Experimental and computational studies of sulfided NiMo supported on pillared clay: catalyst activation and guaiacol adsorption sites.

We report on intermediate (oxysulfides) and sulfided structures of NiMo supported on aluminium pillared clay (Al-PILC) during the catalyst activation process and the prefered guaiacol adsorption sites on the sulfided catalyst. In situ X-ray absorption fine structure (XAFS) together with density functional theory (DFT) calculations confirm the existence of ill-defined suboxides (MoOx, NiOx) and the well-known subsulfides (Mo2S9, Ni3S2) at the first stage which, at a later stage in the process, transform into MoS2 with two edges, oxygen-decorated Mo and Ni with zero sulfur coverage. The freshly sulfided NiMoS2 catalyst under sulfiding agents is mainly terminated by Mo-edge surface with 50% sulfur coverage (Mo-S50) with a disordered Ni-edge surface that can be assigned as NiMoS (1̄010). When exposed to an inert atmosphere such as He gas, the Mo and Ni edges evolved partially into new structures of Mo and Ni edges with zero sulfur coverage, labelled as Mo-Bare and Ni-Bare. Guaiacol is often used as a model compound for lignin and a series of calculations of guaiacol on the structural edges of a sulfided NiMoS2 catalyst show relatively good agreement between the observed and calculated inelastic neutron scattering (INS) spectra for Mo-S50, Ni-Bare, and NiMoS (1̄010) where guaiacol weakly chemisorbed via oxygen atom of OH group. The results also confirm that guaiacol is physisorbed on the basal plane of NiMoS2 in a horizontal (flat-lying) configuration via van der Waals interaction at a separation of about 3.25 Å.

Attitudes of Dutch intensive care unit clinicians towards oxygen therapy.

BACKGROUND: Over the last decade, there has been an increasing awareness for the potential harm of the administration of too much oxygen. We aimed to describe self-reported attitudes towards oxygen therapy by clinicians from a large representative sample of intensive care units (ICUs) in the Netherlands. METHODS: In April 2019, 36 ICUs in the Netherlands were approached and asked to send out a questionnaire (59 questions) to their nursing and medical staff (ICU clinicians) eliciting self-reported behaviour and attitudes towards oxygen therapy in general and in specific ICU case scenarios. RESULTS: In total, 1361 ICU clinicians (71% nurses, 24% physicians) from 28 ICUs returned the questionnaire. Of responding ICU clinicians, 64% considered oxygen-induced lung injury to be a major concern. The majority of respondents considered a partial pressure of oxygen (PaO2) of 6-10 kPa (45-75 mmHg) and an arterial saturation (SaO2) of 85-90% as acceptable for 15 minutes, and a PaO2 7-10 kPa (53-75 mmHg) and SaO2 90-95% as acceptable for 24-48 hours in an acute respiratory distress syndrome (ARDS) patient. In most case scenarios, respondents reported not to change the fraction of inspired oxygen (FiO2) if SaO2 was 90-95% or PaO2 was 12 kPa (90 mmHg). CONCLUSION: A representative sample of ICU clinicians from the Netherlands were concerned about oxygen-induced lung injury, and reported that they preferred PaO2 and SaO2 targets in the lower physiological range and would adjust ventilation settings accordingly.

Adherence to the distress screening through oncology nurses and integration of screening results into the nursing process to adapt psychosocial nursing care five years after implementation.

PURPOSE: Addressing psychosocial distress is an essential part of cancer care. Therefore, nurses at the University Hospital Zurich have been screening all cancer inpatients with the Distress Thermometer (DT) since 2012. Screening is ineffective without any form of psychosocial intervention. We aimed to identify adherence to the screening protocol and how the reported problems influenced the nursing process. We compared changes in the documentation before and after screening implementation. METHODS: This retrospective descriptive study used screening data and documentation of psychosocial items in the nursing process of inpatients at an oncologic ward. These data were compared with data obtained before screening implementation and were collected from electronic health records. All data were analyzed descriptively. RESULTS: 65% (N = 1111) of the 2166 inpatients were screened. With the implementation, more psycho-oncological referrals were made (4.5% vs. 11.7%) and more psychosocial issues were described in the nursing process (24.6% vs. 51.2%). Inpatients mentioned emotional problems in 37.5% (N = 353) and physical problems in 47.4% (N = 504) of cases. 15.7% (147) had a psychosocial nursing diagnosis. Only 10.7% (N = 26) of patients who noted anxiety, also had a nursing diagnosis of "anxiety". In contrast, 71.1% (N = 202) of patients who noted pain, had a nursing diagnosis of "pain". CONCLUSIONS: Although nurses are more sensitised to psychosocial issues after DT implementation, they do not use screening results to adapt nursing documentation to the psychosocial needs of the patients. Further studies are needed to investigate how distress screening and psychosocial issues can be integrated into nurses' daily work.

