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G R Burmester

Publications and source records attributed to G R Burmester.

At least 37 records · Page 2Linked to original sources
PubMed2003

[Pharmacotherapy of rheumatic diseases in the aged].

The optimal drug therapy of inflammatory rheumatic diseases is based on an individual concept of treatment combining several antirheumatic drugs with different modes of acting. In treating older patients this individual concept has to consider special conditions, as these patients often receive further medications due to different indications so that pharmacologic interactions and comorbidity have to be taken into account. Recently, new substances like COX-2-inhibitors, the new disease modifying antirheumatic drug (DMARD) Leflunomide and particularly the cytokine-blockers provide new and highly effective treatment options. The administration of these drugs in elderly patients is discussed.

Aged↗
PubMed2003

[Epidemiology and therapy of Lyme arthritis and other manifestations of Lyme borreliosis in Germany: results of a nation-wide survey].

AIM OF THE STUDY: Only little is known about the epidemiology of Lyme borreliosis in Germany. As an example, it is still unclear if there are regional differences in the incidence of Lyme disease in general or of certain clinical manifestations like Lyme arthritis. Moreover, standardization of diagnostic or therapeutic procedures does not exist. Therefore, a Germany-wide questionnaire-based survey was conducted in order to achieve more epidemiological data and to obtain more information about the diagnostic and therapeutic approaches of general practitioners and specialists. METHODS: A self-designed questionnaire was distributed along with two editions of the journal "Deutsches Arzteblatt" (which is delivered to every physician in Germany) and additionally by a pharmaceutical company. During the collection period from March 1, 1998 to February 28, 1999, patients with Lyme disease were reported and information was given about site of infection, diagnostic procedures, clinical symptoms, treatment, and outcome. RESULTS: Altogether 3935 patients were reported. Their mean age was 43.4 years with the peak incidences around the ages of 10 and 60 years. 37.3% of the questionnaires were sent in by general practitioners, 17.6% by dermatologists, 15.7% by pediatricians, 9.7% by internists, and 2.7% by neurologists. 83% of the patients did not have a special infecion risk. The most frequent clinical Lyme manifestation was erythema migrans (EM), which occurred in 50.9% of the patients. 21.3% suffered from general symptoms. Of special interest, 24.5% of the patients had Lyme arthritis (14.7% mon- or oligoarthritis, 9.8% polyarthritis). Therefore, arthritis was more frequently reported than neuroborreliosis (18.4%). Only 16% of the neuroborreliosis patients and 32% of the arthritis patients remembered having had an EM. 189 patients (4.8%) with lymphadenosis cutis benigna and 100 patients (2.5%) with acrodermatitis chronica atrophicans were reported. In 80.4% of the patients, positive Lyme serology was detected. In a few cases, the diagnosis was established by isolation of borreliae, PCR or histology. 3754 patients were treated by antibiotics. The most frequently used compounds were doxycycline (50.4%), followed by ceftriaxone (22.4%), amoxicillin (13.6%), penicillin (7%), and erythromycin (4.2%) with differences depending on clinical manifestations and specialization of the prescribing physician. In less than 10% of the cases, not evaluated or recommended therapeutic procedures were performed. DISCUSSION: Lyme disease is endemic throughuot Germany. The most frequent manifestations are EM, followed by Lyme arthritis and neuroborreliosis. Less than one third of patients suffering from disseminated or chronic Lyme disease remembered an EM. Most of the physicians taking part in this survey follow treatment recommendations concerning choice of antibiotics and treatment durations.

Adolescent↗
PubMed2003

Efficacy and safety of the fully human anti-tumour necrosis factor alpha monoclonal antibody adalimumab (D2E7) in DMARD refractory patients with rheumatoid arthritis: a 12 week, phase II study.

OBJECTIVES: To evaluate efficacy, dose response, safety, and tolerability of adalimumab (D2E7) in disease modifying antirheumatic drug (DMARD) refractory patients with longstanding, active rheumatoid arthritis (RA). METHODS: During a 12 week, double blind, placebo controlled study, 284 patients were randomly allocated to receive weekly subcutaneous injections of adalimumab 20 mg (n = 72), 40 mg (n = 70), or 80 mg (n = 72) or placebo (n = 70) without concomitant DMARDs. RESULTS: Adalimumab significantly improved the signs and symptoms of RA for all efficacy measures. ACR20 responses with adalimumab were significant at each assessment versus placebo (p</=0.01). Additionally, ACR responses with adalimumab were achieved more rapidly than with placebo, with 82/115 (71%) of the ultimate ACR20 response rate to adalimumab treatment achieved at week 2. At week 12, for adalimumab 20, 40, and 80 mg, ACR20 response rates were 50.7%, 57.1%, and 54.2%, respectively, versus 10.0% for placebo (p</=0.001 for all comparisons); ACR50 rates were 23.9%, 27.1%, and 19.4%, respectively, versus 1.4% for placebo (p</=0.001 for all comparisons); and ACR70 rates were 11.3%, 10.0%, and 8.3%, respectively, versus 0.0% for placebo (p</=0.05 for all comparisons). All adalimumab doses significantly improved all ACR core criteria at all assessments. The 40 mg and 80 mg doses provided similar benefit. Adalimumab at all doses was generally well tolerated, with only mild or moderate adverse events. Completion rates were 87% for adalimumab and 67% for placebo. CONCLUSIONS: Adalimumab given as monotreatment to patients with longstanding, severe RA refractory to traditional DMARDs produced a rapid, sustained response and was safe and well tolerated, with no dose limiting side effects.

