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Biomedical subjects

W L Gross

Publications and source records attributed to W L Gross.

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

Balloon angioplasty of arteries of the upper extremities in patients with extracranial giant-cell arteritis.

OBJECTIVES: To evaluate the outcome of balloon angioplasty in the arteries of the upper extremities in patients with giant-cell arteritis (GCA) and stenosing extracranial involvement. METHODS: Percutaneous transluminal angioplasty (PTA) for symptomatic upper limb artery stenoses (n = 29) and occlusions (n = 1) resistant to medical treatment was carried out in 10 patients (all women, mean age 65 years) with GCA. Vascular lesions were located in the subclavian (n = 4), axillary (n = 10) and brachial (n = 16) arteries. Interventional treatment was accompanied by immunosuppressive drugs in all patients. Follow-up included clinical and serological examination, magnetic resonance angiography and colour duplex ultrasound. RESULTS: Initial technical success of angioplasty was achieved in the case of all vascular lesions. In five patients, marked recurrent stenoses (vascular territories; n = 10/30) were found during follow-up (mean 24 months). The cumulative primary patency rate was 65.2%. All recurrent lesions developed in the territories of the initial long-segment stenoses. Repeated PTA (vascular territories, n = 8; patients, n = 5) provided a cumulative secondary patency rate of 82.6% and a cumulative tertiary patency rate of 89.7%. CONCLUSIONS: Despite a tendency to restenoses, balloon angioplasty of the upper-extremity artery, in combination with immunosuppressive treatment, is an efficient method for the treatment of extracranial GCA.

Aged↗
PubMed2006

[Pulmonary arterial hypertension in collagenoses: clinical features, epidemiology, pathogenesis, diagnosis and treatment].

Pulmonary arterial hypertension (PAH) is a severe vasculopathy, which is characterised by progressive narrowing and obliteration of the pulmonary arterioles and increased endothelin-1 levels. The increase of vascular resistance in the lung vessels leads to chronic pressure overload and to right heart failure, if untreated. PAH often occurs in association with rheumatic-inflammatory diseases (e.g., in 15% of patients with systemic sclerosis (SSc), especially in the limited form or in CREST patients) and determines their prognosis: in advanced stages, untreated patients die within a short period. Therefore all SSc patients, particularly the newly diagnosed ones, should be screened for PAH with echocardiography. If PAH is suspected, a right heart catheter should be performed, and if PAH is confirmed, adequate treatment should be initiated. While few years ago lung transplantation was the only option for patients with severe PAH, in recent years enormous progress was seen in drug treatment. Today prostanoids (Ventavis) and the endothelin receptor antagonist bosentan (Tracleer) are available for patients with PAH in WHO/NYHA stage III: they have substantially improved the prognosis of PAH in the last years. Since few months, also the phosphodiesterase inhibitor sildenafil (Revatio) is available. The combination of drugs with different mode of action will likely further improve the prognosis of PAH patients.

Algorithms↗
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

Promoter polymorphism rs3087456 in the MHC class II transactivator gene is not associated with susceptibility for selected autoimmune diseases in German patient groups.

We analysed whether the single nucleotide polymorphism (SNP) rs3087456 in the promoter of the MHC class II transactivator (MHC2TA) gene is associated with manifestation of rheumatoid arthritis, multiple sclerosis, narcolepsy and Wegener granulomatosis. The recently reported association in a northern population of the MHC2TA variation with these autoimmune diseases is not evident in the German population.

Arthritis, Juvenile↗
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

B lymphocyte maturation in Wegener's granulomatosis: a comparative analysis of VH genes from endonasal lesions.

BACKGROUND: Anti-neutrophil cytoplasmic antibodies (ANCA) directed against proteinase 3 (PR3) are highly specific for Wegener's granulomatosis (WG). Evidence for a pivotal role of PR3-ANCA in the induction of vasculitis has been demonstrated. B cell clusters have been observed within endonasal biopsy specimens. OBJECTIVES: To determine whether B cell selection and maturation take place in granulomatous lesions of WG. METHODS: Granulomatous lesions and the immunoglobulin (VH) gene repertoire from nasal tissue of six WG patients-two active and two smouldering localised WG (ANCA negative, restricted to respiratory tract), plus one active and one smouldering PR3-ANCA positive generalised WG-were characterised by immunohistochemistry, polymerase chain reaction, cloning, DNA sequencing and database comparison. RESULTS: B lymphocyte-rich, follicle-like areas were observed proximal to PR3 positive cells and plasma cells in granulomatous lesions; 184 VH genes from these granulomatous lesions were compared with 84 VH genes from peripheral blood of a healthy donor. The mutational pattern of VH genes from active WG resembled memory B cells. Structural homologies of VH genes from granulomatous lesions to PR3-ANCA encoding genes were detected. Significantly more genes (55%, 45%, and 53%, respectively) from active WG compared with the healthy repertoire carried mutations to negatively charged amino acids within the binding site coding regions, favouring affinity to the positively charged PR3. CONCLUSIONS: Selection and affinity maturation of potentially PR3-ANCA producing autoreactive B cells may start in granulomatous lesions, thereby contributing to disease progression from ANCA negative localised to PR3-ANCA positive generalised WG.

Aged↗
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

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↗