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Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Zeitschrift für Rheumatologie. Supplements is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective To assess the inter- and intraobserver reliability of 26 rheumatologists when performing the 7-joint ultrasound score (US7). Methods Six patients with rheumatoid arthritis were examined by 26 sonographers in 12 rater groups who performed the US7 score. The US7 score includes the clinically dominant wrist, the second and third metacarpophalangeal (MCP) and proximal interphalangeal joints, and the second and fifth metatarsophalangeal (MTP) joints, which were evaluated for synovitis, tenosynovitis/paratenonitis, and erosions from the dorsal side and palmar/plantar aspects by gray-scale and power Doppler (PD) ultrasound. Additional lateral scans were performed at the MCP2 and MTP5 joints. All of the groups repeated the examination in 4 patients in order to calculate the intraobserver reliability. The results of one group that included 2 expert sonographers were considered as the reference standard. Kappa values, median agreement rates (interobserver), and P values (intraobserver evaluation) were calculated. Results The median overall kappa value for detecting synovitis was 0.51, for tenosynovitis/paratenonitis was 0.57, and for erosions was 0.45. In detail, the best interobserver results were found for the detection of erosions in the MTP2 joint from the plantar aspect (κ = 1; median agreement rate 89.4%) and for PD signal detection in the palmar wrist region (κ = 0.79; median agreement rate 78.8%). Good agreement was found for detecting erosions in the MCP2 joint from the radial side (κ = 0.67; median agreement rate 77.3%). Conclusion The inter- and intraobserver reliability of the US7 score shows moderate to substantial kappa values and good agreements. Therefore, this ultrasound score has the potential to be an important imaging tool, including multicenter analysis to assess structural changes. [ABSTRACT FROM AUTHOR]

Objectives To confirm the effectiveness and safety of the interleukin 6-receptor antagonist tocilizumab in patients with rheumatoid arthritis (RA) in a setting close to real-life medical care in Germany. Methods A multicentre open-label phase IIIb study was undertaken. Patients with active RA with a 28-joint Disease Activity Score (DAS28) >3.2 despite previous disease-modifying antirheumatic drugs (DMARDs) were treated with tocilizumab 8 mg/kg every 4 weeks. The primary end point was the proportion of patients achieving LDAS ≤3.2 at week 24; secondary end points included American College of Rheumatology (ACR), European League Against Rheumatism (EULAR) or Clinical Disease Activity Index (CDAI) responses and decrease in acute phase. Analyses in subgroups such as rheumatoid factor (RF)-positive versus RF-negative patients and patients with an inadequate response to treatment with DMARDs (DMARD-IR) versus those with an inadequate response to tumour necrosis factor (TNF) antagonists (TNF antagonist-IR) were performed. Safety was assessed by adverse event documentation. Results 286 patients were treated and 83.6% completed the study. 41.6% had previously been treated with TNF antagonists. 57% of the intention-to-treat patients achieved the primary end point of LDAS, 47.6% achieved DAS remission <2.6 and a EULAR ‘good response’ was achieved by 54.9%; ACR50/70 response rates at week 24 were 50.7% and 33.9%, respectively. The mean±SD decrease in CDAI from baseline to week 24 was 71±29%. C reactive protein levels normalised rapidly within 1 week. Major improvements in fatigue, pain and morning stiffness were observed in the first 4 weeks and further improved until week 24. DAS28, EULAR and ACR responses at week 24 did not differ between RF-positive and RF-negative patients. TNF antagonist-naive patients responded better than patients who had previously failed on TNF antagonists. The safety profile of tocilizumab was comparable to that previously observed in the phase III trial programme. Serious infections were observed in 3.1% of patients. Conclusions Tocilizumab is highly effective in a setting close to real-life medical care with a rapid and sustained improvement in signs and symptoms of RA. A manageable safety profile was seen over the 24-week study period. [ABSTRACT FROM PUBLISHER]

