bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability analysis of memristor‐based complex‐valued recurrent neural networks with time delays
Authors: Rakkiyappan Rajan , Velmurugan Gandhi , Rihan Fathalla A. , Lakshmanan Shanmugam
Published: December 2015

This article addresses stability analysis of a general class of memristor‐based complex‐valued recurrent neural networks (MCVNNs) with time delays. Some sufficient conditions to guarantee the boundedness on a compact set that globally attracts all trajectories of the MCVNNs are obtained by utilizing local inhibition. Moreover, some sufficient conditions for exponential stability and the global stability of the MCVNNs are established with the help of local invariant sets and linear matrix inequalities using Lyapunov–Krasovskii functional. The analysis results in the article, based on the results from the theory of differential equations with discontinuous right‐hand sides as introduced by Filippov. Finally, two numerical examples are also presented to show the effectiveness and usefulness of our theoretical results. © 2014 Wiley Periodicals, Inc. Complexity 21: 14–39, 2016
Organic Carbonates: Efficient Extraction Solvents for the Synthesis of HMF in Aqueous Media with Cerium Phosphates as Catalysts
Authors: Dibenedetto Angela , Aresta Michele , di Bitonto Luigi , Pastore Carlo
Published: December 2015

We describe a process for the selective conversion of C6‐polyols into 5‐hydroxymethylfurfural (5‐HMF) in biphasic systems of organic carbonate/water (OC/W), with cerium(IV) phosphates as catalysts. Different reaction parameters such as the OC/W ratio, catalyst loading, reaction time, and temperature, were investigated for the dehydration of fructose. Under the best reaction conditions, a yield of 67.7 % with a selectivity of 93.2 % was achieved at 423 K after 6 h of reaction using [(Ce(PO4)1.5(H2O)(H3O)0.5(H2O)0.5)] as the catalyst. A maximum yield of 70 % with the same selectivity was achieved after 12 h. At the end of the reaction, the catalyst was removed by centrifugation, the organic phase was separated from water and evaporated in vacuo (with solvent recovery), and solid 5‐HMF was isolated (purity >99 %). The recovery and reuse of the catalyst and the relationship between the structure of the OC and the efficiency of the extraction are discussed. The OC/W system influences the lifetime of the catalysts positively compared to only water.
Simultaneous Recognition of Human Action and Its Location Estimation Based on Multiview Hough Voting
Authors: HARA KENSHO , HIRAYAMA TAKATSUGU , MASE KENJI
Published: December 2015

Remote surveillance of large‐scale equipment such as power plants and building complexes is important to prevent serious attacks and troubles. Automatic human action recognition can reduce the burdens of the surveillance. Multiview video is useful for human action recognition, because it provides robustness to the changes of people's appearance by orientation and occlusion. One problem of conventional multiview action recognition is that it requires both detection and tracking before action recognition. Human pose and motion vary depending on the person's action, and such variances may cause detection and tracking error. To solve this problem, previous work has proposed simultaneous action recognition and location estimation for single‐view videos using Hough voting. In this paper, we extend the Hough voting approach to simultaneous multiview action recognition and location estimation. Our proposed method independently casts votes for the action labels and spatiotemporal reference positions of actions in each view and integrates them using homographical transformations in the multiview extension. We evaluated our method and confirmed that it achieved high accuracy in action recognition and location estimation. The contribution of this paper is that it enables multiview action recognition without prior human detection and tracking.
Development of Ca2+‐Driven Microvalve Powered by Contractile Fiber of Vorticella
Authors: NAGAI MOETO , TANIZAKI KOHEI , KAWASHIMA TAKAHIRO , SHIBATA TAKAYUKI
Published: December 2015

Bioactuators, biological motors in living systems, are promising for integration and functionalization of microsystems. We have developed a Ca2+‐driven microvalve powered by a contractile fiber, a stalk of Vorticella. Cells of Vorticella convallaria were trapped in designed microchambers. Stalks were self‐grown in the chambers and their reversible linear actuations were controlled by regulating the concentration of Ca2+. A cell body, connected to a stalk, opened and closed a microchannel by the contraction and extension of the stalk. The flow field in the chamber was characterized to further optimize the actuation performance.
Application of the AC Superposition Method to Degradation Diagnosis of 22/33‐kV Class XLPE Cables
Authors: KUMAZAWA TAKAO
Published: December 2015

Water trees in the insulator of XLPE cable may considerably reduce the dielectric breakdown voltage, thus being an important lifetime‐governing factor. The ac superposition method we have investigated is a new technique for hot‐line diagnosis of 6.6‐kV XLPE cables, and the diagnostic apparatus using this technique is now widely used in the distribution line field. In order to study the application of the ac superposition method to degradation diagnosis of 22/33‐kV class XLPE cables, we measured deterioration signals of the cables with water trees by a modification of the above diagnostic apparatus. The deterioration signals, hereafter called “ac superposition current”, were generated by an amplitude modulation effect due to the nonlinear resistance of water trees. Moreover, we evaluated the relationship between the ac superposition current and the ac breakdown voltage. It is difficult to judge whether a correlation between then is present or not because of the uneven distribution of the measured data. However, the ac superposition current tends to increase linearly with a decrease in the residual thickness of the insulator. For example, the ac superposition current was about 40 nA when the residual thickness decreased to 3 mm. Thus, we consider that the ac superposition method is effective for degradation diagnosis of 22/33‐kV class XLPE cables.
Design Method for Improving Motor Efficiency of Switched Reluctance Motor
Authors: NAKAZAWA YOSHIHIRO , OHYAMA KAZUHIRO , NOUZUKA KAZUMA , FUJII HIROAKI , UEHARA HITOSHI , HYAKUTAKE YASUSHI
Published: December 2015

