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Biomedical subjects

A Gause

Publications and source records attributed to A Gause.

At least 19 recordsLinked to original sources
PubMed2007

[Revision of the recommendations of the Commission on Pharmacotherapy of the German Society for Rheumatology. Recommendations for supportive therapy for Sjögren's syndrome].

For the treatment of sicca symptoms as a manifestation of Sjögren's syndrome there are various tear substitutes as well as artificial saliva. The appropriate substances are discussed in this article. In addition to reducing symptoms, some of the effective compounds offer the advantage of infection prophylaxis in the form of better lubrication of the mucous membranes in the airways as well as reduced susceptibility to candidiasis. The presence of bromhexin in the catalogue of the statutory medical insurance agencies is recommended. Certain of the available drugs are still only available in foreign pharmacies.

Bromhexine↗
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

[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↗
PubMed2004

Churg Strauss syndrome--successful induction of remission with methotrexate and unexpected high cardiac and pulmonary relapse ratio during maintenance treatment.

OBJECTIVE: To examine the safety and efficacy of methotrexate (MTX) plus low-dose prednisolone for induction of remission in non life- or organ-threatening courses and for remission maintenance in Churg-Strauss syndrome (CSS). METHODS: In an open-label study 11 patients were treated with MTXfor induction of remission at initial diagnosis and relapse. Twenty-five patients received MTX for maintenance of remission. Primary endpoints were the achievement of remission and the incidence of relapses, respectively. Doses of concomitant prednisolone (PRD) and side effects were secondary endpoints. RESULTS: Induction of remission was achieved in 8/11 patients with MTX/PRD. Median time to remission was 5 months (range 2-9). Remission was maintained in 12 of 23 with available long-term follow-up (median 48 months). Eleven patients experienced 8 major and 3 minor relapses with a median time from remission to first relapse of 9 months. With MTX, the median cumulative PRD dose during the induction phase was 6.2 g. In the maintenance phase PRD could be reduced by 53% in responders. Apart from one case of MTX-induced pneumonitis, adverse events were confined to mild/moderate episodes of infection and leucopenia. No opportunistic infections occurred, neither did steroid-specific adverse events. CONCLUSIONS: MTX is safe and effective for the induction of remission in non-life-threatening CSS. It allows a considerable reduction of PRD and thus avoidance of PRD-related adverse events. However, the ability of MTX to prevent relapses in CSS appears limited. The identification of an optimal maintenance regimen and prognostic factors for treatment response requires trials with larger patient numbers.

Adolescent↗
PubMed2003

[Treatment of primary systemic vasculitis with TNF alpha-antagonists].

After the introduction of the TNF alpha blocking drugs Etanercept and Infliximab for the standard therapy of rheumatoid arthritis these effective substances have also been used successfully in many patients with primary systemic vasculitides, who were unresponsive to standard therapy. From pathophysiologic findings their use is justified by the prominent role of TNF alpha in the inflammation of small and large vessels. So far only open studies with a maximum of 20 patients and case reports are published. In summary there are reports of the successful treatment of 7 patients with rheumatoid vasculitis, 39 patients with Wegener's granulomatosis, 3 patients each with microscopic Polyangiitis, and 5 patients each with temporal Arteritis or Takayasu disease with Etanercept as well as with Infliximab. In addition, Infliximab was also used with a good response in severe Polymyalgia rheumatica in 4 cases and in one case of a cryoglobulinemic vasculitis. More than 60 patients with Panuveitis and other manifestations of Behçet's disease were treated with Infliximab or Etanercept according to preliminary reports. Because of the overall positive reports with TNF alpha collected in this review controlled investigations for their use in primary systemic vasculitis are necessary.

Antibodies, Monoclonal↗
PubMed2003

Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis.

OBJECTIVES: To report the successful induction of remission with the monoclonal anti-CD20 antibody rituximab in a patient with hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis and a non-Hodgkin's lymphoma (NHL) resistant to previously advocated conventional treatments. CASE REPORT: The patient was a 45 year old woman with HCV associated cryoglobulinaemic vasculitis, with purpura, arthralgia, constitutional symptoms, and a polyneuropathy. A malignant NHL was found as underlying lymphoproliferative disease. At this stage the disease was refractory to interferon alpha2b and ribavirin and to subsequent immunosuppressive treatment with cyclophosphamide. Six rituximab infusions targeting the CD20 antigen on cells of the B cell lineage induced remission of the vasculitis. Bone marrow biopsy disclosed absence of the NHL. Remission has subsequently been maintained and HCV eliminated with the new pegylated interferon alpha2b and ribavirin for nearly one year. CONCLUSIONS: Transition of the underlying "benign" lymphoproliferative disease to a malignant lymphoma may result in difficult to treat HCV associated cryoglobulinaemic vasculitis. Rituximab offers a new possibility for inducing remission in refractory HCV associated cryoglobulinaemic vasculitis and the lymphoproliferative disorder. After remission, HCV may subsequently be eliminated with pegylated interferon alpha2b and ribavirin.

