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Biomedical subjects

J Sieper

Publications and source records attributed to J Sieper.

At least 127 records · Page 7Linked to original sources
PubMed2000

On the difficulties of establishing a consensus on the definition of and diagnostic investigations for reactive arthritis. Results and discussion of a questionnaire prepared for the 4th International Workshop on Reactive Arthritis, Berlin, Germany, July 3-6, 1999.

OBJECTIVE: There is no agreement on how to classify and diagnose reactive arthritis (ReA) and it is also unclear what kind of specific clinical and laboratory investigations are appropriate. We define relevant points of agreement and identify points of disagreement among an international group of experts in the field. METHODS: Prior to the 4th International Workshop on Reactive Arthritis, Berlin, July 1999, we sent questionnaires to 42 experts identified by personal knowledge and recent publications. RESULTS: The response rate was 81% (n = 34). There was agreement on the nomenclature and recommendation to use the term "reactive arthritis" only if the clinical picture and the microbes involved are HLA-B27 and spondyloarthropathy (SpA) associated, whereas the term "infection related arthritis" is used for all other arthritides related to or associated with infections. A differentiation between acute and chronic ReA with a cutoff of 6 months is recommended. The history of a preceding symptomatic infection is thought to be most relevant for a diagnosis of ReA. The minimal interval between preceding symptoms and arthritis is proposed to be 1-7 days, maximally 4 weeks. The joint pattern in ReA is asymmetrical, with predominance of the lower limbs. SpA related symptoms may contribute to the diagnosis. A search for chlamydia in urine/urethra/cervix is recommended, while in the case of diarrhea enterobacteria should be searched for in stool and antibodies against them in serum. There were also areas of disagreement, such as: Is arthritis essential for the diagnosis of ReA?, Is it oligoarthritis or any arthritis?, What are the role and value of polymerase chain reaction investigation?, The role and value of serology?, Is the diagnostic sensitivity of microbiological tests for ReA increased by HLA-B27 determination? CONCLUSION: The points of agreement will support better communication in this area, and clarification of the disagreements will lead to further studies and discussion.

Arthritis, Reactive↗
PubMed1999

[Abdominal actinomycosis after stomach surgery in a patient with long-term rheumatoid arthritis treated with methotrexate].

HISTORY AND ADMISSION FINDINGS: A 78-year-old woman had a 30-year history of rheumatoid arthritis, of late treated with prednisolone and methotrexate. A week before admission she had first noticed a mass about 3 cm in diameter, at the lower end of a scar from a Billroth II gastric resection for gastric ulcer, performed 4 months before. She reported to have lost 6.5 kg in weight. On admission a moderately mobile, hard mass was palpated on the abdomen. INVESTIGATIONS: Ultrasound and computed tomography revealed a superficial, inhomogenous space-occupying lesion with poorly circumscribed margins. TREATMENT AND COURSE: After two days the skin over the mass became reddened and a laparotomy was performed because an incarcerated herniation was suspected. An abscess and inflammatory adhesions were found in the area of the transverse colon, histologically shown to be a chronic purulent abscess with granular clusters of pathogens indicating actinomycosis. After 3 weeks' treatment with imipenem i.v. the patient became free of symptoms, oral doxycyclin was continued for a further 6 months. CONCLUSION: Actinomycosis should be considered in the differential diagnosis of a tumour of undetermined benignity in the region of the head, chest or abdomen in immunosuppressed patients. This bacterial infection should be thought of especially if the gastrointestinal mucosa has been penetrated by invasive procedures.

Abdominal Abscess↗
PubMed1999

No benefit of long-term ciprofloxacin treatment in patients with reactive arthritis and undifferentiated oligoarthritis: a three-month, multicenter, double-blind, randomized, placebo-controlled study.

