Scandinavian journal of rheumatology. Supplement最新文献

Previous studies evaluating the efficacy and tolerance of tropisetron for the treatment of fibromyalgia (FM) used the drug either intravenously or orally, and at different dosage levels ranging from 2 mg to 15 mg daily. The shortest treatment was a single dose and the longest treatment period covered 28 days. A significant reduction of the pain intensity was achieved by using tropisetron 5 mg per day. Apart from the fact that treatment periods were different, the efficacy of oral and intravenous administration did not differ significantly. Tropisetron was well tolerated; but in the 15 mg group in one of the studies, the decrease in pain was less than in the placebo group, however, the frequency of constipation and other gastrointestinal symptoms increased. Furthermore, it was hypothesized that due to the impacts of CYP2D6 activities, a daily dose of tropisetron 2 mg may be efficacious in slow metabolizers only. Although tropisetron proved to be efficacious in a group of fibromyalgia patients, the dose-response curves cannot yet be explained in a fully satisfactory manner, which may encourage research focusing on possible subgroups of FM.

Preliminary results of an ongoing study on the effectiveness of trigger point injections with tropisetron in 20 patients with late whiplash-associated disorder are presented. The study demonstrated more than 50% pain relief for more than 2 weeks in 52% of the 73 treatment sessions. The duration of effectiveness of the injections showed great intraindividual and interindividual variation.

There is evidence from both human and animal research that 5-hydroxytryptamine3 (5-HT3) receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects including the expression of 5-HT3 receptors in cells of the immune system have not yet been investigated in detail. Therefore, we investigated the expression of the 5-HT3A receptor in primary human monocytes, chondrocytes, T-cells, dendritic cells, and synovial tissue. We found that 5-HT3A receptors are expressed in monocytes, chondrocytes, T-cells, and synovial tissue but not in dendritic cells. Our data show that 5-HT3A receptors are widely expressed in cells of the immune system and that they might play an important role in inflammatory events and in the observed antiphlogistic effects of 5-HT3 receptor antagonists.

There is evidence from both human and animal research that 5-hydroxytryptamine (5-HT)3 receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects have not yet been investigated in detail. Therefore, the antiinflammatory effects of tropisetron and ondansetron were investigated in human monocytes. In human monocytes, both lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion were dose-dependently inhibited by tropisetron starting at a concentration of 5 microg/mL and reaching maximal levels at 25 microg/mL (IC50: 32 microg/mL and 12 microg/mL, respectively). LPS-induced IL-6 and PGE2 release was only slightly inhibited at high doses, whereas LPS-induced release of IL-8 and matrix metalloprotease (MMP)-9 was not affected. In conclusion, our data show that the binding of tropisetron to 5-HT3 receptors results in antiinflammatory effects through inhibition of TNF-alpha/IL-1beta, which might explain the antiphlogistic effects of 5-HT3 antagonists.

Objective: The purposes of the present study were: 1) to investigate how the long-term course of outcome and inflammatory variables could be described in individual patients and suitably summarized in groups of patients; 2) to investigate the associations between outcome and inflammatory variables on the basis of the defined summary measures; and 3) to investigate new prognostic aspects of RA by means of frozen sera and DNA specimens.

Patients and methods: During the period 1966-78, 685 Danish Caucasian patients with RA, classified according to the 1958 American Rheumatism Association (ARA) criteria, were admitted to the Department of Rheumatology of Aarhus University Hospital. For scientific purposes all patients went through the same examination programme, including biochemical variables, clinical evaluation of 68 diarthrodial joints, and radiographic evaluation of 46 diarthrodial joints. Since 1987, data from these patients have been organized in a database. The data are arranged according to onset of disease. This thesis is based on about 600,000 data-points from 257 patients.

Results: The thesis is based on six studies. The first study shows that early symptomatic improvement of RA during gold treatment was stable over several years, but when evaluated radiographically, the condition continued to deteriorate. In the second study, six main types of radiographic progression were identified: (a) a rare type with no radiographic progression at all (<1%); (b) a type with a slow or moderate onset, but an increasing progression rate (exponential growth type) (9%); (c) a linear type (30%); (d) a type with a moderate to fast onset, and a stable progression rate (the square root type) (11%); (e) a type with a fast onset, but a later decreasing progression rate (the first order kinetics type) (30%) and (f) a type characterized by slow onset, then acceleration and later deceleration (the sigmoid type) (20%). The fact that there was a systematic progression was used to define a system of radiographic events, which could be used as outcome measures in prediction models of the long-term course of RA. The third study shows that low serum levels of the complement-activating serum lectin, mannan (mannose) binding protein (lectin) (MBP = MBL), are associated with a higher erythrocyte sedimentation rate (ESR) (p=0.006), joint swelling score (JS score) (p=0.019), limitation of joint motion score (LM score) (p=0.027), and annual increase in radiographic destruction score (R score) (p=0.053). The fourth study demonstrated a highly significant association between summary measures of inflammatory variables and radiographic outcome, as defined in the second study, indicating that the degree of inflammation is important for the development of destructive joint damage in RA. The fifth study showed that MBL-insufficient patients (two defective structural MBL alleles, or one defective allele combined with

