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Biomedical subjects

J Kekow

Publications and source records attributed to J Kekow.

At least 19 recordsLinked to original sources
PubMed2005

Treatment continuation in patients receiving biological agents or conventional DMARD therapy.

OBJECTIVE: To compare drug continuation rates in patients with rheumatoid arthritis who start on a biological agent and in a control group of patients with a change in disease modifying antirheumatic drug (DMARD) treatment after previous DMARD failure. METHODS: Patients with rheumatoid arthritis enrolled in the German biologics register between May 2001 and September 2003 were included in the study. Data were available for 511 patients treated with etanercept, 343 with infliximab, 70 with anakinra, and 599 controls. Propensity scores were used to select a subsample of patients from the control group who were likely to be treated with biological agents because of their disease severity, as well as comparable infliximab and etanercept cases. RESULTS: Treatment continuation after 12 months was similar for etanercept (68.6% (95% confidence interval, 62% to 75%)) and infliximab (65.4% (58% to 73%)) but lower for anakinra (59% (41% to 77%)). Treatment continuation was more likely for patients on combinations of biological agents and DMARDs than for those on infliximab or etanercept alone. Patients treated with biological agents were more severely ill than those in the control group and had more previous DMARD failures. After adjustment for baseline differences, the continuation rates were higher in patients treated with biological agents than in comparable control patients treated with leflunomide or leflunomide/methotrexate. CONCLUSIONS: Treatment continuation of biological agents in clinical practice is less likely than in randomised clinical trials but more likely than in comparable controls treated with conventional DMARDs.

Adolescent↗
PubMed2004

Interleukin 10 promoter microsatellite polymorphisms are associated with response to long term treatment with etanercept in patients with rheumatoid arthritis.

OBJECTIVES: To analyse the association of interleukin 10 (IL10) promoter polymorphisms, which have been shown to be related to IL10 secretion capacity, with the response to long term treatment with etanercept in patients with rheumatoid arthritis (RA). METHODS: Fifty patients with active RA were treated for up to 4 years (median 39 months, range 3-52) with stable doses of etanercept as monotherapy. Treatment response was assessed as defined by the EULAR criteria in an intention to treat analysis, with the last observation carried forward. IL10 promoter microsatellite polymorphisms IL10.R and IL10.G were genotyped by fragment length analysis in patients and 189 healthy controls matched for ethnicity, age, and sex. Haplotypes were reconstructed using a method based on bayesian, coalescent theory with the PHASE software. RESULTS: IL10 microsatellite polymorphisms were not associated with susceptibility to RA. When patients with good treatment response (n = 25) were compared with patients with moderate (n = 17) or no response (n = 8), a significantly different distribution of the prevailing alleles R2, R3 and G9, G13, respectively, became evident. Good treatment response was associated with carriage of the R3 allele or R3-G9 haplotype, whereas the allele G13 and the haplotype R2-G13 predominated in patients with moderate or no response. CONCLUSION: Genotyping of the IL10 promoter microsatellites may be useful in predicting the clinical response to etanercept in patients with RA. The high prevalence of the presumptive IL10 low producer allele R3 in patients with a favourable response suggests that IL10 promotes disease activity in RA under the specific condition of tumour necrosis factor antagonism.

Adult↗
PubMed2004

[Specialties in therapy of osteoporosis in inflammatory joint disease].

The therapeutic specialties of osteoporosis in inflammatory rheumatic diseases has gained mounting interest in the last year. The paper describes special aspects of osteoporosis in rheumatoid arthritis, ankylosing spondylitis and systemic lupus erythematodes. The problems of glucocorticoid therapy are discussed intensively with regard to the recently published recommendations for glucocorticoid-induced osteoporosis. Risk factors of osteoporosis and the therapeutic implications are demonstrated intensively as well as the modifications of the recommendations.

Arthritis, Rheumatoid↗
PubMed2002

Bone substitutes as carriers for transforming growth factor-beta(1) (TGF-beta(1)).

We studied the suitability of three different hydroxyapatite materials (Endobone, Bio-Oss and Algipore) as carriers for the bone growth promoting factor TGF-beta(1). The hydroxyapatite materials either were incubated for 24 h or directly loaded with hrTGF-beta(1) (Diagnostic Products Corporation, DPC) at a concentration of 10 ng hrTGF-beta(1)/mg. For the release experiment the hydroxyapatite materials covered with hrTGF-beta(1) were either suspended in pure phosphate buffered saline (PBS) or human serum albumin (HSA). The concentration of hrTGF-beta(1) was measured every 6 h the first day and then daily at the 2nd, 7th, 14th and 28th day. With Bio-Oss and Endobone the release of growth factor in HSA showed a two-phase kinetics. TGF-beta(1) reached a maximum concentration within the first 24 h and decreased almost linearly until day 28. With Algipore the concentration of growth factor reached a maximum after 12 h and showed a rapid decline until day 2. From day 2 the TGF-beta(1) concentrations remained low. Significantly, more TGF-beta(1) was released into HSA than into PBS. Our study suggests that the hydroxyapatite materials are suitable as TGF-beta(1) carriers.

Biocompatible Materials↗
PubMed2002

Soluble tumour necrosis factor receptor treatment does not affect raised transforming growth factor beta levels in rheumatoid arthritis.

