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J Braun

Publications and source records attributed to J Braun.

At least 37 records · Page 2Linked to original sources
PubMed2006

Detection of a new weak A blood-group allele (Aw11).

BACKGROUND AND OBJECTIVES: Weak ABO variants may escape tests using unlicensed sera. MATERIALS AND METHODS: Prior to transfusion, ABO grouping was performed using an automated system and in-house diluted sera, and manual and bedside test techniques. Genotyping and sequencing were performed using standard methods. RESULTS: Initially, the red blood cells (RBC) of the first-time blood donor were typed as B, but pretransfusion testing carried out using the bedside test indicated the presence of an additional A phenotype. Serological re-examination confirmed the bedside test results, and the allele in question was identified, by genotyping, as a new weak A variant (Aw11). CONCLUSIONS: The use of CE-marked and licensed antisera is recommended to avoid ABO mistyping.

ABO Blood-Group System↗
PubMed2005

Outcome of patients with active ankylosing spondylitis after two years of therapy with etanercept: clinical and magnetic resonance imaging data.

OBJECTIVE: To examine the long-term outcome of patients with active ankylosing spondylitis (AS) clinically and by magnetic resonance imaging (MRI) after continuous treatment with the tumor necrosis factor (TNF) receptor fusion protein etanercept over 2 years. METHODS: Overall, 26 patients with active AS were treated with etanercept 25 mg twice daily subcutaneously, twice weekly with no concomitant disease-modifying antirheumatic drugs (DMARDs) or steroids. The clinical response was assessed by standardized parameters. Inflammatory spinal lesions were quantified by the ASspiMRI-a rating gadolinium-enhanced (T1-weighted gadolinium diethylenetriaminepentaacetic acid) and STIR MRI sequences. The primary outcome was a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) improvement > or =50% after 2 years of etanercept therapy compared with the baseline value of the study. RESULTS: Overall, 21 (70%) of 30 patients completed year 2. In the intent-to-treat analysis, 54% of the patients showed a 50% improvement according to the BASDAI and a 40% improvement according to the Assessment in Ankylosing Spondylitis (ASAS) criteria. In the completer analysis, 9 (43%) of 21 patients were in partial remission according to ASAS criteria. Mean +/- SD BASDAI scores, which were elevated at baseline (6.3 +/- 1.6), remained low: 2.7 +/- 2.4 after 2 years compared with 2.6 +/- 2.2 at week 54. In accordance, all other clinical parameters showed sustained improvement during year 2. The majority of patients had no disease activity flares. MRI evaluation showed a 75% improvement of active spinal lesions, but minor spinal inflammation was still present in 64% of the patients after 2 years. There were 2 serious adverse events leading to discontinuation of etanercept. CONCLUSION: The clinical efficacy and safety of etanercept in patients with active AS without simultaneous administration of DMARDs or steroids over 2 years of continuous treatment is confirmed. Spinal inflammation as depicted by MRI decreased significantly, but a few patients still had some spinal inflammation even after long-term anti-TNF therapy.

Adult↗
PubMed2005

Neutrophil apoptosis, activation and anti-inflammatory cytokine response in granulocyte colony-stimulating factor-treated patients with community-acquired pneumonia.

