Pro-inflammatory cytokines in cryptoglandular anal fistulas

Background: Sphincter-preserving procedures for the treatment of transsphincteric fistulas fail in at least one out of every three patients. It has been suggested that failure is due to ongoing disease in the remaining fistula tract. Cytokines play an important role in inflammation. At present, biologicals targeting cytokines are available. Therefore, detection and identification of cytokines in anal fistulas might have implications for future treatment modalities. The objective of the present study was to assess local production of a selected panel of cytokines in anal fistulas, including pro-inflammatory interleukin (IL)-1β and tumor necrosis factor α (TNF-α). Methods: Fistula tract tissue was obtained from 27 patients with a transsphincteric fistula of cryptoglandular origin who underwent flap repair, ligation of the intersphincteric fistula tract or a combination of both procedures. Patients with a rectovaginal fistula or a fistul

IgM antibody level against proinflammatory bacterial peptidoglycan is inversely correlated with extent of atherosclerotic disease

Objective: Atherosclerosis may lead to acute clinical events by rupture of a vulnerable atherosclerotic plaque. Previously, we demonstrated that peptidoglycan (PGN), a major cell wall component of gram-positive bacteria that induces production of proinflammatory cytokines through TLR2 and CD14, is prevalent in atherosclerotic lesions with histological features associated with plaque vulnerability. We hypothesized that in atherosclerotic patients antibody levels against PGN may differ compared with matched controls. Methods and results: ELISA was performed to measure immunoglobulin levels against PGN in sera of 80 atherosclerotic patients versus 77 control patients with an increased cardiovascular risk, frequency-matched for age, sex and risk factors for atherosclerotic disease. In all patients and controls, intima-media (IMT) thickness was assessed using an array transducer. Significantly lower levels of IgM directed against PGN were found in atherosclerotic patients compared with the control patients without clinically manifested disease (P=0.02). The IgM levels against PGN decreased with increasing mean common carotid IMT thickness (P=0.006). Conclusions: These results show that patients suffering from atherosclerotic disease have decreased IgM levels against PGN. The data suggest that an antibody response against PGN could have a protective effect against the development or activity of atherosclerotic disease

Arthritis by autoreactive T cell lines obtained from rats after injection of intestinal bacterial cell wall fragments

__Abstract__ T cell lines (B13, B19) were isolated from the lymph nodes of Lewis rats 12 days after an arthritogenic injection of cell wall fragments of Eubacterium aerofaciens (ECW), a major resident of the human intestinal flora. These cell wall fragments consist of peptidoglycan polysaccharide complexes (PPC). The cell lines that bear the helper phenotype were arthritogenic in knee or ankle joints upon intravenous injection into irradiated Lewis recipients. B13 was, however, not arthritogenic in irradiated F344 recipients that are largely RT1 identical. The arthritis induced in the knee joints of the irradiated Lewis rats was clearly shown by a 99mtechnetium-pertechnetate scanning technique and was confirmed histologically. In vitro the cell lines showed a proliferative response after stimulation with syngeneic spleen cells alone. The proliferation was significantly higher when bacterial PPC, isolated in soluble form from normal feces or ileostomy fluid were added. Recognition by B13 appeared to be MHC class II restricted. These results show that autoreactive T cell lines can be isolated from rats after injection of bacterial cell wall antigens and that these cell lines can be arthritogenic. This suggests a role for autoreactive T cells in the induction of bacterial cell wall arthritis and might give a clue for the arthritogenic properties of the normal human intestinal flora

Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients

T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal f

Somatostatin receptor subtype expression in cells of the rat immune system during adjuvant arthritis

Somatostatin is a neuropeptide that is widely distributed throughout the body. It acts as a neurohormone and a neurotransmitter an

Proinflammatory bacterial peptidoglycan as a cofactor for the development of central nervous system autoimmune disease

Upon stimulation by microbial products through TLR, dendritic cells (DC) acquire the capacity to prime naive T cells and to initiate a proinflammatory immune response. Recently, we have shown that APC within the CNS of multiple sclerosis (MS) patients contain peptidoglycan (PGN), a major cell wall component of Gram-positive bacteria, which signals through TLR and NOD. In this study, we report that Staphylococcus aureus PGN as a single component can support the induction of experimental autoimmune encephalomyelitis (EAE) in mice, an animal model for MS. Mice immunized with an encephalitogenic myelin oligodendrocyte glycoprotein peptide in IFA did not develop EAE. In contrast, addition of PGN to the emulsion was sufficient for priming of autoreactive Th1 cells and development of EAE. In vitro studies demonstrate that PGN stimulates DC-mediated processes, reflected by increased Ag uptake, DC maturation, Th1 cell expansion, activation, and proinflammatory cytokine production. These data indicate that PGN-mediated interactions result in proinflammatory stimulation of Ag-specific effector functions, which are important in the development of EAE. These PGN-mediated processes may occur both within the peripheral ly

The effect of a medication reconciliation program in two intensive care units in the Netherlands: a prospective intervention study with a before and after design

Background: Medication errors occur frequently in the intensive care unit (ICU) and during care transitions. Chronic medication is often temporarily stopped at the ICU. Unfortunately, when the patient improves, the restart of this medication is easily forgotten. Moreover, temporal ICU medication is often unintentionally continued after ICU discharge. Medication reconciliation could be useful to prevent such errors. Therefore, the aim of this study was to determine the effect of medication reconciliation at the ICU. Methods: This prospective 8-month study with a pre- and post-design was carried out in two ICU settings in the Netherlands. Patients were included when they used ≥ 1 chronic medicine and when the ICU stay exceeded 24 h. The intervention consisted of medication reconciliation by pharmacists at the moment of ICU admission and prior to ICU discharge. Medication transfer errors (MTEs) were collected and the severity of potential harm of these MTEs was measured, based on a potential adverse drug event score (pADE = 0; 0.01; 0.1; 0.4; 0.6). Primary outcome measures were the proportions of patients with ≥ 1 MTE at ICU admission and after discharge. Secondary outcome measures were the proportions of patients with a pADE score ≥ 0.01 due to these MTEs, the severity of the pADEs and the associated costs. Odds ratio and 95% confidence intervals were calculated, by using a multivariate logistic regression analysis. Results: In the pre-intervention phase, 266 patients were included and 212 in the post-intervention phase. The proportion of patients with ≥ 1 MTE at ICU admission was reduced from 45.1 to 14.6% (ORadj 0.18 [95% CI 0.11–0.30]) and after discharge from 73.9 to 41.2% (ORadj 0.24 [95% CI 0.15–0.37]). The proportion of patients with a pADE ≥ 0.01 at ICU admission was reduced from 34.8 to 8.0% (ORadj 0.13 [95% CI 0.07–0.24]) and after discharge from 69.5 to 36.2% (ORadj 0.26 [95% CI 0.17–0.40]). The pADE reduction resulted in a potential net cost–benefit of € 103 per patient. Conclusions: Medication reconciliation by pharmacists at ICU transfers is an effective safety intervention, leading to a significant decrease in the number of MTE and a cost-effective reduction in potential harm. Trial registration Dutch trial register: NTR4159, 5 September 2013, retrospectively registered