FUSION EXPERIMENTS IN SYSTEM MgO-FeO-Cr2O3-Al2O3*

Various methods have been suggested and tried for modifying chrome ores for refractory use. Chrome ores vary widely in chemical composition but are made up chiefly of MgO, Al₂O₃, FeO, and Cr₂O₃ combined as a member of an isomorphous spinel-type series. The problem of modifying chrome refractories by chemical and thermal treatment therefore involves a knowledge of the system MgO-FeO-Cr₂O₃-Al₂O₃. The present study is based on experiments in which two series of chromium oxide-alumina fusions containing 10% and 30% Cr₂O₃, respectively, were fused in an electric-arc furnace with MgO up to 5% and with FeO up to 5%. The determination of the effect of silica and titania on the primary crystallization of these fusions, as indicated by a petrographic method of examination, was the chief purpose of this work.     

Reduced endothelial nitric oxide synthase expression and production in human atherosclerosis

BACKGROUND: NO regulates vascular tone and structure, platelets, and monocytes. NO is synthesized by endothelial NO synthase (eNOS). Endothelial dysfunction occurs in atherosclerosis. METHODS AND RESULTS: With a porphyrinic microsensor, NO release was measured in atherosclerotic human carotid arteries and normal mammary arteries obtained during surgery. eNOS protein expression was analyzed by immunohistochemistry. In normal arteries, the initial rate of NO release after stimulation with calcium ionophore A23187 (10 micromol/L) was 0.42+/-0.05 (micromol/L)/s (n=10). In contrast, the initial rate of NO release was markedly reduced in atherosclerotic segments, to 0.08+/-0.04 (micromol/L)/s (n=10, P<0.0001). NO peak concentration in normal arteries was 0.9+/-0.09 micromol/L (n=10) and in atherosclerotic segments, 0.1+/-0.03 micromol/L (n=10, P<0.0001). Reduced NO release in atherosclerotic segments was accompanied by marked reduction of immunoreactive eNOS in luminal endothelial cells, although specific endothelial cell markers (CD31) were present (n=13). Endothelial cells of vasa vasorum of atherosclerotic segments, however, remained positive for eNOS, as was the endothelium of normal arteries. CONCLUSIONS: In clinically relevant human atherosclerosis, eNOS protein expression and NO release are markedly reduced. This may be involved in the progression of atherosclerosis.     

Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors

The recently introduced antidepressants, the selective serotonin reuptake inhibitors (SSRIs) [citalopram, fluoxetine, fluvoxamine, paroxetine and sertraline], are known for their clinical efficacy, good tolerability and relative safety. They differ from each other in chemical structure, metabolism and pharmacokinetic properties. Therapeutic drug monitoring of these compounds is not widely used, as the plasma concentration ranges within which clinical response with minimal adverse effects appears to be optimal are not clearly defined. Almost all recent assays developed for the quantitative determination of SSRIs and their metabolites in blood are based either on the separation of SSRIs by high performance liquid chromatography (HPLC) or gas chromatography (GC). Citalopram and fluoxetine have been introduced as racemic compounds. There are some differences in the pharmacological profile, metabolism and pharmacokinetics between the enantiomers of the parent compounds and their demethylated metabolites. Stereoselective chromatographic methods for their analysis in blood are now available. With regard to the SSRIs presently available, no clearcut plasma concentration-clinical effectiveness relationship in patients with depression has been shown, nor any threshold which defines toxic concentrations. This may be explained by their low toxicity and use at dosages where serious adverse effects do not appear. SSRIs vary widely in their qualitative and quantitative interaction with cytochrome P450 (CYP) isozymes in the liver. CYP2D6 is inhibited by SSRIs, in order of decreasing potency paroxetine, norfluoxetine, fluoxetine, sertraline, citalopram and fluvoxamine. This may have clinical consequences with some but not all SSRIs, when they are taken with tricyclic antidepressants. Except for citalopram and paroxetine, little is known about the enzymes which control the biotransformation of the SSRIs. There have been many reports on marked pharmacokinetic interactions between fluoxetine and tricyclic antidepressants. Fluoxetine has a stronger effect on their hydroxylation than on their demethylation. Interactions observed between fluoxetine and alprazolam, midazolam and carbamazepine seem to occur on the level of CYP3A. Fluvoxamine strongly inhibits the N-demethylation of some tricyclic antidepressants of the tertiary amine type and of clozapine. This may lead to adverse effects but augmentation with fluvoxamine can also improve response in very rapid metabolisers, as it increases the bioavailability of the comedication. Fluvoxamine inhibits with decreasing potency, CYP1A2, CYP2C19, CYP2D6 and CYP1A1, but it is also an inhibitor of CYP3A. Fluoxetine and fluvoxamine have shown to increase methadone plasma concentrations in dependent patients. Some authors warn about a combination of monoamine oxidase (MAO) inhibitors with SSRIs, as this could lead to a serotonergic syndrome. Studies with healthy volunteers suggest, however, that a combination of moclobemide and SSRIs, such as fluvoxamine, should not present serious risks in promoting a serotonin syndrome. A combination of moclobemide and fluvoxamine has successfully been used in refractory depression, but more studies are needed, including plasma-concentration monitoring, before this combined treatment can be recommended. Paroxetine is a substrate of CYP2D6, but other enzyme(s) could also be involved. Its pharmacokinetics are linear in poor metabolisers of sparteine, and non-linear in extensive metabolisers. Due to its potent CYP2D6 inhibiting properties, comedication with this SSRI can lead to an increase of tricyclic antidepressants in plasma, as shown with amitriptyline and trimipramine. CYP3A has been claimed to be involved in the biotransformation of sertraline to norsertraline. Clinical investigations (with desipramine) confirmed in vitro findings that CYP2D6 inhibition by sertraline is only moderate. (ABSTRACT TRUNCATED)     

