Effects of cyclosporin A administered into the airways against antigen-induced airway inflammation and hyperreactivity in the rat

The immunosuppressant cyclosporin A given orally has anti-asthma properties but carries an undesirable risk of systemic effects. We administered cyclosporin A to Brown Norway rats either orally (p.o.) or topically by intratracheal (i.t.) instillation into the airways before inhaled antigen. Cyclosporin A suppressed the antigen-induced accumulation of activated (CD25⁺) CD4⁺ T lymphocytes and eosinophils in the lung, interleukin-5 mRNA expression in lung tissue and airway hyperreactivity. Intratracheal cyclosporin A suppressed cell accumulation at a 10-fold lower dose than that required orally. Minimum effective doses were 3 mg kg⁻¹ i.t. and 30 mg kg⁻¹ p.o. Intratracheal administration reduced the plasma concentration and systemic exposure compared with an equieffective oral dose, but the reduction (4–5-fold) was not as large as anticipated. Our data suggests that although topical administration to asthmatics would provide some potential for an improved safety margin, it may not offer any major advantage over existing oral therapy. However, the data clearly demonstrate that a novel immunosuppressant with similar anti-inflammatory properties but reduced potential for systemic effects would offer an attractive therapy for severe asthma.     

Characterisation of ten polymorphic microsatellite loci in a coral reef fish (Chromis margaritifer)

Primer pairs for ten microsatellite loci for the damselfish Chromis margaritifer were isolated from a genomic DNA library. The loci were optimised and tested on 48 individuals from a single sampling site. Using three multiplex reactions, each primer pair amplified good quality, reliable and polymorphic product. Number of alleles ranging from 4 to 31 per locus, and average expected heterozygosities ranged from 0.20 to 0.93. No evidence of linkage disequilibrium was detected between any pair of loci, but significant departures from Hardy–Weinberg expectations at three loci suggested the presence of null alleles. Given the worldwide decline of coral reefs, these markers will be invaluable for elucidating patterns of genetic and demographic connectivity among populations of a fish that depends upon threatened coral reef habitat for its survival.     

Initial experience and safety in the treatment of chronic total occlusions with fiberoptic guidance technology: optical coherent reflectometry.

Percutaneous treatment of chronic total coronary occlusions has been limited by procedural complications such as vessel injury or perforation. Optimizing visualization in the vessel with optical coherent reflectometry and a forward-looking fiberoptic guidance technology may improve the safety and efficacy of percutaneous treatment of these lesions.     

MOP-UP: an online tool for finding strain-specific primers or motifs in DNA or protein alignments

MOP-UP is a web-based application that enables efficient searching of nucleic acid or amino-acid alignments for sequences or motifs that are unique to a subset of the members represented in the alignment. This has applications in the design of assays that aim to detect particular strains or species. Since molecular-based characterisation of microbes is becoming increasingly important, MOP-UP can aid microbiologists in finding the best loci on which to base such assays. The program is accessible at: http://www.hpa.org.uk/srmd/bioinformatics/tools/mop-ups.htm.     

“It struck me that they didn't understand pain”: The specialist pain clinic experience of patients with chronic musculoskeletal pain

Objective

To explore the experiences of diagnosis and management among patients who attended a specialist musculoskeletal pain clinic and the factors influencing their interpretation of these experiences.

Methods

A postal questionnaire was sent to potential participants 6–20 months after their first clinic attendance. Data were collected on pain presence, severity, and location; health‐related quality of life; psychological distress; and care‐seeking behavior. Questionnaire data were used to inform combined purposive and theoretical sampling. In‐depth interviews were conducted that probed participants' understanding of their chronic musculoskeletal pain and its management in a specialist musculoskeletal pain clinic.

Results

Fifteen patients were interviewed. Four main themes were identified: spoiled identity (pain limited patients' activities so extensively that it affected their sense of self); diminishing faith in medicine (patients were disappointed with aspects of their care‐seeking experience); making sense of pain (patients made sense of their pain by locating their pain within the context of their lives); and learning to live with the pain (an issue for all patients was whether or not their pain would stop or whether they had to learn to live with it).

Conclusion

Developing, implementing, and evaluating approaches to address patients' spoiled identities might allow us to improve patient‐centered outcomes in chronic musculoskeletal pain.