OBJECTIVE: To investigate the effect of long-term antibiotic treatment in patients with reactive arthritis (ReA) and undifferentiated oligoarthritis. METHODS: One hundred twenty-six patients were treated with ciprofloxacin (500 mg twice a day) or placebo for 3 months, in a double-blind, randomized study. Of these patients, 104 (48 treated with ciprofloxacin and 56 treated with placebo) were valid for clinical evaluation: 55 were diagnosed as having ReA with a preceding symptomatic urogenic or enteric infection and 49 as having undifferentiated oligoarthritis. These 2 groups were randomized separately. The triggering bacterium was sought by serology and/or culture. The percentage of patients in remission after 3 months of treatment was chosen as the primary efficacy parameter. RESULTS: A triggering bacterium could be identified in 52 patients (50%): Chlamydia trachomatis in 13, Yersinia in 14, and Salmonella in 25. No patient was positive for Campylobacter jejuni or for Shigella. No difference in outcome was found between treatment with ciprofloxacin or placebo in the whole group or in subgroups of patients with ReA or undifferentiated oligoarthritis. No difference was seen in patients with a disease duration <3 months. Ciprofloxacin was not effective in Yersinia- or Salmonella-induced arthritis but seemed to be better than placebo in Chlamydia-induced arthritis. This difference was not significant, however, which might be due to the small sample size. CONCLUSION: Long-term treatment of ReA with ciprofloxacin is not effective; however, it might be useful in the subgroup of patients who have Chlamydia-induced arthritis. This has to be proven in a bigger study focusing on patients with Chlamydia-induced arthritis.

Adult↗
PubMed1999

Low secretion of tumor necrosis factor alpha, but no other Th1 or Th2 cytokines, by peripheral blood mononuclear cells correlates with chronicity in reactive arthritis.

OBJECTIVE: To determine Th1 and Th2 cytokine production in patients with reactive arthritis (ReA) in relation to disease outcome and in comparison with rheumatoid arthritis (RA). METHODS: Secretion of tumor necrosis factor alpha (TNFalpha), interferon-gamma, interleukin-10 (IL-10), and IL-4 by peripheral blood mononuclear cells (PBMC) from 53 patients with early ReA (disease duration <8 weeks, 64% HLA-B27 positive) and 30 patients with early, untreated RA (disease duration <6 months) was determined by enzyme-linked immunosorbent assay (ELISA) after ex vivo stimulation. Intracellular cytokine staining with quantification of positive T cells by fluorescence-activated cell sorting (FACS) was performed in 12 ReA patients and 12 RA patients. In 27 ReA patients, cytokine secretion was measured again after 3 months. Patients were followed up for 1 year, and cytokine patterns were correlated with disease duration. RESULTS: TNFalpha secreted by whole PBMC and by T cells was significantly lower, by ELISA and by FACS, in ReA patients than in RA patients, while no significant differences were detected for the other cytokines. ReA patients with a disease duration of > or =6 months showed significantly lower TNFalpha secretion than patients with a disease duration of <6 months (mean +/- SD 385 +/- 207 pg/ml versus 684 +/- 277 pg/ml; P = 0.003). Furthermore, low TNFalpha secretion after 3 months also correlated significantly with a more chronic course of disease. HLA-B27 positive patients secreted less TNFalpha than did those who were B27 negative (338 +/- 214 pg/ml versus 512 +/- 207 pg/ml; P = 0.05), and patients with a more chronic course had a higher frequency of B27 positivity (47% versus 80%; P = 0.01). Among the 27 HLA-B27 positive patients, TNFalpha secretion in those with a disease duration of > or = 6 months was lower than that in the 7 with a disease duration of <6 months (308 +/- 167 pg/ml versus 562 +/- 308 pg/ml; P = 0.04). CONCLUSION: Low TNFalpha secretion and HLA-B27 status correlate with longer disease duration in ReA patients, possibly with an additive effect. The diminished TNFalpha production might reflect a state of relative immunodeficiency contributing to bacterial persistence in ReA.

Adult↗
PubMed1999

[New aspects of treatment and prophylaxis of gastrointestinal side effects caused by non-steroidal-antiinflammatory drugs].

