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J Braun

Publications and source records attributed to J Braun.

At least 91 records · Page 5Linked to original sources
PubMed2003

Long-term efficacy and safety of infliximab in the treatment of ankylosing spondylitis: an open, observational, extension study of a three-month, randomized, placebo-controlled trial.

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.

Acute-Phase Proteins↗
PubMed2003

[Treatment of ankylosing spondylitis and undifferentiated spondyloarthritis with TNF alpha-antagonists].

The spondyloarthritides (SpA) are common inflammatory rheumatic diseases with an overall prevalence of 0.6-1.9%. Ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) are the most common subsets of SpA. Women are almost as frequently affected as men, but the total burden of disease may be similar. At least one third of AS patients are severely affected with impaired function and a poor quality of life similar to patients with rheumatoid arthritis. However, AS starts 20-30 years earlier in life. Thus, AS has a relevant socioeconomic impact on society. After decades of no progress concerning treatment options in SpA, there is now accumulating evidence that the new anti-TNF alpha agents do not only reduce signs and symptoms of AS caused by inflammation but they may also diminish structural damage. Very recent magnetic resonance imaging (MRI) data of a follow-up study support this assumption. The following paper reviews the currently available literature on anti-TNF alpha therapy in AS and uSpA. Efficacy, side effects and experiences with different doses are discussed. In expectation of the approval of infliximab and etanercept for the treatment of active AS international guidelines for initiation, monitoring and discontinuation of these agents have been recently proposed.

Antirheumatic Agents↗
PubMed2003

[Adaption and validation of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) for use in Germany].

OBJECTIVE: The purpose of this study was the validation of a German translation of the Bath Ankylosing Spondylitis Index (BASDAI). PATIENTS AND METHODS: The German translation of the BASDAI was validated using data of 134 patients with ankylosing spondylitis (AS) from a spondyloarthropathy cohort. For validation the BASDAI was compared with parameters assessed by physicians (physicians global, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), spinal mobility (BASMI), swollen joints, enthesitis (yes or no)), and parameters assessed by patients themselves (pain, function (BASFI) and quality of life (SF-12)). The discriminative validity was analyzed by comparison of BASDAI scores of patients subgroups who have different levels of disease severity. The sensibility to change was analyzed by using follow-up data of a clinical trial on efficacy of the anti-tumor necrosis factor (TNF) alpha agent infliximab in 70 AS-patients with active and severe disease. RESULTS: The German translation of the BASDAI was easy to understand, the translation back to English corresponded well with the original English version. The 6 questions of the BASDAI represent different aspects of disease but correlated also well with each other (r < 0.65). There was a good internal consistency for all 6 questions (Cronbach's Alpha 0.82), strong correlations to the physician's global (r = 0.659), pain (r = 789), function (BASFI; r = 0.752) and to CRP and ESR confirming that the BASDAI assesses a comprehensive picture of patient's disease activity. For subgroups of patients with different levels of disease severity or with different manifestations the BASDAI showed good discriminative properties. The BASDAI was sensitive to change during treatment with infliximab (effect size 1.18). CONCLUSION: The German translation of the BASDAI is easy to use, reliable, and sensitive to change for the assessment of disease activity in AS.

Activities of Daily Living↗
PubMed2003

Removal of DNAPL contamination from the saturated zone by the combined effect of vertical upward flushing and density reduction.