BACKGROUND: Despite antibiotic treatment, the mortality of severe community-acquired pneumonia (CAP), especially in patients with severe comorbidity, remains high. Innate defense mechanisms including polymorphonuclear neutrophil (PMN) activation and survival, orchestrated by cytokines, are primarily responsible for the elimination of bacterial organisms from the alveolus. OBJECTIVES: The aim of this study was to evaluate the effect of granulocyte colony-stimulating factor (G-CSF) on PMN activation, apoptosis and cytokine response in patients with CAP. METHODS: Patients received a single dose of G-CSF (1 x 300 or 480 microg s.c.) prior to standard antibiotic treatment (n=8) or standard treatment only (n=8). Apoptosis rate and expression of CD11b, CD66b, CD64 and CD114 surface molecules on systemic PMN were assessed using fluorescence-activated cell sorter analysis. Levels of the interleukin-1 receptor antagonist (IL-1 RA), the soluble tumor necrosis factor receptor inhibitor (sTNF-p55) and G-CSF were measured by ELISA. RESULTS: In the treatment group, 12 h after G-CSF application, neutrophil count increased, neutrophil activation marker CD11b was stimulated (CD11b: 48.6+/-9.7 vs. 71.2+/-17.7, p<0.01), neutrophil apoptosis decreased (apoptosis: 1.36+/-0.27 vs. 0.2+/-0.12%, p <.01) and the concentration of IL-1RA and sTNF-p55 increased (IL-1RA 136.4+/-72.2 vs. 340.1+/-194.6 ng/ml, p<0.01; sTNF-p55,382+/-4,243 vs. 632+/-4,714 ng/ml, p<0.01; control group nonsignificant). These effects were not seen in the control group. CONCLUSIONS: The application of a single dose of G-CSF in patients with CAP caused a prolonged survival and increased activation of neutrophils combined with a sustained release of anti-inflammatory cytokines.

Aged↗
PubMed2005

Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases.

OBJECTIVE: To characterise the immunohistological features of sacroiliitis in ankylosing spondylitis (AS) at different disease stages. METHODS: Biopsy samples from sacroiliac joints (SIJs) of five patients with AS, two with early, three with advanced changes and samples from age matched controls from one necropsy SIJ and two iliac bone marrow (BM) biopsies were studied. Paraffin sections were immunostained in triplicate for T cells (CD3, CD8), macrophages (CD68), and the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma, interleukin (IL) 1beta, IL6, IL10, and transforming growth factor beta1 (TGFbeta1). Stained cells were counted over one entire high power field (x400) per section in BM, cartilage, and other connective tissue (CT). Results are the mean of three sections. RESULTS: CD3+ T cells were numerous in the BM of early AS, and in the CT of one patient with early and one with late AS, with variable proportions of CD8+ T cells. All patients with AS had more CD68+ macrophages than controls in BM and CT; in cartilage, one patient with early and one with late AS had increased CD68+ cells, some being osteoclasts. The patient with very early AS had large numbers of TNFalpha cells in the three tissular areas; for the other patient with early disease they were found only in CT and cartilage. IL6 was seen in 4/4 patients with AS in most areas. Patients with early disease had more T cells, TNFalpha, and IL6, and patients with advanced AS more TGFbeta1. CONCLUSION: The immunohistological findings of a limited sample suggest a role for BM in sacroiliitis, for TNFalpha and IL6 in early, active lesions, and for TGFbeta1 at the time of secondary cartilage and bone proliferation.

Adolescent↗
PubMed2005

Relativistic electron correlation, quantum electrodynamics, and the lifetime of the 1s(2)2s(2)2p2p0(3/2) level in boronlike argon.

The lifetime of the Ar13+ 1s(2)2s(2)2p2p0(3/2) metastable level was determined at the Heidelberg Electron Beam Ion Trap to be 9.573(4)(5). The accuracy level of one per thousand makes this measurement sensitive to quantum electrodynamic effects like the electron anomalous magnetic moment (EAMM) and to relativistic electron-electron correlation effects like the frequency-dependent Breit interaction. Theoretical predictions, adjusted for the EAMM, cluster about a lifetime that is approximately shorter than our experimental result.

Journal Article↗
PubMed2005

Current evidence for the management of ankylosing spondylitis: a systematic literature review for the ASAS/EULAR management recommendations in ankylosing spondylitis.

OBJECTIVE: To assess available management strategies in ankylosing spondylitis (AS) using a systematic approach, as a part of the development of evidence based recommendations for the management of AS. METHODS: A systematic search of Medline, Embase, CINAHL, PEDro, and the Cochrane Library was performed to identify relevant interventions for the management of AS. Evidence for each intervention was categorised by study type, and outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, rate ratio, number needed to treat, and incremental cost effectiveness ratio were calculated for each intervention where possible. Results from randomised controlled trials were pooled where appropriate. RESULTS: Both pharmacological and non-pharmacological interventions considered to be of interest to clinicians involved in the management of AS were identified. Good evidence (level Ib) exists supporting the use of non-steroidal anti-inflammatory drugs (NSAIDs) and coxibs for symptomatic treatment. Non-pharmacological treatments are also supported for maintaining function in AS. The use of conventional antirheumatoid arthritis drugs is not well supported by high level research evidence. Tumour necrosis factor inhibitors (infliximab and etanercept) have level Ib evidence supporting large treatment effects for spinal pain and function in AS over at least 6 months. Level IV evidence supports surgical interventions in specific patients. CONCLUSION: This extensive literature review forms the evidence base considered in the development of the new ASAS/EULAR recommendations for the management of AS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

