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Biomedical subjects

T Stratz

Publications and source records attributed to T Stratz.

At least 37 records · Page 2Linked to original sources

Effect of tropisetron on circulating catecholamines and other putative biochemical markers in serum of patients with fibromyalgia.

OBJECTIVE: The aim of the study was to assess the influence of the 5HT3-receptor antagonist tropisetron on circulating catecholamines as biochemical markers of the activity of the sympathoadrenal system in fibromyalgia. Moreover, serum concentrations of serotonin, somatomedin C, oxytocin, calcitonin-gene-related-peptide, calcitonin and cholecystokinin were assayed as putative markers in pain-related disorders like primary fibromyalgia. METHODS: In 96 patients, who met the ACR classification criteria for fibromyalgia, and in 20 sex and age matched controls concentrations of dopamine, noradrenaline, adrenaline, serotonin and tropisetron were assayed in serum by HPLC with electrochemical detection. All other transmitters were determined by ELISA. RESULTS: There was with the exception of tropisetron, calcitonin and dopamine, no correlation between doses of tropisetron 5, 10, 15 mg respectively and significant changes in circulating transmitters or other transmitters as putative biochemicals markers in primary fibromyalgia. Regarding the prediction of pain reduction to tropisetron, patients with elevated dopamine and/or reduced plasma 5-HT concentrations tended to show a higher response rate. CONCLUSION: Despite these partly disappointing results another prospective pilot study with selected patients vs. age and sex matched controls, double blind and with comparison of other 5HT3-receptor antagonists e.g. dolasetron and granisetron e.g. after i.v. bolus injection is suggested. Still the data obtained in this preliminary paper provide some evidence regarding the present discussion on subgroups of patients with primary fibromyalgia.

Analysis of Variance↗

Efficacy and tolerability of tropisetron in primary fibromyalgia--a highly selective and competitive 5-HT3 receptor antagonist. German Fibromyalgia Study Group.

OBJECTIVE: Based on a potential role for serotonin receptors in fibromyalgia, we investigated the efficacy and tolerability of treatment with tropisetron, a highly selective, competitive inhibitor of the 5-HT3 receptor. METHODS: In this prospective, multicenter, double-blind, parallel-group, dose-finding study, 418 patients suffering from primary fibromyalgia (ACR criteria) were randomly assigned to receive either placebo, 5 mg, 10 mg or 15 mg tropisetron once daily, respectively. The duration of treatment was 10 days. The clinical response was measured by changes in pain-score, visual analog scale (VAS), and the number of painful tender-points. RESULTS: Treatment with 5 mg tropisetron resulted in a significantly higher response rate (39.2%) when compared with placebo (26.2%) (p=0.033). The absolute reduction in pain-score was -13.5% for 5 mg tropisetron, -13.0% for 10 mg tropisetron, and -6.3% for placebo (p<0.05). The effects of 15 mg tropisetron were similar to placebo, thus suggesting a bell-shaped dose-response curve. Compared with placebo, treatment with 5 mg tropisetron led to a significant improvement (p<0.05) in VAS, while a clear trend in terms of clinical benefit was seen with 10 mg tropisetron. The number of painful tender-points was also reduced significantly (p=0.002) in the 5 mg tropisetron group. Of interest, during the 12-month follow-up period, pain intensity of responders on 5 mg and 10 mg tropisetron was still markedly below baseline. The treatment was well tolerated, with gastro-intestinal complaints being the most frequently reported side effects, in keeping with the known safety profile for 5-HT3 receptor antagonists. CONCLUSIONS: This study demonstrates the efficacy of short-term treatment with 5 mg tropisetron once daily in primary fibromyalgia. Treatment was well tolerated and prolonged clinical benefits were seen.

Adolescent↗

Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.

The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.

Administration, Oral↗

Results of the intravenous administration of tropisetron in fibromyalgia patients.

The observed effects on the symptoms of fibromyalgia of daily oral administration of 5 mg of the 5-HT3 receptor antagonist, tropisetron, for 10 days, could be maintained or exceeded with intravenous administration of only 2 mg of the formulation. Following a single i.v. injection of 2 mg tropisetron, a more rapid and profound reduction in pain was achieved than with 5 mg oral tropisetron per day. In individual cases, patients who had previously experienced no reduction in pain from 10 days of 5 mg oral tropisetron daily responded to i.v. therapy. A more favourable and persistent effect on pain, combined with a simultaneous significant improvement in various vegetative and functional symptoms was achieved with five days treatment with 2 mg tropisetron i.v. per day. The results outlined and the possibility for rapid improvements with drug treatment of fibromyalgia should be confirmed in randomised, placebo controlled trials.