A common aspect of innovative remediation techniques is that they tend to reduce the interfacial tension between the aqueous and non-aqueous phase liquids, resulting in mobilization of the organic contaminant. This complicates the remediation of aquifers, contaminated with Dense Non-Aqueous Phase Liquids (DNAPLs), as they are likely to migrate downwards, deeper into the aquifer and into finer layers. A possible solution is the use of swelling alcohols, which tend to reduce the density difference between the aqueous phase and the DNAPL. To avoid premature mobilization upon the initial contact between the DNAPL and the alcohol, several researchers have proposed the use of vertical upward flow of the alcohol. In this paper, we present an equation, which describes the upward mobilization of both continuous and discontinuous DNAPLs and so the important parameters governing the upward controlled mobilization of the DNAPL. The need and required magnitude of this specific discharge was investigated by conducting four column experiments in which the initial density of the DNAPL and the permeability was varied. It was shown that the required flow velocities increase with the permeability of the porous medium and the initial density difference between the aqueous phase and the DNAPL. Whenever the specific discharge falls below the critical value, the DNAPL moves downward. A second set of column experiments looked at the impact of permeability of porous medium on the solubilization and mobilization of DNAPL during alcohol flooding. Columns, packed with coarse or fine sand, containing a residual trichloroethylene (TCE) or perchloroethylene (PCE) saturation were flushed with the alcohol mixture at a fixed specific discharge rate. The induced pressure gradients in the aqueous phase, which were higher in the fine sand, resulted for this porous medium in extensive mobilization of the DNAPL against the direction of the buoyancy force. The density of the first NAPL coming out of the top of the fine sand was close to that of the pure DNAPL. In the coarser sand, the pressure gradients were sufficient to prevent downward migration of the DNAPL, but upward mobilization was minimal. The predominant removal mechanism in this case was the much slower solubilization.

Hydrocarbons↗
PubMed2003

Morphology of canine cumulus-oocyte complexes in pre-pubertal bitches.

The morphology of canine cumulus-oocyte complexes (COCs) before puberty is still unknown. Therefore, the aim of our study was to elucidate the morphological characteristics of pre-pubertal oocytes and cumulus cells by light microscopy, scanning electron microscopy and transmission electron microscopy. The pre-pubertal oocyte was characterized by accumulation of lipid yolk droplets in the cytoplasm as well as high energy metabolism, low protein synthesis and high transcriptional activity of the cumulus cells. The cumulus cells, which revealed a prominent nucleus and few cytoplasm, communicated with each other by few short processes and exhibited merely a small amount of processes reaching the oocyte. Our studies imply that both the oocyte and the cumulus cells of canine COCs before puberty reveal characteristic morphological features which are correlated with changes in oocyte metabolism and cumulus cell communication.

Animals↗
PubMed2003

G-CSF application in patients with severe bacterial pneumonia increases IL-10 expression in neutrophils.

In severe pneumonia, the application of granulocyte-colony stimulating factor (G-CSF) was associated with reduced complications possibly by an induction of anti-inflammatory cytokines. It is not clear, whether G-CSF induces interleukin-10 (IL-10) synthesis in neutrophils. In a randomized study, 15 patients with severe community acquired pneumonia were treated either by a single dose of G-CSF and antibiotic therapy (n=8) or antibiotics alone (n=7). Messenger ribonucleic acid (mRNA) expression of IL-10 and tumor necrosis factor alpha of peripheral blood leukocytes was measured using in-situ hybridization (ISH) and reverse-transcription-polymerase-chain-reaction (RT-PCR). In addition, the cytokine release of lipopolysaccharide (LPS)-stimulated whole blood was measured by ELISA. We detected increased IL-10 mRNA by ISH (140 +/- 8% vs. -11 +/- 5%, P<0.01) and RT-PCR (126 +/- 16% vs. -28 +/- 3%, P<0.01) in the G-CSF-treated group only. In contrast, LPS-stimulated whole blood cells in vitro released significantly less IL-10 compared to the control group (-38.2 +/- 97 vs. -14.8 +/- 6 pg/ml, P<0.02). There was no significant effect on IL-10 serum protein levels and the TNF-alpha release and expression. IL-10 mRNA was detected predominantly in cluster designation 66b (CD66b) positive nucleated blood cells indicating that polymorphonuclear leukocytes are the main source of IL-10 expression after G-CSF stimulation. G-CSF induces transcription of IL-10 mRNA in neutrophils without increased release. This may be due to posttranscriptional effects.

Analysis of Variance↗
PubMed2003

[Sacroiliitis in children with spondyloarthropathy: therapeutic effect of CT-Guided intra-articular corticosteroid injection].

