Biomedical subjects
H Zeidler
Publications and source records attributed to H Zeidler.
[New aspects of bacteriological pathogen diagnosis in rheumatic diseases].
Microbiological diagnosis for rheumatic diseases is increasingly used as part of the diagnostic work-up in rheumatological practice due to growing knowledge about bacteria-induced rheumatic diseases. This review's focus lies on rheumatic diseases, which in contrast to septic-infectious arthritis, are characterized by the inability to culture bacteria from the inflammed joint. These reactive arthritides occur after primary extraarticular bacterial infection. The etiological diagnosis of reactive arthritis is based on the detection of a previous or ongoing bacterial infection. Diagnosis is performed by serology or direct detection of the bacterial organism or parts thereof at the site of entry and recently by molecularbiology-based detection of the bacteria in the inflamed joint. This review reflects the current diagnostic approaches and formulates diagnostic algorithms for specific and well-directed microbiological diagnosis.
[Health economics--more important today than ever?].
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[Health economics research in the area of chronic polyarthritis].
Costs of illness are of major economic relevance in rheumatoid arthritis (RA) as in other chronic diseases. Overall costs of 15,000 Euro/year: 10,000 Euro indirect costs, and 5000 Euro direct costs are estimated, respectively. A further detailed analysis of direct costs underlines that inpatient care (50%) is the most prominent cost driver. Medication costs are also evaluated in detail since they are expected to gain importance with the introduction of the more expensive biologicals. While annual costs for regular disease modifying drugs (DMARDs) vary from 160 to 5000 Euro per patient, costs for the new biologicals amount up to 20,000 Euro (100-125% of the current estimated overall costs). For a comparison of different therapeutic strategies, costs are related to effectiveness in cost-effectiveness analyses. Based on present clinical trials, the ratios of medication costs and response according to the ACR 20-criteria of various DMARDs and biologicals are compared. The most cost-effective medication is sulfasalzine, followed by methotrexate, and leflunomide. Combining etanercept and methotrexate is preferable to methotrexate monotherapy and the combination of infliximab and methotrexate. This review shows that important economic issues in RA have already been addressed by applying cost-of-illness analyses and cost-effectiveness analyses. However, the knowledge about cost-effective therapeutic options is still scarce. Thus, primary data will have to be obtained using standardized approaches. These economic findings can be taken into account in the development of disease-management recommendations for RA-therapy.
[Final report of the Professional Community of Regional Cooperative Rheumatology Centers of Germany concerning model measures of the federal ministry for public health].
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Nodular fasciitis, erythema migrans, and oligoarthritis: manifestations of Lyme borreliosis caused by Borrelia afzelii.
We describe a 35-year old patient with nodular fasciitis, erythema migrans, and gonarthritis four months after a bite of a Borrelia afzelii infected tick. The Borrelia afzelii infection was identified by a polymerase chain reaction and direct sequencing of the amplification product. Borrelia-specific DNA was also detectable in nodular fasciitis tissue. We therefore conclude that Borrelia afzelii can be a causative agent of nodular fasciitis and Lyme arthritis in a highly endemic region of Northern Germany.
[New study of selective COX-2 inhibitors. Protecting the stomach while risking the heart? (interview by Dr. Beate Schumacher)].
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Efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis: a six-week controlled study with comparison against placebo and against a conventional nonsteroidal antiinflammatory drug.
OBJECTIVE: To evaluate the short-term efficacy of celecoxib, a cyclooxygenase 2-specific inhibitor, in the treatment of ankylosing spondylitis (AS). METHODS: The study was a 6-week randomized, double-blind, placebo-controlled trial with 3 treatment arms: placebo, ketoprofen 100 mg twice daily, and celecoxib 100 mg twice daily. Patients who had AS according to the modified New York criteria, without peripheral synovitis and with active disease (pain > or =40 mm on a 100-mm visual analog scale [VAS] and an increase in pain of at least 30% after nonsteroidal antiinflammatory drug withdrawal) were eligible for study. Primary outcome measures were change in pain intensity (VAS) and change in functional impairment (Bath Ankylosing Spondylitis Functional Index [BASFI]). RESULTS: Of the 246 randomized patients, 76 were allocated to receive placebo, 90 ketoprofen, and 80 celecoxib. There were no statistically significant differences between treatment groups at study entry. During the 6 weeks of the study, the decrease in pain and functional impairment was greater in the active treatment groups than in the placebo group, with a trend in favor of celecoxib when the 2 active treatments were compared. The mean changes were -13 mm, -21 mm, and -27 mm (P = 0.006) for pain and 1, -6, and -12 (P = 0.0008) for BASFI score in the placebo, ketoprofen, and celecoxib groups, respectively. During treatment, the number of patients reporting epigastric pain was 6 (8%), 13 (14%), and 10 (13%) in the placebo, ketoprofen, and celecoxib groups, respectively. CONCLUSION: The results of this study confirm the clinically relevant antiinflammatory effect of celecoxib at a 200-mg daily dosage, with significant improvement of both pain and function in patients with AS.
