Biomedical subjects

Juergen Braun

Publications and source records attributed to Juergen Braun.

10 recordsLinked to original sources

PubMed2005

Clinical response to discontinuation of anti-TNF therapy in patients with ankylosing spondylitis after 3 years of continuous treatment with infliximab.

We analyzed the clinical response and the time to relapse after discontinuation of continuous long-term infliximab therapy in patients with ankylosing spondylitis (AS). After 3 years of infliximab therapy, all AS patients (n = 42) discontinued treatment (time point (TP)1) and were visited regularly for 1 year in order to assess the time to relapse (TP2). Relapse was defined as an increase to a value >or= 4 on the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and a physician's global assessment >or= 4 according to the recommendations of the Assessments in Ankylosing Spondylitis (ASAS) working group. After 52 weeks, 41 of the 42 patients (97.6%) had to be reinfused because of relapse. The mean change in the BASDAI between TP1 and TP2 was 3.6 +/- 1.7 and that in the physician's global assessment was 4.4 +/- 1.8 (both P < 0.001). The mean time to relapse was 17.5 weeks (+/- 7.9 weeks, range 7 to 45). Ten patients (24%) showed a relapse within 12 weeks and 38 patients (90.5%), within 36 weeks. After 52 weeks, only one patient had remained in ongoing remission without further treatment with anti-tumor-necrosis factor. Patients who were in partial remission according to the ASAS criteria and those with normal C-reactive protein levels at the time point of withdrawal had longer times to relapse after discontinuation of the treatment. Retreatment with infliximab was safe and resulted in clinical improvement in all patients to a state similar to that before the treatment was stopped. Discontinuation of long-term therapy with infliximab eventually led to relapse of disease activity in all patients but one.

Antibodies, Monoclonal↗

PubMed2005

Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes.

OBJECTIVE: To define the relationship between bone growth (syndesmophytes) and bone loss (osteoporosis) in ankylosing spondylitis (AS). METHODS: Bone mineral density (BMD) at the spine, hip, and radius was measured by dual-energy x-ray absorptiometry (DEXA), dual-energy quantitative computed tomography (DEQCT), and peripheral quantitative computed tomography (pQCT) in 103 patients with AS. Radiographs of the lumbar spine were used to detect syndesmophytes. Patients were divided in 3 groups according to disease duration. RESULTS: Osteopenia at the hip and spine was found by DEXA in 56% and 41%, respectively, of the patients with disease duration < 5 years (n = 27), with an additional 11% and 15% having osteoporosis. In patients with a longer disease duration, > 10 years (n = 28), 29% were osteoporotic at the hip and only 4% at the lumbar spine. In contrast, using spinal DEQCT, 59% of patients with early disease were found to be osteopenic; 36% of patients with long-standing disease were osteopenic and 18% were osteoporotic. More than half the patients (55%) had syndesmophytes (n = 55). With spinal DEQCT there were more patients with syndesmophytes (63%) in the group with reduced bone density than in the group without (45%). This was similar with DEXA measurements at the hip, where 31% compared to 14% had osteoporosis, respectively. Osteocalcin was elevated in 34% of patients, but was not associated with disease activity or BMD. CONCLUSION: The majority of patients with AS had reduced bone density. The method of bone density measurement is critical and should be different depending on disease duration. The finding that more patients with syndesmophytes had reduced bone density than those without suggests that bone growth and bone loss occur in parallel, and the role of inflammation in this process warrants further investigation.

Absorptiometry, Photon↗

PubMed2004

Prospective registration of human head magnetic resonance images for reproducible slice positioning using localizer images.

PURPOSE: To facilitate assessing brain tumor growth and progression of stroke lesions by reproducible slice positioning in human head magnetic resonance (MR) images, a method for prospective registration is proposed that adjusts the image slice position without moving the patient and with no additional scans. MATERIALS AND METHODS: The gradient reference frame of follow-up examinations was adjusted to achieve the same image slice positioning relative to the patient as in the previous examination. The three-dimensional geometrical transformation parameters for the gradients were determined using two-dimensional image registration of three orthogonal localizer images. The method was developed and evaluated using a phantom with arbitrarily adjustable position. Feasibility for in vivo applications was demonstrated with brain MR imaging (MRI) of healthy volunteers. RESULTS: Standard retrospective registration was used for assessing the quality of the method. The accuracy of the realignment was 0.0 mm +/- 1.2 mm and -0.2 degrees +/- 0.9 degrees (mean +/- SD) in phantom experiments. In 10 examinations of volunteers, misalignments up to 49.2 mm and 21 degrees were corrected. The accuracy of the realignment after prospective registration was 0.1 mm +/- 1.5 mm and 0.2 degrees +/- 1.5 degrees. CONCLUSION: Image-based prospective registration using localizer images of the pre- and postexaminations is a robust method for reproducible slice positioning.

