Antibiotic management of acute pharyngitis in primary care.

The Centre for Health Protection of the Department of Health has convened the Advisory Group on Antibiotic Stewardship Programme in Primary Care (the Advisory Group) to formulate guidance notes and strategies for optimising judicious use of antibiotics and enhancing the Antibiotic Stewardship Programme in Primary Care. Acute pharyngitis is one of the most common conditions among out-patients in primary care in Hong Kong. Practical recommendations on the diagnosis and antibiotic treatment of acute streptococcal pharyngitis are made by the Advisory Group based on the best available clinical evidence, local prevalence of pathogens and associated antibiotic susceptibility profiles, and common local practice.

Tivozanib: practical implications for renal cell carcinoma and other solid tumors.

Tivozanib is a recently developed, small-molecule tyrosine kinase inhibitor with specific affinity for the vascular endothelial growth factor receptor (VEGFR) family of kinases. Given known relevance of VHL (Von Hippel-Lindau disease tumor suppressor) deregulation in the clear cell variant of renal cell carcinoma, renal cell carcinoma remains an area of interest and subject of recent registration trials with this approach. TIVO-1, a phase III study evaluating tivozanib versus sorafenib in the first-line setting, met its primary endpoint of progression-free survival (11.9 months for tivozanib vs. 9.1 months for sorafenib), with a manageable toxicity profile, leading to formal consideration of regulatory approval in this setting. This review focuses on the preclinical development, pharmacokinetics and early clinical activity of tivozanib in renal cell carcinoma and other solid tumors.

Axitinib, a new therapeutic option in renal cell carcinoma.

Axitinib is a small-molecule protein-tyrosine kinase receptor inhibitor specifically targeting this family of receptors, in addition to platelet-derived growth factor receptor and proto-oncogene c-Kit. Improved knowledge of kidney cancer development, and specifically mutations in the VHL gene, has supported the targeting of angiogenesis pathways. Axitinib is the most recently approved agent for use in metastatic renal cell carcinoma. This review will focus on the preclinical pharmacology, pharmacokinetics and clinical activity of this agent, and describe its place in the current treatment of renal cell carcinoma.

Sequencing of TNFAIP3 and association of variants with multiple autoimmune diseases.

The TNFAIP3 locus at 6q23, encoding A20, has been associated with multiple autoimmune diseases (AIDs). In this study, we sequence the coding portions of the gene to identify contributing causal polymorphisms that may explain some of the observed associations. A collection of 123 individuals from the Multiple Autoimmune Disease Genetics Consortium (MADGC) collection, each with multiple AIDs (mean=2.2 confirmed diagnoses), and 397 unrelated healthy controls were used for initial sequencing. A total of 32 polymorphisms were identified in the sequencing experiments, including 16 novel and 11 coding variants. Association testing in the entire MADGC collection (1,008 Caucasians with one or more AIDs and 770 unaffected family controls) revealed association of a novel intronic insertion-deletion polymorphism with rheumatoid arthritis (RA) (odds ratio (OR)=2.48, P=0.041). Genotyping of the most common coding polymorphism, rs2230926, in the MADGC collection and additional control individuals revealed a significant association with Sjögren's syndrome (OR=3.38, P=0.038), Crohn's disease (OR=2.25, P=0.041), psoriasis (OR=0.037, P=0.036) and RA (OR=1.9, P=0.025). Finally, haplotype and additional testing of polymorphisms revealed that cases were enriched for 5' and 3' untranslated region variants (one-sided P-value=0.04), but not specifically for common (>2% minor allele frequency), rare, exonic, intronic, non-synonymous or synonymous variants.

Neurotransmitters and peptides in the developing human facial nucleus.

The human facial nucleus can be sub-divided into five structurally discrete regions. Immunohistochemistry was used to locate various neurotransmitters and neuropeptides in the neurons and nerve fibres of the human facial nucleus at 14 and 27 weeks of gestation and in the neonate. Whilst choline acetyltransferase-positive neurons were observed in the facial nucleus at all stages of development, dopamine beta-hydroxylase-positive neurons were only found in the neonate. In addition, afferent nerve fibres positive for choline acetyl-transferase, enkephalin and substance P were observed at all stages of development. In the younger specimens these fibres were evenly distributed; however, in the neonates the fibres were asymmetrically distributed as the different types became concentrated in the various structurally distinct regions of the facial nucleus.