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Biomedical subjects

B Hellmich

Publications and source records attributed to B Hellmich.

At least 19 recordsLinked to original sources
PubMed2006

[Diagnosis und therapy of ANCA-associated vasculitis].

The diagnosis of ANCA-associated vasculitides (AAV) consists of clinical symptoms, results of technical procedures and a characteristic histology. The diagnostic workup should focus on the prominent clinical symptoms and should involve an interdisciplinary team of specialists. The therapy is divided into induction and maintenance treatment. Cyclophosphamid remains standard therapy for the induction of remission, whereas azathioprine, methotrexate and leflunomide are often used for maintenance therapy. The introduction of a stage-adapted treatment has contributed to a significant improvement of the long-time prognosis of patients with AAV.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2006

Bosentan for severe pulmonary arterial hypertension related to systemic sclerosis with interstitial lung disease.

BACKGROUND: The oral dual endothelin (ET) antagonist bosentan has been established as a cornerstone in the treatment of pulmonary arterial hypertension (PAH). ET is believed to be a key pathogenic mediator in systemic sclerosis (scleroderma, SSc), causing fibrotic, hypertrophic and inflammatory processes. PAH is one of the resulting deleterious effects in approximately 15% of SSc patients. MATERIALS AND METHODS: This was an open-label prospective observational study of 8 patients aged 34-73 years with symptomatic, severe PAH related to SSc (WHO class III or IV) and mostly, lung fibrosis. PAH diagnosis was ascertained with echocardiography or right heart catheterization. Patients were treated on top of diuretics and anticoagulants with bosentan 62.5 mg twice daily for 4 weeks followed by a maintenance dose of 125 mg twice daily. RESULTS: The mean 6-minute walk distance (data available in 7 patients) increased from 71.9 (+/- 54.7) m at baseline to 191.9 (+/- 104.6) m after 3 months (P = 0.012) and to 202.6 (+/- 108.1) m after 6 months (P = 0.011), respectively. Six of 8 patients improved in the 6-minute walk test, and these 6 patients also improved in World Health Organization functional class. Two patients did not sufficiently respond to bosentan therapy; one of them died. The tolerability of bosentan was good, and there were no discontinuations. Elevations of hepatic aminotransferases above 3 times the upper limit of normal were not recorded. CONCLUSION: Bosentan treatment was well tolerated in this cohort of SSc patients with interstitial lung disease and was effective for treatment of severe PAH in the majority of patients.

Adult↗
PubMed2006

Head and neck manifestations of Wegener's granulomatosis.

Wegener's Granulomatosis (WG) is a necrotizing granulomatous angiitis that presents the classic ELK triad of ear, nose, throat (E), lung (L), and kidney (K) involvement. Its potential rapid and fatal outcome makes the early recognition--before irreversible organ involvement occurs--mandatory. The aetiology is still unknown. Today, immunosuppressive therapy makes WG a treatable disease with a chronically relapsing course. The otorhinolaryngologist plays an important role in early diagnosis of WG, because in up to 95% of the patients initial WG symptoms are observed in the head and neck region. The majority of these patients show nasal or sinunasal involvement. Common manifestations are sinusitis, crusting of the nose, and development of saddle nose deformity. Other head and neck problems are middle and inner ear symptoms and subglottic stenosis. Follow up and activity assessment of the disease are also important roles to play for the otorhinolarygologist.

Biopsy↗
PubMed2005

Lack of efficacy of rituximab in Wegener's granulomatosis with refractory granulomatous manifestations.

OBJECTIVE: To investigate the safety and efficacy of rituximab (RTX) in patients with refractory Wegener's granulomatosis (WG). PATIENTS AND METHODS: Eight consecutive patients with active refractory WG were included. In all patients disease activity had persisted despite standard treatment with cyclophosphamide and prednisolone, as well as tumour necrosis factor alpha blockade 3 months before inclusion in the study. Patients had particular granulomatous manifestations like retro-orbital granulomata (n=5), nodules of the lungs (n=1), and subglottic stenosis (n=2). RTX was given intravenously every 4th week in combination with the standard treatment in five patients and with methotrexate in two others. Disease extent and activity were monitored clinically by interdisciplinary care, immunodiagnostics (ANCA serology, B cells by flow cytometry), and magnetic resonance imaging. RESULTS: Beneficial response and a reduction in disease activity were seen in three patients, two of whom went into complete remission. In three other patients, disease activity remained unchanged while the disease progressed in the remaining two patients. In all patients peripheral blood B cells fell to zero during treatment with RTX. cANCA titres remained unchanged in all except one patient. CONCLUSION: In this pilot study, B lymphocyte depletion was not associated with a change of the ANCA titres or obvious clinical improvement of refractory granulomatous disease in patients with WG. Further studies are needed to evaluate the role of RTX in WG.

