Autoantibodies against mannose-binding lectin in systemic lupus erythematosus

In systemic lupus erythematosus (SLE), autoantibodies directed against complement components of the classical pathway, especially against C1q, are associated with severe disease and are of prognostic value for flares of lupus nephritis. Mannose-binding lectin (MBL), the recognition unit of the MBL pathway of complement activation, has structural similarities to C1q. Deficiencies of MBL have been shown to predispose to the development of SLE and to influence the course of the disease. We hypothesized that the presence of autoantibodies to MBL, analogous to autoantibodies to C1q in patients with SLE, may contribute to disease development. The occurrence of anti-MBL autoantibodies was assessed by enzyme-linked immunosorbent assay (ELISA) of 68 serum samples from 20 patients with SLE and in serum from 70 healthy controls. Levels of antibodies directed against MBL were significantly higher in patients with SLE compared to healthy subjects. No significant difference was found between patients with active disease compared to those with inactive disease. While the occurrence of anti-C1q autoantibodies was associated with renal involvement, no such relationship was found for anti-MBL autoantibodies. A significant correlation was found between anti-MBL and anti-C1q antibody levels. The level of anti-MBL antibodies was negatively correlated with MBL-complex activity of circulating MBL. Anti-MBL autoantibodies were of the immunoglobulin G (IgG) isotype and the binding site of IgG anti-MBL was located in the F(ab')2 portion. We conclude that anti-MBL are present in sera from SLE patients and influence the functional activity of MBL.     

Do depression and pain intensity interfere with physical activity in daily life in patients with Chronic Low Back Pain?

Patients with chronic pain may have difficulties estimating their own physical activity level in daily life. Pain-related factors such as depression and pain intensity may affect a patients’ ability to estimate their own daily life activity level. This study evaluates whether patients with Chronic Low Back Pain (CLBP) who are more depressed and/or report more pain indeed have a lower objectively assessed daily life activity level or whether they only perceive their activity level as lower. Patients with CLBP were included in a cross-sectional study. During 14 days physical activity in daily life was measured, with both an electronic diary and an accelerometer. Multilevel analyses were performed to evaluate whether a higher level of depression and/or pain intensity was associated with a lower objectively assessed activity level or the discrepancy between the self-reported and objectively assessed daily life activity levels. Results, based on 66 patients with CLBP (mean RDQ score 11.8), showed that the objectively assessed daily life activity level is not associated with depression or pain intensity. There was a moderate association between the self-reported and objectively assessed activity levels (β = 0.39, p < 0.01). The discrepancy between the two was significantly and negatively related to depression (β = −0.19, p = 0.01), indicating that patients who had higher levels of depression judged their own activity level to be relatively low compared to their objectively assessed activity level. Pain intensity was not associated with the perception of a patient’s activity level (β = 0.12, ns).     

Novel insights in localization and expression levels of C5aR and C5L2 under native and post-transplant conditions in the kidney

AimsThe complement system, and especially C5a, plays an important role in the pathophysiology of renal diseases and post-transplant renal injury. The two receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only renal C5aR expression has been reported, although exact localization and alterations in expression after transplantation are unknown.Materials and resultsRenal C5aR and C5L2 expression and localization were analyzed immunohistochemically. C5aR and C5L2 expression was analyzed in human kidney biopsies obtained from living donors and patients suffering from acute tubular necrosis, acute cellular and vascular rejection or IF/TA.C5aR was expressed in the thick ascending limb of Henle's loop and first part of the distal convoluted tubule (DCT). Under inflammatory conditions, C5aR was de novo expressed in proximal tubuli. C5L2 was expressed in the kidney and localized to DCT1, DCT2 and connecting tubule. Persistent distal tubular expression of both receptors was demonstrated after renal transplantation.ConclusionsThis study shows distinct renal expression patterns for C5aR and C5L2. Our findings suggest a functional role for renal C5L2 rather than being a C5a decoy receptor. Future studies focusing on renal C5a–C5aR interaction should take differential C5aR and C5L2 expression into account, alongside abundant C5aR expression on infiltrating cells.     

What do patients know about anesthesiologists? Results of a comparative survey in an U.S., Australian,and German university hospital

Study ObjectivesTo determine patients' knowledge of the role of the anesthesiologist in the hospital.DesignProspective survey instrument.SettingThree university hospitals (University of Virginia, Charlottesville, VA, USA; St. George Hospital University of New South Wales, Sydney, Australia; and University Hospital, Ruhr-University Bochum, Bochum, Germany).Patients900 patients (300 pts per center) undergoing elective surgery.MeasurementsPatients completed a standardized questionnaire before surgery and before speaking to an anesthesiologist.Main ResultsMost patients knew that anesthesiologists were medical doctors (Charlottesville, 58%; Bochum, 83%; Sydney, 71%). The majority (> 75%) underestimated the amount of training required to become anesthesiologist. While patients recognized the role of anesthesiologists in keeping patients asleep and awakening them, many patients did not understand the anesthesiologists' role in treating intraoperative medical problems. Patients had diverse concerns including infection, awakening during surgery, and failure to awaken, although patients were unclear about who was responsible for treating these issues. Outside the operating room (OR), 71% of patients rated Intensive Care Unit treatment as a duty of the anesthesiologist in Bochum, but fewer (P < 0.05) did so from Charlottesville (42%) and Sydney (49%). Understanding of duties outside the OR (resuscitation, teaching medical students, or chronic pain treatment) was very low (< 50%) in all centers.ConclusionPatients underestimated the training and role of the anesthesiologist in the OR and hospital.     