Administration, Oral↗

Do predictors exist for the therapeutic effect of 5-HT3 receptor antagonists in fibromyalgia?

From the findings outlined below, there are no reliable predictors of the therapeutic effect of the 5-HT3-receptor antagonists in fibromyalgia. Neither clinical change in pain and vegetative symptoms, nor alterations in biochemical parameters are appropriate predictors of response. The accompanying psychological changes in the form of depressive disorders appear to be somewhat predictive of decreased therapeutic effect, if such definitive statements can be applied to individual cases. If, following new trials, it becomes possible to judge the response of patients to therapy after 3-5 days treatment with 2 mg intravenous tropisetron then predictors will be unnecessary in practice.

Depression↗

The use of 5-HT3 receptor antagonists in various rheumatic diseases--a clue to the mechanism of action of these agents in fibromyalgia?

In a pilot study, the action of the 5-HT3 receptor antagonist, tropisetron, on different types of local rheumatic pain and inflammatory effects was studied. With intra-articular injection of tropisetron, an improvement in inflammation and pain was obtained in inflammatory rheumatic diseases and activated osteoarthrosis. Also, the majority of patients with localized soft-tissue rheumatic diseases (periarthritis) demonstrated an obvious decrease in their pain following local infiltration of tropisetron. Chronic low back pain and cervical pain responded somewhat to i.v. treatment with tropisetron. The effect of the 5-HT3 receptor antagonists is probable primarily to limit the release of substance P, which acts as a pain and inflammatory mediator, and is itself released by the neurogenic inflammation that occurs after the binding of serotonin to its corresponding receptor. These results should be backed up with placebo controlled studies, which if confirmed, might imply that 5-HT3 receptor antagonists could supplement or replace the local administration of corticosteroids.

Arthritis, Rheumatoid↗

The T102C polymorphism of the 5-HT2A-receptor gene in fibromyalgia.

Based on a possible involvement of serotonergic dysfunction in the pathophysiology of fibromyalgia (FM) and on preliminary reports of a possible genetically driven vulnerability for this disorder we investigated the silent T102C polymorphism of the 5-HT2A-receptor gene in 168 FM patients and 115 healthy controls. Our results showed a significantly different genotype distribution in FM patients with a decrease in T/T and an increase in both T/C and C/C genotypes as compared to the control population (Fisher's Exact test, two-sided, P = 0.008). However, the increase in allele-C102 frequency felt short of significance (P = 0.07). Correlation of genotypes to clinical parameters revealed no influences on age of onset, duration of disease or psychopathological symptoms, measured with the Beck Depression Inventory and the symptom checklist SCL-90-R. In contrast to that the pain score, being a self reported information on pain severity, was significantly higher in patients of the T/T genotype (Mann-Whitney U test, P = 0.028). This suggests that the T102-allele might be involved in the complex circuits of nociception. However, the T102C polymorphism is not directly involved in the aetiology of FM but might be in linkage dysequilibrium with the true functional variant, which has to be unravelled.

Adult↗

Spinal factors in the generation of fibromyalgia syndrome.

In fibromyalgia as well as in low back pain we frequently find disturbances of the posture of vertebral column clinically and radiologically. Also, reduction in the mobility of whole spine and localized movement impairments in both conditions was present. It is likely that the disturbances are responsible for the first manifestations of fibromyalgia in a single localization, especially in lumbar and cervical regions.

Fibromyalgia↗

Pathogenetic aspects of responsiveness to ondansetron (5-hydroxytryptamine type 3 receptor antagonist) in patients with primary fibromyalgia syndrome--a preliminary study.

OBJECTIVE: To study the efficacy of 5-hydroxytryptamine type 3 receptor (5-HT-3R) antagonist (ondansetron) vs paracetamol in primary fibromyalgia (FM) syndrome. METHODS: A double blind, crossover, latin square study of 21 patients with FM. Visual analog scale (VAS) and body drawings were used to record pain intensity. Functional symptoms were determined for using a Likert-type self-developed protocol. Quantitative dolorimetry was applied to assess the number of painful tender points and the average pain threshold. Serum serotonin levels were measured by a commercial ELISA. RESULTS: A marked improvement in pain intensity measured by VAS (p < 0.005), pain score (p < 0.05), tender points (p < 0.05), and average pain threshold (p < 0.01) was obtained with ondansetron, whereas no improvement was seen with paracetamol. After ondansetron treatment, there was also significant reduction in both functional symptoms (p < 0.01) and headache intensity (p < 0.05). In patients who did not respond to ondansetron there was higher baseline pain intensity measured by VAS (p < 0.05) and pain score (p < 0.01), and a lower pain threshold (p < 0.05) compared to those who did respond well. In the responsive group, no significant differences were seen in the serotonin level before and after therapy. Whereas a significant increase in serum serotonin concentration (p < 0.01) was observed in nonresponders after ondansetron treatment. CONCLUSION: Ondansetron appears to be an effective drug in about 50% of patients with FM. There may be 2 subsets of patients with FM that differ clinically and pathogenetically with regard to the disturbance in the 5-HT-3R system.