ASAS/EULAR recommendations for the management of ankylosing spondylitis.

OBJECTIVE: To develop evidence based recommendations for the management of ankylosing spondylitis (AS) as a combined effort of the 'ASsessment in AS' international working group and the European League Against Rheumatism. METHODS: Each of the 22 participants was asked to contribute up to 15 propositions describing key clinical aspects of AS management. A Delphi process was used to select 10 final propositions. A systematic literature search was then performed to obtain scientific evidence for each proposition. Outcome data for efficacy, adverse effects, and cost effectiveness were abstracted. The effect size, relative risk, number needed to treat, and incremental cost effectiveness ratio were calculated. On the basis of the search results, 10 major recommendations for the management of AS were constructed. The strength of recommendation was assessed based on the strength of the literature evidence, risk-benefit trade-off, and clinical expertise. RESULTS: The final recommendations considered the use of non-steroidal anti-inflammatory drugs (NSAIDs) (conventional NSAIDs, coxibs, and co-prescription of gastroprotective agents), disease modifying antirheumatic drugs, treatments with biological agents, simple analgesics, local and systemic steroids, non-pharmacological treatment (including education, exercise, and physiotherapy), and surgical interventions. Three general recommendations were also included. Research evidence (categories I-IV) supported 11 interventions in the treatment of AS. Strength of recommendation varied, depending on the category of evidence and expert opinion. CONCLUSION: Ten key recommendations for the treatment of AS were developed and assessed using a combination of research based evidence and expert consensus. Regular updating will be carried out to keep abreast of new developments in the management of AS.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis.

OBJECTIVE: To update the international recommendations for use of anti-tumour necrosis factor (TNF) agents in the treatment of ankylosing spondylitis. METHODS: The published recommendations on anti-TNF treatment in ankylosing spondylitis formed the basis of the update. A questionnaire was sent to the ASAS (assessment in ankylosing spondylitis) members before the final decisions were agreed upon at an international meeting of the ASAS working group. RESULTS: Only minor changes to the original consensus statement were required. For the initiation of anti-TNF treatment, there should be: a diagnosis of definitive ankylosing spondylitis (normally based on modified New York criteria); active disease for at least four weeks, as defined by a sustained Bath ankylosing spondylitis disease activity index (BASDAI) of > or =4 on a 0-10 scale and expert opinion based on clinical findings; refractory disease, defined by failure of at least two non-steroidal anti-inflammatory drugs during a three month period, failure of intra-articular steroids (if indicated), and failure of sulfasalazine in patients with predominantly peripheral arthritis; and application of the usual precautions and contraindications for biological treatment. For monitoring anti-TNF treatment: both the ASAS core set for clinical practice and the BASDAI should be followed after the initiation of treatment. Discontinuation of anti-TNF treatment in non-responders should be considered after 6-12 weeks. Response is defined by improvement of at least 50% or 2 units (on a 0-10 scale) of the BASDAI. CONCLUSIONS: This updated consensus statement is recommended in guiding clinical practice and as a basis for developing national guidelines. Evaluation and regular update of this consensus statement is subject to further research by the ASAS group.

Antirheumatic Agents↗
PubMed2005

Lack of a difference in increased capillary blood cell velocity in the skin over proximal interphalangeal joints between rheumatoid arthritis and osteoarthritis.