Gastropathies caused by treatment with non-steroidal-antiinflammatory drugs (NSAIDs) are a frequent problem in rheumatology. An increased risk for this complication has been established for patients older than 70 years, for those with a history of ulcer and those under concomitant steroid medication. Especially those patients should be treated with gastroprotective drugs. In differing intensity, protone pump inhibitors, prostaglandine analog and H2 blockers are able to prevent such problems and give some symptomatic relief. Most complications can be prevented using omeprazole, the newest and most expensive drug, in a dosage of 20 mg/day, a higher dosage is not more effective. This drug works also in many cases when the NSAID therapy has to be continued. A significant effect on the prevalence of serious GI effects was only shown for misoprostol in a dosage of 800 microg/day to date. Some influence on the risk for GI events can also be taken by questioning the indication, choice of the NSAID and proper information of the patient. The development of COX-2-selective and even specific NSAIDs might solve some of these drug related GI problems in the near future.

Adult↗
PubMed1999

Cytokines and the immunopathology of the spondyloarthropathies.

In contrast to rheumatoid arthritis (RA), the triggering antigens are known in reactive arthritis (ReA) and Lyme arthritis. Thus, in these arthritides the antigen-specific T-cell response can be investigated in much detail and lessons possibly learned for other spondyloarthropathies (SpA) such as ankylosing spondylitis (AS) where T cells may well also play an important role in the pathogenesis. This article focusses on the immunopathology of the SpA, ReA, and AS with special reference to T cells and cytokines.

Arthritis, Reactive↗
PubMed1999

The elevated ratio of interferon gamma-/interleukin-4-positive T cells found in synovial fluid and synovial membrane of rheumatoid arthritis patients can be changed by interleukin-4 but not by interleukin-10 or transforming growth factor beta.

OBJECTIVES: To quantify the T-helper type (Th) 1 cytokine interferon gamma (IFN-gamma)-positive and the Th2 cytokine interleukin (IL)-4-positive cells in synovial fluid (SF) and synovial membrane (SM) at the single-cell level in rheumatoid arthritis (RA) in comparison to reactive arthritis (ReA), and to manipulate the cytokine pattern of RA patients in vitro. METHODS: Eighteen patients with RA and 17 with ReA were studied. For intracellular staining of cytokines, SF mononuclear cells (MNC) from seven patients with RA, in comparison to eight patients with ReA, were triple stained with anti-IFN-gamma, IL-4 and anti-CD4 or anti-CD8 monoclonal antibodies (mAb) and analysed by flow cytometry. Furthermore, in 13 patients with RA, immunohistology of SM was performed and compared with seven ReA patients. In addition, in six of the RA patients, synovial T cells were grown over 3 weeks in the presence of various cytokines and intracellular cytokine staining analysed by flow cytometry weekly. RESULTS: In SF, the mean percentage of IFN-gamma+/CD4+ T cells in RA was almost 4-fold higher than the number of IL-4+/CD4+ T cells (11.3+/-5 vs 3.02+/-1.04; P=0.0012), while the ratio of IFN-gamma/IL-4+ CD4+ T cells was only 1.59 in ReA (P=0.047 for the ratio difference). A similar result was obtained for SM: the ratio of IFN-gamma/IL-4+ cells in RA was 4.3 (P<0.0001 for the IFN-gamma/IL-4 difference), but only 1.2 for ReA (P=0.02 for the ratio difference). Of the CD3+ cells in SM, 2.8% were positive for IFN-gamma and 0.4% for IL-4 in three RA patients. A decrease in the number of IFN-gamma-positive SF T cells and an increase in the number of IL-4-positive SF T cells could be achieved in vitro through IL-4, but not by IL-10 or transforming growth factor beta. CONCLUSIONS: The Th1 pattern in the joint of RA patients demonstrated at the single-cell level may be important for the pathogenesis of RA and may provide a target for future immunotherapy. Our data suggest a therapeutic role for IL-4.

Adolescent↗
PubMed1999

The detection of DNA from a range of bacterial species in the joints of patients with a variety of arthritides using a nested, broad-range polymerase chain reaction.