Evaluation of the adherence of distress screening with the distress thermometer in cancer patients 4 years after implementation.

PURPOSE: Identifying and assessing psychosocial distress with an appropriate screening instrument is essential when caring for cancer patients. Since 2012, the distress thermometer (DT) has been used by nurses for all cancer inpatients at the Comprehensive Cancer Center Zurich. We wanted to identify nurses' adherence to the screening protocol, differences between screened and not screened patients and the relationship between screening rate and productivity. METHODS: This retrospective descriptive study used screening and referral data as well as socioeconomic and disease-related data of inpatients at the Comprehensive Cancer Center Zurich. This was collected from the electronic patient documentation system. Additionally, data showing the productivity of all wards was used. All data were analyzed descriptive. RESULTS: Since 2012, 40.6% (4541) of the 11,184 patients have been screened. The screening rate was initially significantly lower but settled at 40% after 2 years. There was a higher screening rate among Swiss, married, male, and emergency patients and patients with hematology diseases, brain tumors, or head and neck cancer (p < 0.001). Every fourth patient with a moderate to severe distress level requested referral to a psychosocial service. Significantly more screened patients were referred to the social service (44.7%) than to the psycho-oncology service (9.4%). Only 22.9% of all referrals were made on the day of screening or a day later. There were only two wards of 15 with a significant relationship between productivity and screening rate. CONCLUSIONS: Screening is useful in recognizing distress among patients, but screening practice needs to be reconsidered.

Investigation of sex-specific effects of apolipoprotein E on severity of EAE and MS.

BACKGROUND: Despite pleiotropic immunomodulatory effects of apolipoprotein E (apoE) in vitro, its effects on the clinical course of experimental autoimmune encephalomyelitis (EAE) and multiple sclerosis (MS) are still controversial. As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings. This study aimed to investigate sex-specific effects of apoE on disease course of EAE and MS. METHODS: MOG(35-55) induced EAE in female and male apoE-deficient mice was assessed clinically and histopathologically. apoE expression was investigated by qPCR. The association of the MS severity score (MSSS) and APOE rs429358 and rs7412 was assessed across 3237 MS patients using linear regression analyses. RESULTS: EAE disease course was slightly attenuated in male apoE-deficient (apoE (-/-) ) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 2 [IQR 0.0-4.5]; wildtype = 4 [IQR 1.0-5.0]; n = 10 each group, p = 0.0002). In contrast, EAE was more severe in female apoE (-/-) mice compared to wildtype mice (cumulative median score: apoE (-/-) = 3 [IQR 2.0-4.5]; wildtype = 3 [IQR 0.0-4.0]; n = 10, p = 0.003). In wildtype animals, apoE expression during the chronic EAE phase was increased in both females and males (in comparison to naïve animals; p < 0.001). However, in MS, we did not observe a significant association between MSSS and rs429358 or rs7412, neither in the overall analyses nor upon stratification for sex. CONCLUSIONS: apoE exerts moderate sex-specific effects on EAE severity. However, the results in the apoE knock-out model are not comparable to effects of polymorphic variants in the human APOE gene, thus pinpointing the challenge of translating findings from the EAE model to the human disease.

Macrophage and microglial plasticity in the injured spinal cord.

Macrophages in the injured spinal cord arise from resident microglia and from infiltrating peripheral myeloid cells. Microglia respond within minutes after central nervous system (CNS) injury and along with other CNS cells signal the influx of their peripheral counterpart. Although some of the functions they carry out are similar, they appear to be specialized to perform particular roles after CNS injury. Microglia and macrophages are very plastic cells that can change their phenotype drastically in response to in vitro and in vivo conditions. They can change from pro-inflammatory, cytotoxic cells to anti-inflammatory, pro-repair phenotypes. The microenvironment of the injured CNS importantly influences macrophage plasticity. This review discusses the phagocytosis and cytokine-mediated effects on macrophage plasticity in the context of spinal cord injury.

