Senescence in immunity against helminth parasites predicts adult mortality in a wild mammal.

Our understanding of the deterioration in immune function in old age-immunosenescence-derives principally from studies of modern human populations and laboratory animals. The generality and significance of this process for systems experiencing complex, natural infections and environmental challenges are unknown. Here, we show that late-life declines in an important immune marker of resistance to helminth parasites in wild Soay sheep predict overwinter mortality. We found senescence in circulating antibody levels against a highly prevalent nematode worm, which was associated with reduced adult survival probability, independent of changes in body weight. These findings establish a role for immunosenescence in the ecology and evolution of natural populations.

Nimotuzumab and radiotherapy for treatment of newly diagnosed diffuse intrinsic pontine glioma (DIPG): a phase III clinical study.

BACKGROUND: Diffuse intrinsic pontine glioma (DIPG) is a devastating cancer of childhood and adolescence. METHODS: The study included patients between 3 and 20 years with clinically and radiologically confirmed DIPG. Primary endpoint was 6-month progression-free survival (PFS) following administration of nimotuzumab in combination with external beam radiotherapy (RT). Nimotuzumab was administered intravenously at 150 mg/m2 weekly for 12 weeks. Radiotherapy at total dose of 54 Gy was delivered between week 3 and week 9. Response was evaluated based on clinical features and MRI findings according to RECIST criteria at week 12. Thereafter, patients continued to receive nimotuzumab every alternate week until disease progression/unmanageable toxicity. Adverse events (AE) were evaluated according to Common Terminology Criteria for Adverse Events (CTC-AE) Version 3.0 (CTC-AE3). RESULTS: All 42 patients received at least one dose of nimotuzumab in outpatient settings. Two patients had partial response (4.8%), 27 had stable disease (64.3%), 10 had progressive disease (23.8%) and 3 patients (7.1%) could not be evaluated. The objective response rate (ORR) was 4.8%. Median PFS was 5.8 months and median overall survival (OS) was 9.4 months. Most common drug-related AEs were alopecia (14.3%), vomiting, headache and radiation skin injury (7.1% each). Therapy-related serious adverse events (SAEs) were intra-tumoral bleeding and acute respiratory failure, which were difficult to distinguish from effects of tumor progression. CONCLUSIONS: Concomitant treatment with RT and nimotuzumab was feasible in an outpatient setting. The PFS and OS were comparable to results achieved with RT and intensive chemotherapy in hospitalized setting.

International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

Effects of low-intensity electrical stimulation and adipose derived stem cells transplantation on the time-domain analysis-based electromyographic signals in dogs with SCI.

INTRODUCTION: The application of low-intensity electrical stimulation (LIES) to neural tissue increases neurochemical factors responsible for regeneration as nerve growth factor. Stem cell (SC) therapy for patients with Spinal cord injury (SCI) promote some increase functional improvement. OBJECTIVE: Investigate the electromyographic response in paraplegic dogs undergoing LIES and SC transplantation. METHODS: 27 dogs paraplegics with SCI were divided into three groups with different types of therapy. GADSC: two SC transplants (n = 9); GLIES: LIES (n = 8); GCOMB: two SC transplants and LIES (n = 10). Adipose derived mesenchymal stem cells (ADSCs) were transplanted by lumbar puncture in the amount of 1.2 × 106 cells/50 µL. Acupuncture needles positioned in the interspinous space were used for stimulation. The electrical stimulation was applied with a mean voltage ∼30 mV and four consecutive modulated frequencies (5 Hz, 10 Hz, 15 Hz and 20 Hz) within 5 min each. The patients motor performance was evaluated before (Pre) the procedure and after 30 (Post30) and 60 (Post60) days, from electromyography root mean square (EMGRMS) registered with subcutaneous electrodes in the vastus lateralis muscle, while the animals were in quadrupedal position. RESULTS: All three groups showed a significant intra-group increase of EMGRMS (Pre vs. Post30 or Pre vs. Post60). However, there were no statistically significant differences between Post30 and Post60. The inter-group test (GADSC X GLIES X GCOMB) did not present significance when compared the instants Pre (p = 0.34), Post30 (p = 0.78) and Post60 (p = 0.64). CONCLUSION: Some dogs recovered motor activity, expressed by the EMGRMS, in all groups, in pre vs. post (30 or 60 days) comparisons.

