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Background Genotype (gt)6 HCV is common amongst HCV-positive populations of the Asia–Pacific region but cell culture models for this gt have only recently been developed. Boceprevir (SCH503034) is a clinically available inhibitor of the HCV NS3 protein. We investigated the efficacy of boceprevir for inhibiting replication of a chimeric gt1b replicon encoding a gt6a NS3 protease and defined the development of mutations in the protease when boceprevir treatment was applied. Methods We constructed a chimeric gt1b subgenomic replicon encoding a gt6 NS3 protease (NS3p) sequence (gt6NS3p_gt1b). The boceprevir EC50 value against replication of this replicon was determined using quantitative reverse transcriptase PCR. Next-generation sequencing was used to identify nucleotide changes associated with boceprevir resistance. The replication capacities of chimeric replicons containing mutations associated with boceprevir resistance were determined by colony formation efficiency assays. Results The boceprevir EC50 value for the gt6NS3p_gt1b replicon was 535 ±79 nM. Boceprevir-resistant gt6NS3p_gt1b replicon cell lines could be selected and they demonstrated drug-associated amino acid changes that have previously been reported in other HCV gts. Interestingly, no mutations were observed at A156, a position defined for boceprevir resistance in gt1 NS3p, while mutation at N122, which is rarely reported in boceprevir-resistant gt1 proteases, was frequently observed. Re-introduction of these mutations into the chimeric replicon altered their replication capacity, ranging from complete abolishment of replication (A156T) to increasing replication capacity (V36A, N122S). This report provides the first characterization of gt6 HCV resistance to boceprevir. Conclusions A chimeric HCV replicon encoding gt6 NS3 protease is sensitive to boceprevir and develops drug-resistant mutations at amino acid sites previously reported for other gts. Mutation at N122 also appears to be associated with boceprevir resistance in the gt6 NS3 protease.

Ethical and legal dilemmas frequently arise in paediatric practice. Given the nature of the speciality, these issues are relevant to both the medical and legal professions. To this end, senior figures from the medical and legal professions in the Northern region have met on a regular basis in order to discuss anonymised case material. We report on the proceedings of the seventh such meeting. Six cases are described and key points arising from the subsequent discussion are presented.

The disciplines of medicine, law and ethics frequently impinge upon each other in clinical practice but are seldom given the opportunity to come together in dialogue. It was with this aim that senior professionals from law and medicine met at the fifth Northern Region Paediatric Colloquium. An added dimension to the ethical viewpoint was brought to the meeting by the attendance of local religious leaders for the first time. We report the proceedings of the Colloquium, which adopted the usual format of clinical case presentation followed by discussion.

The latest editions of medical textbooks make only passing references to the icterus accompanying many cases of lobar pneumonia. Cecil1 indicates that jaundice occurs in 5 to 10% of cases of lobar pneumonia and that the lighter form which is observed most frequently seems to have no significance while the deeper jaundice seen in other cases is associated with a toxic hepatitis and a grave prognosis. Musser2 describes the jaundice that is present in a small number of cases of lobar pneumonia as often existing in connection with an enlarged liver and a tender area in the region of the gall bladder. Meakins3 barely mentions jaundice as a result of metastatic lesions in the liver in lobar pneumonia. Emerson,4 in a footnote, suggests that this jaundice may be due to the absorption of alveolar exudate or to a slowing of the portal circulation.During the past year the authors observed 32 cases of lobar pneumonia in adult Negro patients admitted to the medical service of George W. Hubbard Hospital of Meharry Medi...