OBJECTIVE: To further elucidate the immunomodulating effects of anti-tumour necrosis factor alpha treatment in rheumatoid arthritis (RA) by studying changes in plasma levels of transforming growth factor beta (TGFbeta) in patients with RA undergoing etanercept treatment. METHODS: Plasma levels of TGFbeta1 and TGFbeta2 were determined in 26 patients with RA during six months of etanercept treatment and compared with disease activity and laboratory parameters, including matrix metalloproteinase-3 (MMP-3) and interleukin 6 (IL6). RESULTS: Before treatment all patients had raised TGFbeta1, IL6, and MMP-3 levels. In the course of treatment IL6 and MMP-3 levels decreased significantly, accompanied by a drop in serological markers (C reactive protein and erythrocyte sedimentation rate) and clinical disease activity (visual analogue scale and Thompson joint score). By contrast, high levels of latent TGFbeta1 were present in all specimens over the entire six months. TGFbeta2 levels did not change during treatment. CONCLUSION: Etanercept treatment induces subtle changes in the cytokine network. Although the proinflammatory cytokine IL6 is down regulated, the persistence of high TGFbeta plasma levels indicates the existence of as yet unknown mechanisms for TGFbeta overexpression in RA. This may predispose to severe infections and can cause an altered tumour defence.

Antirheumatic Agents↗
PubMed2001

WHO Collaborating Centre consensus meeting on anti-cytokine therapy in rheumatoid arthritis.

Severe adult rheumatoid arthritis is a cause of progressive disability and increased mortality across Europe. A cure for the disease remains elusive, but control of symptoms and maintenance of individual independence is possible. Anti-cytokine therapies offer a new approach to disease management. They are effective after the failure of full doses of methotrexate, and are at least as effective as methotrexate in retarding the progression of radiological changes. Until more is known about the long-term safety and efficacy of these drugs they should be reserved for patients with severe disease who are progressing despite adequate doses of methotrexate or other disease-modifying anti-rheumatic drugs. They should be continued until therapeutic failure or intolerance. A comprehensive health economic evaluation is needed to optimally direct the use of these drugs. This should be undertaken when long-term safety and efficacy studies are completed.

Antibodies, Monoclonal↗
PubMed2000

Neutrophils synthesize and activate TGFbeta2.

Human polymorphonuclear neutrophils (PMN) are regulated by soluble factors such as chemotactic peptides and cytokines. PMN themselves are capable of synthesizing and releasing various cytokines, thereby taking part in the afferent or inductive limb of the immune response. We report for the first time that TGFbeta2 can be synthesized and released by PMN obtained from peripheral blood. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that preparations of PMN express mRNA for transforming growth factor (TGF)beta1 and TGFbeta2 but not for TGFbeta3. Only translation of TGFbeta2 into protein was observed applying different assays. Interestingly, TGFbeta2 in supernatants from stimulated PMN could be detected in the bioactive form.

Animals↗
PubMed2000

Capsule impedes adhesion to and invasion of epithelial cells by Klebsiella pneumoniae.

The adhesion of K21a, K26, K36, and K50 capsulated Klebsiella strains to ileocecal (HCT-8) and bladder (T24) epithelial cell lines was significantly lower than that of their corresponding spontaneous noncapsulated variants K21a/3, K26/1, K36/3, and K50/3, respectively. Internalization of the bacteria by both epithelial cell lines was also significantly reduced. Similarly, a capsule-switched derivative, K2(K36), that exhibited a morphologically larger K36 capsule and formed more capsular material invaded the ileocecal epithelial cell line poorly compared to the corresponding K2 parent strain. None of the capsulated strains exhibited significant mannose-sensitive type 1 fimbriae, whereas two of the noncapsulated variants K21a/3 and K50/3 exhibited potent mannose-sensitive hemagglutinating activity. Although hemagglutinating activity that could be attributed to mannose-resistant Klebsiella type 3 fimbriae was weak in all strains, in several cases the encapsulated parent strains exhibited lower titers than their corresponding noncapsulated variants. Although the level of adhesion to the ileocecal cells is not different from adhesion to bladder cells, bacterial internalization by bladder cells was significantly lower than internalization by ileocecal cells, suggesting that bladder cells lack components required for the internalization of Klebsiella.

Bacterial Adhesion↗
PubMed1998

Humoral immune response to Klebsiella capsular polysaccharides in HLA-B27-positive patients with acute anterior uveitis and ankylosing spondylitis.

Klebsiella is suggested to trigger ankylosing spondylitis (AS) and acute anterior uveitis (AAU) in HLA-B27-positive individuals. Previous investigations showed an increased antibody response to the Klebsiella capsular types K26, K36, and K50 in sera from HLA-B27-positive AS patients. In the present study the prevalence and titers of antibodies against Klebsiella capsular antigens were measured by means of an ELISA in 32 sera from HLA-B27-positive AAU patients either with (n = 10) or without AS (n = 22) and compared with sera from HLA-B27-negative AS-patients (n = 13). Sera from either HLA-B27-positive (n = 45) or negative (n = 40) healthy individuals served as control. Sera from HLA-B27-positive AAU with or without AS showed significantly higher antibody prevalence and IgG-titers against capsular antigens of the Klebsiella serotypes K26, K36, and K50 when compared with sera from HLA-B27-negative AS patients or with healthy controls. These results might be taken to indicate the predominance of these serotypes in the HLA-B27-associated AS and AAU.

Acute Disease↗
PubMed1997

A detailed protocol for the measurement of TGF-beta1 in human blood samples.

Quantification of the multifunctional cytokine Transforming Growth Factor-beta1 (TGF-beta1) in blood samples has aroused increasing interest in recent years, since an abnormal regulation of this cytokine appears to play a key role in the pathogenesis of different diseases, such as autoimmundiseases or malignant tumors. The measurement of TGF-beta1 is complicated by a lot of problems concerning the collection, preparation and handling of blood samples, the platelet contamination, and the TGF-beta1 activation procedure. Here, we recommend detailed instructions for measurement of TGF-beta1 in blood plasma samples which should be followed to exclude the determination of false positive or negative results.

Humans↗