Intradiscal delivery of celecoxib-loaded microspheres restores intervertebral disc integrity in a preclinical canine model.

Low back pain, related to degeneration of the intervertebral disc (IVD), affects millions of people worldwide. Clinical studies using oral cyclooxygenase-2 (COX-2) inhibitors have shown beneficial effects, although side-effects were reported. Therefore, intradiscal delivery of nonsteroidal anti-inflammatory drugs can be an alternative treatment strategy to halt degeneration and address IVD-related pain. In the present study, the controlled release and biologic potency of celecoxib, a selective COX-2 inhibitor, from polyesteramide microspheres was investigated in vitro. In addition, safety and efficacy of injection of celecoxib-loaded microspheres were evaluated in vivo in a canine IVD degeneration model. In vitro, a sustained release of celecoxib was noted for over 28 days resulting in sustained inhibition of inflammation, as indicated by decreased prostaglandin E2 (PGE2) production, and anti-catabolic effects in nucleus pulposus (NP) cells from degenerated IVDs on qPCR. In vivo, there was no evidence of adverse effects on computed tomography and magnetic resonance imaging or macroscopic evaluation of IVDs. Local and sustained delivery of celecoxib prevented progression of IVD degeneration corroborated by MRI, histology, and measurement of NP proteoglycan content. Furthermore, it seemed to harness inflammation as indicated by decreased PGE2 tissue levels and decreased neuronal growth factor immunopositivity, providing indirect evidence that local delivery of a COX-2 inhibitor could also address pain related to IVD degeneration. In conclusion, intradiscal controlled release of celecoxib from polyesteramide microspheres prevented progression of IVD degeneration both in vitro and in vivo. Follow-up studies are warranted to determine the clinical efficacy of celecoxib-loaded PEAMs in chronic back pain.

Screening for late-onset Pompe disease in western Denmark.

OBJECTIVE: Late-onset Pompe disease (LOPD) is a rare autosomal recessively inherited metabolic myopathy caused by reduced activity of the lysosomal enzyme alpha-glucosidase. In a previous screening study at two large neuromuscular university clinics in Denmark, three patients with LOPD were identified out of 103 patients screened. No systematic screening has been performed at the other neurological departments in the western part of Denmark. Thus, patients with a diagnosis of unspecified myopathy were screened for LOPD. MATERIALS AND METHODS: At seven neurological departments in the western part of Denmark, medical records were evaluated for all patients registered with myopathy diagnosis codes (ICD 10 codes: G 71.0-71.9 and G 72.0-72.9) during the period January 1, 2002, to December 31, 2012. If no specific diagnosis has been reached, patients were invited for screening. Dried blood spot (DBS) test was used to analyze the activity of the enzyme alpha-glucosidase. RESULT: A total of 654 patients were identified. From the medical records, information was obtained concerning symptoms, family history, electromyography, muscle biopsy results and creatine kinase levels. Eighty-seven patients (13.3%) (males 61%) at a mean age of 53.3 years (SD 16.5) fulfilled the criteria for screening. A DBS test was performed in 47 (54%) patients. In all patients, the enzyme activity was within reference values. CONCLUSION: None of the screened patients had a reduced activity of the enzyme alpha-glucosidase. Although the cohort studied was small, our findings do not suggest that LOPD is underdiagnosed in patients with unspecified myopathy in western Denmark.

Impact of etiology and duration of pain on pharmacological treatment effects in painful polyneuropathy.

