Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib

Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib.     

国际肝病学会分委员会对急性和亚急性肝功能衰竭命名的建议

SKAcharya编者按：本期刊出国际肝病学会分委员会有关专家对急性肝功能衰竭（AHF）和亚急性肝功能衰竭（SHF）命名的建议。此命名将AHF和SHF视为两个独立的疾病,而不是一个综合征的两个亚型,与我国1995年“病毒性肝炎防治方案”中的重型肝炎分类有诸多差别：①病因方面：AHF和SHF由各种病因（病毒、药物和毒物等）所致,而重型肝炎仅以病毒性肝炎为病因;②病程和时间：AHF在症状出现后4周内、SHF在症状出现后1～6个月内发生,而急性或亚急性重型肝炎均在症状出现后10天内或以后（有的定为4～8周内）发生;③症状特征：AHF及…     

Detection of canine echinococcosis by coproantigen ELISA

ObjectiveTo study the canine echinococcosis by coproantigen ELISA method.MethodsDuring the present investigation experimental infection was established using evaginated worms of Echinococcus granulosus (E. granulosus). To check cross reactivity two pups were infected with Taenia hydatigena (T. hydatigena). In order to detect the presence of antigen, hyperimmune sera were raised against excretory-secretory products of adult worms E. chinococcus granulosus. Faecal sample collected either from experimentally infected pups or from other sources were heated at 70 °C to detect heat stable soluble antigen.ResultsPups harbouring less than 104 worms showed negative results. Samples collected from 14 days onwards from experimentally infected animals harbouring more than 104 worms showed positive value. The maximum positive samples were detected in samples collected from in and around slaughter house and the least number of samples were detected positive maintained by dog squad.ConclusionsThe affinity purified IgG exhibited promising results for detection of canine echinococcosis by indirect ELISA.     

Management guidelines for uninvestigated and functional dyspepsia in the Asia-Pacific region: First Asian Pacific working party on functional dyspepsia

Dyspepsia is most optimally defined as pain or discomfort centred in the upper abdomen. The symptom complex may be caused by peptic ulcer disease, gastro-oesophageal reflux, or gastric cancer but is most often due to functional (or non-ulcer) dyspepsia. While upper endoscopy is the method of choice to determine the underlying cause of dyspepsia, it is expensive. A more pragmatic approach is needed in the Asia-Pacific region where health services are limited. A detailed treatment algorithm is given for managing patients presenting with new-onset dyspepsia and documented functional dyspepsia after endoscopy, and evidence to support this approach is reviewed. Prompt endoscopy is recommended for patients with alarm features. In patients without alarm features, treatment for 2–4 weeks with an empirical anti-secretory or prokinetic agent, followed by investigation using non-invasive Helicobacter pylori testing and treatment for patients who do not respond or relapse, is recommended. Trials of management strategies are now needed to establish the efficacy and cost-effectiveness of the approaches recommended.     

Peak expiratory flow in healthy Turkish children

This study was conducted on 1359 healthy, non-smoking Turkish children (727M, 632F) with a mean age of 11.7 ± 3.4 (6–17) years, in order to determine the normal values of peak expiratory flow (PEF) in Turkish children and to compare various peak-flow meters (PEFMs). PEF values increased with age and height in boys and girls. The relative increase in boys was significantly higher at puberty (p < 0.01). The values of Turkish children were found to be similar to those of Europeans. The results obtained from the three PEFMs were closely correlated.