Optical and structural properties of sputter-deposited nanocrystalline Cu2O films: effect of sputtering gas.

We report the effect of the atomic mass of the sputtering gas (He, Ne, Ar, Kr, and Xe) on the structure and optical properties of nanocrystalline cuprous oxide (Cu2O) thin films deposited by dc magnetron sputtering. The crystal structure and surface morphology were studied by X-ray diffraction (XRD) and atomic force microscopy (AFM) respectively. We find that the atomic mass of the sputtering gas significantly affects the primary crystallite size as well as the surface morphology and texture. Optical reflectance and transmission measurements show that the nanocrystalline thin films are transparent over most of the visible region. The HOMO-LUMO gap obtained from optical absorption spectra show a size-dependent quantum shift with respect to the bulk band gap reported for Cu2O (2.1 eV).

Squamous cell carcinoma of the anal canal and anal margin.

Squamous cell carcinomas of the anal canal and margin are relatively uncommon neoplasms of the distal gastrointestinal tract and surrounding skin. The major risk factors for tumor development have been defined through various epidemiologic studies. Randomized, phase III trials have defined the standard of care for anal cancer tumors to be a combined modality approach of radiation therapy and chemotherapy. This nonsurgical, organ-sparing regimen results in good anal sphincter function in the majority of patients, and treatment efficacy is favorable when compared with historic surgical series. Anal margin tumors are staged and treated as skin cancers, with a more favorable prognosis.

Thrombolysis utilisation in acute myocardial infarction in Bahrain.

We retrospectively studied 114 consecutive patients of acute myocardial infarction diagnosed in the Accident and Emergency department of our hospital, to determine the percentage of eligible patients who actually received thrombolytic therapy, the number of those excluded from receiving such therapy and the various exclusion criteria. We found that 66 patients (57.9%) received thrombolysis with either streptokinase or tissue plasminogen activator (tPA). The remaining 48 (42.1%) were excluded because of delayed presentation to hospital after the onset of symptoms (23.7%), old age or other contraindications. Although the percentage of thrombolysis utilisation in acute myocardial infarction in our centre is much higher as compared to others in the world, we find that there is a scope for improving these figures by reducing the number of patients excluded because of late presentation through health education and improved utilisation of ambulance services.

Interaction of the antitumor antibiotic mitomycin C with Z-DNA.

Mitomycin C (MC), an antitumor antibiotic, alkylated Z-DNAs such as poly(dG-dC)/Co(NH3)3+(6), poly(dG-m5dC)/Mg2+ and brominated poly(dG-dC) upon reductive activation. Computer-generated energy-minimized molecular models indicated that monofunctional alkylation of Z-DNA at the N2-position of guanine by MC did not distort Z-DNA geometry, but bifunctional alkylation, leading to interstrand crosslinks between two N2-positions of guanine was sterically unfavorable. The above three Z-DNA's were exposed both to monofunctionally and bifunctionally activated MC in separate experiments and the resulting covalent MC-polynucleotide complexes were examined for conformation and for covalent MC-adducts, by circular dichroism (CD) spectroscopy and HPLC analysis of nuclease digests, respectively. Monofunctionally activated MC alkylated all three polynucleotides in their Z-forms, resulting in the same monofunctional N2-guanine adduct as that known to be formed with B-DNA. Upon bifunctional activation of MC, poly(dG-dC/Co(NH3)3+(6) reverted to the B-form and bifunctional (cross-link) adducts were detected, identical again with those formed with B-DNA. Poly(dG-m5dC), however, remained in the Z-form after the alkylation and only a monofunctional adduct could be detected. It was concluded that Z-DNA is subject to monofunctional alkylation by MC but cannot be cross-linked. The latter process occurs only when the Z-DNA is labile enough [as is in the case of poly(dG-dC)] to have some B-form in equilibrium at the site of the first formed monolinked adduct; the cross-linking then occurs at such local B-sites, pulling the overall B in equilibrium Z equilibrium irreversibly to the left. These results are in accord with the predictions from the above modeling. The irreversible "lock" by the MC cross-link on B-DNA may be exploited for probing Z-DNA intermediacy in various DNA functions.