OBJECTIVE: Bacteria have been implicated in the pathogenesis of many types of inflammatory arthritides. The aim of this study was to identify any bacterial DNA in synovial fluid (SF) from patients with a range of inflammatory arthritides. METHODS: A highly sensitive, broad-range, nested polymerase chain reaction (PCR) protocol targeting the bacterial 16S rRNA gene was designed and applied to SF from 65 patients with a range of rheumatic diseases. RESULTS: Bacterial DNA was detected in 26 SF samples, including eight from patients with rheumatoid arthritis and five with juvenile arthritides. PCR products were identified by sequencing and searching of bacterial genomic databases; 'best fits' included Haemophilus influenzae, Bordetella and Yersinia. CONCLUSIONS: These finding suggest an association between bacterial infection and inflammatory arthritides in some patients. Further research is required to determine the role of these organisms in the pathogenesis and whether such patients might respond to prolonged antibiotic therapy.

Adolescent↗
PubMed1999

Studying patients with inflammatory back pain and arthritis of the lower limbs clinically and by magnetic resonance imaging: many, but not all patients with sacroiliitis have spondyloarthropathy.

OBJECTIVE: Clinical and magnetic resonance imaging (MRI) data of 170 consecutive patients with inflammatory back pain (IBP) and/or oligoarthritis of the lower limbs were evaluated in a retrospective study. The aim was to determine the frequency of sacroiliitis and spondyloarthropathy (SpA) in this population, and to assess the significance of HLA B27 measurements for diagnosis in early disease. METHODS: Pelvic X-rays were performed in all IBP patients and dynamic MRI of the sacroiliac joints in patients with IBP who had indefinite results on sacroiliac X-rays (n = 32). RESULTS: European Spondyloarthropathy Study Group criteria for SpA were fulfilled by 106/170 patients (62.4%); eight additional patients had symptoms suggestive of SpA (4.7%). The most frequent SpA subset was undifferentiated SpA (uSpA), diagnosed in 46/106 patients (43.4%). Sacroiliitis was detected by MRI in 21/32 patients with IBP and unclear X-rays (65.6%). Of those, 14 were diagnosed as SpA and seven females with moderate unilateral sacroiliitis, but no features of SpA, also not on follow-up (at least 1 yr), were classified as undifferentiated sacroiliitis (US). Ten of the 14 SpA (71.4%) and none of the seven US patients were HLA B27 positive. CONCLUSION: HLA B27 positivity in IBP patients with MRI-proven sacroiliitis positively predicts SpA. uSpA is a frequent SpA subset. There are HLA B27-negative non-SpA patients with moderate unilateral sacroiliitis whom we propose to be classified as US.

Adult↗
PubMed1999

Rheumatologic manifestations of gastrointestinal disorders.

There are many different rheumatic symptoms of gastrointestinal (GI) disorders and a whole range of GI symptoms that occur in rheumatologic disorders. Spondyloarthropathies (SpA) are closely related to the GI tract. Bacterial DNA has been detected in peripheral but not the sacroiliac joints of patients, including enterobacteria; the significance of this finding is not clear yet because antibiotic therapy seems not to be effective. The synovial lymphocyte proliferation of reactive arthritis (ReA) patients to the 60-kD heat-shock protein of Yersinia plays a major role in the immune response. Anti-Klebsiella antibodies are associated with gut lesions in SpA; their significance for the pathogenesis of SpA remains uncertain. ReA patients seem to have an impaired TH1-cytokine response, which might contribute to disease persistence. HLA B27-positive subjects seem to have a low tumor necrosis factor-alpha secretor status, possibly leading to diminished immune responses against certain microbes. In patients with Whipple's disease, Tropheryma whippelii can be cultured from gut biopsy specimens when interleukin-4 is added. The gene for hemochromatosis has been identified. Hepatitis C virus DNA can be found in many patients with cryoglobulinemia. Treatment with interferon-alpha might help in some patients. Effective treatment for primary biliary cirrhosis with ursodeoxycholic acid is not helpful for rheumatic symptoms. The severity of esophageal dysfunction in systemic sclerosis does not correlate with symptoms. GI symptoms do, although not frequently, occur in vasculitides.

Bacterial Infections↗
PubMed1999

Reactive arthritis.

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Arthritis, Reactive↗
PubMed1999

Immunohistological analysis of cytokine expression in human osteoarthritic and healthy cartilage.