Acetaminophen↗

Microheterogeneity of acute phase proteins in patients with clinically active and clinically nonactive osteoarthritis.

Microheterogeneity of two acute phase glycoproteins, alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT), concentrations of AGP, ACT, and C-reactive protein (CRP), and levels of three cytokines: interleukin 1 beta (IL-1-beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were determined in 61 serum samples and 7 synovial fluids (SFs) obtained from patients (n = 61) with osteoarthritis. Using affinity immunoelectrophoresis with concanavalin A (conA), a significant decrease in the reactivity of AGP and ACT with this lectin was found in patients with clinically active osteoarthritis when compared to those with clinically nonactive disease (p < 0.001 and p < 0.05, respectively). There was no increase in the concentration of AGP, ACT, and C-reactive protein (CRP) in the sera examined. In particular, no increase in the serum level of these proteins was found in the patients with clinically active disease. Low concentrations of IL-6 and TNF-alpha were found in most sera and SFs examined. In 6 out of 7 SFs available, IL-6 concentrations were higher than in the respective serum samples but for TNF-alpha the same could be shown in one case only. Low concentrations of IL-1-beta were found in 4 serum samples obtained from patients with clinically active osteoarthritis and in no SF specimen studied. In the entire group, serum level of TNF-alpha correlated weakly with the AGP and ACT reactivity coefficients with conA (r = 0.3634, p < 0.005 and r = 0.3324, p < 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Serotonin concentration in serum of patients with generalized tendomyopathy (fibromyalgia) and chronic polyarthritis].

The serum concentration of serotonin (S-5-HT) was measured in 31 patients with primary fibromyalgia, 21 patients with rheumatoid arthritis (RA) (15 of them with secondary fibromyalgia) and 20 healthy volunteers. Both patients with primary fibromyalgia and rheumatoid arthritis had significantly lower S-5-HT levels when compared to healthy controls, and S-5-HT concentrations in patients with secondary fibromyalgia were even significantly lower than those of RA-patients. Unlike the patients with rheumatoid arthritis, a significant correlation between S-5-HT level and the number of "tender points" as well as mean pressure tenderness at 24 different points was found in patients with primary fibromyalgia. Conversely, in patients with rheumatoid arthritis the S-5-HT level correlated significantly with erythrocyte sedimentation rate. These results suggest different pathological mechanisms of S-5-HT decrease in patients with primary fibromyalgia and rheumatoid arthritis. On the other hand, they raise the question whether secondary fibromyalgia may be a pathogenetically different syndrome mimicking symptomatically primary fibromyalgia.

Adult↗

[Intramuscular etofenamate in the treatment of acute lumbago. Effectiveness and tolerance in comparison with intramuscular diclofenac-Na].

In a controlled multi-center single-blind study, the relative efficacy and tolerance of i.m. injectable preparations of etofenamat(e) and diclofenac sodium were investigated in 96 patients with acute lumbago. Treatment resulted in obvious improvement in function and reduction in pain, no statistical difference being found between the two drugs. In 43% of the patients treated with etofenamat(e) and 27% of those receiving diclofenac, the final medical report indicated very good therapeutic results. Under etofenamat(e) i.m. therapy, no side effects occurred, and in no case did treatment have to be discontinued. Under diclofenac, two patients experienced adverse reactions, one allergic exanthema, and the other itching and a sensation of heat. A further patient experienced no improvement after the first injection and discontinued treatment.

Adolescent↗

[Local treatment of periarthropathies with the 5-HT3-receptor-antagonist tropisetron].