Antibodies, Monoclonal↗
PubMed2002

[Induction of remission with infliximab in therapy-refractory Wegener's granulomatosis - Follow-up of six patients].

UNLABELLED: BACKGROUND AND QUESTION: The prognosis of patients with Wegener's granulomatosis (WG) refractory to standard treatment for the induction of remission (cyclophosphamide and steroids) has been poor so far. We report on the results of the follow-up of six patients refractory to the standard regimen (Fauci's scheme) with progressive, imminent visual loss, pulmonary and renal involvement, respectively. How long can remissions be successfully maintained with anti-TNF-alpha-antibody infliximab? What side effects occur? PATIENTS AND METHODS: Patients received infliximab (3 mg/kg) in addition to standard therapy with cyclophosphamide and steroids. Intervals between the first two infliximab infusions were 2 weeks, thereafter 4 weeks. Based on the impression of higher efficacy patients received 5 mg/kg infliximab for subsequent infusions. RESULTS: Remission was induced after 4-6 infliximab infusions in five patients. Remission has been maintained in four patients for 16-26 months. After 12 months a pulmonary relapse occurred in one patient, who received azathioprine for the maintenance of remission. Infliximab was stopped in another patient because of a suspected infection. In the light of high cumulative cyclophosphamide doses (100 g/275 g) and cyclophosphamide induced hemorrhagic cystitis, infliximab was added to azathioprine in the two patients with a pulmonary relapse and protrusion of the eye with imminent visual loss, respectively. Remission was induced in both patients. A carcinoid of the bronchus was diagnosed in one patient after 12 months in remission. CONCLUSION: Infliximab means a new therapeutic option and offers better perspectives for a patient group with previously bad prognosis.

Adrenal Cortex Hormones↗
PubMed2002

Effectiveness of TNF-alpha blockade with infliximab in refractory Wegener's granulomatosis.

OBJECTIVE: To study the effect of the chimeric monoclonal anti-tumour necrosis factor alpha (TNF-alpha) antibody infliximab in the induction of remission in six patients refractory to standard treatment with cyclophosphamide and corticosteroids. In four patients, other measures for treating refractory Wegener's granulomatosis (WG) that have been advocated previously, i.e. intensified cyclophosphamide therapy and additional intravenous immunoglobulin, were ineffective. METHODS: Patients received infliximab (3 mg/kg in two patients and 5 mg/kg in four patients) with a 2-week interval after the first administration and 4-week intervals between infusions until remission, in addition to cyclophosphamide and corticosteroids. Vasculitis activity was assessed with the Birmingham Vasculitis Activity Score (BVAS). A standardized interdisciplinary approach was used for the follow-up of specific organ involvement. RESULTS: Remission was induced in five patients and corticosteroid doses could be tapered. Acute-phase responses (e.g. C-reactive protein) normalized. Titres of c-ANCA (cytoplasmic pattern antineutrophil cytoplasmic antibodies) were no longer detectable. The BVAS was reduced to zero. The higher dose of infliximab (5 mg/kg) seemed more effective in inducing remission. One patient was withdrawn because of suspected systemic infection. Five patients remained in remission for 6-24 months of follow-up. CONCLUSION: The data suggest that infliximab may provide an effective and more specific therapeutic option in the treatment of active WG refractory to standard treatment.

Antibodies, Monoclonal↗
PubMed2001

B lymphocyte involvement in ankylosing spondylitis: the heavy chain variable segment gene repertoire of B lymphocytes from germinal center-like foci in the synovial membrane indicates antigen selection.

The synovial membrane (SM) of affected joints in ankylosing spondylitis (AS) is infiltrated by germinal center-like aggregates (foci) of lymphocytes similar to rheumatoid arthritis (RA). We characterized the rearranged heavy chain variable segment (VH) genes in the SM for gene usage and the mutational pattern to elucidate the B lymphocyte involvement in AS. Cryosections from an AS-derived SM were stained for B and T lymphocytes. B cells were isolated from different areas of a focus. The rearranged VH genes were amplified by semi-nested polymerase chain reaction (PCR) using oligonucleotides specific for the six different VH families and heavy chain joining segments (JHs). PCR products were cloned and sequenced.Fifty-nine of 70 different heavy chain gene rearrangements were potentially functional. Most of the rearranged genes were mutated (range, 1-15%). Thirty of 70 products had a mutational pattern typical for antigen selection. Most of the rearranged VH genes belonged to the VH3 family (54%), consistent with data from healthy donors and patients with RA, while VH4 genes, in contrast to RA, were identified less frequently (10%) and VH5 genes were over-represented (11%). In contrast to RA, neither VH6 genes nor the autoimmunity-prone VH4-34 were seen, whereas another autoimmunity-prone gene, V3-23, was predominantly used (11%). One VH1-derived and one VH3-derived B cell clone were expanded. CDR3 were shorter and more variable in length than in RA. Comparable with RA and reactive arthritis, there is a biased repertoire of selected VH genes, whereas the panel of represented genes is different and less clonal expansion was observed.

Amino Acid Sequence↗