血清HBV-DNA水平的变化与慢性乙型活动性肝炎的关系

目的:研究慢性肝炎患者HBV-DNA水平与病情变化的关系. 方法:采用荧光标记定量PCR的方法,测定慢性乙型肝炎急性发作患者(HBeAg阳性45例,抗HBe阳性30例)其活动期和恢复期的血清HBV-DNA含量. 结果:HBeAg阳性组血清HBV-DNA含量(Logarrithm copy/mL)在活动期显著高于恢复期[(10.2±1.6) vs (5.3±2.1), P<0.05],抗-HBe阳性组血清HBV-DNA含量(Logarrithm copy/mL)在活动期显著高于恢复期[(7.6±1.3) vs (4.0±2.0), P<0.05]. 另外,活动期血清HBV-DNA含量(Logarrithm copy/mL)在HBeAg阳性组显著高于抗HBe阳性组[(10.2±1.6) vs (7.6±1.3), P<0.05]. 血清HBV-DNA水平与丙氨酸转氨酶(ALT)、门冬氨酸转氨酶(AST)及总胆红素(T-BLLI)之间无相关性. 结论:HBV-DNA复制水平与慢性乙型病毒性肝炎的活动密切相关.     

Concurrent split-course chemotherapy and radiotherapy for unresectable stage III non-small cell lung cancer: preliminary results of a Phase II study]

PURPOSE: We initiated at Hospital de Mulhouse a prospective phase II study to assess a split-course concurrent radiochemotherapy in locally advanced non-small cell lung cancer. MATERIALS AND METHODS: From March 1996 to December 1997, 28 patients were included in our study. All patients had a stage III cancer. The chemotherapy scheduled included vinorelbine (20 mg/m2/d, d1 and d5), cisplatin (20 mg/m2/d, from d1 to d5), and 5-Fluorouracil (350 mg/m2/d, from d1 to d5 by continuous infusion). The planned irradiation dose was 12.5 Gy per week with one daily fraction of 2.5 Gy from d1 to d5. Cycles were repeated every four weeks, for four cycles (50 Gy). Patients with a partial or complete response were proposed a fifth cycle. RESULTS: Of the 28 patients of the study, only 27 were analysed; one patient had a metastatic disease at diagnosis. Major hematologic toxicity occurred in 26% of the patients. One to five cycles of chemoradiotherapy were administrated per patient (median: four). Four patients had received fewer than three cycles and their responses were not assessable. Of the 23 patients assessed, 12 responses (52%) were observed, three CR (13%) and nine PR (39%). Median follow-up was 14 months, and median survival 13.5 months. One- and two-year survival rates were respectively 63% and 14%. Local control rates was 11%, and 44% of the patients had a metastatic evolution. CONCLUSION: Very preliminary results of this phase II study are disappointing, and quite inferior to the published results using chemoradiotherapy with conventional or hyperfractionated radiotherapy. Hematologic toxicity is restrictive. This type of chemoradiotherapy cannot be recommended.     

Detection of neutralizing antibodies against human papillomaviruses (HPV) by inhibition of gene transfer mediated by HPV pseudovirions

The goal of this study was to develop a human papillomavirus (HPV) neutralization assay using HPV pseudovirions generated in vitro. For this purpose, gene transfer efficiency of HPV virus-like particles (VLPs) was improved by using direct interaction between a reporter plasmid and the VLPs. Electron microscopic observation of the interaction between DNA molecules and VLPs revealed that VLPs always interact with a single DNA molecule and that VLPs bind to the end of linearized DNA molecules. An 100-fold improvement in the gene transfer was obtained by simple interaction between a linearized DNA molecule and VLPs. Moreover, direct interaction methods offer the possibility of transferring plasmids a size higher than that of the papillomavirus genome. The approach that we developed to generate HPV-16 and HPV-31 pseudovirions proved to be suitable for testing neutralizing antibodies in human sera both after immunization and after natural infection.     

Gene therapy for cystic fibrosis with aerosolized adenovirus-CFTR: characterization of the aerosol and scintigraphic determination of lung deposition in baboons.