BACKGROUND: The pharmacological treatments for painful polyneuropathy have not changed much for more than a decade, and less than half of the patients obtain adequate pain relief with first line treatments. Therefore, patient-specific factors which could predict drug response are searched for. METHODS: We analysed data from four published, randomized, controlled trials of drugs in painful polyneuropathy to see if diabetic etiology and duration of neuropathic pain had an impact on drug efficacy. The studies had a cross-over design, and had nearly similar outcome recordings as well as a thorough baseline registration of symptoms, signs and quantitative sensory testing. 244 patient records of drug effect distributed over treatments with three antidepressants (imipramine, venlafaxine, escitalopram) and two anticonvulsants (pregabalin, oxcarbazepine) were analysed. RESULTS: Diabetes as etiology of polyneuropathy had no impact on the effect of antidepressants (imipramine, venlafaxine, escitalopram), but there was a significant interaction with treatment effect on anticonvulsants with better effects in diabetics (0.86 NRS points, p = 0.021) with most pronounced interaction for oxcarbazepine (1.47 NRS points, p = 0.032). There was an interaction between duration of neuropathic pain and treatment with antidepressants with better effect with duration less than 3 years (0.62 NRS points, p = 0.036), whereas anticonvulsants tended to work best with duration of pain for more than 3 years. CONCLUSION: Despite the small sample size and limited number of drugs included this study suggests that diabetic etiology of polyneuropathy may impact on the efficacy of anticonvulsants, and duration of neuropathic pain may impact on the efficacy of antidepressants. SIGNIFICANCE: This study found that duration of pain appears to have an impact on the effect of antidepressants in neuropathic pain and that diabetes as etiology for painful polyneuropathy appears to influence pain relief obtained with anticonvulsants.

Autoimmune encephalitis associated with voltage-gated potassium channels-complex and leucine-rich glioma-inactivated 1 antibodies - a national cohort study.

BACKGROUND AND PURPOSE: The aim of this study was to describe clinical and paraclinical characteristics of all Danish patients who tested positive for anti-voltage-gated potassium channels (VGKC)-complex, anti-leucine-rich glioma-inactivated 1 (LGI1) and anti-contactin-associated protein-2 antibodies in the serum/cerebrospinal fluid between 2009 and 2013 with follow-up interviews in 2015 and 2016. METHODS: We evaluated antibody status, symptoms leading to testing, course of disease, suspected diagnosis and time of admission as well as diagnosis and treatment. All magnetic resonance imaging, electroencephalography and 18 F-fluorodeoxyglucose positron emission tomography scans were re-evaluated by experts in the field. RESULTS: A total of 28/192 patients tested positive for VGKC-complex antibodies by radioimmunoassay and indirect immunofluorescence; 17 had antibodies to LGI1 and 6/7 of the available cerebrospinal fluids from these patients were seropositive. These 17 patients all had a clinical phenotype appropriate to LGI1 antibodies. The remaining 11 were LGI1 negative (n = 4) or not tested (n = 7). Of these, two had a phenotype consistent with limbic encephalitis. The remaining phenotypes were Guillain-Barré syndrome, Creutzfeldt-Jakob disease, neuromyotonia and anti-N-methyl-D-aspartate receptor encephalitis. Magnetic resonance imaging abnormalities were demonstrated in 69% of the LGI1-positive patients. Two patients with normal magnetic resonance imaging demonstrated temporal lobe hypermetabolism using 18 F-fluorodeoxyglucose positron emission tomography. Abnormal electroencephalography recordings were found in 86% of the patients. Upon follow-up (median 3.2 years), the median modified Rankin Scale score of anti-LGI1-positive patients was 2 and only two patients reported seizures in the past year. CONCLUSIONS: Patients diagnosed with anti-LGI1 autoimmune encephalitis increased significantly from 2009 to 2014, probably due to increased awareness. In contrast to seropositive anti-VGKC-complex patients, all anti-LGI1-positive patients presented with a classical limbic encephalitis. The majority of patients recovered well.

Soluble and pelletable factors in porcine, canine and human notochordal cell-conditioned medium: implications for IVD regeneration.

During intervertebral disc (IVD) maturation, notochordal cells (NCs) are replaced by chondrocyte-like cells (CLCs) in the nucleus pulposus, suggesting that NCs play a role in maintaining tissue health. Affirmatively, NC-conditioned medium (NCCM) exerts regenerative effects on CLC proliferation and extracellular matrix (ECM) production. The aim of this study was to identify NC-secreted substances that stimulate IVD regeneration. By mass spectrometry of porcine, canine and human NCCM, 149, 170 and 217 proteins were identified, respectively, with 66 proteins in common. Mainly ECM-related proteins were identified, but also organelle-derived and membrane-bound vesicle proteins. To determine whether the effect of NCCM was mediated by soluble and/or pelletable factors, porcine and canine NCCM were separated into a soluble (NCCM-S; peptides and proteins) and pelletable (NCCM-P; protein aggregates and extracellular vesicles) fraction by ultracentrifugation, and tested on bovine and canine CLCs in vitro, respectively. In each model, NCCM-S exerted a more pronounced anabolic effect than NCCM-P. However, glycosaminoglycan (GAG) uptake from the medium into the carrier gel prevented more definite conclusions. While the effect of porcine NCCM-P on bovine CLCs was negligible, canine NCCM-P appeared to enhance GAG and collagen type II deposition by canine CLCs. In conclusion, porcine and canine NCCM exerted their anabolic effects mainly through soluble factors, but also the pelletable NCCM factors showed moderate regenerative potential. Although the regenerative potential of NCCM-P should not be overlooked, future studies should focus on unraveling the protein-based regenerative mechanism from NCCM produced from isolated NCs, e.g. by NCCM fractionation and pathway blocking studies.