Adalimumab↗
PubMed2003

Anakinra: the first interleukin-1 inhibitor in the treatment of rheumatoid arthritis.

Rheumatoid arthritis is an immunologically mediated inflammation of joints of unknown aetiology and often leads to disability. This inflammatory process may also involve extra-articular connective tissue. New therapeutic approaches have been made by inhibition of proinflammatory cytokines. Interleukin-1 (IL-1) is regarded as one of the most important mediators in the development of synovialitis. In this article, anakinra (Kineret), the first direct antagonist to IL-1, is discussed, in particular the efficacy and safety data from clinical trials. More than 10,000 patients have been treated with anakinra with significant improvement of inflammation and pain; the rate of radiologically visible progressive joint damage was significantly reduced. Among the adverse events, injection site reactions were most frequent, followed by a mild increase in infections. No activation of tuberculosis, as in tumour necrosis factor-alpha antagonist administration, has so far been reported.

Antirheumatic Agents↗
PubMed2002

Human platelet supernatant promotes proliferation but not differentiation of articular chondrocytes.

The objective of the study was to evaluate the growth-promoting activity of human platelet supernatant on primary chondrocytes in comparison with fetal calf serum (FCS) supplemented cell culture medium. Furthermore, the differentiation potential of platelet supernatant was determined in three-dimensional artificial cartilage tissues of bovine articular chondrocytes. Proliferation of articular and nasal septal chondrocytes was assayed by incorporation of BrdU upon stimulation with ten different batches of human platelet supernatant. On bovine articular chondrocytes, all these batches were at least as growth-promoting as FCS. On nasal septal chondrocytes, nine out of ten batches revealed increased or equivalent mitogenic stimulation compared with medium supplemented with FCS. Three-dimensional culture and subsequent histological analysis of matrix formation were used to determine the differentiation properties of platelet supernatant on articular chondrocytes. Human platelet supernatant failed to induce the deposition of typical cartilage matrix components, whereas differentiation and matrix formation were apparent upon cultivation of articular chondrocytes with FCS. Proliferation assays demonstrated that human platelet supernatant stimulates growth of articular and nasal septal chondrocytes; however, platelet supernatant failed to stimulate articular chondrocytes to redifferentiate in three-dimensional chondrocyte cultures. Therefore platelet lysate may be suitable for chondrocyte expansion, but not for maturation of tissue-engineered cartilage.

Blood Platelets↗
PubMed2002

[New aspects of molecular biology diagnosis. Array technology and expression profile for characterization of rheumatic diseases].

Increasing availability of high throughput technologies, exponentially growing information about the human genome and gene expression, and the growing global network of databases on systematic biomedical information will change our view on inflammatory rheumatic diseases in a revolutionary way. Several research laboratories have already generated initial extensive datasets on gene expression analysis. Application of this technique has demonstrated that in addition to a precise analysis, verification and validation of the results also on the level of cell populations, a meticulous characterization of the patients according to current conventional clinical, laboratory, imaging and histological standards is essential. For functional interpretation, in vitro tests, animal models and therapeutic studies will provide further information. Bioinformatic structuring and development is needed for the large amounts of data. After an initial genome-wide screening, the objective is to identify those genes, which will allow characterization of the disease, classification according to molecular pathophysiology, evaluation of the prognosis and prediction of the correct and most potent therapeutic regimen. Derived from the improved knowledge about the molecular mechanisms, new and--as to expect--the crucial approaches for an effective therapy against chronic inflammation, organ destruction and pathological immune response in rheumatic diseases will emerge.

Autoantibodies↗
PubMed2002

Prospective two year follow up study comparing novel and conventional imaging procedures in patients with arthritic finger joints.