[Malnutrition and weight loss - nurse assessment of nutritional status and counselling: experiences of patients with newly diagnosed or relapsed cancer]. / Malnutrition und Gewichtsverlust - Erfassen des Ernährungsstatus und Beratung durch Pflegende: Das Erleben von Patienten mit einer neu diagnostizierten oder rezidivierten Tumorerkrankung.

Due to the anorexia-cachexia syndrome, cancer patients are already suffering from nutritional problems and weight loss by the time they receive their diagnosis and start chemotherapy. In the oncology outpatient clinic of a Swiss university hospital, patients currently undergo a nutritional assessment and receive individual counselling at the beginning of cancer treatment. This qualitative study explored cancer patients' experiences with weight loss and nutritional problems as well as how they experienced the assessment and the consecutive counselling by nurses. Interviews were conducted with 12 patients and qualitative content analysis was used for data analysis. Results showed that patients barely registered the weight loss and did not interpret it as an early warning signal. Nevertheless, they attempted to improve their nutritional habits soon after diagnosis, prior to receiving any counselling. The patients did not experience the assessment as troublesome. They appreciated the nurses' advice and implemented the suggestions they found appropriate. This study highlights the importance of patient education regarding weight loss and nutritional problems early in the course of an illness. Patients may not be aware of nutritional problems at this early stage and may lack the necessary specialised knowledge. Assessment and counselling provided by nurses offer targeted measures for prevention of malnutrition and weight loss.

SU-E-T-164: Clinical Implementation of ASi EPID Panels for QA of IMRT/VMAT Plans.

PURPOSE: To investigate various issues for clinical implementation of aSi EPID panels for IMRT/VMAT QA. METHODS: Six linacs are used in our clinic for EPID-based plan QA; two Varian Truebeams, two Varian 2100 series, two Elekta Infiniti series. Multiple corrections must be accounted for in the calibration of each panel for dosimetric use. Varian aSi panels are calibrated with standard dark field, flood field, and 40×40 diagonal profile for beam profile correction. Additional corrections to account for off-axis and support arm backscatter are needed for larger field sizes. Since Elekta iViewGT system does not export gantry angle with images, a third-party inclinometer must be physically mounted to back of linac gantry and synchronized with data acquisition via iViewGT PC clock. A T/2 offset correctly correlates image and gantry angle for arc plans due to iView image time stamp at the end of data acquisition for each image. For both Varian and Elekta panels, a 5 MU 10×10 calibration field is used to account for the nonlinear MU to dose response at higher energies. Acquired EPID images are deconvolved via a high pass filter in Fourier space and resultant fluence maps are used to reconstruct a 3D dose 'delivered' to patient using DosimetryCheck. Results are compared to patient 3D dose computed by TPS using a 3D-gamma analysis. RESULTS: 120 IMRT and 100 VMAT cases are reported. Two 3D gamma quantities (Gamma(V10) and Gamma(PTV)) are proposed for evaluating QA results. The Gamma(PTV) is sensitive to MLC offsets while Gamma(V10) is sensitive to gantry rotations. When a 3mm/3% criteria and 90% or higher 3D gamma pass rate is used, all IMRT and 90% of VMAT QA pass QA. CONCLUSIONS: After appropriate calibration of aSi panels and setup of image acquisition systems, EPID based 3D dose reconstruction method is found clinically feasible.

The low therapeutic efficacy of postoperative chest radiographs for surgical intensive care unit patients.

BACKGROUND: The clinical value of postoperative chest radiographs (CXRs) for surgical intensive care unit (ICU) patients is largely unknown. In the present study, we determined the diagnostic and therapeutic efficacy of postoperative CXRs for different surgical subgroups and related their efficacy to the time after ICU admission. METHODS: A prospective, observational study of consecutive postoperative surgical ICU patients was performed during a 10 month period. We restricted our analysis to CXRs obtained within six hours after admission to the ICU. Diagnostic efficacy was defined by the presence of predefined major abnormalities; therapeutic efficacy was defined by predefined actions taken because of any abnormality found on postoperative CXRs. RESULTS: Of 857 surgical ICU patients, 670 (78%) had a postoperative CXR after admission to the ICU. Of these CXRs, 80 were performed for clinical reasons, and 590 were routinely obtained (i.e., these CXRs were made without a reason other than admission to the ICU itself). The diagnostic efficacy of clinically indicated and routinely obtained CXRs was 18% (14/80) and 13% (79/590), respectively. Of all predefined abnormalities found on CXRs, 60% involved the malposition of invasive devices, such as endotracheal tubes or central venous lines. The therapeutic efficacy of clinically indicated and routinely obtained CXRs was 4% (3/80) and 4% (26/590), respectively. While the diagnostic and therapeutic efficacy of routinely obtained CXRs were not dependent on timing of admission, the diagnostic and therapeutic efficacy of clinically indicated CXRs was higher for CXRs taken closer to the time of ICU admission. CONCLUSION: Although the diagnostic efficacy of clinically indicated and routinely obtained postoperative CXRs in surgical ICU patients appears to be significant, their therapeutic efficacy is low.