In 223 fibromyalgia (FM) patients in a rheumatology practice, a follow-up postal survey was carried out 0.5-2 years after a 5-day intravenous (i.v.) treatment with 5 mg of the 5-HT3 receptor antagonist tropisetron daily on the effect of this treatment. 121 patients returned the completed questionnaire. After subtraction of 22 undeliverable questionnaires, this represented 60.2% of patients contacted for whom an assessment of the tropisetron treatment was possible. A good to very good effect of the treatment on the pain was reported by 45% of the patients, and only 25% reported an unsatisfactory effect. The effect of tropisetron IV lasted between one day and 12 weeks (mean 8.6 +/- 13.6 d). Sleep and general condition were also assessed as good or very good by almost half of the patients. The tolerance of tropisetron was generally good. In comparison with the current treatment and the best treatment with other drugs ever received, tropisetron was rated as more efficacious in almost half of the cases, though an unsatisfactory effect of tropisetron compared to other treatments was reported in 30% of the cases. Considered in comparison to less or at most equally efficacious alternatives, according to this open respective study, IV tropisetron treatment represents a promising option for the treatment of FM even though the study design incorporated many imponderables. Particularly the question of whether the success of treatment can be improved further with a longer lasting treatment or a selection of the patients still needs to be settled.

Background: Various pathophysiological processes can lead to chronic back pain, which necessitates a differentiated therapeutic approach. In addition, psychic and psychosocial processes may influence the clinical picture.

Method: Twenty-five patients with chronic back pain were enrolled in the study. Patients suffering from psychosocial stresses and depressions were excluded from the study. The patients with painful tendinopathies and myofascial pain syndromes were treated with local injections of 5-10 mg tropisetron, and patients with degenerative processes were treated for 5 days with an intravenous (i.v.) bolus injection of 5 mg tropisetron (Navoban). Before treatment and 7 and 14 days later, the visual analog pain scale was filled in. The long-term drug therapy could be continued.

Results: There was a highly significant pain reduction with a very potent effect both in the locally treated group and in the intravenously treated group. Most of the patients could discontinue or reduce their long-term therapy with non-steroidal anti-inflammatory drugs or analgesics.

Conclusion: A marked improvement in pain could be achieved in an open study by treating back pain of a primarily somatic nature with the 5-HT3 receptor antagonist tropisetron. A reduction in pain of > or =50% was reported by 76% of the patients. These results should be substantiated by the corresponding randomized, placebo-controlled, double blind studies that are needed to investigate the true benefit of treating back pain with 5-HT3 receptor antagonists.

Background: Substance P is found at an elevated level in the cerebrospinal fluid of fibromyalgia (FM) patients. Treatment with tropisetron leads in a subgroup of FM patients to pain reduction. The question arises of whether the substance P level in the serum can be changed by tropisetron treatment.

Method: Twenty patients with FM diagnosed according to the ACR criteria were treated for 5 days with a 5 mg tropisetron intravenous (i.v.) bolus injection daily. Before the first injection, 3 h later, and before and 3 h after the last injection, the serum levels of substance P were determined. The determination of this substance was carried out by means of an immunoassay from Assay Design Biotrend, Cologne. To evaluate the success of the tropisetron treatment, patients made a global assessment as 'clearly better', 'better', 'unchanged', or 'poor'. Patients who answered 'clearly better' and 'better' were regarded as responders.

Results: Of the 20 patients, ten reported a good or very good influence on their pain (responders). In these responders, the means of the serum substance P levels were elevated in comparison with the non-responders, though the difference was not significant. In responders, the 5-HT3 receptor antagonist tropisetron produced a significant decrease in the serum substance P levels, while this did not occur in the non-responders.

Conclusion: It is possible that the responders to tropisetron represent a subgroup of FM patients for whom substance P and 5-HT3 receptors play key roles in the development of the pain symptoms.