Gemcitabine and cisplatin versus vinorelbine and cisplatin versus ifosfamide+gemcitabine followed by vinorelbine and cisplatin versus vinorelbine and cisplatin followed by ifosfamide and gemcitabine in stage IIIB-IV non small cell lung carcinoma: a prospective randomized phase III trial of the Gruppo Oncologico Italia Meridionale

PURPOSE: we carried out a phase III randomized trial to compare vinorelbine-cisplatin regimen to gemcitabine-cisplatin regimen, and to a sequential administration of gemcitabine-ifosfamide followed by vinorelbine-cisplatin or the opposite sequence of vinorelbine-cisplatin followed by ifosfamide-gemcitabine according to the 'worst drug rule' hypothesis in patients with locally advanced unresectable stage IIIB or metastatic stage IV non-small cell lung cancer. The primary endpoint was survival parameters, while secondary endpoints included analysis of response rates and toxicity. PATIENTS AND METHODS: patients were randomized to receive: (a) gemcitabine 1000 mg/m(2) on days 1, 8 and 15 plus ifosfamide 1500 mg/m(2) on days 8-12 with mesna uroprotection (GI regimen) followed by vinorelbine 25 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 1 (GI --> VC regimen); (b) the opposite sequence (VC --> GI); (c) vinorelbine plus cisplatin as above described (VC regimen); or (d) gemcitabine 1400 mg/m(2) on days 1 and 8 plus cisplatin 100 mg/m(2) on day 8 (GC regimen). All regimens were given every 4 weeks. All patients were chemotherapy naive and had a ECOG PS 0-2. RESULTS: 400 patients were enrolled into the trial. Interim analysis after inclusion of 243 patients showed that ORR were 19% in the GI --> VC arm, 32% in the inverse sequence arm (CV --> GI), 42% in the VC arm, and 30% in the GC arm. The VC arm was statistically superior over the GI --> VC arm (p = 0.0074), but not over the other regimens. Median TTP was 3.1 months in the GI --> VC arm versus 5.0 months in the VC --> GI arm (p = 0.014). For these reasons the GI --> VC and VC --> GI arm were closed since the 'worst drug rule' hypothesis was rejected. Accrual in the VC and GC arms continued up to 140 and 138 patients respectively. Final ORR were 44% for the VC regimen (4 CR), and 34% for the GC regimen (1 CR). This difference was statistically significant (p = 0.032). OS was 9.0 and 8.2 months, respectively, with no statistically significant difference. The 1-year survival rate was 24 and 20%, respectively for VC and GC regimens. As expected the incidence of phlebitis was higher in the VC arm, while thrombocytopenia, flu-like syndrome and asthenia were more frequent in the GC arm. CONCLUSIONS: the results of this trial indicate that the combination of vinorelbine and cisplatin and that of gemcitabine and cisplatin are equivalent in terms of median TTP and OS, although the vinorelbine-cisplatin regimen is associated with a higher ORR. Both regimens may be considered as reference treatments for future studies. Moreover, our data reject the 'worst drug rule' hypothesis of sequential treatments in NSCCL at least with the combination used in this study.     

Effect of α-difluoromethyl-ornithine on the expression and function of the epidermal growth factor receptor in human breast epithelial cells in culture

We have previously shown that ornithine decarboxylase (ODC) overexpression enhances the transforming effects of HER-2neu and epidermal growth factor (EGF) in normal MCF-10A human breast epithelial cells. Our data suggest that such potentiation may be mediated by activation of the mitogen-activated protein kinase (MAPK) pathway and, possibly, STAT signalling. To further explore the interaction between the polyamine pathway and EGF/HER-2neu signalling in this system, we inhibited endogenous ODC activity with -difluoromethylornithine (DFMO) and assessed the effects of this blockade on the expression of EGF receptors (EGFR) and HER-2neu as well as activation of downstream EGF target genes. We found that DFMO administration to MCF-10A cells increased EGF-R mRNA and protein levels in a dose-response fashion, while HER-2neu expression was not affected. The effect of DFMO was mediated through polyamine depletion since it could be reversed by exogenous putrescine administration. Our results also indicated that the increase in EGFR induced by DFMO was not a non-specific consequence of inhibition of cell proliferation. The upregulated EGFRs were functional since they could be phosphorylated by EGF and they were able to promote phosphorylation of downstream signalling molecules including ERK, STAT-3, and STAT-5. We propose that physiologic levels of ODC activity may be critical for regulation of a yet undefined signalling pathway, whose blockade by DFMO leads to a compensatory increase in functional EGFR.     

Duodenal somatostatinomas associated with von Recklinghausen's neurofibromatosis. Apropos of 2 cases

Somatostatinomas are rare neuroendocrine tumors; they are essentially located in the pancreas and in the duodenum. The association with a neurofibromatosis type I is especially observed when the tumor is located in the ampulla of Vater. These tumors are not associated with a "somatostatin syndrome", but often present with gastrointestinal bleeding, abdominal pain and obstructive jaundice. The diagnosis is confirmed by immunohistochemical studies. The aim of this study is to report 2 cases of metastazing duodenal periampullary somatostatinomas associated with von Recklinghausen's disease and to discuss the prognosis of these tumors. Future genetic research are necessary as point out the familial feature of this association in one of our cases.     

