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C Specker

Publications and source records attributed to C Specker.

At least 19 recordsLinked to original sources
PubMed2007

[The heart in rheumatic diseases].

As systemic immunological disorders inflammatory rheumatic diseases potentially involve organs and structures beyond the musculo-skeletal system including skin and blood vessels. Various neurological, renal, pulmonary, hematological and cardiac manifestations contribute to the broad clinical picture of connective tissue diseases and vasculitides. Regarding cardiac disease all structures of the heart may be affected. Pericarditis in lupus, mitral valve changes in the antiphospholipid syndrome, myocarditis and coronary artery stenosis in the systemic vasculitides are typical examples in systemic rheumatic diseases. Beyond this, pulmonary hypertension in systemic sclerosis or congenital heart block in newborns of lupus patients are further cardiac issues. Since better treatment options led to more long-lasting courses in connective tissue diseases, cardiovascular complications as a consequence of chronic disease- and therapy-related damage gain increasing attention.

Arthritis, Rheumatoid↗
PubMed2007

[Antiphospholipid syndrome].

Antiphospholipid syndrome (APS) is characterized by recurrent arterial or venous thromboembolism or pregnancy loss in association with antibodies directed against anionic phospholipids or plasma proteins bound to anionic phospholipids. A common cause of the huge variety of clinical manifestations is vaso-occlusive disease and not vasculitis in venous or arterial blood vessels of different sizes and sites (i.e. deep vein thrombosis, pulmonary embolism, cerebrovascular disease). In accordance with this, fetal abortion, typically beyond the tenth week of gestation, is also caused by infarctions of blood vessels in the placenta. Establishing the correct diagnosis of APS is not easy. To estimate the risk of thrombotic complications is challenging, as well as the questions of, which, how long and in what strength anticoagulation is recommended. This paper should enable the reader to apply international consensus classification criteria correctly, to interpret the different laboratory tests for anti-phospholipid antibodies and to gain an awareness of the different forms of anticoagulation in order to stratify therapeutic decisions.

Abortion, Habitual↗
PubMed2006

CD134 expression on CD4+ T cells is associated with nephritis and disease activity in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a deviation of the immune system that involves T cell-dependent autoantibody production. The aim of this study was to investigate the role of co-stimulatory markers on T cells in this disease. Twenty-eight patients with SLE as defined by the American College of Rheumatology (ACR) criteria and 11 healthy controls were included into the study. Eleven patients had biopsy-proven lupus nephritis while 17 patients had no clinical evidence of lupus nephritis. Clinical disease activity was assessed according to the systemic lupus erythematosus disease index (SLEDAI). CD4+ T cell populations in the peripheral blood were analysed for the expression of co-stimulatory markers CD45RO, CD70, CD80, CD86, CD137, CD137L, CD134, CD152, CD154 and ICOS. SLE patients showed an increased frequency of peripheral CD4+ T cells expressing high levels of CD80, CD86 and CD134 compared to healthy controls (7.1 +/- 1.5% versus 1.7 +/- 0.9%; P < 0.005; 2.3 +/- 0.4% versus 1.0 +/- 0.2%; P = 0.008, 20.2 +/- 2.0% versus 10.6 +/- 1.9%; P < 0.005, respectively). Significantly higher levels of CD80 on CD4+ T cells were detected in SLE patients with lupus nephritis compared to patients without nephritis (11.9 +/- 3.3% versus 4.0 +/- 0.7%; P < 0.005). There was an increased presence of CD134+ CD4+ cells in SLE patients with lupus nephritis (27.5 +/- 4.0% versus 15.5 +/- 1.3%; P < 0.005). CD80 and CD134 expression was significantly correlated with SLEDAI (r = 0.42, P = 0.03; r = 0.56, P < 0.005). Co-stimulatory molecules on CD4+ T cells are associated with renal disease and disease activity in patients with systemic lupus erythematosus.

Acute Disease↗
PubMed2004

[Disease-oriented Internet use in outpatients with inflammatory rheumatic diseases].