Adult↗
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

Variations in performance characteristics of commercial enzyme immunoassay kits for detection of antineutrophil cytoplasmic antibodies: what is the optimal cut off?

BACKGROUND: Previous studies have shown considerable variation in diagnostic performance of enzyme linked immunosorbent assays (ELISAs) for measuring antineutrophil cytoplasmic antibodies (ANCA) specific for proteinase 3 (PR3) and myeloperoxidase (MPO). OBJECTIVE: To analyse the performance characteristics of different commercially available direct ANCA ELISA kits. METHODS: ELISA kits for detecting PR3-ANCA and MPO-ANCA from 11 manufacturers were evaluated. Serum samples were taken from patients with Wegener's granulomatosis (15), microscopic polyangiitis (15), other vasculitides (10), and controls (40). RESULTS: were compared with data obtained by indirect immunofluorescence (IFT). The diagnostic performance of the tests was analysed and compared by receiver operating characteristic (ROC) curve analysis.Results: Applying the manufacturers' cut off resulted in great variation in sensitivity of the commercial PR3-ANCA kits for diagnosing Wegener's granulomatosis (ranging from 13.3% to 66.7%), and of the MPO-ANCA kits for diagnosing microscopic polyangiitis (ranging from 26.7% to 66.7%). Specificities were relatively constant (from 96.0% to 100%). IFT was superior to all ELISAs (C-ANCA for Wegener's granulomatosis: sensitivity 73.3%, specificity 98%; P-ANCA for microscopic polyangiitis: sensitivity 86.7%, specificity 98%). The sensitivities of PR3-ANCA and MPO-ANCA ELISA kits were increased by lowering the cut off values. This reduced specificity but increased overall diagnostic performance. CONCLUSIONS: The low sensitivity of some commercial kits reflects the high cut off levels recommended rather than methodological problems with the assays. Comparative analyses using sera from well characterised patients may help identify optimum cut off levels of commercial ANCA ELISA tests, resulting in better comparability of results among assays from different manufacturers.

Adult↗
PubMed2005

[Early diagnosis of chronic systemic inflammatory disorders].

Functionally relevant damage caused by chronic systemic inflammatory disorders of autoimmune and/or unknown origin can be reduced or sometimes avoided by early initiation of treatment. This requires a correct diagnosis which makes treatment as early as possible. Due to the often uncharacteristic symptoms at the onset of disease, early diagnosis in systemic inflammatory disorders represents a diagnostic challenge. This review outlines current standards and limitations in the early diagnosis of rheumatoid arthritis, collagen vascular diseases and primary systemic vasculitides. Recent advances especially in serology and imaging techniques have improved early diagnosis of systemic inflammatory disorders.

Arthritis, Rheumatoid↗
PubMed2005

[Polymyalgia rheumatica: myalgic syndrome or occult vasculitis?].

Polymyalgia rheumatica (PMR) is a chronic inflammatory disorder of unknown etiology which typically presents with symmetric myalgias in the shoulder and pelvic girdles. Other clinical signs include the rapid onset of symptoms and the almost exclusive manifestation in the elderly population. In around 20% of cases, PMR is associated with giant cell arteritis (GCA). However, new imaging techniques suggest that the prevalence of subclinical GCA (e. g. aortitis) in PMR is probably higher. Acute phase reactants like erythrocyte sedimentation rate and c-reactive protein are usually elevated. Myalgias are accompanied by synovitis and bursitis of the large proximal joints and can be visualized by ultrasound or magnetic resonance imaging. While the diagnosis of GCA can be verified by temporal artery biopsy, pathognomonic findings for PMR like specific autoantibodies are lacking. Typical for PMR is the rapid response to corticosteroids. Usually the therapy needs to be continued for at least 2 years. Due to adverse events in many cases a corticosteroid saving therapy like methotrexate is needed.

Adrenal Cortex Hormones↗
PubMed2005

[New therapeutic concepts for vasculitis and collagenosis].

