Search PubMed⌕ Search

Biomedical subjects

U Müller-Ladner

Publications and source records attributed to U Müller-Ladner.

At least 19 recordsLinked to original sources

Resistin in rheumatoid arthritis synovial tissue, synovial fluid and serum.

BACKGROUND: Resistin is a newly identified adipocytokine which has demonstrated links between obesity and insulin resistance in rodents. In humans, proinflammatory properties of resistin are superior to its insulin resistance-inducing effects. OBJECTIVES: To assess resistin expression in synovial tissues, serum and synovial fluid from patients with rheumatoid arthritis, osteoarthritis and spondylarthropathies (SpA), and to study its relationship with inflammatory status and rheumatoid arthritis disease activity. METHODS: Resistin expression and localisation in synovial tissue was determined by immunohistochemistry and confocal microscopy. Serum and synovial fluid resistin, leptin, interleukin (IL)1beta, IL6, IL8, tumour necrosis factor alpha, and monocyte chemoattractant protein-1 levels were measured. The clinical activity of patients with rheumatoid arthritis was assessed according to the 28 joint count Disease Activity Score (DAS28). RESULTS: Resistin was detected in the synovium in both rheumatoid arthritis and osteoarthritis. Staining in the sublining layer was more intensive in patients with rheumatoid arthritis compared with those with osteoarthritis. In rheumatoid arthritis, macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) but not T lymphocytes (CD3) showed colocalisation with resistin. Synovial fluid resistin was higher in patients with rheumatoid arthritis than in those with SpA or osteoarthritis (both p<0.001). In patients with rheumatoid arthritis and SpA, serum resistin levels were higher than those with osteoarthritis (p<0.01). Increased serum resistin in patients with rheumatoid arthritis correlated with both CRP (r=0.53, p<0.02), and DAS28 (r=0.44, p<0.05), but not with selected (adipo) cytokines. CONCLUSION: The upregulated resistin at local sites of inflammation and the link between serum resistin, inflammation and disease activity suggest a role for resistin in the pathogenesis of rheumatoid arthritis.

Adult↗

[Chronic anaemia in a patient with hereditary haemorrhagic telangiectasia and juvenile gastric polyposis].

HISTORY: A 52-year-old woman with chronic anaemia presented with recurrent epistaxis, telangiectasias and haemangiomas, suggesting the presence of hereditary haemorrhagic telangiectasia (Osler-Rendu-Weber disease). Moreover, previous investigations had also shown multiple polyps of the stomach. INVESTIGATIONS: A severe microcytic iron deficiency anaemia in combination with hepatic haemangiomas and duodenal angio-dysplasia were detected. Gastrointestinal endoscopy revealed multiple juvenile polyps in the gastric fundus and body, indicating the diagnosis of hereditary haemorrhagic telangiectasia in combination with juvenile polyposis. THERAPY AND COURSE: A gastrectomy was performed because of recurrent gastrointestinal bleeding and the malignant potential of juvenile gastric polyposis. Histopathology confirmed the diagnosis and did not reveal any malignancy. CONCLUSION: The association of hereditary haemorrhagic telangiectasia and juvenile polyposis, as seen in this patient, has been reported repeatedly. A diagnosis of one of the described entities should initiate the screening for evidence of the other one to prevent (life-threatening) complications.

Anemia, Iron-Deficiency↗

Role of adipose tissue as an inflammatory organ in human diseases.

Reviews on the inflammatory role of adipose tissue outside the field of metabolism are rare. There is increasing evidence provided by numerous basic research studies from nearly all internal medicine subspecializations that adipocytes and adipocytokines are involved in primary inflammatory processes and diseases. Therefore, it is the aim of the present review to discuss and to summarize the current knowledge on the inflammatory role of adipocytokines and special types of regional adipocytes such as retroorbital, synovial, visceral, subdermal, peritoneal, and bone marrow adipocytes in internal medicine diseases. Future clinical and therapeutic implications are discussed.

Adipocytes↗

[Therapy for secondary arthropathies: from psoriasis and Reiter's disease to hemochromatosis].

Arthralgia is one of the most common complaints in Western society. The classification of joint diseases with respect to genesis is crucial for the determination of adequate treatment. For inflammatory arthropathies, treatment options have expanded significantly over the last decade. This review summarizes the current treatment of psoriatic arthritis and Reiter's disease, both belonging to the spectrum of seronegative spondyloarthropathies. Regardless of our increasing knowledge of chondrogenesis, the treatment of osteoarthritis is still more or less symptomatic. Premature age of onset and the atypical joint distribution of osteoarthritis should bring metabolic diseases, for example hemochromatosis, into consideration.

Anti-Inflammatory Agents↗

[Evidence-based therapy of Raynaud's syndrome].