Early detection of synovitis in rheumatoid arthritis (RA) and distinction from osteoarthritis (OA) are important to establish the most appropriate treatment. Increased perfusion over affected joints observed by laser Doppler perfusion imaging was supposed to arise from the underlying joint, because it was detected only by a near-infrared laser and not by a less penetrating red laser source. Using laser Doppler anemometry, this study addressed two questions: (1) whether capillary blood cell velocity (CBV) is increased in the skin over finger joints affected by RA or OA; (2) whether there is a difference between RA and OA in CBV above affected proximal interphalangeal (PIP) joints. Levels of soluble adhesion molecules were measured, because they indicate rheumatoid vasculitis raising flow resistance. Thirty-one patients with RA and 20 with OA were investigated. Compared to 18 controls, CBV (mean+/-SEM) was elevated above PIP joints clinically affected by RA (0.35+/-0.06 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and over PIP (0.27+/-0.02 mm/s vs. 0.21+/-0.02 mm/s; P<0.05) and distal interphalangeal joints (0.27+/-0.02 mm/s vs. 0.17+/-0.01 mm/s; P<0.001) affected by OA. Levels of soluble adhesion molecules were not correlated with CBV over PIP joints in RA. These observations demonstrated that elevated blood cell velocity is detectable by laser Doppler anemometry in skin capillaries over interphalangeal joints affected by RA or OA and contradict the previous assumption that there is hyperemia only in the affected joint. The lack of a significant difference in CBV over PIP joints between RA and OA patients might be due to some inflammation also occurring in OA rather than to vasculitic processes in RA associated with elevated levels of soluble adhesion molecules.

Adult↗
PubMed2005

Persistent reduction of spinal inflammation as assessed by magnetic resonance imaging in patients with ankylosing spondylitis after 2 yrs of treatment with the anti-tumour necrosis factor agent infliximab.

OBJECTIVES: Patients with ankylosing spondylitis (AS) benefit from anti-TNF therapy both on a clinical basis and as depicted by magnetic resonance imaging (MRI). It is not known whether spinal inflammation remains suppressed over time. Our objective was to assess spinal inflammation by MRI in AS patients after 2 yr of continuous infliximab treatment. METHODS: Twenty patients with active AS were examined by MRI at baseline, after 3 months (end of placebo-controlled-phase) and after 2 yr of continuous infliximab therapy (5 mg/kg/6 weeks). T1 pre- and post-gadolinium (T1/gadolinium-diethylenetriamine-pentaacetic acid) and short tau inversion recovery (STIR) MRI sequences were performed and read by one blinded reader using the ASspiMRI score. RESULTS: Spinal inflammation, detected by MRI in all patients at baseline, decreased after 3 months only in the infliximab group in both MRI sequences. Persistent improvement of spinal inflammation was seen after 2 yr by scoring STIR sequences, with a mean score of 4.6 +/- 5.9 vs 15.2 +/- 13.2 at baseline (P = 0.01). On an individual level, inflammatory spinal lesions decreased from 6.7 +/- 5.0 per patient at baseline to 2.2 +/- 1.8 after 2 yr (P = 0.003). Improvement in spinal inflammation was found in all patients by both MRI sequences. Only a minor degree but some spinal inflammation was still present after 2 yrs. CONCLUSION: Spinal inflammation in MRI was persistently reduced in all patients constantly treated with infliximab, but it was not completely eradicated. Disease activity parameters did not directly correlate with MRI, but both pointed in the same direction. Both types of information may be useful for the definition of response to anti-TNF therapy.

Adult↗
PubMed2005

Markov model into the cost-utility over five years of etanercept and infliximab compared with usual care in patients with active ankylosing spondylitis.