OBJECTIVE: To investigate osteoarthritic cartilage in comparison to normal cartilage in humans for the presence of the most relevant cytokines/growth factors known to be important for degradation and formation of new cartilage. METHODS: Cartilage from knee or hip joints was obtained from 10 patients with osteoarthritis (OA) and from 7 age matched control patients with intact cartilage. Additionally, normal cartilage from 2 young patients (12 and 17 years old) was obtained after knee traumas. Immunohistological staining of cartilage sections was performed using antibodies for the following cytokines/growth factors: tumor necrosis factor alpha (TNF-alpha), interleukin 1alpha (IL-1alpha), IL-1beta, interferon-gamma, IL-6, IL-4, IL-10, transforming growth factor beta1 (TGF-beta1), insulin-like growth factor I (IGF-I), IGF-II, platelet derived growth factor AA (PDGF-AA), and PDGF-BB. RESULTS: Immunohistochemical stainings were positive for all cytokines in OA cartilage, while only a faint or no staining was found in healthy cartilage. Activated chondrocytes expressing most of the cytokines were located in the middle and partly in the lower layer of cartilage, with the exception of IGF-I, which was expressed exclusively in the upper cartilage layer close to the surface. More chondrocytes stained positive for TNF-alpha than for IL-1, and expression of the degrading cytokine TNF-alpha was inversely correlated to the expression of the regulatory cytokines IL-4, IL-10, and TGF-beta. CONCLUSION: The most relevant cytokines known to be involved in cartilage metabolism are produced by chondrocytes themselves. They are upregulated in OA cartilage, suggesting that they serve some regulatory function and could be a target for future treatment.

Adolescent↗
PubMed1999

The 19 kDa protein of Yersinia enterocolitica O:3 is recognized on the cellular and humoral level by patients with Yersinia induced reactive arthritis.

OBJECTIVE: Gastrointestinal infections with Yersinia enterocolitica O:3 (YE O:3) can trigger reactive arthritis (ReA). The cellular immune response seems to be of pathogenic importance in ReA, since synovial fluid mononuclear cells (SFMC) of patients with ReA have been shown to recognize YE O:3 antigens. One of these, a 19 kDa protein identified as the beta-urease subunit of YE, has been identified as a target of SFMC. We investigated the humoral immune response to this antigen. METHODS: Sera of 32 patients with SFMC proliferation to YE O:3 diagnosed as having ReA (n = 16) and undifferentiated oligoarthritis (UOA, n = 16), and of patients with other rheumatic diseases (n = 32) and healthy persons (n = 12) were investigated for the humoral response to the biochemically purified 19 kDa protein of YE. Anti-19 kDa antibodies (ab) were identified by immunoblotting; ab to the Yersinia outer membrane protein (YOP) antigen were detected by ELISA. Proliferation of SFMC to 19 kDa and other YE O:3 antigens was tested in 12 patients in parallel. RESULTS: SFMC of all 32 patients with ReA and UOA showed the highest proliferation to YE O:3 (13.7+/-7.5), and 10/12 of these patients had the highest stimulation index to the 19 kDa (14.9+/-6.4). Anti-19 kDa IgG ab were detected in 93% and 55% and anti-19 kDa IgA ab in 56% and 36% of the ReA and UOA patients, respectively, compared to 26% (p = 0.002) and 8% (p = 0.001) in controls. IgG ab to the 19 kDa were sensitive (93%) and IgA ab specific (92%) to detect patients with a synovial cellular response to YE. IgG ab to YOP were found in 62% and IgA ab in 46% of the ReA patients and in 32% (p = 0.002) and 13% (p = 0.004) of the controls. CONCLUSION: This study provides evidence of a cellular and a significant humoral immune response to the 19 kDa protein in Yersinia triggered arthritis. Detection of IgG antibodies to the 19 kDa correlates with a synovial cellular immune response in YE induced arthritis. These antibodies can be used as a screening system for research and possibly also for clinical purposes, since absence of such antibodies seems to negatively predict YE O:3 directed immune reactivity.

Adolescent↗