The motor efficiencies of switched reluctance motors (SRMs) are inferior to those of permanent magnet synchronous motors. This paper describes a design procedure for an SRM to obtain a higher motor efficiency. The first step in the design procedure makes clear the principle for improving the motor efficiency. The cross‐sectional and axial shapes of the rotor and stator cores are designed by magnetic field analysis with the two‐dimensional (2D) and 3D finite element method. A high‐efficiency SRM with 12 stator poles and eight rotor poles is designed. The designed SRM was produced experimentally, and was tested to verify its performance. The motor efficiency was improved in comparison to the standard SRM with six stator poles and four rotor poles.
Synthesis, Structure, and Reactivity of (Dihydrogen)(hydrido)iron(II) Complexes Bearing Chiral Diphos­phanes
Authors: Feliz Marta , Estevan Francisco
Published: December 2015

The heterolytic cleavage of molecular hydrogen by [Fe(H2O)6][BF4]2 and the chiral phosphane (+)‐1,2‐bis[(2R,5R)‐2,5‐dimethylphospholano]benzene [(R,R)‐Me‐DuPhos] or its enantiomer [(S,S)‐Me‐DuPhos] yields the (dihydrogen)(hydrido)iron complexes [FeH(η2‐H2){(R,R)‐Me‐DuPhos}2]BF4 ([R,R‐1]BF4) and [FeH(η2‐H2){(S,S)‐Me‐DuPhos}2]BF4 ([S,S‐1]BF4), respectively. These complexes are fluxional in solution at room temperature, and the trans isomers are observed at 200 K. The (Λ)‐cis‐[R,R‐1]BF4 complex was identified crystallographically as the only stereoisomer at room temperature. The energetic and structural differences between the cis (Λ and Δ) and trans isomers were analyzed from a computational (DFT) perspective. The coordinated dihydrogen is displaced by CO or CH3CN ligands to form a mixture of cis and trans isomers of FeH(L)[(R,R)‐Me‐DuPhos]2BF4 {L = CO ([R,R‐2]BF4), CH3CN ([R,R‐3]BF4)} or FeH(L)[(S,S)‐Me‐DuPhos]2BF4 {L = CO ([S,S‐2]BF4), CH3CN ([S,S‐3]BF4)} complexes, and the cis isomers are the major ones. The formation of trans‐[FeH(NMe3)(Me‐DuPhos*)2]BF4 is suggested for the reaction of [R,R‐1]BF4 and [S,S‐1]BF4 with NMe3 {Me‐DuPhos* = [(R,R)‐Me‐DuPhos] or [(S,S)‐Me‐Duphos]}.
Robust Room Temperature Hysteresis in an FeIII Spin Crossover Metallomesogen
Authors: Fitzpatrick Anthony J. , Martinho Paulo N. , Gildea Brendan J. , Holbrey John D. , Morgan Grace G.
Published: December 2015

The high temperature magnetic and structural properties of an amphiphilic iron(III) spin crossover complex are reported. Thermal cycling reveals a scan rate‐dependent 20 K thermal hysteresis in the mT vs. T data close to room temperature. A fast scan rate is essential for the hysteresis but it is robust and reproducible after multiple thermal cycles. Differential scanning calorimetry and cross polarized microscopy are used to show that the magnetic switching aligns with a material state change from solid to ordered liquid phase on warming.
Effect of transect location, transect spacing and interpolation methods on river bathymetry accuracy
Authors: Glenn Jill , Tonina Daniele , Morehead Mark D. , Fiedler Fritz , Benjankar Rohan
Published: December 2015