OBJECTIVE: To estimate the incremental cost-utility of etanercept and infliximab compared with usual care in active ankylosing spondylitis. METHODS: A Markov model over five years with cycle times of three months was computed. Patients included all had active disease, defined as Bath ankylosing spondylitis disease activity index (BASDAI) >or=4 and could reach low disease activity, defined as BASDAI <4. Non-response to tumour necrosis factor alpha (TNFalpha) inhibitors was always followed by cessation of treatment. Response to TNFalpha inhibitors could be followed at any time by either relapse to BASDAI >or=4, leading to cessation of treatment, or toxicity, leading to cessation of treatment if major. Probabilities for efficacy, relapse, and toxicity were derived from two European randomised controlled trials. Utilities and costs assigned to the BASDAI disease states were derived from a two year observational Dutch cohort. In sensitivity analyses probabilities of effectiveness, toxicity, costs, and utilities were varied. RESULTS: Over five years the total quality adjusted life years varied from 2.57 to 2.89 for usual care, compared with 3.13 to 3.42 and 3.07 to 3.35 for etanercept or infliximab. Cumulative costs were between 49,555 to 69,982 for usual care compared with 59,574 to 91,183 or 28,3330 to 106,775 for etanercept and infliximab. This resulted in incremental cost-utility ratios varying between 42,914 and 123,761 per QALY for etanercept compared with usual care and 67,207 to 237,010 for infliximab. The model was sensitive to drug prices. CONCLUSION: Etanercept and infliximab have large clinical effects in ankylosing spondylitis. The present model suggests the high drug costs restricts efficient use in all patients who have a BASDAI >4. The validity of the model is limited by insufficient insight in the natural course of the disease and long term effectiveness and toxicity of TNFalpha inhibitors.

Acute Disease↗
PubMed2005

State-selective quantum interference observed in the recombination of highly charged Hg 75+...78+ mercury ions in an electron beam ion trap.

We present experimental data on the state-selective quantum interference between different pathways of photorecombination, namely, radiative and dielectronic recombination, in the KLL resonances of highly charged mercury ions. The interference, observed for well resolved electronic states in the Heidelberg electron beam ion trap, manifests itself in the asymmetry of line shapes, characterized by "Fano factors," which have been determined with unprecedented precision, as well as their excitation energies, for several strong dielectronic resonances.

Journal Article↗
PubMed2005

Sustained durability and tolerability of etanercept in ankylosing spondylitis for 96 weeks.

OBJECTIVE: To evaluate the continued safety and durability of clinical response in patients with ankylosing spondylitis receiving etanercept. METHODS: 277 patients who had participated in a previous randomised, double blind, placebo controlled 24 week trial were eligible to continue in this open label extension study. All patients who enrolled in the open label extension (n = 257) received subcutaneous etanercept 25 mg twice weekly for up to 72 weeks, for a combined 96 weeks of cumulative trial and open label experience. For the patients who had received etanercept for 24 weeks in the double blind trial, this represented almost 2 years of continuous etanercept treatment. RESULTS: Patients continuing etanercept treatment had a sustained response for almost 2 years, with 74% achieving an ASsessments in Ankylosing Spondylitis 20% (ASAS 20) response after 96 weeks of etanercept treatment. Patients who had received placebo in the preceding double blind trial had similar responses, with 70% of patients attaining an ASAS 20 response after 24 weeks of etanercept treatment and 78% achieving an ASAS 20 response after 72 weeks. Improved spinal mobility was seen in both groups. Etanercept was well tolerated in patients treated for up to 96 weeks. CONCLUSION: The subcutaneous administration of twice weekly doses of etanercept provided sustained durability of response in the improvement of signs and symptoms of ankylosing spondylitis for nearly 2 years.

Adolescent↗
PubMed2005

Magnetic resonance imaging of the spine and the sacroiliac joints in ankylosing spondylitis and undifferentiated spondyloarthritis during treatment with etanercept.

