Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. EORTC Lung Cancer Cooperative Group

26 previously treated patients with progressive recurrent small cell lung cancer (SCLC) were given vinorelbine (Navelbine), 30 mg/m2 weekly. All patients had responded to first-line chemotherapy and were off therapy for at least 3 months. Partial response was observed in 4 out of 25 eligible patients (16%; 95% confidence interval 4-36%), stable disease in 7 patients and progression in 12 patients. The limiting toxicity was a non-cumulative leucopenia (80%, 32% WHO grade 3-4). Reaction at the site of injection was observed in 5 patients, causing treatment discontinuation in 2 cases. Other non-haematological toxicities were moderate. These results suggest acceptable toxicity and some antitumour activity of vinorelbine in pretreated SCLC patients.     

Thrombolytic therapy for unstable angina

Thrombolytic therapy for unstable angina has not gained acceptance as a primary treatment for unstable angina (UA) despite the evidence showing a reduction in mortality when these agents are given for myocardial infarction. The purpose of this review is to examine the clinical value of thrombolytic therapy for UA. The multiple lines of evidence supporting intracoronary thrombus formation as a key mechanism in the pathogenesis of UA are reviewed. Studies examining the effect of thrombolytic therapy on angiographic endpoints have shown little effect on the extent of luminal narrowing, but do reveal a decrease in angiographically detected thrombus. Twelve randomized, controlled trials of thrombolytic agents in 611 UA patients with predefined clinical endpoints have been published. These trials varied widely in design and adjunctive therapy both in treated and control grops. Review of these trials show a tendency to fewer clinical events such as death, infarction, and need for revascularization in treated patients, with a corresponding increase in bleeding complications. Clinical efficacy of thrombolytic therapy cannot be excluded by the available data, perhaps in part because of insufficient numbers of patients treated. Determination of the net clinical value of thrombolytic therapy must await larger and more definitive trials.     

Analysis of interfacial failure in a composite microbundle pull-out experiment

Modeling of the failure of polymer-matrix composites requires substantial information about the mechanisms of failure at the interface, and load redistribution around fiber breaks in the composite. Current interface experiments involving the use of ‘microcomposites’ of single embedded fibers in a matrix generally do not include all the key geometric features of the real composite; in particular, they do not include the effects of fiber volume fraction and the higher matrix shear resulting from closely neighboring fibers. A new experiment was recently devised to assess some of these effects: it is referred to as the single-fiber pull-out from microbundle (SFPOM) experiment. It consists of a hexagonal arrat of seven fibers in a matrix where the outer six fibers are restrained and the center fiber is pulled out. Recent experimental data from tests with this geometry are analyzed here using three mechanical models of the failure process, and parametric studies of the data are performed to assess the appropriateness of each model. Two of the models, based on fracture energy considerations as applied earlier to single embedded fibers in a matrix and adapted to our geometry, were found to model data from the SFPOM experiments poorly. The third model assumes the existence of three zones near a fiber break, including elastic, plastic and frictional debond zones, and was found to provide reasonable fit to the data under realistic assumptions.     

A Specific Stability Indicating Hplc Method to Determine Diclofenac Sodium in Raw Materials and Pharmaceutical Solid Dosage Forms

A high performance liquid chromatography method is described for the determination of diclofenac sodium, its related compounds and degradation products in commercial sources of raw materials and solid dosage forms. This method is specific, accurate and stability indicating. The method employs a reverse-phase octylsilane (C18) column with a mobile phase composed of acetonitrile/methanol/pic B-6 (25:25:50) and detection at 229 nm. The method resolves six principal related compounds with quantitation in the range 0.3-1.5%. Assay recoveries by spiking commercial formulations with diclofenac sodium were 99.64 ± 1.30%. Drug content in several commercial formulations are reported. Accelerated stability tests were conducted on raw materials and drug products and 1-(2,6-dichlorophenyl)-2-indolin-2-one was identified for the first time as a degradation product in solid dosage forms which are stressed under humidity and heat.     

