Summary of the British Thoracic Society guideline for diagnostic flexible bronchoscopy in adults.

Flexible bronchoscopy is an essential, established and expanding tool in respiratory medicine. Its practice, however, needs to be safe, effective and for the right indications to maximise clinical utility. This guideline is based on the best available evidence and is a revised update of the British Thoracic Society guideline on diagnostic flexible bronchoscopy.

Management of peripheral lymph node tuberculosis in routine practice: an unselected 10-year cohort.

BACKGROUND: The varied behaviour of tuberculous lymph nodes during TB chemotherapy can cause clinical uncertainty, resulting in prolonged courses of treatment. OBJECTIVES: To investigate whether results in routine practice in Blackburn, a high-incidence tuberculosis (TB) area in England and Wales, replicated the results of the 6-month chemotherapy trial for lymph node TB conducted by the British Thoracic Society. DESIGN: All TB cases managed at the Blackburn Chest Clinic are recorded prospectively. Patients with lymph node TB were identified over a 10-year period. RESULTS: A total of 100 patients with lymph node TB were listed in the database. Fine-needle aspiration was performed in 49 patients, while 66 underwent incisional lymph node biopsy. Culture confirmation was achieved in 60 cases. Sinus and new lymph node development was comparable between our study and the BTS trial. After cessation of treatment, 10 patients developed new/enlarged lymph nodes, but further investigations revealed that only three patients had relapsed TB. CONCLUSION: The varied behaviour of lymph node TB during and after treatment causes clinical uncertainty. Six months of chemotherapy is effective for fully susceptible TB in routine clinical practice in England. Investigation of new signs is important in differentiating patients with relapsed TB from normal varied behaviour.

Familial glucocorticoid resistance caused by a novel frameshift glucocorticoid receptor mutation.

CONTEXT: Familial glucocorticoid resistance is a rare condition with a typical presentation of women with hirsutism and hypertension, with or without hypokalemia. OBJECTIVE: The aim was to determine the cause of apparent glucocorticoid resistance in a young woman. PATIENTS AND METHODS: We studied a family with a novel glucocorticoid receptor (GR) mutation and a surprisingly mild phenotype. Their discovery resulted from serendipitous measurement of serum cortisol with little biochemical or clinical evidence for either hyperandrogenism or mineralocorticoid excess. RESULTS: The causative mutation was identified as a frameshift mutation in exon 6. Transformed peripheral blood lymphocytes were generated to analyze GR expression in vitro. Carriers of the mutation had less full-length GR, but the predicted mutant GR protein was not detected. However, this does not exclude expression in vivo, and so the mutant GR (Δ612GR) was expressed in vitro. Simple reporter gene assays suggested that Δ612GR has dominant negative activity. Δ612GR was not subject to ligand-dependent Ser211 phosphorylation or to ligand-dependent degradation. A fluorophore-tagged construct showed that Δ612GR did not translocate to the nucleus in response to ligand and retarded translocation of the wild-type GR. These data suggest that Δ612GR is not capable of binding ligand and exerts dominant negative activity through heterodimerization with wild-type GR. CONCLUSION: Therefore, we describe a novel, naturally occurring GR mutation that results in familial glucocorticoid resistance. The mutant GR protein, if expressed in vivo, is predicted to exert dominant negative activity by impairing wild-type GR nuclear translocation.