OBJECTIVE: To carry out a prospective two year follow up study comparing conventional radiography, three-phase bone scintigraphy, ultrasonography (US), and three dimensional (3D) magnetic resonance imaging (MRI) with precontrast and dynamic postcontrast examination in detecting early arthritis. The aim of the follow up study was to monitor the course of erosions during treatment with disease modifying antirheumatic drugs by different modalities and to determine whether the radiographically occult changes like erosive bone lesions of the finger joints detected by MRI and US in the initial study would show up on conventional radiographs two years later. Additionally, to study the course of soft tissue lesions depicted in the initial study in comparison with the clinical findings. METHODS: The metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints (14 joints) of the clinically more severely affected hand (soft tissue swelling and joint tenderness) as determined in the initial study of 49 patients with various forms of arthritis were examined twice. The patients had initially been divided into two groups. The follow up group I included 28 subjects (392 joints) without radiographic signs of destructive arthritis (Larsen grades 0-1) of the investigated hand and wrist, and group II (control group) included 21 patients (294 joints) with radiographs showing erosions (Larsen grade 2) of the investigated hand or wrist, or both, at the initial examination. RESULTS: (1) Radiography at the two year follow up detected only two erosions (two patients) in group I and 10 (nine patients) additional erosions in group II. Initial MRI had already detected both erosions in group I and seven (seven patients) of the 10 erosions in group II. Initial US had depicted one erosion in group I and four of the 10 erosions in group II. (2) In contrast with conventional radiography, 3D MRI and US demonstrated an increase in erosions in comparison with the initial investigation. (3) The abnormal findings detected by scintigraphy were decreased at the two year follow up. (4) Both groups showed a marked clinical improvement of synovitis and tenosynovitis, as also shown by MRI and US. (5) There was a striking discrepancy between the decrease in the soft tissue lesions as demonstrated by clinical findings, MRI, and US, and the significant increase in erosive bone lesions, which were primarily evident at MRI and US. CONCLUSIONS: Despite clinical improvement and a regression of inflammatory soft tissue lesions, erosive bone lesions were increased at the two year follow up, which were more pronounced with 3D MRI and less pronounced with US. The results of our study suggest that owing to the inadequate depiction of erosions and soft tissue lesions, conventional radiography alone has limitations in the intermediate term follow up of treatment. US has a high sensitivity for depicting inflammatory soft tissue lesions, but dynamic 3D MRI is more sensitive in differentiating minute erosions.

Adult↗
PubMed2002

Shwartzman phenomenon in a patient with active systemic lupus erythematosus preceding fatal disseminated intravascular coagulation.

The recurrence of widespread and diverse vascular lesions is a hallmark of systemic lupus erythematosus (SLE). Inflammatory and thrombotic mechanisms almost invariably associated with circulating antiphospholipid antibodies play a role in the pathogenesis of SLE-related vascular disease. Both mechanisms can coexist in the same patient. Vasculitis is most commonly induced by the local deposition of immune complexes. However, some SLE patients have an inflammatory complement-mediated vascular injury in the absence of immune complex deposition. We report on a fatal case of disseminated intravascular coagulation (DIC) in a young woman with active SLE. Hemorrhagic lesions due to localized intravascular coagulation (Shwartzman phenomenon) preceded disseminated intravascular coagulation accompanied by disseminated cardiac necrosis. Immune complex 'independent' and other mechanisms of vascular injury and states of hypercoagulability will be discussed.

Adult↗
PubMed2001

Gastrointestinal toxic side effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2-specific inhibitors.

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation but are frequently associated with gastrointestinal side effects, including life-threatening bleeding or perforation of gastroduodenal ulcers. Conventional NSAIDs are nonselective inhibitors of two isoforms of cyclooxygenase (COX): COX-1 and COX-2. The inhibition of COX-1 is believed to be responsible for inducing mucosal injury primarily by impairing prostaglandin-dependent mucosal protective mechanisms. The latest development in reducing the incidence of ulcers and ulcer complications associated with conventional NSAIDs is the use of recently approved COX-2-specific inhibitors (CSIs). This article critically reviews the data on gastrointestinal toxic side effects for conventional NSAIDs without as well as with prevention therapy. In addition, we compare these data with those for the CSIs, namely, celecoxib and rofecoxib. Finally, we offer recommendations on the clinical use of these drugs, emphasizing the need to balance clinical effectiveness with the avoidance of potential gastrointestinal side effects.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Insights from a novel three-dimensional in vitro model of lyme arthritis: standardized analysis of cellular and molecular interactions between Borrelia burgdorferi and synovial explants and fibroblasts.

