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OBJECTIVESWe sought to evaluate whether oral anticoagulant (AC) therapy given for five months was superior to standard (control) therapy in patients with unstable angina receiving aspirin.BACKGROUNDThe long-term risk of myocardial infarction (MI) or death remains high in patients with unstable angina, despite the use of aspirin. Therefore, additional treatments are necessary.METHODSOf the 10,141 patients entering the main trial, 3,712 were randomized 12 to 48 h later to receive oral AC therapy (n = 1,848) or standard therapy (n = 1,864).RESULTSOne-hundred forty patients (7.6%) suffered from cardiovascular death, MI or stroke while receiving oral AC, compared with 155 patients (8.3%) on standard therapy (relative risk [RR] 0.90, 95% confidence interval [CI] 0.72 to 1.14; p = 0.40). The rates of the primary outcomes plus refractory angina were 16.7% (n = 308) versus 17.5% (n = 327) (RR 0.95, 95% CI 0.81 to 1.11; p = 0.53). Countries were divided into good or poor compliers (based on the use of oral AC above or below 70% at 35 days), without knowledge of results by country. In good-complier countries, oral AC was discontinued in only 10.4% of patients at seven days and in 23.6% by five months, compared with 27.6% and 44.9%, respectively, in poor complier countries. There were significant reductions in the risks of both the primary (6.1% vs. 8.9%; RR 0.68, 95% CI 0.48 to 0.95; p = 0.02) and secondary outcomes (11.9% vs. 16.5%; RR 0.70, 95% CI 0.55 to 0.90; p = 0.005) with oral AC in the good-complier countries. There was little difference in the poor-complier countries (9.0% vs. 7.8% for the primary and 21.3% vs. 18.5% for the secondary outcomes, tests for interactions comparing the RRs for the primary and secondary outcomes were p < 0.02 and p = 0.002, respectively, between the two sets of countries). In the overall study, there was an excess of major bleeding (2.7% vs. 1.3%; p = 0.004), which was larger in the good-complier countries (RR 2.71) compared with the poor-complier countries (RR 1.58). There were also reductions in cardiac catheterization (RR 0.80; p = 0.004) and coronary revascularization procedures (RR 0.82; p = 0.06) in the good-complier countries, but not in the poor-complier countries (RR 0.98 and 1.06, respectively, p for interaction of 0.06 and 0.04, respectively).CONCLUSIONSOverall, oral AC led to a small, nonsignificant reduction in the risk of the primary and secondary outcomes. Stratifying the countries or centers by their rates of compliance to oral AC suggested that good compliance to oral AC could potentially lead to clinically important reductions in major ischemic cardiovascular events.

The adsorption of tetradecylpyridinium (TDPy) and lauryl sulphate (LS) ions on polar, low charged adsorbents, i.e. fumed silica (Aerosil Ox 50) and fumed titanium dioxide (P25), was studied, as well as in the presence of chemisorbed octadecyldimethylsilane (ODDMS) residues on the adsorbent surfaces. The influence of different counterions on the adsorption of TDPy and of ODDMS group density is demonstrated on silica at low pH values and, consequently, low surface charge density. The adsorption on ODDMS groups is confirmed for TDPy on surface-modified TiO 2 . The LS anions, not adsorbed to bare silica, are also adsorbed to the negatively charged silica surface in the presence of ODDMS groups. The results are discussed taking into consideration different proposals for the structure of the adsorbates, in particular the state of saturation adsorption. The behaviour of the surfactant ions can be best explained assuming small surface aggregates (micelles) if the surface density of primary adsorption sites, including ODDMS anchor groups, is lower than 0.3 mmol m −2 .

A novel technique for the manufacture of water-insoluble film coatings on drug-loaded saccharose pellets is described. The method is based on the simultaneous spraying of aqueous solutions of a film-forming polymer and an appropriate crosslinking agent. Crosslinking of the polymer was achieved in situ in the film during coating of the pellets in a fluidized bed. Uniform film coatings were formed without additives. Pan coating with sequential spraying of the components yielded similar results, however, it was more time consuming. The anionic polymer, sodium alginate, was combined with different cationic crosslinking agents, such as calcium ions, aluminum ions, Cetrimide (tetradecyltrimethylammonium bromide), and Eudragit E (copolymer of dimethylaminoethylmethacrylate and neutral methacrylic acid esters) (in 0.1 N HCl) in aqueous solutions. The swelling behavior of the cast films in water depended on the crosslinking component and the film thickness. For studying the in vitro drug release through the film coatings, the pellets were drug-loaded with acetaminophen and indomethacin as model drugs. Alginate films crosslinked with calcium ions showed the most promising features for controlled drug release. The release rate of the model drug acetaminophen proved to be almost independent of the pH of the dissolution fluid (pH 7.4 phosphate buffer, 0.1 N HCl). During drug release, the coatings did not disintegrate in 0.1 N HCl, but slowly disintegrated in buffer solution. Indomethacin was released at considerably smaller rates.

The hydrolysis of the chemisorbate of p -hydroxybenzoic acid methyl ester (PHBAME) on porous silica (KG 100) incorporated in lipophilic vehicles such as liquid paraffin, synthetic oil Miglyol® 818 and white petrolatum was examined in dissolution media at pH 2 and 7.4, respectively. Chemisorbed PHBAME on KG 100 is released more rapidly in alkaline than in acidic dissolution fluids. Dispersions of the PHBAME-KG 100 chemisorbate in lipophilic vehicles modify the hydrolysis significantly. Drug release from chemisorbate dispersed in lipophilic vehicles may be controlled by the polarity of the vehicles. However, the viscosity of the vehicle, and not the polarity, exerts the strongest influence on the drug release.