Digital elevation models (DEMs) of river channel bathymetries are developed by interpolating elevations between data collected at discrete points or along transects. The accuracy of interpolated bathymetries depends on measurement error, the density and distribution of point data, and the interpolation method. Whereas point measurement errors can be minimized by selecting the most efficient equipment, the effect of data density and interpolation method on river bathymetry is relatively unknown. Thus, this study focuses on transect‐based collection methods and investigates the effects of transect location, the spacing between transects, and interpolation methods on the accuracy of interpolated bathymetry. This is accomplished by comparing four control bathymetries generated from accurate and high resolution, sub‐meter scale data to bathymetries interpolated from transect data extracted from the control bathymetries using two transect locating methods and four interpolation methods. The transect locating methods are a morphologically‐spaced and an equally‐spaced model. The four interpolation methods are Ordinary Kriging, Delaunay Triangulation, and Simple Linear, which are applied in curvilinear coordinates (Delaunay Triangulation is also applied in Cartesian coordinates), and Natural Neighbor only in Cartesian Coordinates. The bathymetric data were obtained from morphologically simple and complex reaches of a large (average bankfull width = 90 m) and a small (average bankfull width = 17 m) river. The accuracy of the developed DEMs is assessed using statistical analysis of the differences between the control and interpolated bathymetries and hydraulic parameters assessed from bankfull water surface elevations. Results indicate that DEM accuracy is not influenced by the choice of transect location method (with same averaged cross‐section spacing) or a specific interpolation method, but rather by the coordinate system for which the interpolation method is applied and the spacing between transects. They also show negligible differences between the mean depths and surface areas calculated from bathymetries with dense or coarse spacing. Copyright © 2016 John Wiley & Sons, Ltd.
An approach for measuring confinement and assessing the influence of valley setting on river forms and processes
Authors: Fryirs Kirstie A. , Wheaton Joseph M. , Brierley Gary J.
Published: December 2015

Valley setting and confinement (or lack thereof) are primary controls on river character and behaviour. Although there are various proxies for valley confinement, direct measures that quantify the nature and extent of confinement are generally lacking and/or inconsistently described. As such they do not lend themselves to consistent analysis over large spatial scales. Here we clearly define forms of confinement to aid in quantification of degrees of confinement. Types of margin that can induce confinement are differentiated as a valley margin, valley bottom margin, and/or anthropogenic margin. Such margins sometimes overlap and share the same location, and in other situations are separated, giving immediate clues as to the valley setting. We apply this framework to examples from Australia, United States and New Zealand, showing how this framework can be applied across the spectrum of river diversity. This method can help to inform interpretations of reach‐scale river behaviour, highlighting the role of antecedent controls on contemporary forms and processes. Clear definitions of confinement are shown to support catchment‐scale analysis of river patterns along longitudinal profiles, and appraisals of the geomorphic effectiveness of floods and sediment flux in catchments (e.g. process zone distribution, lateral sediment inputs and (dis)connectivity). Copyright © 2015 John Wiley & Sons, Ltd.
Multiple‐access relay channels with non‐causal channel state information at the relay
Authors: Osmani‐Bojd Mohammad , Hodtani Ghosheh Abed
Published: December 2015

In this paper, we study state‐dependent multiple‐access relay channel (MARC). (i) Inner and outer bounds are derived for two‐user state‐dependent discrete memoryless MARC in which channel state information is known non‐causally at the relay (informed relay). The inner bound is obtained by using decode and forward strategy and a combination of binning scheme and codeword splitting. Also, by applying Fano's inequality, we obtain an outer bound for state‐dependent MARC with channel state at the relay. (ii) Furthermore, we extend the results of discrete alphabet to Gaussian case as a discrete time and continuous alphabet model. Our general Gaussian results subsume previous special ones and specifically gives a general version for the Costa's theorem. (iii) We show numerically that the achievable rate region of Gaussian MARC with cognition of the relay about interference is larger than the achievable rate region of Gaussian MARC without any knowledge about interference. Also, by numerical examples, we investigate the capacity‐achieving case in high signal to noise ratios at the relay. Copyright © 2014 John Wiley & Sons, Ltd.
Improve the mechanical property and flame retardant efficiency of the composites of poly(lactic acid) and resorcinol di(phenyl phosphate) (RDP) with ZnO‐coated kenaf
Authors: Zhou Lu , Ju Yaqing , Liao Fenghui , Yang Yuanyuan , Wang Xinlong
Published: December 2015

The kenaf coated with zinc oxide (ZnO) was prepared and characterized by X‐ray diffraction, scanning electron microscopy, and X‐ray photoelectron spectroscopy. The ZnO‐coated kenaf and the flame retardant resorcinol di(phenyl phosphate) were blended with poly(lactic acid) (PLA) by solution compounding and melt blending to prepare the flame‐retarded PLA composites. The thermal stability, the mechanical property, and the flame retardancy of the PLA composites were improved evidently. The tensile strength of the prepared PLA composites could reach up to 62.3 MPa in comparison with 55.4 MPa of the pure PLA. The dense and compact char residues were observed after the combustion of the PLA composites containing ZnO‐coated kenaf, whereas there were serious dripping phenomena and no char formation during the combustion of the pure PLA. The use of ZnO‐coated kenaf could increase flame retardant efficiency obviously. The mechanism of flame retardancy was discussed. Copyright © 2014 John Wiley & Sons, Ltd.
Development of a creep‐free stress‐strain law for fire analysis of steel structures
Authors: Torić Neno , Sun Rui Rui , Burgess Ian W.
Published: December 2015