Pain, spasticity and quality of life in individuals with traumatic spinal cord injury in Denmark.

STUDY DESIGN: Cross-sectional survey. OBJECTIVES: To estimate the prevalence, predictors and impact of self-reported pain and spasticity and examine variables affecting quality of life in individuals with a traumatic spinal cord injury (SCI). SETTING: Nationwide, Denmark. METHODS: An anonymous questionnaire was sent out to individuals with a traumatic SCI. The questionnaire included questions about demographics and SCI characteristics, pain, spasticity and quality of life. RESULTS: In total, 537 questionnaires were completed. Seventy-three percent reported chronic pain of which 60% used descriptors suggestive of neuropathic pain. The average pain intensity and interference were 5.6 (s.d. 2.3) and 5.0 (s.d. 2.8), respectively, on a 0-10 numeric rating scale (NRS), and 28.1% reported severe pain. Seventy-one percent reported spasticity. Average interference of spasticity was 2.9 (s.d. 2.7). Quality of life scores were 6.5 (s.d. 2.5) for life and life situation, 5.5 (s.d. 2.6) for physical health and 6.7 (s.d. 2.6) for mental health on the NRS (0-10). Female gender was associated with lower mental health scores and tetraplegia with lower physical health scores, and high pain interference and shorter time since injury were associated with lower quality-of-life scores for all three parameters. Pain with descriptors suggestive of neuropathic pain was associated with lower quality-of-life scores than pain without such descriptors. CONCLUSION: Chronic pain and spasticity are common problems after SCI, and in particular, high pain interference is associated with lower quality of life.

[Pneumothorax during right-sided nephrectomy in a heifer]. / Pneumothorax als Komplikation einer rechtsseitigen Nephrektomie bei einem Jungrind.

A 250-kg heifer had signs of colic attributable to urolithiasis of the right kidney. Medical treatment did not result in resolution of clinical signs, and nephrectomy was carried out. The surgery was started with the heifer standing, and the 13th rib was resected. However, during blunt dissection of the kidney, air suddenly entered the pleural space and the heifer had acute severe dyspnoea. The hole in the pleural cavity was sutured and a chest drain was placed. Inhalation anaesthesia was then induced and nephrectomy could be completed without further complications. The heifer was discharged 11 days postoperatively, and was healthy and had been integrated into the herd 12 months after surgery. Pneumothorax must be considered a possible complication of rib resection in right-sided nephrectomy in cattle.

The species-specific regenerative effects of notochordal cell-conditioned medium on chondrocyte-like cells derived from degenerated human intervertebral discs.

During intervertebral disc (IVD) maturation, the main cell type shifts from notochordal cells (NCs) to chondrocyte-like cells (CLCs). NCs secrete factors with regenerative potential, making them an interesting focus for regenerative treatments. During initial development, these strategies preferably employ non-human donors due to easy availability of their NC-rich nucleus pulposus (NP) tissue. To increase the success of translating these strategies for clinical application, this study aimed to delineate whether NC-secreted factors of different species have a regenerative effect on human CLCs. Human, canine and porcine NC-rich NP tissue and NC-conditioned medium (NCCM) were analysed biochemically and histologically. Human CLC micro-aggregates from degenerated IVDs were cultured in human, canine or porcine NCCM. Collagen, glycosaminoglycan (GAG) and DNA content was determined and histology was performed. Canine and porcine NPs were richer in NCs than human NPs. Human NPs contained the highest collagen content, whereas the DNA and GAG content of canine NPs was significantly higher than that of human or porcine NPs. NCCM from all species significantly increased the DNA and GAG content of the human CLC micro-aggregates. Porcine and canine NCCM were significantly more potent than human NCCM in inducing GAG deposition, whereas only human NCCM induced collagen type II production. Secreted factors from human, canine and porcine NC-rich NPs exerted regenerative effects on human CLCs, indicating a cross-species effect. Bioactive compound(s) are present in NCCM of different species that may reverse human IVD degeneration, supporting further research into strategies based on NC-technology employing canine or porcine models for their translation into humans.