Implant exudate leucocyte response to anti-inflammatory drug treatment

Implantation of artificial materials elicits a local inflammatory response. In this study a chamber model technique, allowing sampling of the inflammatory exudate for further analysis in vitro, was used. Male Sprague-Dawley rats were injected daily with two different anti-inflammatory drugs, betamethasone and indomethacin, and the local cellular response was compared with a control group. The retrieved exudate was evaluated with respect to the number of leucocytes, cell viability, differential counts and serum-opsonized zymosan stimulated chemiluminescence (CL). In all groups the majority of cells were polymorphonuclear granulocytes (PMNGs). Betamethasone and high-dose indomethacin (1.92 mg kg^-1 body weight day^-1) treatment caused a marked reduction in the number of accumulated leucocytes 6 days after implantation. A substantial inhibition of the CL response was observed 6 days after treatment with betamethasone (4.23 mg kg^-1 body weight day^-1). An increased CL responsiveness was observed after 24 h with low-dose indomethacin (0.03 mg kg^-1 body weight day^-1) and after 6 days with high-dose indomethacin (1.92 mg kg^-1 body weight day^-1) treatment. In summary, depending on the anti-inflammatory drug treatment, dose and time after implant surgery, either an inhibition or stimulation of leucocyte accumulation and activation was observed. This study shows the possibilities of sampling the inflammatory exudate adjacent to a biomaterial implanted in vivo. This chamber model may be useful for the analysis of the inflammatory reaction around an implanted biomaterial during pharmacological treatment.     

Modeling of silicon diffusion in gallium arsenide

A model is developed and a study is performed for amphoteric diffusion of silicon in gallium arsenide. A comparison of predictions with experimental data indicated adequacy of the devised model and high efficiency of the numerical method for solving the diffusion equation.Belorussian State University, Minsk. Minsk Radio Engineering Institute. Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 65, No. 5, pp. 567–572, November, 1993.     

Nonlinear oscillations of a vapor bubble in the region of the main resonance

Nonlinear spherical vapor bubble oscillations in the main resonance region in a viscous incompressible fluid under the action of a periodically varying external pressure are considered using the multiscale method. Saddle-node type bifurcations that appear when the amplitude or frequency of the external effect changes are investigated.Institute of Thermal Physics of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg. Translated from Inzhenerno-Fizicheskii Zhurnal, Vol. 65, No. 2, pp. 164–170, August, 1993.     

THE INFLUENCE OF LOAD MISALIGNMENT DURING UNIAXIAL LOW-CYCLE FATIGUE TESTING—II: APPLICATIONS

Abstract— Models for predicting scatter bands due to bending have been applied to four alloys, namely AISI 316L, Nimonic 101, 9 Cr-1 Mo, and IN 718. The alloys were tested extensively by 26 laboratories in an international round robin exercise sponsored by the Community Bureau of Reference (BCR) of the EC. After initially selecting data for analysis on the basis of their confirmed conformance to the ASTM bending criterion, it has been shown that in all four materials a major fraction of the data scatter could be attributed to bending. Furthermore, at the lowest strain range the predicted bending component represents the highest proportion of the experimental interlaboratory scatter. Many laboratories did not report any measure of bending and so could not be used in the initial analysis. However, a further interesting deduction from the models is that the entire BCR data-set can be encompassed within a scatter band based upon a bending criterion that is twice the allowable ASTM limit. Differences in the extent of scatter between materials at a given total strain range can be attributed to the gradient of the logarithmic plot of total strain range as a function of lifetime.     

A micromechanics model for the prediction of static strength of off-axis unidirectional laminates

In this paper a micromechanics model using the concentric cylinder assemblage model and the Mori-Tanaka average stress scheme is used to predict the static strength of unidirectional angle ply laminates. The predicted strengths agree with experimental results for Glass/Epoxy and Graphite/Epoxy systems.