL may reduce l-arginine availability to eNOS for NO production, and thus vasodilation, by up-regulating arginase.

Other fungi previously found in the oral cavity of immunocompromised patients include Penicillium, Geotrichum, Aspergillus, Scopulariopsis,

Hemispora, and Hormodendrum [89, 111, 112], although the representation of species seems to correlate with the geographic area of sampling [113]. Recently, Mukherjee et al. used pyrosequencing to characterize the oral microbiota of 12 HIV-infected patients and 12 healthy subjects [114]. The core oral bacterial microbiota comprised 14 genera, of which 13 were common between patients and healthy HDAC inhibitor subjects. In contrast, the core oral mycobiota differed more between HIV-infected and -uninfected individuals, with Candida being the predominant species in immunocompromised patients (98 versus 58% in healthy subjects). Among HIV-infected patients, Candida, Epicoccum, and Alternaria were the most common genera, while in uninfected participants, the most abundant fungi were Candida, Pichia, and Fusarium. Increase in Candida colonization, particularly that of C. albicans, was associated with a concomitant decrease in the abundance of Pichia — a resident oral fungus representing the 33% of healthy oral mycobiota, Selleckchem DMXAA suggesting an antagonistic relationship. Indeed,

Pichia has been shown to inhibit growth of pathogenic fungi such as Aspergillus and Candida by inhibiting the ability of these genera to adhere, germinate, and form biofilms in vitro [114]. Oral Candida colonization is a known risk factor for invasive Candidiasis [115]. Similarly, fungal caused periodontal disease is associated with rheumatoid arthritis [116] and atherosclerosis (-)-p-Bromotetramisole Oxalate [117], suggesting that bacterial and fungal microbiota from the oral cavity may contribute to the development

of certain human diseases. The human respiratory tract represents the major entry point for numerous microorganisms, primarily airborne viruses, bacteria, and fungal spores. Certain characteristics of these microorganisms, such as Aspergillus spp., coupled with the local host immune response, determine whether the microorganisms will be cleared by the immune system or adhere to and colonize the airways, leading to acute or chronic pulmonary disease [118]. The lower respiratory tract (trachea, bronchi, and pulmonary tissue), previously thought to be sterile when healthy, has recently been shown to clearly harbor a low level bacterial microbiota, which changes during disease (reviewed in [119]). Any microbe, be it a bacterium or a fungus, reaching the lower respiratory tract encounters the efficient cleansing action of the ciliated epithelium. Microorganisms are also subsequently removed by coughing, sneezing, and swallowing. However, if the respiratory tract epithelium becomes damaged, as in the case of bronchitis or viral pneumonia, the individual may become susceptible to infection by pathogens descending from the nasopharynx (upper respiratory tract).

B7-H3/pMXC and B7-H3/pMXs-neo were used for SCCVII, EL4, E.G7, B16 cells and J558L cells, respectively. Tumour www.selleckchem.com/products/Staurosporine.html cells were retrovirally transduced with B7-H3.28 For infecting EL4, SCCVII and B16 cells, pVSV-G was co-transfected

to generate pan-tropic retrovirus. After drug selection, transfectants expressing high levels of B7-H3 were sorted by flow cytometry as described previously.31 The TLT-2 complementary DNA was inserted into pMXs-IG, and control IRES-GFP (pMXs-IG) or TLT-2/pMXs-IG was retrovirally transduced into OT-I CD8+ T cells stimulated with OVA peptide (SIINFEKL).28 GFP+ cells were sorted by flow cytometry and used as mock- or TLT-2-transduced OT-I CD8+ T cells. CD4+ and CD8+ T cells from BALB/c mice were isolated by negative selection, as described previously.28 The purity of the CD4+ and CD8+ T cells was over 95% and 90%, respectively, as confirmed by flow cytometry. For the anti-CD3 mAb-induced co-stimulation assay, isolated T cells (2 × 105/well) were co-cultured with mitomycin C-treated parental P815 or B7-H3-transduced P815 (B7-H3/P815) cells at the indicated responder : stimulator ratios, in the presence of anti-CD3 mAb (145-2C11, 0·2 μg/ml in CD4+ T cells and 1·0 μg/ml in CD8+ T cells). The proliferative responses for the final 18 hr of the 3-day culture and IFN-γ production in the culture

supernatants at 72 hr were then measured.32 Anti-CD3 ACP-196 mAb-induced redirected cytotoxicity against P815 and B7-H3/P815 cells was measured by the 6-hr JAM test.33,34 Splenocytes from OT-1 mice were cocultured with mitomycin C-treated E.G7 cells for 3 days for in vitro sensitization.