Raynaud's syndrome has a prevalence of 3-5% in the general population. Despite its high frequency, the majority of available therapies have not been validated in randomized controlled trials. Effective therapies with a high level of evidence include the calcium channel blocker nifedipine. As analyzed by meta-analyses, nifedipine showed improvement of the peripheral circulation, as well as reduction of both the intensity and frequency of attacks in patients with primary and secondary Raynaud's syndrome as compared to placebo. Similar results in a metaanalysis were obtained for intravenous infusions of iloprost in patients with secondary Raynaud's phenomenon associated with systemic sclerosis. In addition, intravenous infusions of iloprost improved healing of fingertip ulcers in patients with systemic sclerosis. Therapies with significant effects in single randomized controlled trials include angiotensin II-receptor type 1 antagonists (losartan), the calcium channel blockers felodipine und amlodipine, serotonin-reuptake-inhibitors (fluoxetine) und phosphodiesterase-V-inhibitors (sildenafil, vardenafil). However, the results for these promising substances have to be confirmed in long-term trials with larger patient numbers.

3',5'-Cyclic-GMP Phosphodiesterases↗

[Systemic sclerosis--a challenge in rheumatology].

The connective tissue disease systemic sclerosis (SSc) is still a challenge to every rheumatologist. SSc is characterized by progressing fibrosis of the skin and internal organs, abnormal activation of the immune system and distinct changes in microcirculation. Although it is a rare disease with a prevalence of about 20:100,000 one may come across it in daily practice. SSc is classified into limited and diffuse forms. Both entities usually involve internal organs. Life expectancy is limited and depends predominantly on the extent of the organs involved. Therefore, it is essential to diagnose SSc early and to identify and closely monitor the organs involved.

Antibodies, Antinuclear↗

Connective tissue diseases and pregnancy.

Connective tissue diseases (CTD) such as systemic lupus erythematosus diffuse or limited systemic sclerosis and numerous others affect women frequently during the childbearing period. Every pregnancy in a patient with CTD should be regarded as high-risk pregnancy, and requires intensive monitoring and immediate treatment of clinical problems. For these reasons, for women suffering from CTD, who are pregnant or who intend to become pregnant, an interdisciplinary setting addressing all aspects of rheumatology, ob-gyn and neonatalogy needs to be provided. This setting includes particular diagnostic tools and laboratory parameters prior to and during pregnancy as well as in the post-partal period. Aside overt organ dysfunction, key problems in pregnant CTD patients consist mainly of haemostaseological problems such as antiphospholipid antibodies, neonatal lupus erythematosus, congenital heart block and drug therapy of the underlying disease, which will be outlined in this review.

Connective Tissue Diseases↗

Vasculitis of the aortic arch and cardiac valves as the cause of relapsing fever of unknown origin in an elderly, white man.

Here, we report the case of fever of unknown origin (FUO) in a 77-year-old white man. The patient presented with a 3-week history of fever (between 38.5 and 39 degrees C) and general malaise. These symptoms had occurred about five to seven times during the past 30 years, and despite repeated hospitalizations, no diagnosis was made. Physical examination did not reveal any specific signs of infection nor did the patient fulfill the criteria for any rheumatic disease including vasculitides. Blood chemistry showed a greatly elevated C-reactive protein (CRP; 158.2 mg/l) and an erythrocyte sedimentation rate >100 mm, indicating an active inflammatory process, and leukocytes were significantly elevated (20,000/mul). Rheumatological parameters showed only nonspecific changes. Finally, a 2-[(18)F]-fluoro-2-deoxy-D: -glucose-positron emission tomography was performed, revealing a markedly enhanced glucose uptake in the ascending aorta and the cardiac valves, indicating vasculitis as the cause of FUO in this patient. Based on this finding, treatment was started with corticosteroids, and 2 days after the initiation of treatment, the patient had normal body temperature, and after 5 days, CRP values had returned to normal. After tapering and final complete removal of steroid treatment, the patient was still free of symptoms, hence no disease-modifying antirheumatic drug therapy was necessary.

Aged↗

Increase in bone mineral density of patients with rheumatoid arthritis treated with anti-TNF-alpha antibody: a prospective open-label pilot study.

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with rheumatoid arthritis (RA; without osteoporosis) treated with infliximab. METHODS: Twenty-six patients (19 women, seven men) aged 54.2 yr (range 27-75), with persistently active RA despite a high dose of non-steroidal anti-inflammatory drugs and/or treatment with methotrexate or leflunomide, were studied. Mean duration of disease was 9.8 yr. Patients receiving or having received bisphosphonates or hormone replacement therapy were excluded. The patients were treated with 3.5 mg/kg infliximab at weeks 0, 2, 6 and then every 6-8 weeks. Lumbar and femoral BMD was measured by dual-energy X-ray absorptiometry at baseline and 12 months later. Serum osteocalcin and serum crosslaps were measured at baseline (week 0) and after 12 months. Twelve patients were taking calcium (1 g/day) and vitamin D (800 IU/day). Twenty patients were receiving methotrexate (mean dose 12.5 mg/day), six patients were receiving leflunomide (mean dose 20 mg/day) and nine patients were concomitantly receiving corticosteroids at a mean daily dose of 10 mg. RESULTS: After 12 months of infliximab therapy, there was a significant increase in BMD in the spine (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.001) and the femoral neck (BMD, P < 0.001; T-score, P < 0.001; Z-score, P < 0.01). With regard to the root mean square average, there was a significant increase in BMD at the left femoral neck (11.6% for a root mean square of 6%) but only a trend towards improvement in the spine (2.7% for a root mean square of 4%) during the study period. There was a significant increase in osteocalcin serum levels between baseline and after 12 months (P < 0.01) and a significant decrease in the marker for bone resorption (P < 0.01) but no change in serum calcium was observed. However, the changes in markers of bone metabolism and BMD were not correlated. CONCLUSION: The data support the hypothesis that anti-TNF therapy may exert beneficial effects on bone metabolism in RA patients.