Brain↗

PubMed2004

Current concepts in the therapy of the spondyloarthritides.

Recent success in the treatment of patients with the more severe forms of spondyloarthritides (SpA) has dramatically changed old paradigms. There is evidence that anti-tumor necrosis factor (TNF)-alpha therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis. Based on recent data on more than 1000 patients with AS and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis (RA). The currently available anti-TNFalpha agents, infliximab, etanercept, and adalimumab, are approved for the treatment of RA in the US and in Europe. TNFalpha blockers may even be considered as a first-line treatment in patients with active AS whose condition is not sufficiently controlled with NSAIDs, as in the case of axial disease. There is preliminary evidence that both agents also work in other SpA, such as undifferentiated SpA. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term anti-TNFalpha therapy and whether radiologic progression and ankylosis can be stopped. Furthermore, it seems that anti-TNFalpha therapy can also improve clinical manifestations of other inflammatory spinal disorders, such as sciatica and back pain caused by disc herniation, or possibly even intermittent inflammatory states of degenerative disc disease. Severe adverse events from treatment with anti-TNFalpha continue to be rare. Tuberculosis can be largely prevented by appropriate screening. As it stands now, the benefits of anti-TNFalpha therapy in AS seem to outweigh the shortcomings.

Clinical Trials as Topic↗

PubMed2003

Electromagnetic actuator for generating variably oriented shear waves in MR elastography.

Magnetic resonance elastography (MRE) is a recently developed technique for determining the mechanical properties of biological tissue. In dynamic MRE, electromagnetic units (actuators) are widely used to generate shear waves in tissue. These actuators exploit the interaction between the static magnetic field B(0) and an annular coil supplied with alternating currents. Therefore, coil movements are restricted to selected orientations to B(0). Conventional actuators transfer this movement collinearly to B(0) into the tissue. In this study, an electromagnetic actuator was introduced that overcomes this limitation. It is demonstrated that different directions of mechanical excitation can be generated and monitored by MRE. Different spatial components of the propagation of the shear waves were determined using agarose phantoms. The technique allows maximum contrast for MRE images of objects with anisotropic strain components such as muscle tissue.

Anisotropy↗

PubMed2003

Biologic therapies in the spondyloarthritis: new opportunities, new challenges.

Therapeutic options for patients suffering from the more severe forms of spondyloarthritis have been rather limited in the last decades. There is now accumulating evidence that antitumor necrosis factor therapy is highly effective in spondyloarthritis, especially in ankylosing spondylitis and psoriatic arthritis. Based on the data recently published on more than 500 patients with ankylosing spondylitis and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis. The antitumor necrosis factor-alpha agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis in the United States and partly in Europe. The situation in spondyloarthritis is different from that of rheumatoid arthritis because there is an unmet medical need, especially in ankylosing spondylitis: no therapies with disease-modifying antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, tumor necrosis factor blockers may even be considered a first-line treatment in a patient with active ankylosing spondylitis and psoriatic arthritis whose condition is not sufficiently controlled with nonsteroidal antiinflammatory drugs in the case of axial disease, and sulfasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg was required, and intervals between 6 and 12 weeks were necessary to suppress disease activity constantly-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are no studies yet on adalimumab (standard rheumatoid arthritis dose, 20-40 mg subcutaneously every 1-2 weeks) in spondyloarthritis. Infliximab was very recently approved for AS in Europe. The efficacy of etanercept was first demonstrated in psoriatic arthritis, and it is now approved for this indication. A double-blind study has also been performed in ankylosing spondylitis, with similarly clear efficacy. There is preliminary evidence that both agents do also work in other spondyloarthritis, such as undifferentiated spondyloarthritis. Ideally, both agents will be approved soon for the short-term treatment of severe, uncontrolled spondyloarthritis. In parallel, studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term antitumor necrosis factor therapy and whether radiologic progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can be largely prevented by appropriate screening. At it stands now, the benefits of antitumor necrosis factor therapy in ankylosing spondylitis seem to outweigh these shortcomings.

Antibodies, Monoclonal↗

PubMed2003

Novel approaches in the treatment of ankylosing spondylitis and other spondyloarthritides.