The cells were harvested, separated into CD8+ T cells, and used as in vitro-sensitized not OT-I CD8+ T cells. Cytotoxicity against E.G7 and B7-H3/E.G7 was measured by a 6-hr JAM test. For the in vivo cytotoxicity assay, E.G7 and B7-H3/E.G7 cells were labelled with CellTracker Orange [5-(and-6)-(((4-chloromethyl)benzoyl)amino)] tetramethylrhodamine (CMTMR; 10 μm, Invitrogen, Carlsbad, CA) and/or carboxyfluorescein diacetate succinimidyl ester (CFSE; 10 μm, Invitrogen). The CMTMR-labelled cells (2 × 106) were mixed with a twofold number of CFSE-labelled parental E.G7 (A-mix) or B7-H3/E.G7 (B-mix) cells (4 × 106) and then the mixed cells were injected intraperitoneally (i.p.) into OT-I mice. Peritoneal exudate cells (PEC) were analysed by flow cytometry after 24 hr. B6 mice were sensitized in vivo by peritoneal injection with DBA/2-originated allogeneic P815 or B7-H3/P815 cells (2 × 107 cells) to evaluate CTL against the alloantigen. After 8 days, PEC were collected and cytotoxicity against P815 and B7-H3/P815 was measured as described above. The OT-I mice received a peritoneal injection of mitomycin C-treated OVA-expressing EL4 (E.G7 or B7-H3/E.G7) cells (2 × 107) to induce OVA-specific CTL. Three days later, PEC were harvested and cytotoxicity against E.G7 and B7-H3/E.G7 was assessed as described above.

NALT cells were readily isolated, KU57788 yielding approximately 2.5 × 105 viable cells per palate. Because we had exsanguinated the mice from the inferior vena cava, we noted few erythrocytes; thus more than 96% of the cells were the following immune cells: CD3+ cells (53.5

± 3.8%; mean ± SD; n =3); CD4+ cells (38.6 ± 2.6%; mean ± SD; n =3); CD8+ cells (17.5 ± 2.5%; mean ± SD; n =3); B220+ cells (40.0 ± 3.7%; mean ± SD; n = 3); Mac-1+ cells (1.5 ± 0.4%; mean ± SD; n =3); CD11c+ cells (0.6 ± 0.0%; mean ± SD; n =3); and Ly-6G+ cells (0.3 ± 0.1%; mean ± SD; n =3). The cell yield from NALT and their phenotypic composition were essentially the same as those reported previously (17, 18), showing that they had been accurately prepared. Figure 2 shows the time-dependent selleck inhibitor changes in the total number of cells in NALT or submandibular lymph nodes of BALB/c mice after one i.n. injection of cedar pollen. The total number of NALT cells did not change significantly from days 0–14 after

i.n. injection of the allergen (Fig. 2a); and the percentages of B220+, CD3+, Mac-1+, CD11c+, and Ly-6C+ cells were also unchanged (data not shown). In contrast, the total number of submandibular lymph node cells started to increase on day 3 after i.n. injection of the allergen, reached a peak (≈ threefold that of the PBS-injected AZD9291 molecular weight control) on day 10, and declined to the basal level by day 14 (Fig. 2b). Of particular interest, the percentage of B220+ cells on day 0 (≈ 36%) started to increase from day 3 (≈ 49%), reached a plateau on days 5–10 (54–55%), and decreased to the basal level by day 14 (≈ 42%). In contrast, those of CD3+ cells, Mac-1+, CD11c+, and Ly-6C+ cells decreased time-dependently and returned to the basal level by day 14 (data not shown), suggesting that B220+ cells (e.g., B or pre-B cells) in the submandibular lymph nodes might be the cells that respond to i.n. injections of allergen. Bulk cells from submandibular lymph

nodes from mice that had been treated once i.n. with allergen produced a significant amount of IgE Ab on day 7 (mean ± SE, 3.8 ± 1.0 ng/mL; n= 30) with a peak on day 10 (7.8 ± 1.6 ng/mL; n =30). The concentrations then decreased to the control level by day 14 (0.1 ± 0.1 ng/mL; mean ± SEM; n= 30), demonstrating time-dependent changes in the amount of IgE Ab similar to the changes in total cell numbers. In contrast, the bulk cells from the NALT from mice that had been treated once i.n. with allergen did not produce significant amounts of IgE (n =12) on days 0–14. The bulk cells of the axillary lymph nodes, Peyer’s patches, inguinal lymph nodes, and mesenteric lymph nodes produced 1.8 ± 0.3 (mean ± SEM; n =15), 1.3 ± 1.4 (mean ± SD; n =9), 0.5 ± 0.3 (mean ± SD; n =9), 0.1 ± 0.3 (mean ± SD; n =9) ng/mL IgE on day 10, respectively (data not shown).