OBJECTIVE: On behalf of the "systemic inflammatory rheumatic diseases network" comprehensive, nationwide horizontal and vertical cross-linking of research and care is to be developed for the first time. The quality of scientific work and patient care is to be increased in the medium term through this improved communication and co-operation. Our objective was to determine what hardware and software are available to the patients involved, with a view to the Internet being used as a basis for communication. The ultimate aim was to provide patients with an adequate source of information on care. METHODS: A survey was carried out among 400 patients attending our outpatient clinics. Data on the hardware and software used and on Internet access and patterns and degree of utilization were collected using a unilateral questionnaire. RESULTS: 326 patients filled in the questionnaire. 163 of those responding had Internet access, with younger and better educated patients using the Internet significantly more frequently. No dependency was noted on gender or marital status. Mean time duration for Internet use was longer in men. 55.8% of the internet users searched for medical questions. Major search topics included up to date therapeutic options (46.6%) and information on specific diseases (28.8%). CONCLUSION: Internet is an important information medium for patients. Technical requirements and high motivation make communication practicable for about 50% of patients. To ensure acceptance, the Internet platform of the systemic inflammatory rheumatic diseases network needs to be aligned to patients' requirements, bearing in mind the need for extensive high-value, reliable scientific information to be offered on the website.

Adult↗
PubMed2004

Health care and burden of illness in systemic lupus erythematosus compared to rheumatoid arthritis: results from the National Database of the German Collaborative Arthritis Centres.

During the past 20 years, outcome studies in the rheumatic diseases have, on the one hand, given increasing evidence of the unfavourable long-term prognosis of rheumatoid arthritis (RA) and on the other hand determined continuous improvement of prognosis in systemic lupus erythematosus (SLE). The aim of the study was to investigate how this translates into the current spectrum of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) seen by rheumatologists in Germany and to compare aspects of the burden of disease, disease outcomes and treatment between these two important rheumatic diseases using a large clinical database. Current health care was analysed with data from the German rheumatological database of 10 068 patients with RA and 1248 patients with SLE seen by rheumatologists in 2001. In addition, of a total of 3546 patients with SLE and 24 969 patients with RA seen at the German Collaborative Arthritis Centres between 1994 and 2001, 3465 cases of SLE were matched by age, sex, disease duration and referral status with a corresponding RA case. There were considerable differences in treatment of patients before referral to a rheumatologist and in rheumatologic care. In 2001, patients with SLE were treated by their rheumatologists mainly with antimalarials (AM, 37%), azathioprine (29%) and nonselective NSAIDs (16%). Of them, 61% received at least one immunosuppressive drug (including AM) plus glucocorticoids. In RA, methotrexate was the predominant medication (63%), and 56% received at least one immunosuppressive drug plus glucocorticoids. Matched pairs analysis showed that SLE patients with a short disease duration were almost equally burdened by pain, functional limitations and reduced health status as RA patients. After a disease duration of >10 years, however, patients with RA showed poorer outcomes than those with SLE: RA patients reported significantly more often severe pain (30% in RA versus 17% in SLE) and poor global health status (52 versus 38%), and their disease activity as well as severity was rated higher by the rheumatologists. In conclusion, comparing large groups of RA and SLE patients we found a similar burden in early but not in late disease. Taking into account limitations as to the generalizability of the results (recruitment in rheumatologic care, cross-sectional data, underestimation of SLE-specific outcomes), the discrepancy between the high increase in disease-related negative outcomes with longer disease duration in RA but not in SLE indicates a better long-term prognosis in SLE concerning the items observed. The great disparity in treatment intensity between rheumatologists and nonrheumatologists shows that the involvement of a specialist is needed equally in both diseases.

Adult↗
PubMed2000

[Arthropathy in beta-thalassemia minor].

CASE REPORT: A 25-year-old Turkish patient presented with a "swelling" of the ankles which now persisted for 5 years. He had previously been diagnosed as having HLA-B27 negative spondylarthropathy with peripheral joint involvement. The symptoms failed to respond to different therapies. Serological markers and radiological procedures revealed beta-thalassemia minor. DISCUSSION: Symptoms, diagnostic procedures and differential diagnostic options are discussed.

Adult↗
PubMed2000

[Combination of antimalarial drugs mepacrine and chloroquine in therapy refractory cutaneous lupus erythematosus].

Antimalarials represent the first line in treatment of cutaneous lupus erythematosus (LE). However, some patients show no improvement on monotherapy with chloroquine or hydroxychloroquine. A 30-year-old female patient had treatment-resistant cutaneous LE exhibiting features of both LE tumidus and subacute cutaneous LE. Previously, the patient had been unsuccessfully treated with chloroquine, hydroxychloroquine, dapsone, and azathioprine, each in combination with variable doses of prednisolone. However, the LE lesions increased during these therapeutic regimens. A combination of chloroquine and mepacrine therapy led to improvement and then total clearing after 4 months of treatment.

Adult↗
PubMed2000

Relapsing polychondritis in childhood--case report and short review.