The therapeutic options for patients suffering from severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is now accumulating evidence that anti-TNF therapy is highly effective in SpA, especially in ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Based on the data recently published on what is now several hundred AS and PsA patients, this treatment seems to be even more effective than the same therapy in rheumatoid arthritis (RA). The anti-TNF-alpha agents currently available, infliximab (Remicade); Centocor), etanercept (Enbrel); Amgen) and adalimumab (Humira; Abbott), are approved for the treatment of RA in the US; infliximab and etanercept are approved in Europe. The situation in SpA is different to RA because there is an unmet medical need, especially in AS, since no therapies with disease-controlling antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, TNF blockers might even be considered as first-line immunosuppressive agents in patients with active AS and PsA who are not sufficiently treated by non-steroidal anti-inflammatory drugs and sulfasalazine, if peripheral arthritis is present. For infliximab, a dosage of 5 mg/kg at intervals between 6 and 12 weeks was necessary to constantly suppress disease activity; this is also a major aim of long-term treatment. No dose-finding studies have yet been performed. The standard dose of etanercept is 25 mg s.c. twice-weekly. No studies on adalimumab (standard RA dose 20 - 40 mg s.c. every 2 weeks) have yet been conducted in SpA. The efficacy of etanercept was first demonstrated in PsA and etanercept is now approved for this indication. A double-blind study has also been performed in AS, with similarly clearcut efficacy. There is preliminary evidence that both agents do also work in other SpA such as undifferentiated SpA. Infliximab has recently been approved for short-term treatment of severe uncontrolled AS; the approval for etanercept is pending. Studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis might be preventable but it remains to be shown whether patients benefit from long-term anti-TNF therapy and whether radiological progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. Tuberculosis can be mostly prevented if patients are checked for previous contact with tuberculosis. Currently, the benefits of anti-TNF therapy in AS seem to outweigh these shortcomings.

Animals↗

PubMed2003

Role of novel biological therapies in psoriatic arthritis: effects on joints and skin.

Psoriatic arthritis (PsA) is a partly debilitating disease that may affect small and large joints and the spine. Patients with PsA are divided into different subgroups according to joint involvement and their disease may be classified as part of the spectrum of spondyloarthritides or seronegative rheumatoid arthritis. Traditional treatment comprises nonsteroidal anti-inflammatory drugs, systemic and intra-articular corticosteroids and disease-modifying antirheumatic drugs such as sulfasalazine, methotrexate and cyclosporin. On the basis of the very recent studies performed in the US and Germany, patients with severe disease can be treated with anti-tumour necrosis factor (TNF) therapy. Biologicals such as etanercept and infliximab have been used successfully to treat PsA. While etanercept is a 75kD TNF receptor fusion protein that binds to TNFalpha and TNFbeta, infliximab is a chimeric monoclonal antibody that binds to TNFalpha both in its soluble form in the serum and on the cell membrane. Adalimumab is a fully humanised antibody recognising TNFalpha that has not been tested in PsA to date. Another biological agent, alefacept, is directed against the adhesion molecule lymphocyte function-associated antigen (LFA)-2, which is known to interfere with T-cell activation. Alefacept has been shown to be efficacious in a limited number of patients with PsA. Taken together, there has been definite recent progress in the treatment of PsA. Severely affected patients may especially have substantial benefit from therapy with biologicals directed against TNFalpha and other targets.

Alefacept↗

PubMed2002

Therapy of ankylosing spondylitis and other spondyloarthritides: established medical treatment, anti-TNF-alpha therapy and other novel approaches.

Therapeutic options for patients with more severe forms of spondyloarthritis (SpA) have been rather limited in recent decades. There is accumulating evidence that anti-tumor-necrosis-factor (anti-TNF) therapy is highly effective in SpA, especially in ankylosing spondylitis and psoriatic arthritis. The major anti-TNF-alpha agents currently available, infliximab (Remicade(R)) and etanercept (Enbrel(R)), are approved for the treatment of rheumatoid arthritis (RA) in many countries. In ankylosing spondylitis there is an unmet medical need, since there are almost no disease-modifying antirheumatic drugs (DMARDs) available for severely affected patients, especially those with spinal manifestations. Judging from recent data from more than 300 patients with SpA, anti-TNF therapy seems to be even more effective in SpA than in rheumatoid arthritis. However, it remains to be shown whether patients benefit from long-term treatment, whether radiological progression and ankylosis can be stopped and whether long-term biologic therapy is safe.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2002

Feature-based, automated segmentation of cerebral infarct patterns using T2- and diffusion-weighted imaging.

Diffusion-weighted imaging enables the diagnosis of cerebral ischemias very early, thus supporting therapies such as thrombolysis. However, morphology and tissue-characterizing parameters (e.g. relaxation times or water diffusion) may vary strongly in ischemic regions, indicating different underlying pathologic processes. As the determination of the parameters by a supervised segmentation is very time consuming, we evaluated whether different infarct patterns may be segmented by an automated, multidimensional feature-based method using a unified segmentation procedure. Ischemias were classified into 5 characteristic patterns. For each class, a 3D histogram based on T(2)- and diffusion-weighted images as well as calculated apparent diffusion coefficients (ADC) was generated from a representative data set. Healthy and pathologic tissue classes were segmented in the histogram as separate, local density maxima with freely shaped borders. Segmentation control parameters were optimized in a 3-step procedure. The method was evaluated using synthetic images as well as results of a supervised segmentation. For the analysis of cerebral ischemias, the optimal control parameter set led to sensitivities and specificities between 1.0 and 0.9.

Algorithms↗