Indirect medical costs in early rheumatoid arthritis: composition of and changes in indirect costs within the first three years of disease.
OBJECTIVE: To investigate 1) the magnitude of indirect costs, 2) changes in cost components, and 3) correlations between changes in cost and social, clinical, and occupational variables within the first 3 years of rheumatoid arthritis (RA). METHODS: We evaluated the indirect costs per person-year in 133 consecutive gainfully employed out-patients with early RA, in a prospective multicenter followup study. Costs due to RA-related sick leave, work disability, and other work loss were assessed using the human capital approach. Variables associated with reduction in lost productivity were tested by multivariate logistic regression analysis. RESULTS: Mean +/- SEM annual indirect costs were $11,750 +/- 1,120 per person. During the 3-year period of observation, a marked reduction in the costs associated with sick leave was seen, which exceeded the increase in costs due to work disability and other work loss. This phenomenon resulted in an overall reduction in indirect costs of 21%. The final logistic regression model of reduced loss of productivity included 3 variables: no problems with standing (odds ratio [OR] 7.1), no problems with working speed (OR 4.1), and no problems with outdoor work (OR 3.1). CONCLUSION: High indirect costs in early RA were demonstrated. An overall decrease of costs can be seen in the first 3 years, due to the reduction in sick leave. Since the absence of problems due to strenuous working conditions was found to be associated with a reduction in indirect costs, it is assumed that early intensified vocational rehabilitation, apart from controlling disease activity by adequate treatment, might help to reduce indirect costs.
Chlamydia and Borrelia DNA in synovial fluid of patients with early undifferentiated oligoarthritis: results of a prospective study.
OBJECTIVE: More than 50% of patients with synovitis involving 1-4 joints remain classified as having undifferentiated oligoarthritis (UOA) after 1 year of disease. The clinical presentation is often similar to that of reactive arthritis (ReA) and other spondylarthropathies or to Lyme arthritis. We therefore determined how often Chlamydia trachomatis (Ct) and Borrelia burgdorferi (Bb) can be identified in patients with UOA, by using an extensive laboratory approach. METHODS: We prospectively studied 52 patients with UOA who presented at an early synovitis clinic in a region highly endemic for Lyme disease. Patients were examined by standardized clinical and immunoserologic procedures. Synovial fluid was screened for the presence of Ct and Bb DNA by polymerase chain reaction (PCR). Urine was tested for Ct DNA by ligase chain reaction, and serum was tested for Ct antibodies by enzyme-linked immunosorbent assay and Bb antibodies by hemagglutination test and Western blotting. PCR results in the UOA patients were compared with the results in cohorts of patients with definite rheumatoid arthritis (RA), Lyme arthritis, and Chlamydia-induced arthritis (CIA). RESULTS: In the synovial fluid of 9 of 52 patients with UOA (17%), we found Ct DNA, and in 6 of the 52 patients (12%), Bb DNA was found. The frequency of bacteria-specific DNA was 50% (7 of 14) in CIA patients and 69% (11 of 16) in patients with Lyme arthritis. No Bb or Ct DNA was found in the synovial fluid of the 31 RA patients. CONCLUSION: With optimized PCR protocols, it is possible to detect considerable levels of Bb and Ct DNA in the synovial fluid of patients with UOA. Although the presence of bacterial DNA does not unequivocally prove its etiologic significance, we suggest that at least one-third of patients with UOA may have a form of ReA that involves asymptomatic primary infection.