New insight into the effects of heparinoids on complement inhibition by C1‐inhibitor

Complement activation is of major importance in numerous pathological conditions. Therefore, targeted complement inhibition is a promising therapeutic strategy. C1‐esterase inhibitor (C1‐INH) controls activation of the classical pathway (CP) and the lectin pathway (LP). However, conflicting data exist on inhibition of the alternative pathway (AP) by C1‐INH. The inhibitory capacity of C1‐INH for the CP is potentiated by heparin and other glycosaminoglycans, but no data exist for the LP and AP. The current study investigates the effects of C1‐INH in the presence or absence of different clinically used heparinoids on the CP, LP and AP. Furthermore, the combined effects of heparinoids and C1‐INH on coagulation were investigated. C1‐INH, heparinoids or combinations were analysed in a dose‐dependent fashion in the presence of pooled serum. Functional complement activities were measured simultaneously using the Wielisa^®‐kit. The activated partial thrombin time was determined using an automated coagulation analyser. The results showed that all three complement pathways were inhibited significantly by C1‐INH or heparinoids. Next to their individual effects on complement activation, heparinoids also enhanced the inhibitory capacity of C1‐INH significantly on the CP and LP. For the AP, significant potentiation of C1‐INH by heparinoids was found; however, this was restricted to certain concentration ranges. At low concentrations the effect on blood coagulation by combining heparinoids with C1‐INH was minimal. In conclusion, our study shows significant potentiating effects of heparinoids on the inhibition of all complement pathways by C1‐INH. Therefore, their combined use is a promising and a potentially cost‐effective treatment option for complement‐mediated diseases.     

A Case of Severe Chlorite Poisoning Successfully Treated With Early Administration of Methylene Blue,Renal Replacement Therapy,and Red Blood Cell Transfusion: Case Report

The case of a 55-year-old man who attempted suicide by ingesting <100 mL of 28% sodium chlorite solution is presented. On arrival in the intensive care unit, the patient appeared cyanotic with lowered consciousness and displayed anuria and chocolate brown serum.Initial laboratory tests revealed 40% of methemoglobin. The formation of methemoglobin was effectively treated with methylene blue (10% after 29 hours).To remove the toxin, and because of the anuric acute renal failure, the patient received renal replacement therapy. Despite these therapeutic measures, the patient developed hemolytic anemia and disseminated intravascular coagulation, which were treated with red blood cell transfusion and intermittent hemodialysis. These interventions led to the improvement of his condition and the patient eventually fully recovered. Patient gave written informed consent.This is the third known case of chlorite poisoning that has been reported. Based upon this case, we suggest the management of sodium chlorite poisoning to comprise the early administration of methylene blue, in addition to renal replacement therapy and transfusion of red blood cells.     

No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis,frontotemporal dementia,and inclusion body myopathy

Inclusion body myopathy (IBM) associated with Paget disease of the bone, frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS), sometimes called IBMPFD/ALS or multi system proteinopathy, is a rare, autosomal dominant disorder characterized by progressive degeneration of muscle, brain, motor neurons, and bone with prominent TDP-43 pathology. Recently, 2 novel genes for multi system proteinopathy were discovered; heterogenous nuclear ribonucleoprotein (hnRNP) A1 and A2B1. Subsequently, a mutation in hnRNPA1 was also identified in a pedigree with autosomal dominant familial ALS. The genetic evidence for ALS and other neurodegenerative diseases is still insufficient. We therefore sequenced the prion-like domain of these genes in 135 familial ALS, 1084 sporadic ALS, 68 familial FTD, 74 sporadic FTD, and 31 sporadic IBM patients in a Dutch population. We did not identify any mutations in these genes in our cohorts. Mutations in hnRNPA1 and hnRNPA2B1 prove to be a rare cause of ALS, FTD, and IBM in the Netherlands.     

Reproducible radiographs of acetabular prostheses

35 patients with a smooth, threaded acetabular Mecron type prosthesis were examined with the aid of a table top with wiremarkers and a fixed 30-degree wedge to allow for reproducible positioning. Under fluoroscopic control, pelvic and spot films were made. The inter- and intraobserver variability of anteversion and inclination angle measurements of the prostheses had a standard deviation of less than 1 degree. The method can be applied to other acetabular prostheses as well.