After improvement of the prognosis of the primary systemic vasculitides and systemic lupus erythematosus from a desperate diagnosis with hardly a one year survival after diagnosis to a 5-year-survival-rate of more than 90% actual therapeutic regimes aim at those patients refractory to standard therapeutic regimes, not achieving a remission by standard approaches or having organ damage or contraindications. Furthermore less toxic regimes are looked for with the aim to avoid secondary complications of the standard therapy. New drugs used successfully in rheumatology, transplantation medicine and haematology are used for these purposes in the last years. Recent experiences with Infliximab, Mycophenolate Mofetil, Rituximab und Deoxyspergualin for the treatment of the small vessel vasculitides and systemic lupus erythematosus are reviewed.

Anti-Inflammatory Agents↗
PubMed2005

[Glucocorticoids: importance in the treatment of vasculitis].

Only the modification of natural steroids in the middle of the last century gave insights into the structural requirements for the biological activity of the glucocorticoids (GC). While the delta-4,3-keto-11-beta, 17-alpha,21-trihydroxyl configuration is needed for the GC-activity, an artificial additional double binding in position 1 and 2 lead to a four fold increase of the GC-activity. Of the artificial GC, prednisolone is the most frequently used compound and essential in the therapy of vasculitis today. Dosage, duration and way of application depend on the diagnosis, disease stage, -extend as well as -activity. Considering the use and side-effects of the GC, experiences from cohort-studies of the late 80-ties help at clinical decision making. For giant cell arteritis (GCA) it was shown, that doses of less then 60 mg/day are needed for the induction of remission. Concerning the visual loss in GCA, time of initiating GC-therapy seems more important than the dosage. In the treatment of ANCA-associated vasculitis therapy with GC, later in combination with cyclophosphamide, lead to a significant reduction of mortality. Due to the fact of an increasing survival rate, therapy-related morbidity becomes a more and more important issue. There is a proven correlation between the dosage respectively duration of the GC-therapy and the risk of GC-associated side-effects, especially the incidence of severe infections. This article gives a short review of the present data of the role of GC in the treatment of vasculitis.

Anti-Inflammatory Agents↗
PubMed2005

[Early diagnosis of vasculitides].

The often unspecific symptoms like myalgias, fever and weight loss at the onset of vasculitides are a frequent cause for a delay in diagnosis. Organ-specific symptoms like hemoptysis, dyspnoea, epistaxis, edema and organ infarcts a present when organ dysfunction occurs as a result of vasculitis. Targeted serologic testing including antineutrophil cytoplasm antibodies (ANCA) and cryoglobulins allows early diagnosis of certain vasculitides. Modern imaging techniques like magnetic resonance imaging, computed tomography, positron-emission tomography and ultrasound are cornerstones for an early diagnosis as they allow the detection of subclinical disease and are helpful in the identification of a site for biopsy. Bioptic proof of vasculitis is still the gold standard for diagnosis. Functionally relevant damage caused by systemic inflammatory disorders can by reduced or sometimes avoided by early initiation of treatment. This requires a correct diagnosis is made as early as possible.

Diagnosis, Differential↗
PubMed2005

Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome.

Churg-Strauss syndrome (CSS) belongs to the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and is further characterized by severe eosinophilia and, often, granulomatous inflammation. The therapeutic efficacy of recombinant interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blockade point toward a central role of cytokines in the pathogenesis of CSS. Recent data show that, in contrast to other primary systemic vasculitides, peripheral blood mononuclear cells (PBMCs) secrete not only large amounts of T helper type 1 (Th1) cytokines, particularly IFN-gamma, but also release T helper type 2 (Th2) cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). Interleukin-5 is the most potent stimulator of eosinophil production and functional activation of mature eosinophils, the key effector cells in CSS. Data are presented showing that PBMCs from patients with CSS cultured with T cell-specific stimuli secrete significantly increased amounts of IL-5 compared with healthy controls, suggesting that IL-5 contributes substantially to the development of eosinophilia in CSS. As recombinant IFN-alpha downregulates IL-5 production of CD4(+) T cells in vitro, the increased secretion of IL-5 in patients with CSS may provide the clue for the therapeutic efficacy of recombinant IFN-alpha in the disease. Variations in the balance between Th1 and Th2 cytokines at different disease stages could contribute to the distinct clinical courses seen in patients with CSS, which can range from prominent Th1-mediated generalized vasculitis and granulomatous inflammation on one end of the spectrum to Th2-mediated systemic hypereosinophilia on the other. Although the association of ANCAs with CSS point toward an autoimmune origin of the disease, there is no direct evidence as yet for a direct pathogenic role of ANCAs in CSS.

Antibodies, Antineutrophil Cytoplasmic↗