OBJECTIVE: To assess the changes in inflammatory lesions of the spine and the sacroiliac (SI) joints as detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) and undifferentiated spondyloarthritis (uSpA) with predominant axial symptoms during treatment with etanercept. METHODS: MRI of the spine and/or the SI joints of patients with active AS or axial uSpA was performed at baseline (TP0, n = 25), after 6 weeks (TP1, n = 20), and after 24 weeks of continuous treatment with etanercept (TP2, n = 12). T1 weighted spin echo pre -(T1), post-gadolinium (T1/Gd-DTPA) and short tau inversion recovery (STIR) MRI sequences were used to assess chronic and active spinal lesions using the scoring system ASspiMRI. Active and chronic SI lesions were assessed using a simple scoring system. RESULTS: By use of the definite STIR sequence, significant regression of spinal inflammation was already seen already after 6 weeks in the patients treated with etanercept (mean (SD) 11.2 (13.8) at TP0 v 6.8 (7.9) at TP1; p = 0.023) but not in patients treated with placebo. Continuous treatment with etanercept for 24 weeks reduced active spinal changes by 69% (p = 0.012). T1/Gd-DTPA sequences gave similar results. There was only a trend for a decrease of active inflammatory lesions of the SI joints. CONCLUSIONS: Etanercept treatment in patients with active AS and uSpA leads to regression of active inflammatory lesions of the spine as depicted by MRI. The potential role of etanercept on deceleration of chronic spinal changes needs further study.

Acute Disease↗
PubMed2005

Radiographic progression in patients with ankylosing spondylitis after 2 years of treatment with the tumour necrosis factor alpha antibody infliximab.

BACKGROUND: Anti-tumour necrosis factor (TNF) treatment is clinically efficacious in patients with active ankylosing spondylitis (AS) and leads to improvement of spinal inflammation, as assessed by magnetic resonance imaging. It is unclear whether anti-TNF treatment affects chronic spinal changes in AS. OBJECTIVES: To analyse the effect of infliximab on the radiographic course of AS over 2 years. METHODS: Complete sets of lateral radiographs of the cervical spine and lumbar spine were available from 82 patients from two sources: 41 patients (group 1) had been treated with infliximab (5 mg/kg/6 weeks) as part of a recent randomised controlled trial and 41 patients (group 2) were part of the early German AS cohort (GESPIC), without controlled interventions. Radiographs were obtained at baseline and after 2 years and scored by the modified Stokes AS Spinal Score (mSASSS). RESULTS: Patients in the infliximab group were older, had a longer disease duration, and more radiographic damage at baseline. The mean (SD) mSASSS change was 0.4 (2.7) and 0.7 (2.8) for groups 1 and 2, respectively (p = NS). Radiographic damage at baseline was a predictor for more radiographic progression. Patients with baseline damage who were treated with infliximab showed a trend for less radiographic progression. No correlations between clinical parameters and radiographic progression were found. CONCLUSIONS: Patients with AS treated with infliximab had less radiographic progression after 2 years. Patients with prevalent radiographic damage are prone to develop more damage over time. Infliximab may decelerate radiographic progression in such patients. Larger studies are needed to prove that anti-TNF treatment inhibits structural damage.

Adult↗
PubMed2005

Persistent clinical response to the anti-TNF-alpha antibody infliximab in patients with ankylosing spondylitis over 3 years.

OBJECTIVE: Infliximab, a monoclonal antibody against tumour necrosis factor alpha (TNF-alpha), is approved in Europe for the treatment of patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. This report provides analyses from a 3-yr extension study, as a follow-up to both the 1- and 2-yr open label extensions of the original 3-month randomized controlled trial of infliximab in patients with AS. METHODS: Of the 49 patients with AS who completed the second year of the study, 46 continued treatment with infliximab 5 mg/kg every 6 weeks up to week 156. The Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index, the Bath AS Metrology Index, patient's and physician's global assessments, quality of life (Short Form-36), C-reactive protein (CRP) and erythrocyte sedimentation rate were assessed throughout the study period. RESULTS: The improvement of signs and symptoms observed in the majority of the patients during the first and second year was sustained throughout the third year of the study. Forty-three patients (62% of the 69 patients enrolled at baseline and 93% of the patients who started the third year) completed week 156. In the intention-to-treat analysis, an ASAS '5 out of 6' and ASAS 40% response was seen by 46% and 50% of the patients, respectively. The scores for other efficacy assessments were similar to the values observed at weeks 54 and 102. Median CRP levels remained low (1.5 mg/l at week 156). There were no relevant side-effects and no discontinuation because of drug-related adverse events during the third year of the study. CONCLUSIONS: Patients with AS receiving infliximab for 3 yr showed a durable clinical response without loss of efficacy. Long-term infliximab treatment was well tolerated by patients in this study.

Adult↗