This paper presents a practical procedure for obtaining creep‐free stress‐strain laws for steel exposed to fire, on the basis of codified stress‐strain laws that consider creep implicitly. The applicability of the proposed procedure has been tested on two commonly used stress‐strain laws for steel at elevated temperature, the Eurocode 3 law and a Ramberg–Osgood model, both of which have implicit consideration of creep. The simulation of two published steel coupon experiments on steel of grades S275 and S355 shows that both the Eurocode and Ramberg–Osgood stress‐strain laws produce inaccurate predictions of creep in fire at elevated temperatures. The proposed procedure was thereby used to extract the implicit creep according to the heating rates of the transient coupon tests and to derive the creep‐free stress‐strain laws. It has been shown that, by combining the creep‐free stress strain law obtained by the proposed methodology with an explicit creep model, a more realistic prediction of steel behaviour in the selected coupon test studies can be achieved. Copyright © 2015 John Wiley & Sons, Ltd.
“Order through Fluctuation”: An Evolutionary Epistemology for Human Systems**
Authors: Dell Paul F. , Goolishian Harold A.
Published: December 2015

Most approaches to systems theory, group theory and family theory suffer from two major inadequacies. First, they are heavily oriented toward structure (e.g. structure of the system) as opposed to process. Second, because of this bias, such theories overemphasize stability at the expense of change and transformation. In contrast, Ilya Prigogine's concept of “order through fluctuation” demonstrates how systems suddenly organize themselves and, equally suddenly, make discontinuous shifts from one coherent order to another. As a paradigm, “order through fluctuation” constitutes a basic nonequilibrium ordering principle that governs the forming and unforming of systems at all levels.
The Evolution of the One‐Way Screen
Authors: Cade Brian W. , Cornwell Max
Published: December 2015

Technology can both reflect and contribute to new theoretical formulations and new methods. This phenomenon is examined in relation to one‐way screens. While the screen itself has undergone only modest physical transformation, there have been several important changes in ways of thinking about its therapeutic significance. These changes are identified.
The Australian Family: 1788–1888‐1988
Authors: Browne Elspeth
Published: December 2015

In this year, the Australian bicentennial, a review of the Australian family is timely. Families — their structure, duration and function — change in response to their environmental context. Aboriginal families were uniquely adapted to their environment, and while first European colonisation was not intended as family settlement, families soon became established. In 1888, the conventional nuclear family was clearly in evidence as a response to an industrialising society. Changes are evident in the family of the 1980s, changes which have implications as this country looks forward to its third century.
Man Up: Young Men's Lived Experiences and Reflections on Counseling
Authors: Reed Eva E.
Published: December 2015

The author interviewed 6 young men about their perceptions of masculinity and their experiences with counseling. Through a phenomenological approach, 3 themes emerged: characteristics of men, perceptions of social expectations, and experiences with counseling. All participants characterized men as emotionally reserved, protective and supportive, powerful, sexually motivated, honorable, and goal oriented. Findings are discussed in terms of theoretical and counseling implications.
Mechanism of Action, Pharmacokinetics, Adverse Effects, and Therapeutic Uses of Amiloride Hydrochloride, A New Potassium‐Sparing Diuretic
Authors: Vidt Donald G.
Published: December 2015

Amiloride hydrochloride is a new, orally administered, potassium‐sparing diuretic with mild natriuretic and diuretic properties. Its primary site of action is the distal tubule of the nephron where it selectively blocks sodium transport, thereby inhibiting sodium‐potassium exchange. The mechanism of action of amiloride is independent of aldosterone. It is excreted unmetabolized in the urine and feces. Peak serum levels are seen at three hours, and the serum half‐life is six hours. The drug can probably be safely administered to patients with hepatic dysfunction but should be used cautiously, if at all, in patients with renal insufficiency. Amiloride is well tolerated, and serious toxicity is rare. It should prove useful in edematous states and hypertension. When amiloride is used in fixed combination with a thiazide diuretic the risk of hypokalemia is minimal.
Trimethoprim: Mechanisms of Action, Antimicrobial Activity, Bacterial Resistance, Pharmacokinetics, Adverse Reactions, and Therapeutic Indications
Authors: Gleckman Richard , Blagg Noel , Joubert Dennis W.
Published: December 2015

Trimethoprim has recently been marketed as a single‐entity product for the treatment of initial episodes of uncomplicated symptomatic urinary tract infections; it was previously available only in combination with sulfamethoxazole. Trimethoprim exerts antimicrobial activity by blocking the reduction of dihydrofolate to tetrahydrofolate, the active form of folic acid, by susceptible organisms. It has inhibitory activity for most gram‐positive aerobic cocci and some gram‐negative aerobic bacilli. Resistance to trimethoprim may be either intrinsic or acquired. Acquired resistance most commonly stems from a chromosomal mutation that results in the production of a dihydrofolate reductase enzyme which is less vulnerable to trimethoprim inhibition.