Relapsing polychondritis (RP) is a disease of unknown etiology and it is characterized by inflammation of the cartilage. While the clinical picture of RP in adults is well described, RP in childhood is poorly documented. We describe a young girl presenting with acute dyspnea, stridor and polyarthritis. The diagnosis of RP was made 2 years after first presentation, when auricular chondritis occurred. Based on a MEDLINE search, reports on RP in childhood were reviewed. The frequency of chondritis and systemic manifestations of RP in children was compared to data in adults and found to be very similar. RP in childhood can be a life-threatening and debilitating disease.

Adult↗
PubMed2000

[Documentation concepts in MedNet-Rheuma (competence network "Inflammatory-rheumatic systemic diseases")].

Concepts of documentation rely not only on the contents required and technical demands, but the procedures covered and in medical applications especially security aspects are also matters of critical concern. Even though the need for effective documentation (i.e., adequate in content, availability, feasibility and easy to retrieve analysis) is not a question, tasks and aims (for example, quality of patient care) deserve attention and establishing efforts have to be analyzed regarding their structural and personal prerequisites and implications before particular tools for documentation can be developed.

Computer Security↗
PubMed1999

Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus.

The etiology of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is still unknown. In several cases, however, xenobiotics (i.e. drugs and occupational agents) were identified as etiologic agents and associations with certain polymorphic alleles of xenobiotic-metabolizing enzymes have been reported. Cytochrome P4501A1 (CYP1A1) and N-acetyltransferase 2 (NAT-2) are xenobiotic-metabolizing enzymes of phase 1- and phase 2-metabolism, respectively. CYP1A1 may activate drugs and other chemicals to reactive metabolites. NAT-2 is the most important enzyme in acetylation of aromatic amines, and thus may be responsible for detoxification of many of these compounds. Two polymorphisms of the human CYP1A1 gene, a point mutation in the 3' flanking region of the gene (Msp1) and a mutation in exon 7 leading to an isoleucine-valine-exchange in the heme-binding region of the enzyme, have been described and may lead to a higher basal and inducible enzyme activity. With respect to NAT-2, several alleles which combine for the two phenotypes "fast" and "slow" acetylators have been described. We analyzed the gene frequencies of the CYP1A1 polymorphisms and the phenotypes of NAT-2 in patients suffering from idiopathic SLE or SSc. CYP1A1 polymorphisms were analyzed in genomic DNA by PCR, whereas NAT-2 phenotypes were measured by the caffeine method. For CYP1A1 polymorphisms, 106 patients have been typed until now. The SLE group (n = 68) exhibited a significant increase (p < 0.05) in the mutant Val-allele (OR = 2.59) when compared to controls (n = 184). However, no significant differences in allele frequencies for MspI in the SLE group and for both CYP1A1 polymorphisms in the SSc group could be observed. Regarding the NAT-2 phenotype, patients suffering from SLE (n = 88) 75% and SSc (n = 26) 80.2%, respectively, were slow acetylators compared to 55% slow acetylators in the healthy German population (p < 0.05). The observed increased frequencies of the CYP1A1 mutant Val-allele and the slow actylator phenotype in idiopathic autoimmune disease support our concept that in slow acetylators non-acetylated xenobiotics may accumulate and are subsequently metabolized by other enzymes into reactive intermediates. Thus, enhanced formation of reactive metabolites could alter self-proteins presented to the immune system thus stimulating autoreactive T cells which induce autoimmunity.

Alleles↗
PubMed1999

Cerebral microembolism, a disease marker for ischemic cerebrovascular events in the antiphospholipid syndrome of systemic lupus erythematosus?

OBJECTIVES: We investigated whether the detectability of microembolic Doppler signals (MES) in the intracranial circulation may help to define the individual cerebrovascular risk in systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS). MATERIAL AND METHODS: Retrospective cross-sectional study of 70 patients with SLE with or without APS, and 30 controls with a history of cerebral ischemia of unknown cause. Of all patients, 38 had a clinical history of APS and 32 did not. RESULTS: 15 patients with APS (39%) showed MES. In contrast, all patients without APS and 29 of 30 controls were microemboli-negative. MES were more strongly associated with cerebrovascular symptoms than with APS, antiphospholipid antibodies, or cardiac pathology. The time elapsed since the last ischemic cerebrovascular symptom was significantly shorter in microemboli-positive patients than in microemboli-negative patients (P<0.001). CONCLUSION: MES may be related to disease activity in patients with SLE and APS. Their detection may help to assess individual cerebrovascular risk and contribute to therapeutic decision making and therapeutic monitoring.

Adolescent↗
PubMed1998

RheumaNet--a novel Internet-based rheumatology information network in Germany.