[Reversible cerebral vasoconstriction syndrome. Challenge for diagnostics and intensive care therapy]. / Reversibles zerebrales Vasokonstriktionssyndrom. Herausforderung für Diagnostik und Intensivtherapie.

Reversible cerebral vasoconstriction syndrome (RCVS) is a disease of unclear incidence frequently affecting middle aged women and is usually associated with use of adrenergic or serotoninergic substances. The exclusion of relevant differential diagnoses, such as aneurysmal subarachnoid hemorrhage, primary cerebral angiitis, posterior reversible encephalopathy syndrome and carotid artery dissection is critical in terms of time and significance. Thunderclap headache as well as multiple and multilocular vasospasms with direct or indirect angiography without substantial findings in cerebrospinal fluid diagnostics are typical symptoms. The necessity for intensive care treatment is often justified by initial acute impairment of vital functions and possible development of cerebral or extracerebral complications. Because the exact pathophysiology remains unknown, a specific therapy does not exist. This poses significant challenges in intensive care medicine, which are illustrated on the basis of the case study presented.

[Traumatic dissection of the carotid artery: challenges for diagnostics and therapy illustrated by a case example]. / Traumatische Karotisdissektion : Herausforderungen der Diagnostik und Therapie anhand eines Fallbeispiels.

Traumatic dissection of the carotid artery is an easily overlooked consequence of trauma with notable morbidity and mortality which can be observed in up to 4% of cases involving multiple trauma. Certain mechanisms and patterns of injury as well as specific symptoms should serve as indicators of a dissection and should therefore result in further diagnostic measures. An early diagnosis is of major relevance. This report describes the case of a 45-year-old victim of a traffic accident who showed symptoms of a dissection which had initially not been diagnosed.

Density and genetic relatedness increase dispersal distance in a subsocial organism.

Although dispersal distance plays a major role in determining whether organisms will reach new habitats, empirical data on the environmental factors that affect dispersal distance are lacking. Population density and kin competition are two factors theorised to increase dispersal distance. Using the two-spotted spider mite as a model species, we altered these two environmental conditions and measured the mean dispersal distance of individuals, as well as other attributes of the dispersal kernel. We find that both density and relatedness in the release patch increase dispersal distance. Relatedness, but not density, changes the shape of the dispersal kernel towards a more skewed and leptokurtic shape including a longer 'fat-tail'. This is the first experimental demonstration that kin competition can shape the whole distribution of dispersal distances in a population, and thus affect the geographical spread of dispersal phenotypes.

Heme oxygenase-1 end-products carbon monoxide and biliverdin ameliorate murine collagen induced arthritis.

OBJECTIVES: Heme oxygenase-1 (HO-1) which degrades Heme to free iron, biliverdin and carbon monoxide (CO) plays an important role in inflammation. There are, however, conflicting data concerning the role of HO-1 in rheumatoid arthritis (RA) and the therapeutic potential of individual heme degradation products remains to be determined. We therefore investigated the effect of CO and biliverdin upon therapeutic administration in the murine collagen induced arthritis (CIA) model of RA. METHODS: CIA was induced in DBA/1 mice. Anti-CII antibody levels were determined by ELISA. Mice were scored for paw swelling and grip strength. After the first clinical signs of arthritis one group of animals was treated with biliverdin, the second group was treated with CO. After 60 days all animals were sacrificed and analysed for histomorphological signs of arthritis. RESULTS: All animals immunised with CII developed serum anti-CII antibodies. Antibody levels were decreased in the CO-treated group. Both, Biliverdin and the CO-treated animals, showed an improvement in clinical disease activity. Histological analysis revealed significantly less inflammation, erosion and reduced numbers of osteoclasts in CO-treated animals only, whereas cartilage degradation was prevented in both biliverdin and CO-treated animals. CONCLUSIONS: Our data demonstrate a beneficial effect of CO, in particular, and biliverdin, on inflammation and bone destruction in the CIA mouse model.