Gastrointestinal intolerance and skin eruptions are the most common untoward reactions resulting from the administration of trimethoprim. Trimethoprim constitutes very effective therapy for women with acute symptomatic urinary tract infections caused by E. coli, and the compound compares favorably with alternative standard agents, such as ampicillin and cephalexin. The safety of trimethoprim in the pregnant woman has not been established. Since indiscriminate use of trimethoprim could foster the emergence of trimethoprim resistance, thereby negating the value of both trimethoprim and trimethoprim‐sulfamethoxazole, trimethoprim should only be prescribed for well defined indications. Trimethoprim is currently being investigated as definitive therapy for a wide range of infections, including bacterial exacerbations of chronic bronchitis, bacterial pneumonia, and typhoid fever. Initial reports are encouraging. (Pharmacotherapy 1981;1:14–20)
Evaluation of the Analgesic Efficacy of Ibuprofen
Authors: Miller Russell R.
Published: December 2015

Ibuprofen is a derivative of propionic acid that was originally marketed in the United States as an antirheumatic agent in 1974. In 1979, it was approved for use as an analgesic. Of the 18 published double‐blind clinical trials reviewed, only 6 were well designed. These six studies provide strong evidence that ibuprofen is effective for dental pain due to tooth extractions, dysmenorrhea and episiotomy pain. Thus, ibuprofen appears to be an effective drug for mild to moderate pain. It is as effective or more effective than aspirin, codeine or propoxyphene. Recommended initial dosage is 300 mg every six hours, increasing as needed to 400 mg every four hours. Adverse effects are relatively minor and infrequent.
Chemistry, Pharmacology, Pharmacokinetics, Adverse Effects, and Efficacy of the Antidepressant Maprotiline Hydrochloride
Authors: Wells Barbara G. , Gelenberg Alan J.
Published: December 2015

Maprotiline, a tetracyclic antidepressant with sedative properties, exhibits strong inhibitory effects on norepinephrine uptake across nerve cell membranes but interferes relatively little with serotoninergic mechanisms. The biological half‐life of unchanged maprotiline in blood averages 43 hours. Though several studies suggest a more rapid onset of antidepressant effects with maprotiline than with amitriptyline or imipramine, this issue remains unresolved.

The adverse effect profile of maprotiline is similar to that of the tricyclic antidepressants, except that rashes are about twice as frequent with maprotiline as with amitriptyline or imipramine. The most frequent adverse reactions are anticholinergic effects and sedation. Data suggest less frequent and severe anticholinergic side effects with maprotiline than with amitriptyline. Maprotiline may be less likely to induce orthostatic hypotension and tachycardia than standard tricyclic antidepressants, but clinically important differences in cardiovascular effects remain to be conclusively demonstrated. Many patients benefit from the convenience of once daily dosing.

Maprotiline is comparable in antidepressant efficacy to the tricyclic antidepressants.
Pharmacology, Toxicology, Clinical Efficacy, and Adverse Effects of Calcium Polycarbophil, An Enteral Hydrosorptive Agent
Authors: Danhof Ivan E.
Published: December 2015

Calcium polycarbophil is the calcium salt of polyacrylic acid crosslinked with divinyl glycol. It is chemically and physiologically inert. In dilute alkali it possesses marked hydrophilic capacity (60 to 100 times its weight), which is the basis for its therapeutic use. In daily dosages of 4 to 5 g in adults, it appears to be quite safe, is non‐toxic, does not interfere with digestion or absorption, and does not cause gastrointestinal irritation. It appears to be effective in the treatment of both constipation and diarrhea due to functional or organic causes. Several days of continuous use are necessary before effectiveness becomes apparent. Clinical studies, of which there are relatively few, range from uncontrolled, unblinded evaluations of an almost anecdotal nature to well controlled, double‐blind, crossover studies. Additional carefully controlled studies on dietary influences, exercise, and patient compliance would be helpful. Adverse effects, which are minimal, include epigastric fullness or heaviness, abdominal distention and bloating, and flatulence. As with all bulk‐forming agents, calcium polycarbophil should not be used by persons who have stenotic lesions of the gastrointestinal tract.
Clinical Management of Urinary Tract Infection
Authors: Fang Leslie S. T. , Tolkoff‐Rubin Nina E. , Rubin Robert H.
Published: December 2015

The clinical management of urinary tract infection has changed considerably over the last two decades due to the recognition of several important factors:

All urinary tract infections are not the same; in particular, deep tissue infection of the kidney and/or prostate requires a very different form of clinical management than does superficial mucosal infection of the bladder.

Consistent with these differences, it is now clear that conventional 7–14 day treatment courses are not ideal for most forms of urinary tract infections; deep tissue infection requires more intensive therapy and superficial mucosal infection needs less intensive therapy.

In particular, single dose antimicrobial therapy has been a major advance in the management of the most common form of urinary tract infection — acute uncomplicated urinary tract infection of the adult female; such therapy is safe, effective, inexpensive, and the response provides useful clinical information.

The recognition of the etiology of the acute urethral syndrome in most patients (true bacteriuria or Chlamydia trachomatis infection) had led to an effective therapeutic approach to this problem.

A logical approach to the problem of recurrent urinary tract infection has emerged that is both cost‐effective and clinically effective.

Finally, a clearer picture of those populations that would benefit most from anatomical study of the urinary tract has been developed.