For cystic fibrosis (CF) gene therapy using an aerosolized adenovirus expressing the CFTR gene, optimization of the inhalation conditions is a prerequisite to obtain sufficient amount of CFTR protein expression in the target areas of the respiratory tract. For such a purpose, in vivo radioisotopic imaging of the radiolabeled virus is a unique strategy for a quantitative assessment of the actual deposition. In the present study, an adenovirus CFTR (AdCFTR) was labeled with 99m Technetium gamma emitting isotope in such conditions that its bioactivity was preserved. The 99mTc-AdCFTR aerosol was characterized using both laser diffraction and cascade impaction for sizing with further determination of nebulized and inhalable fractions. After administration to baboons, scintigraphic quantitation of the regional lung distribution was performed and the actual dose deposited in the target area was estimated and expressed as an equivalent viral titer. Since a virus scintigraphy is not realistic in a hospital setting, we have developed an approach using 99mTc-DTPA (diethylene triamino pentaacetic acid) that could be used to predict the virus deposition. Indeed, similarities observed between 99mTc-DTPA and 99mTc-adenovirus aerosol imaging patterns validates the use of the 99mTc-DTPA scintigraphy that we propose as a pretherapeutic test for each patient prior to gene transfer.     

Dynamic tomographic digital subtraction angiography using temporal filtration

A variation of temporal recursive filtering for intravenous and intra-arterial digital subtraction angiography (DSA) is described. It results in a dynamic tomographic DSA display that may improve intravenous DSA performance by removing the confusion introduced by vessel overlap and reducing the severity of motion artifacts. A conventional circular tomographic apparatus was modified by the addition of a 23-cm image intensifier-television chain and made to run continuously at one revolution each 1.5 seconds. The video output was processed by the recursive filter in a two-step process resulting in a dynamic tomographic display of arterial opacification. Theory and results of initial animal studies are presented.     

Pulmonary arteriography: comparison of cough stimulation effects of diatrizoate and ioxaglate

Twenty-five patients were observed in a prospective crossover study to determine whether the new low-osmolality contrast agents would be less prone than conventional agents to produce coughing during pulmonary arteriography. Selective left and right pulmonary arteriography (two views of each side) was performed with alternating administrations of diatrizoate sodium meglumine and ioxaglate sodium meglumine. Twenty-one patients had all four injections while four patients received injections on only one side. Sixteen of 25 patients coughed on at least one injection of diatrizoate, with three of these experiencing explosive coughing. One of 25 patients coughed with ioxaglate, and that was only minimally. This difference is statistically significant (P less than .001, on the basis of McNemar chi 2 test for paired data). When no coughing occurred, the quality of the diatrizoate and ioxaglate radiographs was indistinguishable. We conclude that ioxaglate is useful in pulmonary arteriography because of its lack of cough stimulation.     

Comparative assays in three laboratories of serum specimens containing pregnancy-specific β1 glycoprotein with different proportions of the α variant

Following several reports that the α component of pregnancy-specific β₁ glycoprotein (SP1) gives dose-response curves that are flatter than those of the β component when assayed by radioimmunoassay of the competitive type, a collaborative study was carried out by 3 laboratories to examine whether radial immunodiffusion or rocket immunoelectrophoresis give a similar result. Five sera from pregnant women at the 34–39th week of gestation with β : α ratios of 0.8–4.7 were assayed by both the latter methods against either the IARC 78 610 reference preparation or the SP1 Behring standard.When preparations were assayed by rocket immunoelectrophoresis (two laboratories), the dose-response curves were parallel. When preparations were assayed by radial immunodiffusion (two laboratories), parallelism was observed (one laboratory) after the addition of polyethylene glycol, the presence of which is necessary to visualize immune precipitates in which α is involved.Discrepancies observed when methodologies such as competitive radioimmunoassay are used, in which there are limited amounts of antibodies, are explained, at least partially, by the fact that the β component has a greater relative affinity for the antibody as higher concentrations of β : α mixtures are assayed. However, when antibody is present in excess, as in radial immunodiffusion and rocket immunoelectrophoresis, no such difference in affinity seems to occur.