That is precisely what Sperling found, even for large arrays of items, as long as the subset to be reported was relatively small (e.g., three to five items). A recent study by Blaser and Kaldy (2010) reported a similar pattern of results in 6-month-old infants. They presented infants with an array https://www.selleckchem.com/products/Paclitaxel(Taxol).html of up to 10 items varying in shape and color for a brief 1-sec duration and then highlighted two of the items by removing them from the array for 1/2 sec. When these removed items reappeared, one of them had changed. The dependent measure was whether infants looked at the changed item. As

in Sperling (1960), if all of the items in the array were encoded into STM, then regardless of which subset was highlighted, infants should detect the changed item and look longer at it. However, if infants cannot encode all of the items in the array, there will be a set-size limit beyond which the novelty preference for the changed item will fail to exceed chance. This pattern of results was precisely

what Blaser and Kaldy found—at set sizes of 2, 4, and 6 infants looked longer at the changed item, but at set sizes of 8 and 10 they did not. These results suggest that 6-month-olds have a STM capacity of at least six items in a briefly presented array. Along with prior results on WM, these results also confirm that infants have more limited information-processing capacities than adults, although their capacities are still rather impressive given PLX4032 cell line the absence of task instructions, motivation, and training. What then mitigates Problem 2—the Rutecarpine inability to keep track of all possible statistics? Over the past two decades, a variety of constraints have been proposed and verified experimentally to account for the naïve learner’s ability to overcome the computational explosion problem (i.e., attempting to keep track of everything).

These constraints include the following. Attentional biases—infants appear to “naturally” attend to object shape and to the whole object rather than its parts (Smith, 2003), to syllables rather than phonemes (Bertoncini & Mehler, 1981), to a variety of Gestalt principles (Bhatt & Quinn, 2011) such as proximity, synchrony, and stream segregation (within an octave), and to limit inferences to a single possibility (i.e., mutual exclusivity in object names; Markman, Wasow, & Hansen, 2003). Social cues—infants appear to be guided in their attention by the gaze, manual exploration, and pointing gestures of their caregivers (Baldwin, 1993). Environmental simplification—infants benefit from a variety of ways in which caregivers declutter or enhance stimuli in their proximal environment (Kuhl et al., 1997). Cross-situational statistical learning—infants can determine by a simplified “process of elimination” that names and objects are linked even when these linkages are inferred rather than overt (Smith & Yu, 2008).

Secretion of some chemokines, such as CCL-2, CCL-5, CXCL-5

and CXCL-8, was significantly reduced when anti-IL-15 mAb was added to the culture medium (Fig. 4b). However, other cytokines, including CCL-4, CCL-11, granulocyte–macrophage SCH727965 price colony stimulating factor and vascular endothelial growth factor were not affected. These data suggest that blocking by anti-IL-15 antibodies has a selective effect on secretion, of particular chemokines, rather than causing a general non-specific suppression of FDC function (Fig. 4c). CD14, CD44, CD54 (ICAM-1) and CD106 (VCAM-1) are some of the major surface molecules that play important roles in the cellular interactions between GC-B cells and FDCs.6 We therefore investigated the effect of blocking of the IL-15 signal on FDC surface expression of CD14, CD44, CD54 (ICAM-1) and

CD106 (VCAM-1) via FACS analysis. However, the expression of these surface proteins was not altered by anti-IL-15 mAb treatment (Fig. 5). During GC formation, stromal cells in primary follicles proliferate rapidly and differentiate into FDCs.6 Both TNF-α and LT from GC-B cells have been considered essential soluble factors for FDC development because genetically DAPT datasheet engineered TNF-α-knockout and LT-knockout mice are defective in GC formation. However, a number of gene-knockout mouse studies do not distinguish between FDC development in primary B-cell follicles rather than in the GC.6 Therefore, a proliferation assay with in vitro culture of human primary FDCs could be a plausible system with which to investigate the FDC development during the mature GC formation. Although in vitro culture of human primary FDCs has been established, and studied for decades, only a few proliferation factors, including TNF-α and IL-1β, have been identified.54,55 Previously, we demonstrated

that IL-15 expressed in human tonsillar FDCs enhanced the proliferation of GC-B cells.13 The function of IL-15 has not been extensively studied in FDCs because there is little difference in the humoral immune response of genetically modified mice.25–27 We therefore investigated the biological function of IL-15 on human FDCs. In the present study, we examined Histamine H2 receptor the functional role of IL-15 in FDCs using human primary FDCs. First, we found that the addition of IL-15 enhanced recovery of the FDC proliferation in cultures and that the addition of anti-IL-15 antibody reduced the recovery of cultured FDCs. The FDCs have the IL-15R components necessary for signal transduction by IL-15, as well as IL-15 binding. These observations strongly suggest that IL-15 plays a functional role in FDCs. Interestingly, the effect of IL-15 in increasing the recovery of cultured FDCs is mainly attributed to enhanced proliferation rather than protection from apoptosis, as determined by CFSE labelling.