With these advances, this most common of bacterial infections affecting man throughout his lifespan has become much easier to control.
A Comparative Evaluation of Moxalactam: Antimicrobial Activity, Pharmacokinetics, Adverse Reactions, and Clinical Efficacy
Authors: Fitzpatrick Brian J. , Standiford Harold C.
Published: December 2015

Although moxalactam is not, technically speaking, a cephalosporin it is chemically and microbiologically so closely related to those compounds that it can be viewed as a member of the cephalosporin family. Moxalactam has a spectrum of activity that includes both gram positive and gram negative bacteria. Its gram positive activity is less than earlier cephalosporins, but its activity against the Enterobacteriaceae is similar to that of the aminoglycoside family of antibiotics in most comparative studies. Although moxalactam is considerably less active against gram positive bacteria than cefotaxime, another third generation cephalosporin, its higher and more prolonged serum levels probably offset this disadvantage. Compared to cefoperazone, the stability of moxalactam to many types of beta lactamases produced by gram negative bacteria may be advantageous in the therapy of infections caused by hospital‐acquired pathogens. Clinical studies suggest that moxalactam can be used for empiric therapy of suspected gram negative infections when Pseudomonas and other non‐fermentative bacteria, such as Acinetobacter, are not suspected. Impressive improvements in the survival of patients with gram negative enteric bacillary meningitis have been reported. Although moxalactam, cefotaxime, and cefoperazone have activity against Pseudomonas aeruginosa, none of these antibiotics should be used alone as therapy for suspected or proven severe systemic infections caused by this pathogen. Cost is a major problem with all of the new cephalosporin‐like antibiotics. While this high cost may be partially balanced by the use of a single agent compared to an antibiotic combination for therapy in some situations, these antibiotics are not cost effective for prophylactic use. Superinfection with fungi, such as Candida, and Streptococcus faecalis have occurred, and toxicities, such as bleeding due to vitamin K deficiency and disulfuram‐like reactions, have also been reported. Reports of resistance to moxalactam and the other third generation cephalosporins are of major concern and indicate the need to closely monitor antibiotic susceptibility patterns of hospital acquired organisms if these antibiotics are to be used for empiric therapy of suspected gram negative non‐pseudomonas sepsis.
Cinoxacin: Mechanism of Action, Spectrum of Activity, Pharmacokinetics, Adverse Reactions, and Therapeutic Indications
Authors: Scavone Joseph M. , Gleckman Richard A. , Fraser Donald G.
Published: December 2015

Cinoxacin, a chemotherapeutic agent that inhibits bacterial DNA synthesis, has recently been approved for the treatment of initial and recurrent bacterial urinary tract infections. Although closely related to nalidixic acid, cinoxacin possesses some distinct characteristics: rapid attainment of therapeutic urinary concentrations and greater activity against strains of Enterobacteriaceae that cause urinary tract infections. Biopharmaceutical properties include serum protein binding of approximately 70%, 50–60% excretion of intact drug in the urine of patients with normal renal function, and an elimination half‐life of approximately one hour. The elimination half‐life is increased in patients with decreased renal function and when probenecid is coadministered.

Adverse events occur infrequently and consist of nausea, vomiting, headache, dizziness, and hypersensitivity reactions. The drug compares favorably with standard therapies for the treatment of bacterial cystitis and recurrent urinary tract infections. Initial studies demonstrate that cinoxacin has substantial efficacy as a prophylactic agent for those women who experience recurrent, symptomatic urinary tract infections.
Microbiology, Pharmacology, and Clinical Use of Mezlocillin Sodium
Authors: McCloskey Richard V. , LeFrock Jack L. , Smith Bruce R. , Aronoff George R.
Published: December 2015

The acylureido penicillin mezlocillin is active against gram‐positive, gram‐negative, and anaerobic bacteria. It easily penetrates the outer membrane of gram‐negative bacteria, and it has a strong affinity for penicillin binding protein 3. Its stability to 3‐lactamases is weak. Mezlocillin is synergistic when given in combination with aminoglycoside antibiotics. In pharmacokinetic studies mezlocillin conforms to a two compartment open model; its pharmacokinetic properties are dose‐dependent. The half‐life of the drug is about 1 hour after intravenous injection and 1.5 hours after intramuscular injection. Protein binding ranges from 16 to 42%, and 55% of a dose is excreted in the urine. Biliary excretion ranges from 0.5 to 25%. Clinical trial cure rates were as follows: bacteremia (78%), respiratory tract (62%), urinary tract (81%), gynecological (86%), bone and joint (55%), intraabdominal (67%) and skin and soft tissue (59%). The frequency of adverse reactions was 7.7%. Interstitial nephritis, CNS toxicity, and bleeding have not been reported.
Mental Confusion in a Patient Treated with Metronidazole — A Concentration‐Related Effect?
Authors: Schentag Jerome J. , Ziemniak John A. , Greco Joseph M. , Rainstein Miguel , Buckley Richard J.
Published: December 2015

We report a case of serious mental confusion, hallucinations, and agitation in a 65 year old man, occurring in close relationship to the intravenous administration of metronidazole. The patient was treated twice, but at different dosages. The confusion and hallucinations occurred at the recommended daily dose of 2.0 g, but did not return at a daily dose of 500 mg. Metronidazole serum concentrations were obtained throughout both courses of therapy; CSF and tissue concentrations were obtained at autopsy. The mental confusion was associated with peak serum concentrations of approximately 40 μg/ml. Symptoms resolved within 24–48 hr after stopping metronidazole, and resolution was consistent with a metronidazole half life of 14 hr. We conclude that metronidazole can be associated with a dose‐ and serum concentration‐related mental confusion state, and that this side effect appears completely reversible upon discontinuing the drug.
Cost‐Effective Antibiotic Prescribing
Authors: Gleckman Richard , Gantz Nelson M.
Published: December 2015