Myrioconium sp. strain UHH 1-13-18-4 is an ascomycete anamorph isolated from the river Saale, Central Germany. An extracellular, monomeric, and glycosylated laccase with a molecular mass of 72.7 kDa as determined by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry and an isoelectric point below 2.8 was purified from CuSO4 and vanillic acid amended liquid fungal cultures grown in malt extract medium. The catalytic efficiencies ( k cat/ K m) for the oxidation of syringaldazine, 2,6-dimethoxyphenol, and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonate) were 67.3, 46.9, and 28.2 s−1 mM−1, respectively, with K m values of 4.2, 67.8, and 104.9 μM. After pre-incubation at different pH values and temperatures for 1 h, more than 80% of the initial laccase activity was retained between pH 4 to 6 and 15°C. The laccase-encoding gene was identified and sequenced at both the genomic and complementary DNA (cDNA) level, and corresponding structural characteristics and putative regulatory elements of the promoter region are reported. The identification of two tryptic peptides of the purified enzyme by mass spectrometry confirmed the identity of the functional laccase protein with the translated genomic sequence of the Myrioconium sp. laccase. Myrioconium sp. laccase shows the highest degree of identity with laccases from ascomycetes belonging to the family Sclerotiniaceae, order Helotiales. [ABSTRACT FROM AUTHOR]

For rationalizing molecular analysis of field-collected roots in diversity studies on arbuscular mycorrhiza, we compared three different approaches. After DNA extraction from 50 root samples of Plantago lanceolata grown on monoculture plots at a former arable field site, (1) DNAs were amplified separately by nested PCR and each amplicon was cloned separately; (2) DNAs were amplified separately by nested PCR, 1 μl of each amplicon was pooled, and a single cloning was made from the resulting amplicons mix; and (3) DNAs were pooled and the single amplicon derived from the nested PCR was cloned. Based on these three different methods, 109 nuclear ribosomal internal transcribed spacer sequences were obtained. Methods 1 and 2 enabled the detection of almost similar levels of arbuscular mycorrhizal fungal diversity. However, method 1 was expensive and time-consuming as much more cloning had to be done. Method 3 was completely biased by preferential amplification of nontarget organisms, which were only detected in low frequencies by the other methods. [ABSTRACT FROM AUTHOR]

Aims: An association between inflammatory bowel disease (IBD) and spondyloarthropathies (SpA) has repeatedly been reported. The aim of the present study was to investigate whether serologic markers of IBD, e.g. antibodies against Saccharomyces cerevisiae (ASCA), antibodies against exocrine pancreas (PAB) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) are present in HLA-B27-associated SpA. Methods: 87 patients with HLA-B27-positive SpA and 145 controls were tested for ASCA, PAB and pANCA employing ELISA or indirect immunofluorescence, respectively. Antibody-positive patients were interviewed regarding IBD-related symptoms using a standardized questionnaire. Results/Conclusion: When compared to the controls, ASCA IgA but not ASCA IgG levels were significantly increased in patients with SpA, in particular in ankylosing spondylitis (AS) and undifferentiated SpA (uSpA). pANCA were found in increased frequency in patients with SpA whereas PAB were not detected. The existence of autoantibodies was not associated with gastrointestinal symptoms but sustains the presence of a pathophysiological link between bowel inflammation and SpA. Copyright © 2004 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVE: Treatment of ankylosing spondylitis (AS) with infliximab, an anti-tumor necrosis factor alpha monoclonal antibody, was shown to be efficacious in patients with active disease during a 3-month treatment period. The purpose of this study was to evaluate the efficacy and safety of infliximab treatment of AS for a 1-year period. METHODS: This study was an open, observational, extension study of a 3-month, randomized, placebo-controlled trial. All patients who had tolerated infliximab (infliximab/infliximab group) or placebo (placebo/infliximab 12-week crossover group) therapy for 3 months entered the open extension trial (n = 65). Infliximab was administered at a dosage of 5 mg/kg every 6 weeks after the induction phase (weeks 0, 2, and 6). The primary end point was a 50% improvement in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). RESULTS: At week 54, a total of 54 of the 69 patients (78%) continued to take infliximab. The intent-to-treat primary efficacy analysis at week 54 showed that 47% of patients in the infliximab/infliximab group (95% confidence interval 31-63) and 51% of the patients in the placebo/infliximab group (95% confidence interval 36-67) achieved 50% improvement in BASDAI scores. In the analysis of those who completed the study, the mean BASDAI scores improved between weeks 0 and 54 in both treatment groups: from 6.6 to 2.4 in the infliximab/infliximab group and from 6.3 to 2.6 in the placebo/infliximab group. The dosage of nonsteroidal antiinflammatory drugs was reduced in approximately 70% of the patients. There were significant improvements in measures of functioning, metrologic parameters, and quality of life. Between weeks 12 and 54, a total of 4 patients had serious adverse events that were possibly related to infliximab and resulted in their discontinuing the study. CONCLUSION: Infliximab therapy in AS patients resulted in a rapid and significant improvement in BASDAI scores (>50% improvement) and a durable response for 1 year. The safety profile of infliximab in AS was comparable to that observed in the postmarketing experience for the approved indications. [ABSTRACT FROM AUTHOR]