PURPOSE: The prospective investigation of the therapeutic effect of CT-guided intra-articular corticosteroid injection into inflammatory sacroiliac (SI) joints compared to conventional treatment with nonsteroidal anti-inflammatory drugs (NSAIDS) in children with juvenile spondyloarthropathy (jSpA) and the determination of the role of dynamic magnetic resonance imaging (MRI) in establishing the indication and monitoring the therapy. MATERIALS AND METHODS: The study comprises 89 children with known jSpA who were diagnosed by MRI to have a unilateral or bilateral sacroiliitis. Therapy with NSAIDS was initiated or continued in all 89 patients. Four weeks after the diagnostic MRI, two groups were distinguished according to the clinical response to NSAIDS, with group 1 consisting of 33 responders and group 2 of 56 non-responders. The patients of group 2 were treated with CT-guided intra-articular corticosteroid injection (low-dose injection) while the therapy with NSAIDS was continued. A total of 83 SI joints were punctured without complications, 27 bilaterally and 29 unilaterally. The indication for the intervention was based on inflammatory activity as determined by MRI. The therapy was monitored by clinical follow-up every 8 to 12 weeks over a period of 20 months. Follow-up by dynamic MRI was performed in all 56 children of group 2 and in 15 of the 33 children of group 1 within 8 +/- 4 months of the initial examination. RESULTS: A total of 87.5% of the children in group 2 showed a statistically significant decrease in their subjective complaints from 6.9 +/- 3.4 to 1.8 +/- 1.7 (p < 0.05) as measured on a visual analog scale (VAS from 0 to 10). Improvement was seen as early as 1.5 +/- 1.0 weeks after the intervention and lasted for a mean of 12 +/- 6 months. The children in group 1 already showed similar improvement of the VAS from 6.8 +/- 3.2 to 1.5 +/- 1.4 (p < 0.05) during the initial four weeks of NSAIDS therapy, with the improvement lasting for the 20-month observation period. The follow-up dynamic MRI (0.1 mmol/kg body weight) during therapy showed a statistically significant lower contrast-enhancement in both groups (group 1: 117 +/- 43 % versus 38 +/- 24 %, p < 0.05; group 2: 127 +/- 59 % versus 38 +/- 22 %, p < 0.05). One third of the patients of group 2 showed progression of joint destruction despite absence of subjective complaints. CONCLUSION: CT-guided intra-articular corticosteroid injection has proven an effective, symptomatic, and uncomplicated therapy of acute sacroiliitis in patients with jSpA. Dynamic MRI has a role in establishing the indication for intervention but its role for any follow-up is restricted to cases with inconclusive clinical response.

Adolescent↗
PubMed2003

Comparison of statistically derived ASAS improvement criteria for ankylosing spondylitis with clinically relevant improvement according to an expert panel.

OBJECTIVE: To investigate whether the recently developed (statistically derived) "ASsessment in Ankylosing Spondylitis Working Group" improvement criteria (ASAS-IC) for ankylosing spondylitis (AS) reflect clinically relevant improvement according to the opinion of an expert panel. METHODS: The ASAS-IC consist of four domains: physical function, spinal pain, patient global assessment, and inflammation. Scores on these four domains of 55 patients with AS, who had participated in a non-steroidal anti-inflammatory drug efficacy trial, were presented to an international expert panel (consisting of patients with AS and members of the ASAS Working Group) in a three round Delphi exercise. The number of (non-)responders according to the ASAS-IC was compared with the final consensus of the experts. The most important domains in the opinion of the experts were identified, and also selected with discriminant analysis. A number of provisional criteria sets that best represented the consensus of the experts were defined. Using other datasets, these clinically derived criteria sets as well as the statistically derived ASAS-IC were then tested for discriminative properties and for agreement with the end of trial efficacy by patient and doctor. RESULTS: Forty experts completed the three Delphi rounds. The experts considered twice as many patients to be responders than the ASAS-IC (42 v 21). Overall agreement between experts and ASAS-IC was 62%. Spinal pain was considered the most important domain by most experts and was also selected as such by discriminant analysis. Provisional criteria sets with an agreement of >or=80% compared with the consensus of the experts showed high placebo response rates (27-42%), in contrast with the ASAS-IC with a predefined placebo response rate of 25%. All criteria sets and the ASAS-IC discriminated well between active and placebo treatment (chi(2)=36-45; p<0.001). Compared with the end of trial efficacy assessment, the provisional criteria sets showed an agreement of 71-82%, sensitivity of 67-83%, and specificity of 81-88%. The ASAS-IC showed an agreement of 70%, sensitivity of 62%, and specificity of 89%. CONCLUSION: The ASAS-IC are strict in defining response, are highly specific, and consequently show lower sensitivity than the clinically derived criteria sets. However, those patients who are considered as responders by applying the ASAS-IC are acknowledged as such by the expert panel as well as by patients' and doctors' judgments, and are therefore likely to be true responders.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Up regulation of the production of tumour necrosis factor alpha and interferon gamma by T cells in ankylosing spondylitis during treatment with etanercept.