Antibiotics are often misused, resulting in a high frequency of adverse effects, emergence of drug‐resistant organisms, and excessive costs. The high cost of antibiotics is currently receiving the greatest attention. Considerable cost savings can be achieved by appropriate prescribing of antibiotics for patients receiving these drugs prophylactically as well as for those with established infections. This article cites specific examples of how cost‐effective antibiotic prescribing practices can realize substantial cost savings without any diminished quality in patient care.
Chemistry, Pharmacology, Antiarrhythmic Efficacy and Adverse Effects of Tocainide Hydrochloride, An Orally Active Structural Analog of Lidocaine
Authors: Alpert Joseph S. , Haffajee Charles I. , Young Michael D.
Published: December 2015

Tocainide is an orally effective antiarrhythmic agent, structurally and pharmacologically similar to lidocaine. It appears to be free of marked negative hemodynamic or electrophysiologic effects in patients with heart disease, despite a high frequency of minor and often transient central nervous system and gastrointestinal side effects. Tocainide is effective in suppressing ventricular arrhythmias in a variety of settings. This agent may be a useful addition to our antiarrhythmic armamentarium.
Theophylline A “State of the Art” Review
Authors: Hendeles Leslie , Weinberger Miles
Published: December 2015

Theophylline is a bronchodllator and respiratory stimulant that is effective in the treatment of acute and chronic asthma, Cheyne‐Stokes respirations, and apnea/bradycardia episodes in newborns. It is also used as an adjunct in the treatment of congestive heart failure and acute pulmonary edema, but it has no established efficacy in patients with chronic irreversible airways obstruction. Benefits and risks from theophylline relate directly to serum concentration, which is a function of both dose and elimination characteristics of the drug in an individual patient. When used to treat acute symptoms, an initial loading dose based on a mean volume of distribution is required to rapidly obtain maximum bronchodilator effect. Because of large interpatient differences in elimination, constant intravenous infusion rates for continued therapy must be guided by monitoring serum theophylline concentration at intervals until a steady‐state serum concentration is reached within the 10–20 μg/ml therapeutic range. Intravenous, oral or rectal solutions and plain uncoated tablets are appropriate for acute therapy, while reliably absorbed slow‐release formulations offer therapeutic advantages for the management of chronic asthma, particularty in patients with rapid elimination. Dosage for long‐term therapy is determined by starting with low doses that allow virtually complete acceptance of the medication followed by gradual increases, if tolerated, at three day intervals until mean age‐specific doses are reached. Subsequent adjustment in dosage regimens are then based upon serum concentration measurements. Most clinical laboratories now measure theophylline, and newer systems have been developed to provide emergency results within minutes at a reasonable cost. In cases of theophylline poisoning, the drug must be rapidly removed to prevent life‐threatening toxicity. When serum concentrations are in excess of 60 μg/ml charcoal hemoperfusion dialysis may be indicated, even in the absence of obvious signs of toxicity.
Indapamide: Clinical Pharmacology, Therapeutic Efficacy in Hypertension, and Adverse Effects
Authors: Mroczek William J.
Published: December 2015

Indapamide will soon be marketed in the United States as an oral antihypertensive agent and diuretic. Its molecular structure includes both a polar sulfamoyl chlorobenzamide moiety and a lipid‐soluble methylindoline molety. It differs chemically from the thiazides in that it does not possess the thiazide ring system and it contains only one sulfonamide group. Indapamide is rapidly and well absorbed after oral Ingestion, and it has a long terminal half‐life in whole blood which permits once daily administration. Indapamide is extensively metabolized by the liver with excretion of unchanged drug accounting for approximately 5% of the total dose. Although indapamide is thought to exert its antihypertensive effect by its diuretic action, several investigations employing laboratory animal preparations have documented a direct vascular action. It has been categorized as a calcium channel blocking agent and this may account for a portion of its antihypertensive effectiveness. In both the treatment of edema and as an antihypertensive agent, indapamide appears to be comparable to hydrochlorothiazide, chlorthalidone and furosemide and seems to have no clinically important advantage over these agents. Side effects associated with indapamide are minimal and appear to be comparable to those observed with other antihypertensive diuretics. Based on few published studies, indapamide appears to be a useful long acting antihypertensive and diuretic agent that is well tolerated and associated with minimal biochemical abnormalities or side effects.
Sufentanil Citrate: A New Opioid Analgesic for Use in Anesthesia
Authors: Rosow Carl E.
Published: December 2015

