Search

Item does not contain fulltext, BACKGROUND: Anti-drug antibodies are associated with treatment failure to anti-TNF agents in patients with inflammatory bowel disease (IBD). AIM: To assess whether immunogenicity to a patient's first anti-TNF agent would be associated with immunogenicity to the second, irrespective of drug sequence METHODS: We conducted a UK-wide, multicentre, retrospective cohort study to report rates of immunogenicity and treatment failure of second anti-TNF therapies in 1058 patients with IBD who underwent therapeutic drug monitoring for both infliximab and adalimumab. The primary outcome was immunogenicity to the second anti-TNF agent, defined at any timepoint as an anti-TNF antibody concentration ≥9 AU/ml for infliximab and ≥6 AU/ml for adalimumab. RESULTS: In patients treated with infliximab and then adalimumab, those who developed antibodies to infliximab were more likely to develop antibodies to adalimumab, than patients who did not develop antibodies to infliximab (OR 1.99, 95%CI 1.27-3.20, p = 0.002). Similarly, in patients treated with adalimumab and then infliximab, immunogenicity to adalimumab was associated with subsequent immunogenicity to infliximab (OR 2.63, 95%CI 1.46-4.80, p < 0.001). For each 10-fold increase in anti-infliximab and anti-adalimumab antibody concentration, the odds of subsequently developing antibodies to adalimumab and infliximab increased by 1.73 (95% CI 1.38-2.17, p < 0.001) and 1.99 (95%CI 1.34-2.99, p < 0.001), respectively. Patients who developed immunogenicity with undetectable drug levels to infliximab were more likely to develop immunogenicity with undetectable drug levels to adalimumab (OR 2.37, 95% CI 1.39-4.19, p < 0.001). Commencing an immunomodulator at the time of switching to the second anti-TNF was associated with improved drug persistence in patients with immunogenic, but not pharmacodynamic failure. CONCLUSION: Irrespective of drug sequence, immunogenicity to the first anti-TNF agent was associated with immunogenicity to the seco

Introduction The effect of cryotherapy on joint positioning presents conflicting debates as to whether individuals are at an increased risk of injury when returning to play following cryotherapy application at the lower limb. Objectives The aim of this study was to investigate whether a 20 minute application of crushed ice at the knee affects knee joint position sense immediately post and up to 20 mins post ice removal, during a small knee bend. Method 17 healthy male participants took part in the study performing a functional task. Using three-dimensional motion analysis (Qualisys Medical AB Gothenburg, Sweden), kinematics of the knee were measured during a weight bearing functional task pre and immediately post, 5, 10, 15 and 20 minutes post cryotherapy intervention. Skin surface temperature (Tsk) cooling was measured via infrared non-contact thermal imaging (Flir Systems, Danderyd, Sweden) over the anterior and medial aspect of the knee. Results Results demonstrated significant reductions in the ability to accurately replicate knee joint positioning. A significant increase (P ≧ 0.05) in rotational movement in the transverse plane occurred, 20 minutes post ice removal. Discussion A 20-minute application of crushed ice to the anterior aspect of the non-dominant knee has an adverse effect on knee joint repositioning and dynamic stability, 20 minutes after ice is removed. In consideration of returning a land-based athlete to dynamic functional activities, post cryotherapeutic intervention at the knee, clinicians should consider these findings due to the potential increase risk of injury.

This aim of this paper was to explore commonalities between HIV/AIDS related conditions, obesity and other disabling impairments as health-related barriers that limit opportunity and advancement in society and the workplace. Taking a number of examples from original fieldwork and European Union and United Kingdom law, we posit that ‘disability discrimination’ under European Union law remains an indefinite, imprecise and incomplete area that requires greater alignment with the social model of disability. The principle attributes of societal discrimination towards people living with HIV and obese people are that these conditions are perceived to be primarily or in some instances, solely caused by controllable factors related often to behaviours and lifestyle choices. Strong beliefs that these conditions are controllable, is perceived as a justification and in some instances encouragement for the creation of stigma and discriminative behaviours that are unjust and uninformed. The structure of the paper is as follows. First, this paper postulates how and why stigma exists towards both individuals with disabilities and also obese individuals and people living with HIV; second, reviews the legal framework on disability discrimination in both United Kingdom and European Union courts that are directly relevant to the concepts of obesity and HIV-AIDS; third, presents critical thoughts as to the extent to which emerging decisions of the Court of Justice of the European Union concerning obesity and HIV-AIDS accord with the social model of disability; and fourth, offers an analysis of the implications of the United Kingdom and European framework and suggests possible interventions in this area.

Obesity discrimination in employment and recruitment has become a topic of focus for research examination with increasing reports of discrimination by colleagues and managers. Whilst a limited number of legal cases have emerged, disability law is consulted in line with the expectation of anti-discriminatory practices at work. In line with disability law, whether obesity is defined as a disability or not has an impact on the outcome of a court ruling. Ambiguity when defining obesity through either the medical or social model means there are many questions that remain unanswered which might lead to inconsistency in court rulings.

There is a need for cancer treatments to be selectively cytotoxic to cancer cells so as to reduce adverse side effects. In this study, a cancer cell line (HeLa cells) and a non-cancer cell line (HF-32) were exposed to an extract from the plant Sarcostemma viminale. Cytopathic effects and apoptosis were measured by morphological changes, annexin V/propidium iodide (PI) and 4′,6-diamidino-2-phenylindole (DAPI) staining assays. Also, a novel mixed culture flow cytometry assay was performed exploiting the overexpression of p16INK4a in HeLa cells to demonstrate the change in numbers of HeLa and HF-32 cells post-exposure to the extract. At 1 % (v/v) after 48 h of exposure, HeLa cells showed >75 % cytopathic effect, 77 % were in apoptosis or dead by the annexinV/PI assay, and 100 % had nuclear changes by DAPI staining; there was a reduction of 76 % in the number of cells by mixed culture assay. In contrast, for the HF-32 cells, only 5 % showed any cytopathic effect, there were no more cells in apoptosis or dead (34 %) than in the control by the annexinV/PI assay, <1 % of cells had nuclear changes by DAPI staining, and there was a slight increase in cell numbers by the mixed culture assay. Results from these assays clearly demonstrate that the extract from S. viminale destroyed the cancer HeLa cells quickly and at a low concentration, whilst the non-cancer HF-32 cells survive. This study indicates that extracts from S. viminale may be a specific anticancer agent.