All substances used in the local treatment for periarthropathies, such as local anesthetics, corticosteroids or botulinum toxin A, possess certain disadvantages. Finding alternatives to these agents in the local treatment of the disease therefore seems desirable. Comparative studies proved a local injection of the 5-HT3 receptor antagonist, tropisetron (Navoban(R)), to be more effective than an injection of the local anesthetic prilocaine in treating periarthropathies of different localizations. A comparison between the local injection of 10 mg of depot dexamethasone combined with 60 mg of lidocaine and 5 mg of tropisetron showed that the two regimens had the same effect. These findings demonstrate that a local injection of 5 mg tropisetron does represent an alternative to the local treatment with corticosteriods plus local anesthetics. However, these results should be corroborated by additional studies.

Acetanilides↗

[Can thermal therapy of ankylosing spondylitis induce an activation of the disease?].

A randomized, open, controlled study was carried out in eight patients with spondylitis ankylosans, in a cross-over procedure including total body cryotherapy and whole spine paraffin mud packs. The effect of both therapies on clinical status and different laboratory data was investigated. No clinical changes were seen after either therapy; in contrast, in answering the spine function questionnaire patients reported an improvement after cryotherapy and a worsening after thermotherapy, but because of the small number of patients no positive conclusion was possible. The acute phase proteins (alpha-1-AGP, alpha-1-ACT, alpha-2-haptoglobin and alpha-2-coeruloplasmin) did not show any changes, only CRP increased after thermotherapy and declined after cryotherapy. Interesting changes were seen in the glycosylation profile of alpha-1-AGP: after thermotherapy an increase of bi-antennary oligosaccharides occurred, observed as appearance of a third peak in the affinity immunoelectrophoresis with con A and an increase of reactivity-coefficient of alpha-1 and glycoprotein which was also seen in the exacerbation of AS. This shows, that an activation of the inflammatory process may be possible by thermotherapy (perhaps because of an amplification of Il-6 production), but not by cryotherapy. Similar studies should be conducted in larger numbers of patients.

Acute-Phase Proteins↗

[Recording muscle spasm in the musculus erector spinae using in vivo 31P magnetic resonance spectroscopy in patients with chronic lumbalgia and generalized tendomyopathies].

Using 31P nuclear magnetic resonance, the following parameters were determined in the resting musculus erector spinae of five patients suffering from chronic low back pain, five patients with fibromyalgia, and five healthy controls: Inorganic phosphate (Pi), phosphocreatine (PCr), ATP gamma, ATP alpha, ATP beta. The intracellular pH was derived from the chemical shift of Pi referenced to the PCr resonance. In addition, the Pi-Index was calculated according to the formula: Pi/(Pi + PCr). We discovered a tendency towards a shift of the Pi resonance in the alcalic direction, which was the larger, the stronger muscle spasm was found on palpation. The pH showed the most reliable relationship to the clinical status of muscle spasm. The surprising finding that there is no acidification within the spasmed muscle indicates that generalized hypoxia does not exist in this tissue. This has already been shown with PO2 measurements. An intracellular acidification is only recorded during maximal isometric contraction. Thus, ischemia cannot be responsible for pain experienced during muscle spasm.

Acid-Base Equilibrium↗

[Determination of regional rate of glucose metabolism in lumbar muscles in patients with generalized tendomyopathy using dynamic 18F-FDG PET].

Generalized tendomyopathy (GTM), or fibromyalgia (FM), is a disease characterized by wide-spread pain in the musculoskeletal system which usually begins at a single site, e.g., as low-back pain or cervical syndrome, and develops into generalized pain over months or years. The disorder affects primarily women, beginning around the age of 35 and reaching its peak during or after the menopause. Its etiology is still unknown. Secondary forms are observed particularly in rheumatoid arthritis. In order to get more information on FM we determined the local metabolic rate of glucose in vivo in the skeletal muscle (lumbar region) with dynamic 18F-FDG positron emission tomography (PET). 2 healthy volunteers and 6 female patients with FM reaching in age from 31 to 53 years were scanned. As 18F-FDG PET scanning is a metabolic tool, it is crucial to observe standardized conditions of metabolic steady-state. We used, therefore, the hyperinsulinemic euglycemic insulin clamp technique to stimulate the myogenic glucose uptake under stable plasma-glucose levels. The local metabolic rates of glucose utilization were estimated with a non-linear least squares fit on the 3 compartment 18F-FDG-model. A lumped constant of 0.67 was assumed. Under glucose clamp conditions patients with FM showed a significantly (p < 0.001) lower metabolic rate of glucose (4.3 +/- 1.1) mumol/100 g tissue/min compared with normal volunteers (8.5 +/- 2.3 mumol/100 g/min). Due to a significantly (p < 0.005) increased glucose backflow from tissue into the vascular space (k2 in the kinetic model) the rate of phosphorylation was markedly reduced in patients with FM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