More CLEC16A gene variants associated with multiple sclerosis.

OBJECTIVES: Recently, associations of several single-nucleotide polymorphisms (SNPs) within the CLEC16A gene with multiple sclerosis (MS), type-I diabetes, and primary adrenal insufficiency were reported. METHODS: We performed linkage disequilibrium (LD) fine mapping with 31 SNPs from this gene, searching for the region of highest association with MS in a German sample consisting of 603 patients and 825 controls. RESULTS: Four SNPs located in intron 19 of the CLEC16A gene were found associated. We could replicate the finding for SNP rs725613 and were able to show for the first time the association of rs2041670, rs2080272 and rs998592 with MS. CONCLUSION: All described base polymorphisms are mapping to one LD block of approximately 50 kb within intron 19 of the CLEC16A gene, suggesting a pivotal role of this region for susceptibility of MS and possibly also for other autoimmune diseases.

IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations.

Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated.

Clonal expansions of pathogenic CD8+ effector cells in the CNS of myelin mutant mice.

Tissue damage in the CNS is critically influenced by the adaptive immune system. Primary oligodendrocyte damage (by overexpression of PLP) leads to low-grade inflammation of high pathological impact, which is mediated by CD8+ T cells. To yield further insight into pathogenesis and nature of immune responses in myelin mutated mice, we here apply a detailed immunological characterization of CD8+ T cells in PLP-transgenic and aged wild type mice. We provide evidence that T effector cells accumulate in the CNS of PLP-transgenic and wild-type mice and show a higher level of activation in mutant mice, indicated by surface markers and clonal expansions, as demonstrated by T cell receptor CDR3-spectratype analysis. Vbeta-Jbeta similarities suggest specificity against a common antigen, albeit we could not find specific responses against myelin-antigen-derived peptides. The association of primary oligodendrocyte damage with secondary expansions of pathogenic cells underlines the role of adaptive immune reactions in neurodegenerative and neuroinflammatory diseases.

[Guidelines for intensive care in cardiac surgery patients: haemodynamic monitoring and cardio-circulatory treatment guidelines of the German Society for Thoracic and Cardiovascular Surgery and the German Society of Anaesthesiology and Intensive Care Medicine]. / Die intensivmedizinische Versorgung herzchirurgischer Patienten: Hämodynamisches Monitoring und Herz-Kreislauf-Therapie S3-Leitlinie der Deutschen Gesellschaft für Thorax-, Herz- und Gefässchirurgie (DGTHG) und der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI).

Hemodynamic monitoring and adequate volume-therapy, as well as the treatment with positive inotropic drugs and vasopressors, are the basic principles of the postoperative intensive care treatment of patient after cardiothoracic surgery. The goal of these S3 guidelines is to evaluate the recommendations in regard to evidence based medicine and to define therapy goals for monitoring and therapy. In context with the clinical situation the evaluation of the different hemodynamic parameters allows the development of a therapeutic concept and the definition of goal criteria to evaluate the effect of treatment. Up to now there are only guidelines for subareas of postoperative treatment of cardiothoracic surgical patients, like the use of a pulmonary artery catheter or the transesophageal echocardiography. The German Society for Thoracic and Cardiovascular Surgery and the German Society for Anaesthesiology and Intensive Care Medicine made an approach to ensure and improve the quality of the postoperative intensive care medicine after cardiothoracic surgery by the development of S3 consensus-based treatment guidelines. Goal of this guideline is to assess available monitoring methods and their risks as well as the differentiated therapy of volume-replacement, positive inotropic support and vasoactive drugs, the therapy with vasodilators, inodilators and calcium-sensitizers and the use of intra-aortic balloon pumps. The guideline has been developed according to the recommendations for the development of guidelines by the Association of the Scientific Medical Societies in Germany (AWMF). The presented key messages of the guidelines were approved after two consensus meetings under the moderation of the Association of the Scientific Medical Societies in Germany (AWMF).