高效液相色谱法测定寒痹停片中士的宁含量

目的：建立用ＨＰＬＣ测定寒痹停片中士的含量的方法。方法：氰基柱;流动相－甲醇－水－三乙胺－乙酸（９８００：１５５：１５：３０）;紫外检测波长２５４ｎｍ。结果：在４～２０ｕｇ／ｍｌ范围内,标准曲线回归方程为：Ｙ＝－２８０３＋８９６７ｘ（ｒ＝０．９９９７）,ＲＳＤ＝１．６５％?加样回收率的平均值为９９．８２％。结论：实验表明,这是一个适用于生产控制和产品质量检验的简单、快速、准确的方法。     

Chondrodysplasia punctata after warfarin in early pregnancy. Case report and summary of the literature

A third case of chondrodysplasia punctata after exposure to warfarin alone in early pregnancy is described. The clinical course of the child during the first 18 months is outlined. The use of warfarin in early pregnancy must be avoided because of its established teratogenic effects in causing this syndrome, in addition to an overall increase in perinatal mortality.     

Efficacy of face masks in preventing inhalation of airborne contaminants

Use of surgical face masks has been advocated to protect clinicians from inhalation of aerosols containing organic and inorganic particulates. This study examined the ability of a 22 micron tracer particle to bypass the filtering capability of face mask material by peripheral marginal leakage of inspired air. For two popularly used face masks taped to a facial moulage, recovery of the tracer particle by an in vitro system was very low. When the masks were placed in the manner in which the product is commonly worn, however, significantly higher numbers of particles were recovered. Passage of inspired air around the periphery of two types of face masks appears to circumvent the masks' ability to screen airborne contaminants.     

Caudal-posteroanterior view in coronary arteriography

Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography.     

Organization of serotonin 1A and 1B receptors in the nucleus of the solitary tract

We utilized 3H-8-hydroxy-N,N-dipropyl-2-aminotetralin (3H-DPAT) and 125I-iodocyanopindolol (125I-CYP) to label serotonin (5HT) 1A and 5HT1B receptors, respectively, in sections of the rat brain after characterizing the pharmacologic specificity of these agents. We then used quantitative autoradiography to measure the concentrations of 5HT1A and 5HT1B receptors in individual subnuclei of the nucleus of the solitary tract (NTS) and adjacent structures of the dorsal vagal complex. The highest 5HT1A receptor concentrations were observed within the central and intermediate subnuclei of the NTS, with low quantities of 3H-DPAT binding sites observed in the hypoglossal nucleus and dorsal motor nucleus of the vagus. In contrast, the density of 5HT1B receptors was relatively homogeneous through all NTS subnuclei, with the highest concentrations localized within the ventrolateral subnucleus. The hypoglossal and dorsal motor nuclei had slightly higher 5HT1B receptor densities than the NTS subnuclei, whereas the area postrema had a very low density. These data suggest that 5HT1A receptors are organized in a manner consistent with the cytoarchitectural and hodological parcellation of the NTS into individual subnuclei. The high concentrations of 5HT1A receptors in the central and intermediate subnuclei suggest a role for these receptors in medullary reflex pathways subserving deglutition. The relatively high density of 5HT1B receptors in the ventrolateral subnucleus suggests that these receptors modulate respiratory neurons, whereas the diffuse organization of 5HT1B receptors in the remaining subnuclei suggests that they are associated with central 5HT afferent pathways to the NTS. Further studies will be required to understand the physiologic role of 5HT1 receptors within the NTS.     

低血糖指数膳食改善超重老年糖尿病患者氧化应激水平

目的:观察低血糖指数的膳食对2型糖尿病患者氧化应激状态的影响。方法:2004-10/11在上海市静安区二个社区卫生服务中心招募受试者,经医生明确诊断为2型糖尿病、病程超过6个月,体质量指数≥24kg/m2的老年糖尿病志愿者43名,受试者对试验知情同意。采用随机交叉试验随机分配至低血糖指数饮食组和高血糖指数饮食组,每种膳食分别连续使用4周,间隔洗脱期4周,比较试验前后患者超氧化物歧化酶、脂质过氧化产物丙二醛和谷胱甘肽过氧化物酶含量的变化。结果:受试者依从性好,除1人因试验期间发现肿瘤而退出试验,42名志愿者按设计要求完成试验。膳食干预后低血糖指数饮食组和高血糖指数饮食组的超氧化物歧化酶活力分别升高了15.68%和21.33%,丙二醛水平分别下降23.94%和21.55%,谷胱甘肽过氧化物酶活力分别升高了15.74%和17.09%;干预后低血糖指数饮食组丙二醛下降水平与高血糖指数饮食组比较差异有显著性意义(P<0.05),而超氧化物歧化酶和谷胱甘肽过氧化物酶活性两组间差异无显著性意义(P>0.05)。结论:在控制总能量的基础上给予平衡膳食能够改善其氧化应激水平,采用低血糖指数食物有助于氧化应激水平的改善。