OBJECTIVE: To develop a novel 3-dimensional (3-D) in vitro model of Lyme arthritis to use in the study of the interactions between Borrelia burgdorferi (Bb) and human synovial host cells with respect to phagocytosis and potential persistence of Bb as well as the induction of proinflammatory cytokines and chemokines. METHODS: Two distinct culture systems, consisting of synovial membrane explants or interactive synovial cells embedded in 3-D fibrin matrices, were chosen. Both systems were artificially infected with Bb, and the interactions between Bb and synovial tissue/cells were studied by histology, immunohistochemistry, and electron microscopy. Functional analyses included the induction/secretion of cytokines by Bb in the model system. RESULTS: Both culture systems proved to be stable and reproducible. The host cells and spirochetes showed high levels of viability and maintained their physiologic shape for >3 weeks. Bb invaded the synovial tissue and the artifical matrix in a time-dependent manner. Host cells were activated by Bb, as indicated by the induction of interleukin-1beta and tumor necrosis factor alpha. Electron microscopic analysis revealed Bb intracellularly within macrophages as well as synovial fibroblasts, suggesting that not only professional phagocytes, but also resident synovial cells are capable of phagocytosing Bb. Most interestingly, the uptake of the spirochetes appeared to cause severe damage of the synovial fibroblasts, since the majority of these cells displayed ultrastructural features of disintegration. CONCLUSION: A novel 3-D in vitro model has been established that allows the study of distinct aspects of Lyme arthritis under conditions that resemble the pathologic condition in humans. This reproducible, standardized model supplements animal studies and conventional 2-D cultures. The disintegration of synovial fibroblasts containing Bb or Bb fragments challenges the concept of an intracellular persistence of Bb and may instead reflect a mechanism that contributes to the inflammatory processes characteristic of Lyme arthritis.

Borrelia burgdorferi Group↗
PubMed2001

The stress protein BiP is overexpressed and is a major B and T cell target in rheumatoid arthritis.

OBJECTIVE: The ubiquitously expressed intracellular protein formerly designated p68 has been identified as autoantigen at both the antibody and the T cell level in rheumatoid arthritis (RA). METHODS: We used 2 independent approaches, Edman degradation and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry, to characterize p68, and we compared its features with those of the endoplasmic reticulum stress protein BiP. RESULTS: In synovial sections from RA patients, BiP was highly overexpressed as compared with control sections. Under in vitro stress conditions, BiP was found to translocate to the nucleus and the cell surface. BiP-specific autoantibodies were present in 63% of 400 RA patients, in 7% of 200 patients with other rheumatic diseases, and in none of the healthy subjects. Thus, BiP-specific autoantibodies represent a new diagnostic marker in RA. Furthermore, we found that BiP-specific T cell reactivity was altered in RA. In healthy individuals and patients with other rheumatic diseases, BiP-reactive T cells were undetectable. In RA, overt T cell reactivity to BiP was observed or could be induced by specifically blocking antigen presentation to potentially regulatory T cells. CONCLUSION: Since overexpression of BiP has been shown to decrease the sensitivity of cells to killing by cytotoxic T cells, BiP overexpression and BiP-specific autoimmunity may be involved in the pathogenesis of RA.

Arthritis, Rheumatoid↗
PubMed2001

Strong acceleration of murine lupus by injection of the SmD1(83-119) peptide.

OBJECTIVE: The mechanisms of IgG anti-double-stranded DNA (anti-dsDNA) antibody induction are incompletely understood. We recently demonstrated a high prevalence of autoantibodies to the C-terminus of SmD1 in patients with systemic lupus erythematosus (SLE) that was closely associated with anti-dsDNA reactivity. The aim of the present study was to analyze the influence of the SmD1 C-terminus on the generation of pathogenic anti-dsDNA antibodies in a murine model of SLE. METHODS: Female lupus-prone prenephritic (NZB x NZW)F1 mice (NZB/NZW mice) as well as female control BALB/c, NZW, and (BALB/c x NZW)F, mice (CWF1 mice) were subcutaneously injected with keyhole limpet hemocyanin (KLH)-coupled SmD1(83-119). Controls received injections of recombinant SmD1 (rSmD1), KLH-rSmD1, KLH-coupled randomized peptide of SmD1(83-119), ovalbumin, or saline. Animals were monitored for survival and proteinuria and for levels of plasma creatinine, urea, and autoantibodies. In addition, histologic examinations were performed and T cell responses against SmD1(83-119) peptide and rSmD1 protein were determined in SmD1(83-119)-treated and -untreated NZB/NZW mice. RESULTS: Immunization with KLH-SmD1(83-119), but not with control peptide, significantly accelerated the natural course of lupus in NZB/NZW mice, with premature renal failure and increased development of anti-dsDNA antibodies. Control strains of mice remained healthy, with no relevant anti-SmD1(83-119) antibodies detectable even after immunization. In contrast to findings in control mice, a T cell response against SmD1(83-119) was already present in unmanipulated NZB/NZW mice, and this response was further amplified after immunization. CONCLUSION: The SmD1(83-119) peptide can influence the pathogenic anti-dsDNA response in the NZB/NZW murine lupus model. The data suggest that an SmD1(83-119)-specific T cell response is critical. Therefore, modulation of these autoantigen-specific T cells by tolerance induction may provide a therapeutic approach to specific immunosuppression in lupus.

Animals↗