Induced drug resistance inhibits selection of initiated cells and cancer development

Compounds exerting a mitoinhibitory effect on normal hepatocytes are potent promoters in the resistant hepatocyte model of chemical carcinogenesis in combination with stimulation of regenerative growth by partial hepatectomy or treatment with carbon tetrachloride. 2- Acetylaminofluorene (2-AAF) almost completely inhibits liver cell regeneration after partial hepatectomy, allowing only resistant cells to participate in regenerative growth. After initiation by diethylnitrosamine and promotion with 2-AAF and partial hepatectomy (PH), focal growth of initiated cells generates liver lesions which occupy 40% of the hepatic volume three weeks after PH. In this work the mechanism for the anti promoting effects of phenobarbital and 3- methylcholantrene were investigated as well as their effects on the development of malignant hepatocellular carcinoma in the resistant hepatocyte model. Treatment with phenobarbital or, especially, 3- methylcholanthrene rendered normal rat hepatocytes resistant to the mitoinhibitory effect of 2-AAF. In combination with 2-AAF/PH, 3- methylcholanthrene shortened the regenerative growth period to less than one week. In the Solt-Farber protocol for experimental hepatocarcinogenesis, treatment with phenobarbital or 3- methylcholanthrene during promotion with 2-AAF/PH permitted hepatocytes surrounding the focal lesions to respond with regenerative growth. The foci and surrounding liver grew until the liver/body mass index reached the control value. With phenobarbital treatment the total focal volume was 20% of the liver volume three weeks after PH, whereas the corresponding value in the case of 3-methylcholanthrene was only 1%. Labelling index data supported the conclusion that growth of the liver lesions in the resistant hepatocyte model was dependent on differential inhibition of normal hepatocyte growth by the promoter and that the size of the foci obtained was related to the length of time after PH required to complete liver regeneration. 3-methylcholanthrene induced 2- AAF resistance prevented the development of large persistent nodules and hepatocellular carcinoma while phenobarbital delayed cancer development with several month. The data thus supports the idea that the degree of clonal expansion during promotion determines the size of the population at risk for malignant transformation, as well as the final frequency of carcinomas.      

铒激光擦皮术后色素沉着的防治对策

０　引言　东方人接受皮肤磨削术治疗后色素沉着的发生率明显高于西方人．尽管采用了目前被认为是最适宜亚洲人的铒激光治疗,色素沉着仍可发生．因此,在实施该手术治疗前应严格掌握适应证,制定严密的预防治疗措施,使得色素沉着的发生率降至最低,从而最大限度的防止医疗纠纷的发生．１　对象和方法１．１　对象　２１例患者,男２例,女１９例,平均年龄２９．２（０８～４８）岁．皱纹祛除８例,浅表疤痕７例,浅咖啡斑、黑子５例,不良纹眉１例．铒激光其它适应证：①老年斑;②细小皱纹;③“白皮肤”雀斑;④痤疮后疤痕⑤色素减退…     

Inhaled dry powder mannitol in children with cystic fibrosis: A randomised efficacy and safety trial

Introduction

Inhaled mannitol has beneficial effects on lung function, mucociliary clearance, quality of life and sputum properties. This trial examined the efficacy of inhaled mannitol in children with cystic fibrosis (CF).

Screening for asymptomatic carriage of Trichophyton tonsurans in household contacts of patients with tinea capitis: results of 209 patients from South London

BACKGROUND: There is currently an epidemic of tinea capitis in urban areas of developed countries caused by Trichophyton tonsurans. Recurrence or re-infection with dermatophyte is not uncommon after adequate oral treatment. Asymptomatic carriers who are household contacts may partly explain this observation by forming a reservoir for infection. PATIENTS/METHODS: Two-hundred and nine household contacts of patients with tinea capitis were examined and screened for asymptomatic carriage of dermatophyte. RESULTS: Only 7.2% had clinically evident disease yet 44.5% had silent fungal carriage on the scalp. Children under 16 years were much more likely to be carriers than adults (P < 0.001) and males were less likely than females to be affected (P < 0.01). CONCLUSION: This evidence poses questions about factors relevant in transmission of dermatophytes. The authors propose that all household contacts of patients with tinea capitis should be offered screening to eradicate a potential reservoir of infection.     

Immunotherapy in biliary tract cancers: Current evidence and future perspectives

Bile duct tumors are comprised of tumors that originate from both intrahepatic and extrahepatic bile ducts and gallbladder tumors. These are aggressive tumors and chemotherapy is still the main treatment for advanced-stage disease and most of these cases have a poor overall survival. Strategies are aimed at treatments with better outcomes and less toxicity which makes immunotherapy an area of ​​significant importance. Recent Food and Drug Administration approvals of immune checkpoint inhibitors (ICI) for agnostic tumors based on biomarkers such as microsatellite instability-high and tumor mutation burden-high are important steps in the treatment of patients with advanced bile duct tumors. Despite limited responses with isolated checkpoint inhibitors in later lines of systemic treatment in advanced disease, drug combination strategies have been demonstrating encouraging results to enhance ICI efficacy.     

Prolonged migraine aura without headache arrested by sumatriptan. A case report with further considerations

The case of a 42-year-old woman with prolonged migraine visual aura without headache, whose long-lasting episodes of visual aura were successfully controlled by oral sumatriptan, is reported. Effectiveness of sumatriptan was unequivocal, since, after taking sumatriptan, duration of aura would drop from 1.5 h to approximately 20 min. This case suggests that sumatriptan may cross the blood-brain barrier and block spreading depression.     

Misdiagnosis of tuberculosis and the clinical relevance of non—tuberculous mycobacteria in Zambia

ObjectiveTo determine the accuracy of TB diagnosis of TB in Zambia in the era of increasing HIV prevalence.MethodsSputum of the clinically diagnosed TB cases was additionally subjected to liquid culture and molecular identification. This study distinguished between TB cases confirmed by positive Mycobacterium tuberculosis (M. tuberculosis) cultures and mycobacterial disease caused by non-tuberculous mycobacteria (NTM).ResultsOnly 49% of the 173 presumptively diagnosed TB cases was M. tuberculosis cultured, while in 13% (22) cases, a combination of M. tuberculosis and NTM was found. In 18% of the patients only NTM were cultured. In 28%, no mycobacteria was cultivable. HIV positive status was correlated with the isolation of NTM (P <0.05).ConclusionsThe diagnosis of tuberculosis based on symptoms, sputum smear and/or chest X-ray leads to significant numbers of false-positive TB cases in Zambia, most likely due to the increased prevalence of HIV. The role of NTM in tuberculosis-like disease also seems relevant to the false diagnosis of TB in Zambia.