Macrolides: A Canadian Infectious Disease Society position paper

Since the introduction of erythromycin in 1965, no new compounds from the macrolide antimicrobial class were licensed in Canada until the 1990s. Clarithromycin and azithromycin, since their introduction, have become important agents for treating a number of common and uncommon infectious diseases. They have become prime agents in the treatment of respiratory tract infections, and have revolutionized the management of both genital chlamydial infections, by the use of single-dose therapy with azithromycin, and nontuberculous mycobacterial infections, by the use of clarithromycin. The improvement of clarithromycin and azithromycin over the gastrointestinal intolerability of erythromycin has led to supplanting the use of the latter for many primary care physicians. Unfortunately, the use of these agents has also increased the likelihood for misuse and has raised concerns about a resultant increase in the rates of macrolide resistance in many important pathogens, such as Streptococcus pneumoniae. This paper reviews the pharmacology and evidence for the current indications for use of these newer agents, and provides recommendations for appropriate use.Key Words: Azithromycin, Clarithromycin, Erythromycin, Macrolides, Review, Therapeutic useErythromycin A is a naturally occurring, microbiologically active compound of the macrolide class of antibiotics. Chemical modification of erythromycin A''s 14-membered lactone ring has led to the formation of semisynthetic derivatives with not only improved bioavailability and tolerability, but also expanded spectrums of microbiological activity and improved pharmacokinetic profiles. Such modifications produced clarithromycin, classified as a macrolide because it retains the central 14-membered lactone ring (1,2), and azithromycin, classified as an azalide due to its 15-membered aglycone ring (1). The latter two compounds are the newest agents in the macrolide class licensed for use in Canada. Roxithromycin and dirithromycin are available in other countries.These compounds are clinically active against Gram-positive and Gram-negative cocci, and Gram-negative bacilli (primarily Haemophilus influenzae, Legionella species, Moraxella catarrhalis, Campylobacter jejuni, Bordatella pertussis and Helicobacter pylori). Azalides such as azithromycin have exhibited superior activity against Gram-negative pathogens and are generally less active against Gram-positive pathogens. Intracellular pathogens such as Chlamydia species, Mycoplasma species, Ureaplasma species, Borrelia species and nontuberculous mycobacteria species show varying susceptibilities. On the basis of their microbial activity, both the macrolides and azalides have been shown to be clinically useful in the treatment of uncomplicated skin and soft tissue infections, upper and lower respiratory tract infections, sexually transmitted Chlamydia trachomatis infection and peptic ulcer disease. Additionally, the improved pharmacokinetic profiles and acid stability exhibited by the newer agents may lead to enhanced patient adherence through less frequent dosing and improved bioavailability in the presence of food.     

Hormone profiling in a novel enteroendocrine cell line pGIP/neo: STC-1

Objective.GIP is a peptide hormone of therapeutic interest in type 2 diabetes and obesity. This study evaluated pGIP/neo STC-1 as a potential K-cell model for studying GIP secretion.Methods.We evaluated cellular storage and medium accumulation of GIP along with other gastrointestinal peptides cholecystokinin (CCK), peptide YY (PYY), obestatin and ghrelin over 72 h and probed possible intracellular signals (PKA, PKC, Ca^2 + and GPCR) involved in peptide hormone synthesis/secretion.Results.Results demonstrate for the first time that pGIP/Neo STC-1 cells produce and secrete 3 to 6 times more GIP than STC-1. The cells clearly retain the ability to synthesize and secrete CCK and PYY but reduced levels indicate a shift towards a predominantly K-cell phenotype. Furthermore, gastric peptides such as obestatin and ghrelin are not produced in either STC-1 or pGIP/Neo STC-1 cells.Discussion.This study demonstrates the potential usefulness of pGIP/Neo cells for studying GIP secretion and further investigations will establish its suitability for investigating hormone release in vitro.     

以病人为中心的口腔科门诊数字化建设初探

目的：总结以病人为中心的口腔科门诊数字化建设的经验。方法：从诊疗手段、就医流程、医疗文书以及科室管理4个方面总结广州军区武汉总医院口腔科门诊数字化建设的概况。结果：2009年以来开始进行El腔科门诊的数字化建设,经过3年多的运行,科室工作流程优化明显,提高了工作效率和医疗服务质量。结论：科室的数字化建设有助于提高科室的工作效率和医疗服务质量,充分体现了”以病人为中心”这一理念。     

Informativeness of the spoken narratives of younger and older adolescents with specific language impairment and their counterparts with normal language

A large body of literature describing the narrative skills of young children with and without language impairments exists. However, there has been only limited study of the informativeness of narratives of adolescents with normally developing language (NL) and those of adolescents with specific language impairment (SLI), even though narratives play an important role in adolescents' complex social and academic lives and there is emerging evidence that narrative abilities in young children portend their later language proficiency. This study examined the informativeness of oral narratives produced by four groups of adolescents: younger adolescents with NL (mean age = 13years:2 months), older adolescents with NL (15:10), younger adolescents with SLI (13:2) and older adolescents with SLI (15:9). The results indicated that the narratives produced by the SLI adolescents consisted of fewer informative and more irrelevant/inaccurate responses than the narratives of their peers with NL. The SLI adolescents also tended to give more vague responses in their narratives than their NL counterparts, as well tending not to provide any responses to the pictures representing the story. Taken together, these results painted a picture of SLI adolescents producing less satisfying, complete, and cohesive narratives, findings consistent with those of the research on children with SLI. Language status more than age appeared to be the factor that affected the likelihood of the adolescents providing or not providing informative responses. These results suggested that the performance of adolescents with SLI may not catch up to the level of performance of their NL counterparts during adolescence.     

Interdisciplinary management in the paediatric patient: restoration of a complicated crown-root fracture

Complicated crown-root fractures in permanent teeth present both patient-centred and restorative problems when treating the adolescent. This case highlights an alternative and conservative technique for the management of a traumatically involved maxillary left central incisor in a 12-year-old boy. The injury was successfully managed through an interdisciplinary approach using a combination of endodontics, minor oral surgery and orthodontics. The approach resulted in utilizing the patient's own tooth fragment to facilitate restoration back into successful function and aesthetics with the absence of any pathological changes.