Sufentanil citrate is a potent analogue of fentanyl that has been evaluated primarily for use in opioid anesthesia. It is a pure mu receptor agonist and produces the typical spectrum of opioid effects. The major side effects are truncal rigidity and prolonged respiratory depression. In doses of 4–30 μg/kg sufentanil produces hypnosis and suppresses most hemodynamic and hormonal responses to surgery without producing significant cardiovascular depression. In this respect sufentanil and fentanyl have clear advantages over morphine, meperidine and potent inhalation anesthetics. Compared to fentanyl, sufentanil has a more rapid onset and shorter duration of action. The relatively high concentration of commercially available sufentanil injection will make it much more convenient for its intended application than fentanyl injection. This new agent will be used primarily for open‐heart surgery and major operations in patients with severe cardiovascular compromise.
Etoposide: A Semisynthetic Epipodophyllotoxin Chemistry, Pharmacology, Pharmacokinetics, Adverse Effects and Use as an Antineoplastic Agent
Authors: Sinkule Joseph A.
Published: December 2015

Etoposide (VP 16) is a semi‐synthetic derivative of 4'‐demethylepipodophyllotoxin, a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum) and the Indian species Podophyllum emodi Wallich. Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose‐limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and GI toxicity (nausea, vomiting, stomatitis) occur in about 20–30% of patients given recommended dosages.

Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non‐small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front‐line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years.

Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
Acute Intermittent Porphyria: Pathophysiology and Treatment
Authors: Khanderia Ujjaini , Bhattacharya Arjun
Published: December 2015

Acute intermittent porphyria is caused by an inherent error of porphyrin metabolism characterized by a deficiency of porphobilinogen deaminase and increased activity of delta‐aminolevulinic acid synthase, key enzymes necessary for the biosynthesis of heme. During an attack patients may have abdominal pain, vomiting, muscle weakness, constipation and neuropsychiatric symptoms. In the majority of individuals the disease remains clinically latent throughout life. Various drugs and chemicals, hormones and nutritional factors predispose to clinical attacks, probably by inducing hepatic delta‐aminolevulinic acid synthase. Avoidance of these substances is important in preventing attacks. Screening of family members to detect genetic carriers permits precautionary measures. Management of attacks includes symptomatic therapy, high carbohydrate intake and intravenous administration of hematin.
Piretanide: A Loop‐Active Diuretic
Authors: Marsh James D. , Smith Thomas W.
Published: December 2015

Piretanide is a high‐ceiling, loop‐active diuretic that has been developed for treatment of congestive heart failure, hypertension and edematous states caused by renal and hepatic diseases. Piretanide is structurally related to furosemide and bumetanide; when administered orally, 6 mg of piretanide is as effective as 40 mg of furosemide, and when administered intravenously, 12 mg of piretanide is as effective as 40 mg of furosemide.

Piretanide enhances water and sodium excretion in patients with congestive heart failure, with nephrotic syndrome and with cirrhosis and ascites. Adverse effects reported to date are limited to those attributable to excess loss of fluid and electrolytes. Under some conditions, piretanide appears to be less potassium wasting than thiazide diuretics or other loop‐active diuretics.
Dose Dependency for Absorption and Elimination Rates of Theophylline Implications for Studies of Bioavailability
Authors: Milavetz Gary , Weinberger Miles , Vaughan Leigh
Published: December 2015

Dose dependency for absorption and elimination rates of theophylline were examined by administering 2‐mg/kg and 6‐mg/kg doses of a theophylline solution to 8 adult volunteers. The area under the concentration‐time curve extrapolated to infinity after the lower dose was 84% of that calculated after the higher dose. This is associated with a decrease in the slope of the terminal portion of the elimination curve to varying degrees after the higher dose in all 8 patients (p < 0.001). A significantly smaller fraction of the higher dose was absorbed at 15 minutes (0.46 vs. 0.77, p < 0.002), but the differences were trivial by 30 to 45 minutes. Dose dependency for elimination may cause changes in a steady‐state serum concentration during multiple dosing that is disproportionately larger than changes in dosage. In addition, the slower elimination at higher serum concentrations may confound the assessment of bioavailability of slow‐release formulations when the doses used result in a substantial disparity in the range of serum concentrations attained for the slow‐release formulation and the reference. The use of unequal doses adjusted to provide similar peak serum concentrations appears to minimize this potential error.
Analgesic Effect of Acetaminophen, Phenyltoloxamine and Their Combination in Postoperative Oral Surgery Pain
Authors: Forbes James A. , Barkaszi Billie A. , Ragland Robert N. , Hankle John J.
Published: December 2015

In this factorial study, 148 outpatients with pain after oral surgery were randomly assigned, on a double‐blind basis, a single oral dose of acetaminophen 650 mg, phenyltoloxamine 60 mg, a combination of acetaminophen 650 mg with phenyltoloxamine 60 mg, or placebo. Using a self‐rating record, subjects rated their pain and its relief hourly for 6 hours after medication. Measures of total and peak analgesia were derived from these subjective reports. The acetaminophen effect was significant for every measure of total and peak analgesia. The phenyltoloxamine effect was not significant for any measure of analgesia. Although efficacy was lower for the acetaminophen‐phenyltoloxamine combination than for acetaminophen alone, for every variable, the contrast for interaction was not statistically significant. The results of this study differ from those of previous studies in patients with headache and musculoskeletal pain. All adverse effects were transitory and consistent with the known pharmacologic profiles of the study medications or the backup analgesic.