Mechanism of monofunctional and bifunctional alkylation of DNA by mitomycin C.

The relative amounts of monofunctional and bifunctional alkylation products of DNA with mitomycin C (MC) depend on whether one or both masked alkylating functions of MC are activated reductively; adduct 8 is the result of one function and adducts 7 and 9, formed as a pair, are the result of both functions being activated [Tomasz, M., Lipman, R., Chowdary, C., Pawlak, J., Verdine, G. L., & Nakanishi, K. (1987) Science (Washington, D.C.) 235, 1204-1208]. To determine the mechanism governing this differential reactivity of MC with DNA, MC-Micrococcus luteus DNA complexes formed under varying conditions in vitro were digested to nucleosides and adducts. Adduct distribution, analyzed by high-performance liquid chromatography, served as the measure of monofunctional and bifunctional activation. H2/PtO2 and xanthine oxidase/reduced nicotinamide adenine dinucleotide (NADH) activated MC mostly monofunctionally, and Na2S2O4 activated the drug bifunctionally under comparable conditions. Excess MC selectively suppressed, but excess PtO2 selectively promoted, bifunctional activation by H2/PtO2; excess xanthine oxidase and/or NADH also had promoting effects. O2 tested in the Na2S2O4 system was inhibitory. 10-Decarbamoyl-MC acted strictly monofunctionally under all conditions. Monoadducts bound to DNA were converted to bis adducts upon rereduction. A mechanism with the following features was derived: (i) Activation of MC at C-1 and C-10 is sequential (C-1 first). (ii) A one-time reduction is sufficient for both. (iii) Activation of the second function may be selectively inhibited by kinetic factors or O2. (iv) 7 and 9 are coproducts of bifunctional activation; their ratio depends on the DNA base sequence. (v) Activation of the second function involves an iminium intermediate. Direct applications to the action of MC in vivo are discussed.

Comparable steady-state bioavailability between two preparations of conventional-release procainamide hydrochloride.

The pharmacy and therapeutics committee-based clinical evaluation can be a useful tool in the economic and functional effectiveness of a restrictive formulary system. We utilized this concept to evaluate a generic formulation of procainamide hydrochloride (PA) for admission to our formularies. The study performed was a randomized, single-blind, crossover comparison of the serum-concentration profiles of two preparations (Squibb vs. Ascot) of conventional-release PA. Ten outpatients requiring chronic PA therapy for the control of ventricular dysrhythmias were evaluated. The resultant dose-adjusted data showed no significant difference between mean serum PA concentrations at any sample time, area under the serum concentration-time curves, mean peak serum PA concentrations achieved, or peak-trough fluctuations. Relative bioavailability was calculated to be 0.972 +/- 0.59. The Ascot preparation demonstrated a delay of 15 minutes before the onset of absorption; however, it also showed an earlier tmax in comparison to the Squibb formulation. Generic substitution of Ascot PA in place of Squibb PA may be implemented with significant cost savings.

Evaluating a restrictive formulary system by assessing nonformulary-drug requests.

Nonformulary-drug requests were used to evaluate a restrictive formulary system in a large university hospital, and a telephone survey of eight similar hospitals was conducted to assess the restrictiveness of their formulary systems. Nonformulary-drug requests were evaluated by two drug information pharmacists over a 12-month period (January-December 1984) to assess the frequency with which nonformulary items were ordered, the costs associated with the procurement of nonformulary drug products, and the rationales given by physicians when ordering nonformulary products. Of all nonformulary requests, 65% were for drugs previously evaluated by the pharmacy and therapeutics committee and denied admission to the formulary. A cost savings of $1887 would have resulted if formulary alternates had been used instead of nonformulary products. Excluding 22% of nonformulary items that were requested for the continuation of preadmission drug therapy, only 13% of the rationales for the remaining requests were appropriate. Although the eight other hospitals surveyed said they had restrictive formularies, all had frequent requests and procedures for procuring nonformulary items and some formularies included most available drugs. The formulary system at the study hospital was considered restrictive, but procedures for nonformulary-drug requests limited the effectiveness of the system. If any benefit is to result from formulary systems, hospitals must strengthen their enforcement of formulary restrictions.