Phase II study of nimotuzumab, a humanized monoclonal anti-epidermal growth factor receptor (EGFR) antibody, in patients with locally advanced or metastatic pancreatic cancer.

INTRODUCTION: Nimotuzumab is a humanized monoclonal antibody that binds to the EGFR. Based on phase I data, the recommended dose has been established at 200 mg weekly. This study was aimed at evaluating the safety and efficacy of nimotuzumab monotherapy in patients (pts) with locally advanced or metastatic pancreatic cancer. METHODS: Pts who failed first line standard chemotherapy for advanced disease and had at least one measurable lesion were eligible for the study. Nimotuzumab was given intravenously at 200 mg once weekly for 6 weeks (wks). Follow up by CT scan was performed after 8 weeks. Pts continued receiving treatment 3-weekly until disease progression or unacceptable toxicity occurred. Endpoints included tumor response (RECIST), progression-free survival (PFS), and safety. RESULTS: A total of 56 pts were enrolled for treatment (ECOG status of 1 [n = 41] or 0 [n = 15]), the majority (47 pts) had metastatic disease. Nearly half of the pts [n = 26] received ≥2 regimens. Pts evaluable for response: n = 36; CR: 0; PR: 0; SD: 6 pts. Median PFS for pts with SD was 19.2 weeks, for all pts 6.7 weeks (95% CI: 6.43-7.14 weeks). PFS after 1 year was 10.3% with a median overall survival of 18.1 weeks. Treatment-related adverse events were generally mild including rash grade 1 in 5 pts. After a single dose of 200 mg, the t(1/2) was calculated to 45 h. CONCLUSION: These data confirm that nimotuzumab is safe and very well tolerated. To improve efficacy, a randomized, placebo-controlled trial with Gem has been initiated.

[Acquired von Willebrand's disease type 2A following arteriovenous fistula for haemodialysis?]. / Erworbenes von-Willebrand-Syndrom Typ 2A als Begleiterscheinung eines Dialyseshunts?

Acquired von Willebrand's disease (aVWD) is considered to be an underestimated cause of unexplained bleeding. Adsorption of von Willebrand factor (VWF) to tumour cells or hydroxyethyl starch and elimination of VWF by autoantibodies as well as shear stress-induced mechanical alteration of VWF with concomitant cleavage by enzymes may lead to an acquired deficiency of VWF and a bleeding disorder. We report a 39-year-old woman who developed spontaneous bleeding five years after surgical creation of an arteriovenous fistula (AVF) for haemodialysis treatment. AVWD type 2A was diagnosed after successful renal transplantation. One year after surgical closure of the AVF, the aVWD could not be verified again. Thus, the aVWD may have developed because of altered blood flow and shear stress inside the arteriovenous fistula.

Effects of degradable Mg-Ca alloys on dendritic cell function.

Degradable magnesium alloys are new materials for implants used in orthopedic and trauma surgery. The aim of this study was to investigate the influence of degradable magnesium alloys on the function of dendritic cells (DC) as these cells represent the major antigen presenting cells of the body. MgP (pure magnesium), MgCa 0.6 (0.6% calcium), MgCa 0.8 (0.8% calcium), MgCa 1.0 (1% calcium), and MgCa 1.2 (1.2% calcium) alloys were degraded in cell culture medium. In parallel, murine bone marrow-derived DC were incubated with increasing concentrations (0.1-10 mmol/L) of magnesium chloride and calcium chloride, respectively. Incubation of DC with degradation media over 6 days had no influence on cell viability and only marginal influence on DC migration. Also, the production of TNFα and expression of CD86 was not enhanced by incubation with degraded magnesium alloys. The mixed leukocyte reaction revealed that there was also no increase of the T-cell proliferation in comparison to untreated controls. However, there was a trend toward macrophage development at the expense of DC expansion and an enhanced DC migration was induced by incubation with higher magnesium concentrations. Particularly the latter should be verified in in vivo experiments.