BACKGROUND: Treatment of active ankylosing spondylitis (AS) with the recombinant, soluble tumour necrosis factor alpha (TNFalpha) receptor molecule etanercept has been shown to be clinically highly effective. The precise mechanism of action, however, is not known. OBJECTIVE: To assess the change in the cytokine secreting ability of CD4+ and CD8+ T cells and macrophages during etanercept treatment. PATIENTS AND METHODS: Peripheral blood mononuclear cells from 10 patients with AS treated with 25 mg etanercept and 10 patients with AS treated with placebo were investigated during treatment given twice weekly subcutaneously. Production of cytokines by T cells was investigated after in vitro stimulation by flow cytometry. RESULTS: Twelve weeks of etanercept treatment induced a significant increase in the number of interferon gamma (IFNgamma) positive (14.2% (9.6-19.5%) before v 24.4% (13.4-36.4%) after) and TNFalpha positive CD4+ T cells (p=0.008 for both cytokines) and IFNgamma positive (37.5% (19.0-45.4%) before v 52.9% (33.2-60.0%) after) and TNFalpha positive CD8+ T cells (p=0.008 for both cytokines) upon phorbol myristate acetate/ionomycin stimulation, but not in the placebo group. Furthermore, etanercept treatment induced a significant increase in the number of IFNgamma positive CD8+ T cells (p=0.024 at 12 weeks) and a non-significant increase of TNFalpha positive CD8+ T cells after in vitro stimulation with the aggrecan derived peptides. CONCLUSIONS: Neutralisation of peripheral TNFalpha does not induce a down regulation of the ability of T cells to produce TNFalpha but rather an up regulation, possibly due to a counterregulatory mechanism.

Antirheumatic Agents↗
PubMed2003

International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis.

OBJECTIVE: To obtain an international consensus about the use of anti-tumour necrosis factor alpha (anti-TNF alpha) for treating patients with ankylosing spondylitis (AS). METHODS: These recommendations were developed by a review of published reports in combination with expert opinion, including a Delphi exercise, and a consensus meeting of the ASsessments in AS (ASAS) Working Group. RESULTS: The final consensus comprises the following requirements: (1) For the initiation of anti-TNF alpha therapy: (a) a diagnosis of definitive AS; (b) presence of active disease for at least four weeks as defined by both a sustained Bath AS Disease Activity Index (BASDAI) of at least 4 and an expert opinion based on clinical features, acute phase reactants, and imaging modalities; (c) presence of refractory disease defined by failure of at least two non-steroidal anti-inflammatory drugs during a single three month period, failure of intra-articular steroids if indicated, and failure of sulfasalazine in patients with peripheral arthritis; (d) application and implementation of the usual precautions and contraindications for biological therapy. (2) For the monitoring of anti-TNF alpha therapy: both the BASDAI and the ASAS core set for clinical practice should be followed regularly. (3) For the discontinuation of anti-TNF alpha therapy: in non-responders, consideration should be made after 6-12 weeks' treatment. Response is defined as improvement of (a) at least 50% or 2 units (on a 0-10 scale) of the BASDAI, (b) expert opinion that treatment should be continued. CONCLUSION: This consensus statement on anti-TNF alpha treatment in AS may be used for guidance in clinical decision making and as the basis for the development of guidelines. Evaluation of the healthcare consequences of this consensus is subject to further research by the ASAS group.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2003

Effect of microbial phytase on energy availability, and lipid and protein deposition in growing swine.