Absorptiometry, Photon↗

Association of 1.25 vitamin D3 deficiency, disease activity and low bone mass in ankylosing spondylitis.

Vertebral fractures due to osteoporosis are a common but frequently unrecognized complication in established ankylosing spondylitis (AS). It is known that inflammatory activity in rheumatic diseases (i.e., proinflammatory cytokines) itself plays a possible role in the pathophysiology of bone loss. The aim of this study was to analyze whether inflammatory activity and an alteration of the vitamin D metabolism play a substantial role in the loss of bone mass in AS. In this cross-sectional study, 58 patients with established AS and an age- and sex-matched control group were examined. The vitamin D status was investigated, as was, in parallel, the relationship to disease activity (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], Bath Ankylosing Spondylitis Disease Activity Index [BASDAI]), markers of bone metabolism (parathyroid hormone [PTH], 1.25 vitamin D3, 25 vitamin D3), calcium, bone alkaline phosphatase (bone-AP), urine cross-links, and plasma tumor necrosis factor alpha (TNFalpha). Bone mineral density was measured by quantitative computed tomography (QCT) of the lumbar spine. Osteoporosis was diagnosed in early as well as in progressive stages of AS (23/58=39.6%). Furthermore, serum levels of 1.25 vitamin D3 and PTH were negatively correlated with disease activity and TNFalpha. The excretion of cross-links showed a positive correlation with disease activity and TNFalpha, and 1.25 vitamin D3 and PTH were positively correlated with bone-AP. TNFalpha also positively correlated with disease activity. AS patients with osteoporosis showed significantly increased CRP, ESR, cross-links and PTH and a significantly decreased 1.25 D3. Osteoporosis is frequent in AS and high disease activity is associated with an alteration in vitamin D metabolites and increased levels of bone resorption in active AS. Our findings propose a close association of BMD, bone metabolism and inflammatory activity, possibly related to vitamin D inflammation interactions.

Adolescent↗

[Rheumatoid arthritis].

The development of novel anti-rheumatic drugs revolutionizes currently therapeutic strategies and diagnostic management of patients with rheumatoid arthritis, facilitating the goal of true remission instead of only symptomatic treatment as in former years. Since early treatment is known to be crucial for the longterm outcome, imaging modalities such as magnetic resonance imaging and high-frequency ultrasonography including Doppler sonography, which allow direct visualization of very early pathologic alterations of synovitis, or even initial destruction, become increasingly important. Besides the established therapy with methotrexate, new drugs such as leflunomide or the use of various combination therapies have been successfully introduced into the therapeutic armamentarium. Especially the introduction of cytokine-antagonists such as TNF-a inhibitors target the aim of remission. In addition, the upcoming therapeutic agents, which influence very effectively the inflammatory and destructive process need also to be integrated into the concert of different therapeutic strategies in the management of patients with rheumatoid arthritis, which includes the mandatory complementary factors such as physiotherapy, ergotherapy and orthopedic surgery.

Adult↗

Balneotherapy in rheumatic diseases--an overview of novel and known aspects.

Balneotherapeutic applications to treat rheumatic diseases have a long-term tradition and are based on established scientific principles, and the majority of rheumatic diseases most frequently include balneotherapy. However, as other therapeutic strategies, balneological interventions require scientific proof of their effect and efficacy. Notably, recent studies providing evidence of the thermic and chemical effects on the immune system and cytokine milieu have enforced the revival of the traditional balneological interventions. This review provides an overview of the known as well as the novel aspects of balneotherapy and their clinical relevance in the treatment of rheumatic diseases.

Balneology↗

Molecular imaging: novel tools in visualizing rheumatoid arthritis.

Molecular imaging is a rapidly emerging field in biomedical research, aiming at the visualization, characterization and quantification of molecular and cellular processes non-invasively within intact living organisms. To sense biological processes such as gene expression, angiogenesis, apoptosis or cell trafficking in vivo, imaging reporter agents that interact specifically with molecular targets and appropriate imaging systems are currently under development. In rheumatoid arthritis, these novel tools will be used to evaluate physiological and pathophysiological processes, to facilitate diagnosis and monitor therapeutic regimens, to enable reliable prognosis and to support the development of new therapies. In this review, we summarize the basic principles of molecular imaging, such as the development of molecular imaging agents, the actual capabilities of different imaging modalities and the most recent advances in molecular imaging, demonstrating the potential of this technology. With regard to their applicability in rheumatic diseases, we discuss potential molecular targets, current experimental approaches and the future prospects for molecular imaging in rheumatoid arthritis.

Animals↗