Lipopolysaccharide does not alter small airway reactivity in mouse lung slices

The bacterial endotoxin, lipopolysaccharide (LPS) has been associated with occupational airway diseases with asthma-like symptoms and in acute exacerbations of COPD. The direct and indirect effects of LPS on small airway reactivity have not been fully elucidated. We tested the hypothesis that both in vitro and in vivo LPS treatment would increase contraction and impair relaxation of mouse small airways. Lung slices were prepared from naïve Balb/C mice and cultured in the absence or presence of LPS (10 µg/ml) for up to 48 h for measurement of TNFα levels in conditioned media. Alternatively, mice were challenged with PBS or LPS in vivo once a day for 4 days for preparation of lung slices or for harvest of lungs for Q-PCR analysis of gene expression of pro-inflammatory cytokines and receptors involved in airway contraction. Reactivity of small airways to contractile agonists, methacholine and serotonin, and bronchodilator agents, salbutamol, isoprenaline and rosiglitazone, were assessed using phase-contrast microscopy. In vitro LPS treatment of slices increased TNFα release 6-fold but did not alter contraction or relaxation to any agonists tested. In vivo LPS treatment increased lung gene expression of TNFα, IL-1β and ryanodine receptor isoform 2 more than 5-fold. However there were no changes in reactivity in lung slices from these mice, even when also incubated with LPS ex vivo. Despite evidence of LPS-induced inflammation, neither airway hyperresponsiveness or impaired dilator reactivity were evident. The increase in ryanodine receptor isoform 2, known to regulate calcium signaling in vascular smooth muscle, warrants investigation. Since LPS failed to elicit changes in small airway reactivity in mouse lung slices following in vitro or in vivo treatment, alternative approaches are required to define the potential contribution of this endotoxin to altered small airway reactivity in human lung diseases

Juvenile idiopathic arthritis and the temporomandibular joint : a case-control study of magnetic resonance imaging findings in relation to clinical and psychosocial factors.

AIM: In juvenile idiopathic arthritis (JIA), the temporomandibular joint (TMJ) is a particularly challenging joint to assess both clinically and with imaging. The aim of this article is to investigate TMJ magnetic resonance imaging (MRI) findings in relation to clinical and psychosocial factors in patients with JIA and healthy individuals related to TMJ arthritis in JIA. MATERIALS: In total, 45 patients (6-16 years) with JIA and 16 healthy age- and sex-matched controls were examined according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The subjects answered questionnaires about psychosocial factors (pain intensity, pain-related disability, depression, stress, catastrophising, pain locations, and jaw function) and underwent bilateral MRI of the TMJ. RESULTS: There were no significant differences between JIA patients and healthy individuals in any of the TMJ MRI findings. Moderate/severe changes among JIA patients were found only for effusion, synovial thickening, condylar flattening, and erosion, with no moderate/severe changes in healthy individuals. In JIA patients, orofacial pain intensity was related to TMJ bone marrow oedema, and pain in jaw muscles during jaw function was related to TMJ bone marrow oedema and erosion. There were no significant correlations between psychosocial aspects and MRI findings. CONCLUSION: This study indicates a substantial overlap of TMJ MRI findings in both the inflammatory domain and the damage domain between JIA patients and healthy individuals. In JIA patients, the inflammatory MRI sign of bone marrow oedema seems to influence orofacial pain intensity

Adjuvant chemotherapy in colorectal cancer: A joint analysis of randomised trials by the Nordic gastrointestinal tumour adjuvant therapy group

Due to uncertainties regarding clinically meaningful gains from adjuvant chemotherapy after colorectal cancer surgery, several Nordic Groups in the early 1990s initiated randomised trials to prove or reject such gains. This report gives the joint analyses after a minimum 5-year follow-up. Between October 1991 and December 1997, 2 224 patients under 76 years of age with colorectal cancer stages II and III were randomised to surgery alone (n = 1 121) or adjuvant chemotherapy (n = 1 103) which varied between trials (5FU/levamisole for 12 months, n = 444; 5FU/ eucovorin for 4 = 5 months according to either a modified Mayo Clinic schedule (n = 262) or the Nordic schedule (n = 397). Some centres also randomised patients treated with 5FU/ leucovorin to +/- levamisole). A total of 812 patients had colon cancer stage II, 708 colon cancer stage III, 323 rectal cancer stage II and 368 rectal cancer stage III. All analyses were according to intention-to-treat. No statistically significant difference in overall survival, stratified for country or region, could be found in any group of patients according to stage or site. In colon cancer stage III, an absolute difference of 7% ( p = 0.15), favouring chemotherapy, was seen. The present analyses corroborate a small but clinically meaningful survival gain from adjuvant chemotherapy in colon cancer stage III, but not in the other presentations