Two experiments were conducted to determine the effect of phytase on energy availability in pigs. In Exp. 1, barrows (initial and final BW of 26 and 52 kg) were allotted to four treatments in a 2 x 2 factorial arrangement. Corn-soybean meal (C-SBM) diets were fed at two energy levels (2.9 and 3.2 x maintenance [M]) with and without the addition of 500 phytase units/kg of diet. The diets contained 115% of the requirement for Ca, available P (aP), and total lysine, and Ca and aP were decreased by 0.10% in diets with added phytase. Pigs were penned individually and fed daily at 0600 and 1700, and water was available constantly. Eight pigs were killed and ground to determine initial body composition. At the end of Exp. 1, all 48 pigs were killed for determination of carcass traits and protein and fat content by total-body electrical conductivity (TOBEC) analysis. Six pigs per treatment were ground for chemical composition. In Exp. 2, 64 barrows and gilts (initial and final BW of 23 and 47 kg) were allotted to two treatments (C-SBM with 10% defatted rice bran or that diet with reduced Ca and aP and 500 phytase units/kg of diet), with five replicate pens of barrows and three replicate pens of gilts (four pigs per pen). In Exp. 1, ADG was increased (P < 0.01) in pigs fed at 3.2 x M. Based on chemical analyses, fat deposition, kilograms of fat, retained energy (RE) in the carcass and in the carcass + viscera, fat deposition in the organs, and kilograms of protein in the carcass were increased (P < 0.10) in pigs fed the diets at 3.2 vs. 2.9 x M. Based on TOBEC analysis, fat deposition, percentage of fat increase, and RE were increased (P < 0.09) in pigs fed at 3.2 x M. Plasma urea N concentrations were increased in pigs fed at 3.2 x M with no added phytase but were not affected when phytase was added to the diet (phytase x energy, P < 0.06). Fasting plasma glucose measured on d 28, ultrasound longissimus muscle area (LMA), and 10th-rib fat depth were increased (P < 0.08) in pigs fed phytase, but many other response variables were numerically affected by phytase addition. In Exp. 2, phytase had no effect (P > 0.10) on ADG, ADFI, gain:feed, LMA, or 10th-rib fat depth. These results suggest that phytase had small, mostly nonsignificant effects on energy availability in diets for growing pigs; however, given that phytase increased most of the response variables measured, further research on its possible effects on energy availability seems warranted.

6-Phytase↗
PubMed2002

Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.

UNLABELLED: BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.

Adult↗
PubMed2002

[Technique and value of arthrosonography in rheumatologic diagnosis--3: Ultrasound diagnosis of the ankle joint, foot and toes].

The clinical investigation of ankles, feet, and toes is frequently equivocal in rheumatology. Sonography can distinguish between underlying pathologies. We suggest following standard scans: 1) anterior longitudinal scan to diagnose effusions in the ankle and talonavicular joints, to display erosive and osteoarthrotic pathologies, and to diagnose tenosynovitis of the extensor tendons; 2) anterior transverse scan to document the findings in an additional dimension; 3) lateral transverse scan and 4) lateral longitudinal scan to diagnose tenosynovitis of the peroneus tendons; 5) medial transverse scan and 6) medial longitudinal scan to diagnose tenosynovitis of the flexor tendons; 7) posterior longitudinal scan and 8) posterior transverse scan to evaluate the Achilles tendon, the retrocalcaneal bursa, and the posterior recess of the ankle joint. Additionally we suggest optional scans: 9) plantar longitudinal scan for the plantar fascia and the plantar calcaneal surface; 10) distal anterior longitudinal scan to evaluate the midtalar joints; 11) distal anterior longitudinal scan to evaluate the toes; and 12) plantar, distal transverse scan to evaluate the flexor tendons of the toes. Additionally, the correlating longitudinal and transverse scans can be used to confirm the findings. The frequency of the transducer should be about 7.5 MHz for ankles and the peroneus, flexor, and extensor tendons. Ten to over 20 MHz are possible for more superficially located structures. Using modern equipment with higher resolution a hypoechoic border may be normal up to 3 mm in the ankle joints, the MTP joints, and around the peroneus tendons, and up to 4 mm around the tibialis posterior tendons.

Ankle Joint↗