Chemokine receptors play a crucial role in the recruitment of leucocyte subsets into inflamed tissue. Using FACS analysis we have studied the surface expression of different CC- and CXC-chemokine receptors on synovial fluid (SF) and peripheral blood leucocytes from 20 patients with various forms of arthritis. In the SF the majority T cells stained positive for CCR5 (93%) and CCR2 (57%), compared to the peripheral blood (36% and 25%). In addition, most of the T cells expressed CXCR4 in both compartments, with a somewhat higher percentage in the SF (90%) versus peripheral blood (83%). To date little information is available on chemokine receptor expression on monocytes in arthritis. We report a marked increase of CCR5+ monocytes in the SF (87%) compared to the peripheral blood (22%). In contrast, the frequency of CXCR1+, CXCR2+, CXCR4+ and CCR1+ monocytes was considerably lower in the SF than in the peripheral blood. Moreover, we report the expression CXCR4 on neutrophils in the SF. Approximately 60% of neutrophils stained positive for CXCR4 in the SF, while in the peripheral blood the number of CXCR4+ neutrophils was low (24%). Surface expression of CXCR1 and CXCR2 was significantly reduced on SF neutrophils (53% and 68%) compared to the peripheral blood. Chemokine receptors are differentially expressed on leucocyte subsets in arthritis. The identification of their pattern of expression might help to identify suitable targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

A 40-year old homosexual AIDS patient recovering from a Pneumocystis carinii pneumonia developed a Cryptococcus neoformans infection with involvement of the central nervous system (CNS) which could be treated successfully with amphotericin B and flucytosine. After a symptomfree interval of 4 1/2 months, a new acute fatal disease of the CNS did not reveal a cryptococcosis relapse but a necrotizing Toxoplasma encephalitis, a cytomegalovirus infection and striking cultural findings of Staphylococcus aureus in all organs examined. Neither by culture nor by histology Cr. neoformans could be detected in the CNS or in the other organs examined. The temporal course of the Cr. neoformans infection and its specific diagnosis are commented. It is demonstrated that (during or after successful therapy of Pneumocystis carinii pneumonia) a specific cultural examination of specimens from the respiratory tract for Cr. neoformans is needed, in order to recognize a Cr. neoformans infection in its primary stage, i. e. before hematogenous dissemination of Cr. neoformans leading to the secondary stage of the infection. [ABSTRACT FROM AUTHOR]

Urinary and fecal total, isomer I, and isomer III coproporphyrin excretion of a Rotor's syndrome patient and his family were determined. The proprositus showed increased urinary total coproporphyrin excretion (248 µg/24 h) and a shift of the coproporphyrin isomer I/III relation (70%/30%). The propositus's father and two siblings also had elevated renal excretion of coproporphyrin I. Total coproporphyrin excretion was enhanced only in the propositus's father and one sibling, while being normal in another sibling. All family members that could be investigated showed considerably decreased fecal porphyrin excretion. In Rotor's syndrome porphyrin excretion is mainly renal. The coproporphyrin isomer I/III relation is shifted towards isomer I. Phenotypically normal relatives with normal bilirubin plasma levels may have alterations in both their renal and enteral coproporphyrin excretion. [ABSTRACT FROM AUTHOR]