[Specialist network "Inflammatory-rheumatic systemic diseases." Developmental perspectives for rheumatology in Germany].
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[Combined basic therapeutic drugs. From individual hope to targeted use].
Accumulating evidence suggests that treatment of rheumatoid arthritis (RA) with two or more disease-modifying antirheumatic drugs (DMARDs) is more efficient than single agent therapy. Randomized clinical trials demonstrated the efficacy of various combinations such as methotrexate plus sulfasalazine plus hydroxychloroquine, methotrexate plus ciclosporine or methotrexate plus infliximab, respectively. In contrast to these data, however, most German rheumatologists use combination therapy in a small percentage of patients with active RA. Thus, consensus criteria should be defined when and how to use combination therapy in the treatment of active disease. We suggest that combination therapy should be started if active disease is still present after three months of treatment with a single standard DMARD, mostly methotrexate, plus low dose prednisolone and that combination DMARD therapy should be used before TNF blocking agents.
[Introduction of the Hannover Competence Center].
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Expression of Chlamydia trachomatis genes encoding products required for DNA synthesis and cell division during active versus persistent infection.
During persistent infection, the intracellular bacterial pathogen Chlamydia trachomatis is viable but severely attenuates the production of new, infectious elementary bodies (EBs). To investigate the reasons for this lack of new EB output, we analysed the expression of chlamydial genes encoding products required for DNA replication and cell division, using in vitro models of active versus persistent infection and synovial tissue samples from patients with chronic Chlamydia-associated arthritis. Hep-2 cells were infected with K serovar C. trachomatis and harvested at t = 0-48 h post-infection (p.i; active). Human monocytes were infected similarly and harvested at t = 1-7 days p.i. (persistent). RNA preparations from infected/uninfected cells and patient samples were subjected to reverse transcription-polymerase chain reaction (RT-PCR) targeting polA, dnaA, mutS and parB mRNA, related to chlamydial DNA replication/segregation; these were expressed in infected Hep-2 cells from 11 to 48 h p.i; ftsK and ftsW, related to cell division, were expressed similarly. Real-time PCR analyses demonstrated that significant accumulation of chlamydial chromosome began at about 12 h p.i. in infected Hep-2 cells. In infected human monocytes, polA, dnaA, mutS and parB mRNA were produced from days 1-7 p.i. and were weakly expressed in patient samples. Real-time PCR indicated the continuing accumulation of chlamydial chromosome during the 7 day monocyte infection, although the rate of such accumulation was lower than that occurring during active growth. However, transcripts from ftsK and ftsW were detected only at 1 day p.i. in infected monocytes but not thereafter, and they were absent in all patient samples. Thus, genes whose products are required for chlamydial DNA replication are expressed during persistence, but transcription of genes whose products are required for cytokinesis is severely downregulated. These data explain, at least in part, the observed attenuation of new EB production during chlamydial persistence.
Effects of azithromycin and rifampin on Chlamydia trachomatis infection in vitro.
An in vitro cell culture model was used to investigate the long-term effects of azithromycin, rifampin, and the combination of azithromycin and rifampin on Chlamydia trachomatis infection. Although standard in vitro susceptibility testing indicated efficient inhibition by azithromycin, prolonged treatment did not reveal a clear elimination of chlamydia from host cells. Chlamydia were temporarily arrested in a persistent state, characterized by culture-negative, but viable, metabolically active chlamydia, as demonstrated by the presence of short-lived rRNA transcripts. Additionally, azithromycin induced generation of aberrant inclusions and an altered steady-state level of chlamydial antigens, with the predominance of Hsp60 protein compared to the level of the major outer membrane protein. Treatment with azithromycin finally resulted in suppression of rRNA synthesis. Chlamydial lipopolysaccharide and processed, functional rRNA were detectable throughout the entire incubation period. These in vitro data show a good correlation to those from some recent clinical investigations that have reported on the persistence of chlamydia, despite appropriate antibiotic treatment with azithromycin. Rifampin was highly active by in vitro susceptibility testing, but prolonged exposure to rifampin alone for up to 20 days resulted in the emergence of resistance. No development of resistance to rifampin was observed when chlamydia-infected cells were incubated with a combination of azithromycin and rifampin. This combination was shown to be more efficient than azithromycin alone, in that suppression of rRNA synthesis occurred earlier. Thus, such a combination may prove more useful than azithromycin alone.