Knowledge transfer in medicine has traditionally been achieved through personal communication, the medical literature, conferences and continuous medical education. However, many of these methods of communication have the problem of currentness, and the latest knowledge is mostly transferred with a certain delay. In particular, chronic disease management is frequently burdened by missing, incomplete or delayed communication. We present the implementation of a novel, Internet-based information system (RheumaNet) to facilitate rapid communication and information transfer between the 21 German Multipurpose Arthritis Centres (MACs). Medical information, agendas, urgent notifications, guidelines, etc., can be exchanged easily via electronic mail, file transfer protocol or the World Wide Web. RheumaNet allows interactive on-line communication as a common platform for joint projects or remote consultation. It supports a set of 'core documentation' that has been used by all German MACs for several years. RheumaNet was used for the organization, on-line presentation and evaluation of the 1997 annual meeting of the German Rheumatology Society and is currently appointed to establish its public representation in the 'Web'. An on-line version of the 'Quality Assurance Textbook' of German rheumatology is achieved with database-derived 'dynamic' Web pages, allowing easy access to any information within it. Advances in the future include the development of on-line patient information bulletin boards, on-line questionnaires, the coordination of rehabilitation and educational tools for medical students, and professional training.

Arthritis, Rheumatoid↗
PubMed1998

The p68 autoantigen characteristic of rheumatoid arthritis is reactive with carbohydrate epitope specific autoantibodies.

OBJECTIVE: The autoantigen p68 is a target of autoantibodies as well as autoreactive T cells with a high specificity in rheumatoid arthritis (RA). The binding characteristics of the autoantibodies to their antigen were now analysed biochemically and cytologically. METHODS: Deglycosylation techniques as well as lectin and sugar competition experiments were performed to p68 to discover if the antibodies detected a glycoepitope, Its antigenicity was investigated applying anti-p68 antibodies derived from RA patients in comparison with polyclonal rabbit anti-p68 antibodies. RESULTS: p68 specific antibodies from RA patients did not to bind to p68 that had been deglycosylated by alkaline beta-elimination, O-glycosidase or periodate treatment. In contrast, binding of p68 specific antibodies raised in rabbit was unaffected by either deglycosylation protocol. Furthermore, lectins specific for the carbohydrate N-acetylglucosamine competed with p68 specific antibodies from RA patients for antigen bindings. N-acetylglucosamine by itself also competed with patient derived anti-p68 antibodies for p68 binding. Again, rabbit and anti-p68 antibodies did not elicit these competitive effects. Applying cytoimmunofluorescence, p68 was present in the cytoplasm or endoplasmic reticulum and also in low abundance on the cell surface. Under heatshock conditions, p68 was detectable in the nucleus. CONCLUSIONS: Autoimmunity to p68 during RA is carried by anti-carbohydrate autoantibodies. The carbohydrate modification of p68 appears to be N-acetylglucosamine, which may reflect the regulation of intracellular localisation of the antigen. It is hypothesised that a shift in glycosylation pattern accompanied by an unphysiological localisation of the antigen could trigger antigenicity of p68 during the pathogenesis of IRA.

Arthritis, Rheumatoid↗
PubMed1998

Detection of cerebral microemboli in APS--introducing a novel investigation method and implications of analogies with carotid artery disease.

Patients with antiphospholipid syndrome (APS) are prone to thromboembolism. So far, the only predictive parameters for further complications are their number in patient's history and perhaps the titre of aPL. Derived from clinical investigation of stroke and obvious analogies between cerebrovascular ischemia (CVI) in patients with carotid artery disease (CAD) and patients with APS, a novel non-invasive method is introduced using transcranial Doppler (TCD) long-term monitoring to detect high energy ultrasonic signals (so called 'microemboli') in the cerebral vasculature. In patients with CAD, these microemboli proved to correlate with past and impending symptoms of CVI permitting therapeutic stratification by their detectability. In SLE and APS. this technique enabled identification of very similar signals in cerebral bloodstream of APS patients. Microemboli were highly associated with the history of CVI and the titre of aPL. Detection of microemboli offers new possibilities in risk estimation, therapeutic stratification and in studying pathophysiology of APS.

Acoustics↗
PubMed1998

High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus.