Comparative evaluation of macrodilution and chromogenic agar screening for determining fluconazole susceptibility of Candida albicans

A simple screening method for fluconazole susceptibility using CHROMagar Candida with fluconazole was compared with the National Committee for Clinical Laboratory Standards (NCCLS) macrobroth method. In this agar dilution method, susceptible Candida albicans colonies are smaller on medium with fluconazole than on fluconazole-free medium. Yeasts with decreased susceptibility have normal-sized colonies on medium containing fluconazole. On agar with 16 micrograms of fluconazole per ml, 32 of 34 strains with NCCLS MICs of > or = 16 micrograms/ml were correctly predicted, as were 66 of 68 with MICs of < 16, an agreement of 96%. On agar with 8 micrograms of fluconazole per ml, 38 of 41 isolates with MICs of > or = 8 were correctly predicted, as were 59 of 61 isolates with MICs of < 8, an agreement of 95%. This agar dilution methods appears to highly correlate with NCCLS macrobroth methods for detection of C. albicans and may be an effective screen for fluconazole susceptibility.     

Reduction of hospital resources utilization in vascular surgery: a four-year experience

PURPOSE: Managed care whether through risk or through capitated contracts results in reduction in resources, reduced length of hospital stay, and reduced utilization of hospital resources (collectively referred to as resource reductions). These resource reductions will become even more noticeable as a greater proportion of Medicare patients who need vascular operations select a managed-care senior product. We examined the results of a 4-year experience with resource management in an academic vascular surgery practice during which best practice plans were developed and implemented. METHODS: We analyzed hospital cost data, which included both total hospital and intensive care unit length of stay, average units per operation for laboratory, pharmacy, and radiology services and operating room and direct hospital costs for 257 carotid endarterectomies performed over fiscal years (FY) 1994, 1995, 1996, and 1997 (6 month data) and 175 infrainguinal bypass procedures performed during the same period. RESULTS: For carotid endarterectomy, length of stay decreased 66% over the 4-year period to an average of 2.07 days in FY97. Both radiology and pharmacy utilization were reduced after the first year of institution of best practice plans (56% and 32% respectively) with 4-year total reductions of 86% and 55% by FY97. The most notable changes included elimination of routine postoperative laboratory testing, use of aspirin rather than low-molecular-weight dextran, emphasis on oral rather than intravenous vasoactive drugs, and routine use of duplex scanning alone rather than angiography for diagnosis after FY94-95. The length of operating room time for carotid endarterectomy remained relatively constant from FY94 to FY97. As a result of these multiple factors, our study showed a 30% decrease in total average direct hospital costs for carotid endarterectomy from $9974 to $7002 in this 4-year period. Infrainguinal bypass graft procedures showed a progressive decrease in total cost of 28% for patients without complications to $15,186 but remained unchanged for those with complications. Laboratory use, pharmacy use, and radiology use were not significantly different. CONCLUSIONS: Case management for patients undergoing carotid endarterectomy and infrainguinal bypass grafting involving an integrated team of vascular surgeons, surgical house staff, a dedicated vascular nurse, and a social work case manager resulted in dramatic reductions both in length of stay and hospital resource utilization. As these costs decreased, operating room expenses assumed increasing importance. Operating room costs account for 60% of the direct costs of carotid endarterectomy and a comparable percentage for uncomplicated infrainguinal bypass grafting. Further substantial reductions in direct hospital costs will depend primarily on reductions in operating room costs, particularly those related to length of time in the operating room.     

Effect of natural radioactivity on optical fibers of underseacables

For undersea cables radiation doses between 2.5 and 25 rad are to be expected during a working life of 25 years. The majority of previous investigations of the radiation sensitivity of optical fibers, however, apply dose rates ≳1 rad/s and total dose values ≳3×10 ³ rad. The present paper describes ⁶⁰Co irradiations of a Ge-doped single mode fiber with dose rates between 10 ^-4 and 20 rad/s. Expected loss increase of an undersea optical fiber cable at 1550 nm wavelength with a temperature of 2°C is derived by three different methods. The most comfortable and reliable one, the `dose rate transformation method', yields, for example, a loss of only 0.0244 dB/100 km after 25 years of irradiation with a dose rate of 0.4 rad/s. This method could be the basis of a standard test procedure for the effect of natural radioactivity on optical fibers for very long repeaterless terrestrial and undersea cables     

Endothelial dysfunction and nitrogen monoxide (NO; nitric oxide)

Emotion processing deficits may have an important effect on the quality of life of Alzheimer's disease (AD) patients and their families, yet there are few studies in this area and little is known about the cause of such deficits in AD. This study sought to determine if some AD patients have a disruption in a specific right hemisphere emotion processing system, and to determine if the processing of emotional facial expression is more vulnerable to the pathology of AD than is the perception of emotional prosody. It was specifically hypothesized that patients with greater right hemisphere dysfunction (low spatial AD patients) would be impaired on emotion processing tasks relative to those with predominantly left hemisphere dysfunction (low verbal AD patients). Both groups showed impairment on emotion processing tasks but for different reasons. The low verbal patients performed poorly on the affect processing measures because they had difficulty comprehending and/or remembering the task instructions. In contrast, low spatial AD patients have emotion processing deficits that are independent of language and/or memory and may be due to a more general visuoperceptual deficit that affects the perception of static but not dynamic affective stimuli.