Does acetaminophen activate endogenous pain inhibition in chronic fatigue syndrome/fibromyalgia and rheumatoid arthritis? : a double-blind randomized controlled cross-over trial

Background: Although enhanced temporal summation (TS) and conditioned pain modulation (CPM), as characteristic for central sensitization, has been proved to be impaired in different chronic pain populations, the exact nature is still unknown. Objectives: We examined differences in TS and CPM in 2 chronic pain populations, patients with both chronic fatigue syndrome (CFS) and comorbid fibromyalgia (FM) and patients with rheumatoid arthritis (RA), and in sedentary, healthy controls, and evaluated whether activation of serotonergic descending pathways by acetaminophen improves central pain processing. Study Design: Double-blind randomized controlled trial with cross-over design. Methods: Fifty-three women (19 CFS/FM patients, 16 RA patients, and 18 healthy women) were randomly allocated to the experimental group (1 g acetaminophen) or the placebo group (1 g dextrose). Participants underwent an assessment of endogenous pain inhibition, consisting of an evaluation of temporal summation with and without conditioned pain modulation (CPM). Seven days later groups were crossed-over. Patients and assessors were blinded for the allocation. Results: After intake of acetaminophen, pain thresholds increased slightly in CFS/FM patients, and decreased in the RA and the control group. Temporal summation was reduced in the 3 groups and CPM at the shoulder was better overall, however only statistically significant for the RA group. Healthy controls showed improved CPM for both finger and shoulder after acetaminophen, although not significant. Limitations: The influence of acetaminophen on pain processing is inconsistent, especially in the patient groups examined. Conclusion: This is the first study comparing the influence of acetaminophen on central pain processing in healthy controls and patients with CFS/FM and RA. It seems that CFS/ FM patients present more central pain processing abnormalities than RA patients, and that acetaminophen may have a limited positive effect on central pain inhibition, but other contributors have to be identified and evaluated

Four-year follow-up of infliximab therapy in rheumatoid arthritis patients with long-standing refractory disease: attrition and long-term evolution of disease activity

Although there is strong evidence supporting the short-term efficacy and safety of anti-tumour necrosis factor-α agents, few studies have examined the long-term effects. We evaluated 511 patients with long-standing refractory rheumatoid arthritis treated with intravenous infusions of infliximab 3 mg/kg at weeks 0, 2, 6, and 14 and every 8 weeks thereafter for 4 years. Among the initial 511 patients included in the study, 479 could be evaluated; of these, 295 (61.6%) were still receiving infliximab treatment at year 4 of follow-up. The most common reasons for treatment discontinuation were lack of efficacy (65 patients, 13.6%), safety (81 patients, 16.9%), and elective change (38 patients, 7.9%). Analysis of disease activity scores (DAS28 [disease activity score based on the 28-joint count]) over time showed that, after the initial rapid improvement during the first 6 to 22 weeks of therapy, a further decrease in disease activity of 0.2 units in the DAS28 score per year was observed. DAS28 scores, measured at week 14 or 22, were found to predict subsequent discontinuation due to lack of efficacy. In conclusion, long-term maintenance therapy with infliximab 3 mg/kg is effective in producing further reductions in disease activity. Disease activity measured by the DAS28 at week 14 or 22 of infliximab therapy was the best predictor of long-term attrition

DAS28 best reflects the physician's clinical judgment of response to infliximab therapy in rheumatoid arthritis patients: validation of the DAS28 score in patients under infliximab treatment

This study is based on an expanded access program in which 511 patients suffering from active refractory rheumatoid arthritis (RA) were treated with intravenous infusions of infliximab (3 mg/kg+methotrexate (MTX)) at weeks 0, 2, 6 and every 8 weeks thereafter. At week 22, 474 patients were still in follow-up, of whom 102 (21.5%), who were not optimally responding to treatment, received a dose increase from week 30 onward. We aimed to build a model to discriminate the decision to give a dose increase. This decision was based on the treating rheumatologist's clinical judgment and therefore can be considered as a clinical measure of insufficient response. Different single and composite measures at weeks 0, 6, 14 and 22, and their differences over time were taken into account for the model building. Ranking of the continuous variables based on areas under the curve of receiver-operating characteristic (ROC) curve analysis, displayed the momentary DAS28 (Disease Activity Score including a 28-joint count) as the most important discriminating variable. Subsequently, we proved that the response scores and the changes over time were less important than the momentary evaluations to discriminate the physician's decision. The final model we thus obtained was a model with only slightly better discriminative characteristics than the DAS28. Finally, we fitted a discriminant function using the single variables of the DAS28. This displayed similar scores and coefficients as the DAS28. In conclusion, we evaluated different variables and models to discriminate the treating rheumatologist's decision to increase the dose of infliximab (+MTX), which indicates an insufficient response to infliximab at 3 mg/kg in patients with RA. We proved that the momentary DAS28 score correlates best with this decision and demonstrated the robustness of the score and the coefficients of the DAS28 in a cohort of RA patients under infliximab therapy

Standard methods for Apis mellifera venom research

Honey bees have a sting which allows them to inject venomous substances into the body of an opponent or attacker. As the sting originates from a modified ovipositor, it only occurs in the female insect, and this is a defining feature of the bee species that belong to a subclade of the Hymenoptera called Aculeata. There is considerable interest in bee venom research, primarily because of an important subset of the human population who will develop a sometimes life threatening allergic response after a bee sting. However, the use of honey bee venom goes much further, with alleged healing properties in ancient therapies and recent research. The present paper aims to standardize selected methods for honey bee venom research. It covers different methods of venom collection, characterization and storage. Much attention was also addressed to the determination of the biological activity of the venom and its use in the context of biomedical research, more specifically venom allergy. Finally, the procedure for the assignment of new venom allergens has been presented. Las abejas meliferas tienen un aguijon que les permite inyectar sustancias venenosas en el cuerpo de un oponente o atacante. El aguijon es un ovipositor modificado que solo se manifiesta en el insecto hembra, siendo este una caracteristica que define a las especies de abejas que pertenecen al subclado de himenopteros llamada Aculeata. Hay un interes considerable en la investigacion del veneno de abeja, principalmente debido a que un porcentaje importante de la poblacion humana desarrollara una respuesta alergica - a veces mortal - a la picadura de abeja. Sin embargo, el uso del veneno de la abeja melifera abarca mucho mas, con presuntas propiedades curativas en terapias antiguas e investigaciones recientes. El presente trabajo tiene como objetivo estandarizar metodos seleccionados para la investigacion del veneno de las abejas meliferas. Cubre diferentes metodos de recoleccion, caracterizacion y almacenamiento de veneno. Tambien se presto mucha atencion a la determinacion de la actividad biologica del veneno y su uso en el contexto de la investigacion biomedica, mas especificamente la alergia al veneno. Finalmente, se ha presentado el procedimiento para la asignacion de nuevos alergenos de veneno