Increased in vitro apoptosis and altered expression of apoptosis-related molecules have been reported in systemic lupus erythematosus (SLE). It was speculated that autoantigens released from apoptizing cells may contribute to the etiopathogenesis of SLE by both activation of autoreactive lymphocytes and the formation of immune complexes. Conflicting data about the level of cellular apoptosis from animal models for SLE and human SLE indicate different pathomechanisms. In the present study we analysed the count of circulating early apoptotic cells and its correlation with the clinical activity in SLE compared with the amount in primary systemic vasculitis (PSV). The percentage of early apoptotic cells determined by Annexin V-FITC binding cells was significantly increased in peripheral blood of SLE patients compared with normal healthy donors (NHD) and PSV (NHD 5.62%, SLE 13.68%, PSV 8.69%). Analysis of lymphocytes revealed significantly increased counts in the T cell populations (NHD 5.15%, SLE 12.22%, PSV 10.01%), whereas the increase in B cells did not reach significance level (NHD 9.20%, SLE 18.95%, PSV 16.59%). Apoptotic cell count revealed no correlation to SLAM-Score or to immunosuppressive therapy, corticosteroid-dosage or absolute lymphocyte count. The general increase of circulating apoptotic cells may indicate an impaired clearance in SLE patients, independent of clinical activity or therapeutic interventions. Autoantigens from apoptotic cells may contribute to both activation of autoreactive lymphocytes and formation of immune complexes.

Activities of Daily Living↗
PubMed1997

Acquired factor VIII inhibitors in nonhemophilic patients.

Antibodies against factor VIII occur in about 15-35% of hemophilia A patients and induce refractoriness to factor VIII substitution. In most cases, these antibodies are of the IgG class. Strategies to avoid or to treat such inhibitors are controversial. In very rare cases, factor VIII inhibitors also develop in nonhemophilic patients. Although there are anecdotal reports that these antibodies may disappear spontaneously without occurrence of bleeding tendencies, in the majority of patients the clinical course is characterized by severe hemorrhages. From 1980 to 1995, we observed ten nonhemophilic patients with acquired factor VIII inhibitors at our hospital. In most cases, a sudden bleeding tendency was observed shortly after an injury or surgery. Coagulation tests showed a prolonged aPTT and a decreased F VIII level. Other deficiencies of blood-clotting factors and acquired or hereditary von Willebrand's disease were excluded. Therapy with F VIII concentrates did not produce the expected increase. Measurement of F VIII inhibitor levels in Bethesda units/ml (BU/ml) revealed maximal values in the range of 2-128 BU/ml. Immunosuppressive therapy with azathioprine or cyclophosphamide in combination with methylprednisolone led to complete disappearance of the inhibitor, normalization of the coagulation tests, and complete remission of the bleeding tendency in seven treated patients within 6 weeks. Although the clinical course is not predictable and inhibitors may disappear spontaneously, combined therapy with methylprednisolone and azathioprine or cyclophosphamide is recommended for patients with bleeding tendency. In pregnancy, therapy should be started only with methylprednisolone; post-partum, azathioprine should be used additionally if methylprednisolone as a single drug does not lead to complete remission. In emergency situations, therapy with high doses of human factor VIII concentrate may be used. When bleeding does not cease, the additional use of activated prothrombin-complex concentrates or porcine factor VIII is indicated. Possible side effects may include hepatitis and short-lived intravascular thrombin production.

Adult↗
PubMed1997

Rheumatoid arthritis: autoreactive T cells recognising a novel 68k autoantigen.

OBJECTIVE: A 68k autoantigen has been identified by specific antibodies from patients with rheumatoid arthritis (RA). This study considered whether or not this antigen is a target for T cells and thus may play a part in T cell mediated immunopathology of active RA. METHODS: The 68k antigen was isolated and used in a nitrocellulose bound form to stimulate T cells. Proliferation of T lymphocytes of peripheral blood as well as synovial fluid was measured. RESULTS: Peripheral blood T cells specifically proliferating against the 68k antigen were detected in 19 of 27 patients with RA (70%). For T cells isolated from peripheral blood, proliferation peaked on day 10. When T cells were isolated from actively inflamed synovial fluid, the proliferation kinetics shifted to a peak on day 3. Blockade of HLA class II antigens resulted in an increase of proliferation in the case of HLA-DP. Applying HLA-DP specific antibodies capable of inhibiting antigen presentation mediated by this molecule, T cells of 17 of 27 RA patients (63%) proliferated to a higher extent than with the 68k antigen alone. The phenomenon that an increased proliferation occurred upon blockade of a particular HLA class II family member was also demonstrated for DQ and DR: the 68k antigen likewise stimulated T cells restricted for DP or DQ, respectively. CONCLUSIONS: The novel 68k antigen is a target of both T and B cellular immune responses and as such could play a part in the immune dysfunction of RA. The finding that blocking of certain HLA class II molecules functioning in antigen presentation (for example, via HLA-DQ) results in a higher instead of lower proliferation in vitro, may argue for the presence of antigen specific suppressive T cells.

Adult↗