Chitosan, a natural, biocompatible polymer, is becoming popular in dosage form design. In our study the design factors affecting the release of lidocaine and lidocaine chloride from chitosan hydrocolloids and gels were studied. In hydrocolloids a relatively high viscosity was found at low concentrations of chitosan caused by the increased effective volume of the polymer molecules, due to the reflection of the same charges in the chains. The drug release is slow and sustained, being influenced by the chitosan content. The mechanism of chitosan gel formation is not known exactly, but it is clear that for gel formation the length of the chitosan chains and the degree of reacetylation are responsible. The release profile of gels follows almost zero order kinetics. Also, the degree of reacetylation is responsible for the release behaviour. The rotational motion of nitroxides (Tempol, spin-labeled lidocaine) determined by EPR experiments showed practically equal rotational motion at different degrees of reacetylation. Thus, it was concluded that the free spaces, available for nitroxide rotation, were not changed significantly. The degree of reacetylation affects the translational diffusion more strongly.

The in vitro release of physi- and chemiadsorbates of p-hydroxybenzoic acid methyl ester (PHBAME) on a colloidal (Aerosil 0 × 50; BET surface 50 m2 g−1) and a porous silica support (KG 100; mean pore size 10 nm, BET surface 300 m2 g−1) in an acidic dissolution fluid was investigated and the release kinetics described by mathematical modeling with an analog-hybrid computer. The release from physiadsorbates on both the colloidal and the porous silica proved to be a fast process, best described by two release constants. The release from the chemiadsorbates, however, is based on different mechanisms: from the plain surface of colloidal silica (fractal dimension 2.0) the drug release can be best described by two hydrolysis reaction rates while four different reaction rates were evaluated for the release of PHBAME from the porous support. From the reaction rates and the activation energies it is concluded that the hydrolysis of the surface link between the PHBAME and the silica surface, the Si-O-c bond is strongly influenced by the surface character of the supports, described by their different fractal dimensions (porous support fractal dimension 2.56).

Chondrosarcoma represents the most common malignant tumour of the chest wall, with a tendency for local recurrence after resection. Here we report the successful complete resection of a giant, local recurrent chondrosarcoma of the chest wall (max. diameter 25 cm), in a patient with hereditary multiple exostoses, who had had a wide resection 8 years before. Clinical features and surgical management are described.

The interactions between phenolic compounds and polyethylene glycols were investigated by IR-spectroscopy. The intensifies of these interactions, which are mainly due to hydrogen bonding, showed a strong correlation with the Hammelt σ-constants of the meta and para and the ortho substituted phenolic compounds, respectively. Bulk substituents in the o-position to the phenolic hydroxyl, as well as internal hydrogen bonding of substituted phenols, considerably reduce the association with the polymer. From the spectroscopic data the enthalpies of the interactions were calculated thus confirming the hydrogen bonding interaction.

With tne floating-zone technique we have obtained super-pure, uncompensated silicon of p -type with a resistivity above 100 000 Ωcm. The intrinsic conductivity of these samples reaches near to 40°C. The intrinsic density n i (obtained over a range from 50° to 100°C agrees quite closely with the n i -values determined by other investigators. The distribution coefficient k of boron is slightly below 0.9.

The temperature dependence of the threshold current density was examined for a series of GaAs injection lasers with different lengths but otherwise identical structure. From a plot of threshold current density as a function of reciprocal length at constant temperature, the gain and loss factor can be calculated. The laser losses exhibit only a small temperature dependence in the range from 4·2 to 300°K. The reciprocal gain factor, however, has the same temperature dependence as the threshold current density j t . The detailed nature of the temperature dependence of j t does depend on the length of the laser and on the doping level in the active region. The influence of these two parameters is discussed and compared with theoretical predictions.

Zusammenfassung Es werden elektrische Leitfahigkeit und Halleffekt an synthetischen Zinkoxydeinkristallen mit Fremdzusatzen im Temperaturgebiet von 65 bis 700°K gemessen. Dabei ergibt sich ein ahnliches Verhalten wie bei anderen Halbleitern, z.B. Germanium, Silizium. Die nach Konzentration und Beweglichkeit ausgewerteten Ergebnisse werden mit den bekannten theoretischen Vorstellungen verglichen. Es gelingt unter bestimmten Voraussetzungen einen Wert fur die effektive Elektronenmasse abzuschatzen.

The adsorption of cationic and anionic surfactants on three hydrophilic silicas and one hydrophobic (methylated) colloidal silica was studied in the presence of organic solvents. Cationic surfactants (alkylpyridinium chlorides and alkyltrimethylammonium chlorides) are strongly bound by hydrophilic silicas in a weak polar solvent (CHCl3). While pyridinium and ammonium as the head group have no marked influence upon adsorption, the hydrocarbon chain length (in the range C4-C10) determines the surface areas occupied by adsorbed surfactant molecules. Homologs with longer hydrocarbon chains (C12-C18) all occupy equal areas in the saturated adsorption layer. Polar organic solvents (alcohols) reduce the adsorption of cationic surfactants on hydrophilic silicas. In the presence of dimethyl sulfoxide, no adsorption is observed. Maximum adsorption of dioctyl sodium sulfosuccinate is attained in the presence of carbon tetrachloride. Solvents with hydrogen-bonding abilities (dimethyl sulfoxide and dioxane) prevent adsorption of anionic surfactants (dioctyl sodium sulfosuccinate and sodium alkyl sulfates). It is suggested that the silanol groups on the surface, which are capable of hydrogen bonding and electrostatic interactions, are the active adsorption sites of the silica. If their number is reduced, the adsorption is diminished to the same extent.