Influence of high tibial osteotomy on bone marrow edema in the knee.

To determine the influence of high tibial osteotomy on subchondral bone marrow edema in medial osteoarthritis of the varus knee, full leg-length radiographs and magnetic resonance imaging were performed in 20 patients (20 knees) before surgery, 1 year postoperatively, and at a mean of 7 years postoperatively. The extent of bone marrow edema in the medial compartment was quantified with magnetic resonance imaging in two planes using the formula for a prolate ellipsoid as follows: length x width x depth x pi/6. We used the Japanese Orthopaedic Association knee score for clinical evaluation. At the last followup, all knees with valgus alignment (10/10) showed reduced edema. In contrast, bone marrow edema increased or remained unchanged in four of 10 knees with neutral or varus alignment. The percentage of satisfactory results was 100% (10/10) in valgus knees and only 30% (3/10) in neutral or varus knees. Extent of bone marrow edema at the followup correlated with the mechanical axis and knee score. Because of the prognostic value of bone marrow abnormalities in the medial compartment observed on magnetic resonance imaging, early lateral closing wedge osteotomy should be considered in patients with varus malalignment and bone marrow edema even in mild cases of medial osteoarthritis.

Analysis of the C/T(-1) single nucleotide polymorphism in the CD40 gene in multiple sclerosis.

The costimulatory CD40-CD40L pathway plays a critical role in the generation and maintenance of adaptive immune responses. Genetic interference of CD40-CD40L interactions strongly influences the onset and course in many autoimmune disease models including experimental autoimmune encephalomyelitis. We analysed the association of a single nucleotide polymorphism of the CD40 gene (C/T(-1)) in 287 patients with multiple sclerosis (MS) and 184 matched controls. No significant differences were found in the frequency of the C/T(-1) polymorphism between the patients with MS and the controls (53% vs 49%) or among different MS subtypes. Cell surface expression of CD40 did not differ within the different genotypes, but carriers of the T allele showed a trend for a lower stimulatory index compared with individuals with the CC genotype. Although these subtle differences indicate functional consequences in the immune stimulatory capabilities related to the CD40 C/T(-1) polymorphism, our population-based study found no association with disease susceptibility or disease course in MS.

Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: preliminary data in an animal model.

BACKGROUND AND PURPOSE: The detection of cell infiltration is critical for the diagnosis and monitoring of inflammatory disorders, especially in the central nervous system (CNS). Superparamagnetic iron oxide (SPIO) particles have recently been introduced as a contrast agent to detect macrophage migration in vivo by MR imaging. We tested the hypothesis that focal hyperechogenicity due to SPIO-laden macrophages can also be visualized on high-resolution sonography. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced by myelin-oligodendrocyte glycoprotein (MOG) in congenic Lewis rats, an animal model mimicking many aspects of human multiple sclerosis. At the height of disease, rats underwent MR imaging with a 1.5T unit. Animals were injected with SPIO particles 24 hours before imaging. Control rats either received no contrast agent or were injected with SPIO particles without prior induction of EAE. Immediately after MR imaging, the rats were sacrificed, and the brains were removed and placed in saline. Sonography was performed directly after brain removal. Brains were embedded in paraffin, and sections were stained for iron with Perls stain and for macrophages with ED1 immunohistochemistry. RESULTS: SPIO-enhanced sonography of rat brains during a relapse of EAE specifically showed marked focal echogenicity in EAE-typical areas of the brain, including the periventricular region, the cerebellum, and the brain stem. The sonographic results corresponded to in vivo MR imaging findings of the respective animals as well to the clinical symptoms of EAE and to histology showing iron-laden macrophages in demyelinated lesions. CONCLUSION: SPIO particles allow the detection and demarcation of inflammatory CNS lesions on sonograms by specific macrophage imaging.

Spontaneous osteonecrosis of the knee: biochemical markers of bone turnover and pathohistology.