Optimised sample DNA preparation for detection of Chlamydia trachomatis in synovial tissue by polymerase chain reaction and ligase chain reaction.
OBJECTIVE: Molecular biology techniques such as polymerase chain reaction (PCR) and ligase chain reaction (LCR) are routinely used in research for detection of C trachomatis DNA in synovial samples, and these methods are now in use in some clinical laboratories. This study aimed at determining the method best suited to molecular diagnosis of C trachomatis by examining four standard DNA preparation methods using chlamydia spiked synovial tissue and chlamydia infected monocytes. METHODS: Synovial tissue from a chlamydia negative patient with rheumatoid arthritis was spiked with defined numbers of C trachomatis elementary bodies (EB). Purified human peripheral monocytes from normal donors were infected with the organism at a multiplicity of infection 1:1 in vitro and harvested after four days. DNA was prepared from all samples by four methods: (1) QIAmp tissue kit; (2) homogenisation in 65 degrees C phenol; (3) incubation at 97 degrees C; (4) proteinase K digestion at 97 degrees C. DNA from methods 1 and 2 was subjected to PCR using two different primer sets, each targeting the C trachomatis omp1 gene. LCR was done on DNA prepared by each method. RESULTS: In synovial tissue samples spiked with EB, and in monocytes persistently infected with the organism, preparation of template using the QIAmp tissue kit (method 1) and the hot phenol extraction technique (method 2) allowed sensitive detection of C trachomatis DNA. These methods also produced template from both sample types for LCR. DNA prepared by heat denaturation (method 3) allowed only low sensitivity chlamydia detection in LCR and did not work at all for PCR. Proteinase K digestion plus heat denaturation (method 4) gave template that did not allow amplification in either PCR or LCR assays. CONCLUSIONS: The sensitivity of detection for C trachomatis DNA in synovial tissue by PCR and LCR depends strongly on the method used for preparation of the amplification template. LCR targeting the multicopy chlamydial plasmid and two nested PCR assay systems targeting the single copy omp1 gene showed roughly equivalent sensitivity. Importantly, template preparation method and the specific PCR primer system used for screening must be optimised in relation to one another for highest sensitivity.
The national database of the German Collaborative Arthritis Centres: I. Structure, aims, and patients.
OBJECTIVE: To describe the aims, principles, and content of the German rheumatological database and to present data on patient mix and healthcare provision for the year 1998. METHODS: The German rheumatological database contains clinical and patient derived data of the outpatients with inflammatory rheumatic diseases seen at one of the 24 collaborative arthritis centres. The case mix, institutional context, and demographic features of 25 653 patients from the year 1998 were analysed. RESULTS: 51% of the patients had rheumatoid arthritis, 23% seronegative spondyloarthropathies, including ankylosing spondylitis, psoriatic arthritis, and reactive arthritis, and 19% had vasculitis, including SLE (5%). The distribution of the age at onset of patients with RA with < or = 2 years' disease duration was comparable with recent incidence data from population studies. The case mix differed between university departments and rheumatology hospitals as well as individual practices. 65% of the male and 46% of the female patients at ages 18-60 were still in gainful employment, the rates of employment were 14% below the population rates for women, and 11% below those for men. 62% of all patients had seen a rheumatologist within the first year of disease, 73% within the first two years. Ankylosing spondylitis was seen in rheumatological care much later than all other diseases (only 39% within the first year). The mean number of contacts with a rheumatologist was five a year; rheumatologists in individual practices saw their patients seven times a year on the average. Together with visits to the non-specialist doctor mainly treating the patient, the mean number of visits to the doctor for a rheumatic condition was 20 a year. CONCLUSION: Large databases like this one give information about the patient case mix in different healthcare settings, about treatment practice, and about the consequences of disease. Patients treated in specialised rheumatology units in Germany are referred earlier than in the past, which probably reflects better regional cooperation due to the implementation of arthritis centres. University departments and outpatient clinics of rheumatology hospitals contribute considerably to the specialised care of patients with arthritis and connective tissue diseases.