We report on the progress of a new modified method of phlebotomy, erythrocytapheresis, as a means of fast therapeutic removal of erythrocytes from the circulation. We performed erythrocytapheresis in 65 patients. In 18 patients with central venous thrombosis of the eye, the beneficial effect of this procedure proved superior to the traditional approach. In 29 patients with primary or secondary polycythemia, hemoglobin, hematocrit, and blood viscosity could be lowered drastically for up to 11 months by a single erythrocytapheresis. We performed erythrocytapheresis in an effort to deplete the iron stores in patients with hemochromatosis (14 cases) and in patients with porphyria cutanea tarda (4 cases). Several consecutive erythrocytaphereses were necessary, however, to even slightly lower the amounts of stored iron as measured by serum iron, iron-binding capacity, and serum ferritin in these patients. The intervals between treatment were 2 to 11 months, thus much longer than the intervals between blood-lettings. We did not observe any adverse side effects. There was no significant influence on the clotting system, and no reactive thrombocytosis as described after phlebotomies. [ABSTRACT FROM AUTHOR]

Serological typing with the microlymphocytotoxicity test (MLCT) and flow cytometry (FC) using HLA-B27 antisera is commonly used for the determination of HLA-B27. However, in some patients tested more than once, negative results have turned out to be positive at following investigations. We retested by polymerase chain reaction (PCR) samples from 20 randomly selected patients with reactive arthritis or Reiter's syndrome who had now been followed for 20 yr. Ten of the patients were originally tested to be HLA-B27 positive and 10 HLA-B27 negative by the MLCT. All 10 serologically HLA-B27 positive individuals were also positive in the PCR. However, 2/10 patients interpreted as being HLA-B27 negative were positive by PCR. At this time, the same two patients were also positive in the routine MLCT and FC using four different monoclonal antibodies against HLA-B27. PCR is superior to serological techniques to determine HLA-B27 positivity unequivocally, since it is based on the detection of HLA-B27 gene sequences. [ABSTRACT FROM PUBLISHER]

The association of HLA-B27 and seronegative spondyloarthropathies, especially ankylosing spondylitis has been known for almost two decades. The spontaneous development of spondyloarthropathy like joint disease in HLA-B27 transgenic rats verifies the suspicion that the HLA-B27 antigens are directly responsible for disease development. With the recently revealed crystal structure of HLA-B27 and understanding of the class I molecule in general, a new hypothesis can be formulated based on the assumption that the pathogenesis of these diseases is a subversion of the physiological function. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the influence of glibenclamide on insulin release via insulinotropic gut factors and via a direct action on the pancreas. Maximum peripheral IRI levels appeared 1 minute after intragastric administration of the minimal effective dose of glibenclamide to rats. The corresponding drug levels were high (600 ng/g) in the duodenal mucosa, but low (2 ng/ml) in the peripheral serum. These concentrations were too low to cause insulin release by direct action on the pancreas. Intragastric glibenclamide increased the amount of 'duodenal insulin releasing activity' (DIRA) in the mucosa immediately after drug administration. When glibenclamide was dissolved in plasma at a high concentration (1 μg/ml) and then injected into the coeliac trunk of an in-situ rat pancreas preparation, no additional effect on portal IRI levels was measured as compared with injection of serum alone. In contrast significant IRI release was noticed when glibenclamide was dissolved in serum (1 μg/ml) of rats pretreated with the drug intragastrically. The plasma of pretreated rats without addition of glibenclamide was ineffective. The results suggest that glibenclamide may have two effects, one releasing insulin at the pancreas directly, and the other inducing the release of a gastrointestinal factor which amplifies the first effect. Neither glibenclamide nor the factor alone can provoke an IRI release under physiological conditions. The possible importance of these findings for the regulation of insulin secretion is discussed. [ABSTRACT FROM AUTHOR]

Copyright of Archiv für Toxikologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Klinische Wochenschrift is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Naunyn-Schmiedebergs Archiv für Experimentelle Pathologie und Pharmakologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)