OBJECTIVE: The aim of this study was to evaluate bone metabolism in patients with spontaneous osteonecrosis (ON) of the medial femoral condyle. METHOD: In 22 consecutive patients, undergoing total knee arthroplasty, biochemical markers of bone metabolism were measured in aspirates from cancellous bone and in samples obtained simultaneously from peripheral blood. Specimens of the medial femoral condyle were available for histologic examination and the lesion size, assessed on radiographs, was compared with the results from bone turnover measurements. Twenty patients with osteoarthritis (OA) of the knee served as a control. Bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide (ICTP) were studied. RESULTS: Mean serum levels of analytes were not different in patients with ON and OA. The serum concentrations averaged 16.2 vs 13.3 ng/mL (OC), 10.2 vs 12.1 ng/mL (bone ALP), 4.6 vs 4.1 ng/mL (ICTP), and 33.2 vs 40.4 ng/mL (PINP) in patients with ON and OA, respectively. In samples obtained from cancellous bone, mean concentrations of all markers were elevated significantly when compared to serum levels. The mean marker concentrations in samples obtained from cancellous bone were 33.8 vs 43.3 ng/mL (OC), 34.6 vs 37.3 ng/mL (bone ALP), 64.8 vs 36.1 ng/mL (ICTP, P=0.02), and 208.0 vs 176.2 ng/mL (PINP) in patients with ON and OA, respectively. The lesion size was at mean 440.5+/-275.8mm(2) in knees with ON and did not correlate with either serum or bone concentrations of all markers tested (P>0.1). CONCLUSION: The marked elevation of markers in samples obtained from cancellous bone pointed at increased turnover in both diseases when compared to healthy individuals. In line with histologic findings of necrosis of subchondral bone, focal degradation of collagen type I was more pronounced in knees with ON. Mean serum concentrations of all markers, however, were not different from healthy individuals and thus did not provide any useful clue in the diagnosis spontaneous ON.

Impact of the Asp299Gly polymorphism in the toll-like receptor 4 (tlr-4) gene on disease course of multiple sclerosis.

In multiple sclerosis patients, infection is often associated with disease deterioration. Lipopolysaccharide (LPS) from gram-negative bacteria signals via the toll-like receptor 4 (TLR-4) pathway. Therefore, we investigated the role of an Asp299Gly mutation in the TLR-4 receptor in 890 MS patients with multiple sclerosis and 350 healthy controls. No association of different genotypes with MS susceptibility, MS subtypes, or disease severity was found. In vitro LPS stimulation studies showed a significantly lower proliferation of PBMCs from donors heterozygous for the Asp299Gly mutation in comparison to PBMCs from individuals with the wild-type genotype (p=0.01). However, these functional changes seem not to have any impact on the clinical presentation of MS patients with different TLR-4 genotypes.

Hallux valgus and cartilage degeneration in the first metatarsophalangeal joint.

This study relates the extent of cartilage lesions within the first metatarsophalangeal joint to hallux valgus. We prospectively examined 265 first metatarsophalangeal joints of 196 patients with a mean age of 54.2 years at operation for the existence of cartilage lesions. Grade I lesions were found in 41 feet (15.5%), grade II in 82 (30.9%), grade III in 51 (19.3%), grade IV in 20 (7.5%). Only 71 (26.8%) showed no cartilage lesion. Cartilage lesions were found within the metatarsosesamoid and metatarsophalangeal compartments in 66 feet (34.0%), within the metatarsophalangeal compartment in 26 (13.4%) and within the metatarsosesamoid compartment in 102 (52.6%). A statistically significant correlation was found between the grade of cartilage lesion and the hallux valgus angle, both for the changes within the metatarsophalangeal and the metatarsosesamoid joints.

Analysis of the monocyte chemoattractant protein 1 -2518 promoter polymorphism in patients with multiple sclerosis.

Cytokines and chemokines like the proinflammatory chemokine, monocytechemoattractant protein 1 (MCP-1) are important for the recruitment of inflammatory cells into multiple sclerosis (MS) lesions. Recently, a nucleotide substitution from adenosine to guanosine (A-->G) at position -2518 of the MCP-1 promoter was shown to be associated with increased MCP-1 expression. We analysed MCP-1 genotypes in 634 MS patients and 405 healthy controls. The allelic frequencies were comparable between both groups. No correlation was found between genotype and disease course, disease severity or age of disease onset. Although statistically no+ significant mRNA expression and MCP-1 secretion were elevated in patients carrying the mutant allele. Thus, our data could not reveal any association between the MCP-1 -2518 polymorphism and susceptibility to or clinical disease course of MS.