Undoubtedly, the laboratory mouse has proven to be an invaluable model for biological research and most of what we know today about mammalian biology is derived from research carried out with Mus musculus. Nonetheless, to reject other animal models is to ignore the

need to address evolutionary divergence among mammals by studying biology across an array of genotypes. Moreover, the opportunity to exploit unique biological models or intriguing insights can be squandered. Clarity about the nature of immunologic tolerance was developed because Owen and Medawar capitalized on the unique properties of the placental vasculature of twin calves. Rowson’s frustrations with uterine infections in embryo transfer recipients gave impetus to his fruitful Staurosporine mw studies that established progesterone as a key hormone regulating uterine immunity. The papers in this special issue of the American Journal of Reproductive Immunology highlight additional examples whereby farm animals are being used to develop

concepts pertinent to a wide range of mammalian species. Domestic farm animals are not the only mammalian species that can make useful research models, of course, but they offer advantages of availability, ease of handling, cost, and a well-described biology and husbandry. When Medawar was struck with the idea of using the calf in his research, he Roxadustat datasheet turned to colleagues at the Animal Breeding and Genetics Research Organization in Edinburgh. Today, unfortunately, the infrastructure for conducting farm animal research is eroding.21,22 For example,

the number of scientist years working in animal production or protection in the United States declined 22% from 1985 to 2006 and doctorates awarded in the animal sciences in the United States declined by 30% from 1985 to 2004. An increase in Sclareol investments in basic research using farm animals will have a positive impact not only on agricultural productivity but on understanding mammalian biology and enhancing human health. During the initial preparation for this paper, I was fortunate enough to attend the celebrations surrounding the 100th Anniversary of the Dept. of Genetics at the University of Florida. In the course of the event, I heard details of the contributions of Ray Owen to the idea of immunologic tolerance that I was unaware of previously. Medawar had acknowledged his debt to Owen in his Nobel Lecture but, until I heard the details in Madison, I knew little about Owen or his work. I acknowledge Millard Susman, James Crow and Ray Owen for sharing images and information about this important time in reproductive immunology. “
“This study investigated whether angiotensin II type 1 receptor agonistic autoantibodies (AT1-AAs) mediate the increased release of soluble endoglin (sEng) in women with preeclampsia. Serum samples were obtained from women with normal pregnancies or with preeclampsia.

Twenty-one patients whose diagnosis had been made between 1 and 3 months before the commencement of dialysis was excluded from the analysis. The main clinical features of the late diagnosis group at presentation were dyspnoea/pulmonary oedema (41%), severe hypertension (26%),

severe asthenia (22%) and apathy/mental changes (8%). The rate of pulmonary infections (17.9% vs 5.1%, P < 0.01) and mean systolic blood pressure (172 ± 4 mmHg vs 161 ± 4 mmHg) were significantly higher in the late diagnosis group. All patients in the late diagnosis group required a CVC for initiation of dialysis. In the early diagnosis group, 33% of patients had a vascular access created electively. Creatinine clearance at the time of initiation of dialysis was significantly lower in the late dialysis group (4.4 ± 0.5 mL/min vs 6.4 ± 0.5 mL/min, P < 0.01). buy CHIR-99021 Survival at 6 months was significantly decreased (69% vs 87%, P < 0.01) and the risk of death was 2.77 times higher in the late dialysis group. In multivariate

analysis, the most significant predictors of poor outcome were age, intercurrent pulmonary infection and low serum albumin at the commencement of dialysis. In Ratcliffe et al.’s retrospective review of characteristics of all patients accepted for dialysis in the Oxford Unit in 1981, criteria for commencement of dialysis were uraemic symptoms associated with a creatinine clearance buy Fulvestrant less than 6 mL/min.31 Thirty-two patients were referred >1 month (early diagnosis Aprepitant group) and 23 patients were referred <1 month (late diagnosis group) before the commencement of dialysis. In the early referral group, 91% of patients commenced dialysis electively, 72% had a functioning fistula at the time of initiation of dialysis and 22% were commenced on continuous ambulatory peritoneal dialysis. Only two patients required initiation of dialysis via a CVC. In the late referral group, 39%

of patients commenced haemodialysis via a CVC. ‘Serious complications’, which significantly prolonged the length of stay in hospital, were significantly more frequent in the late diagnosis group (70% vs 9%, P < 0.001). Jungers et al. retrospectively reviewed records of 250 patients who commenced dialysis at the Necker Hospital between January 1988 and December 1990.32 The records of patients who required emergency dialysis and who had been referred within 4 weeks of commencing dialysis were identified. Of the total cohort, 25% were in this late referral category. From these patients, 20 records were randomly selected and compared with a control group of 20 age- and sex-matched patients who had been regularly followed up at the renal clinics for at least 6 months prior to the commencement of dialysis.