bluuebunny/crossref_metadata_2025 huggingface dataset:
Graphene‐Encapsulated Nanosheet‐Assembled Zinc–Nickel–Cobalt Oxide Microspheres for Enhanced Lithium Storage
Authors: Zhang Qiaobao , Chen Huixin , Han Xiang , Cai Junjie , Yang Yong , Liu Meilin , Zhang Kaili
Published: December 2015

The appropriate combination of hierarchical transition‐metal oxide (TMO) micro‐/nanostructures constructed from porous nanobuilding blocks with graphene sheets (GNS) in a core/shell geometry is highly desirable for high‐performance lithium‐ion batteries (LIBs). A facile and scalable process for the fabrication of 3D hierarchical porous zinc–nickel–cobalt oxide (ZNCO) microspheres constructed from porous ultrathin nanosheets encapsulated by GNS to form a core/shell geometry is reported for improved electrochemical performance of the TMOs as an anode in LIBs. By virtue of their intriguing structural features, the produced ZNCO/GNS core/shell hybrids exhibit an outstanding reversible capacity of 1015 mA h g−1 at 0.1 C after 50 cycles. Even at a high rate of 1 C, a stable capacity as high as 420 mA h g−1 could be maintained after 900 cycles, which suggested their great potential as efficient electrodes for high‐performance LIBs.
Generation of Terahertz Waves Using Ultrashort Electron Beams from a Photocathode Radio‐Frequency Gun Linac
Authors: KAN KOICHI , YANG JINFENG , OGATA ATSUSHI , KONDOH TAKAFUMI , GOHDO MASAO , SHIBATA HIROMI , YOSHIDA YOICHI
Published: December 2015

Ultrashort (picosecond or femtosecond) electron beams are useful for electromagnetic radiation production in the terahertz (THz) range because the inverse of a 1 ps bunch length corresponds to a frequency of 1 THz. The electron beams were generated by a photocathode radio‐frequency (RF) gun linac. Electron beams with an energy of about 4 MeV at the RF gun exit were accelerated to about 30 MeV in a linac. The accelerated electron beams were compressed by a magnetic bunch compressor, resulting in femtosecond pulse width. THz radiation of the order of 0.1 THz based on coherent Cherenkov radiation (CCR) using hollow dielectric tubes and Smith−Purcell radiation (SPR) using a metallic grating or metasurface are described.
Image Binarization by Dynamic Convex Quadrilateral Region Segmentation Using GA
Authors: NAKAMURA SOMA , SAITOH FUMIHIKO
Published: December 2015

The method that binarizes an image by local thresholds in separated image areas is useful when the image has uneven brightness. A method was proposed to separate an image dynamically for local thresholding to generate a binary image by using a genetic algorithm (GA). However, the existing method used only horizontal and vertical lines for image separation. This paper suggests a method of separating an image dynamically using diagonal lines for local thresholding in order to generate a binary image by using a GA and of evaluating binary images. The experimental results show that the images binarized by the proposed method have good separation of objects from the background, and that they include less noise and blur than those binarized by the existing method.
Precise Positioning Control Using Online Modification of Reference Trajectory
Authors: OKUYAMA ATSUSHI
Published: December 2015

A control method for improving tracking performance with respect to a reference trajectory has been developed. The proposed control system has an inner/outer control structure. The inner control system is the existing control system based on a conventional PID controller, which is designed in advance and is independent of the outer control system. In order to improve tracking performance, the outer control system is designed based on optimal preview control theory and is added to the outside of the inner control system. A polynomial trajectory is used as the reference trajectory and is fed to the outer control system. The reference trajectory is modified online to minimize tracking error. The modified reference trajectory is derived as a control input signal from the outer control system and is fed to the inner control system. The effectiveness of the proposed control method is confirmed using numerical simulations in a benchmark problem for hard disk drives (HDDs).
Evaluation of the Effect of Geometrical Configuration on FM‐Band Crosstalk Characteristics between Two Parallel Signal Traces Including Their Divided Ground Patterns on Printed Circuit Boards for Vehicles
Authors: IIDA MICHIHIRA , MAENO TSUYOSHI , WANG JIANQING , FUJIWARA OSAMU
Published: December 2015

Electromagnetic disturbances in vehicle‐mounted FM radios are mainly caused by conducted noise currents flowing through wiring harnesses from printed circuit boards (PCBs) with the slits of ground patterns. To suppress these noise currents from PCBs, we previously performed Finite‐Difference Time‐Domain (FDTD) simulation and measurement using multiple simple two‐layer PCB models in which the ground patterns were divided into two parts with different widths, and revealed that both results agreed well with the fact that crosstalk cannot always be reduced by increasing the width of divided ground patters, but had the smallest values (dipping point) at a specific spacing between the divided ground patterns. In order to clarify the above result, we calculated crosstalk using a formula developed from a simplified equivalent circuit model consisting of inductances, derived from their geometrical mean distances (GMDs) from the traces and ground patterns, and found that the calculation results also had dipping point. However, the specific spacing and crosstalk values were different from the simulations and measurements. In the present study, to improve calculation accuracy, we considered nonuniformity of the current distribution in the ground patterns instead of a uniform current distribution, and obtained crosstalk evaluation results which agreed better with simulations and measurements.
Unconformity‐bounded stratigraphy in the Plio‐Pleistocene continental record: new insights from the Alessandria Basin (NW Italy)
Authors: Irace Andrea , Monegato Giovanni , Tema Evdokia , Martinetto Edoardo , Gianolla Daniele , Vassio Elena , Bellino Laura , Violanti Donata
Published: December 2015

Combined stratigraphic and bio‐magnetostratigraphic analyses on a fluvial sequence from the southern margin of the Alessandria Basin (at the junction between the Alps and the Apennines) provide evidence for the first documentation of a late Piacenzian–Gelasian continental record in northern Italy. The basin experienced general growth at the margins and ongoing subsidence in the depocentre, during overthrusting onto the Po Foreland Basin. The studied fluvial succession is 25–30 m thick and can be divided into three units (MRZ1, MRZ2 and MRZ3) delimited by erosional unconformities (S1, S2 and S3). The MRZ1 and MRZ2 units (shallow to confined braided systems) are chronologically restricted between 2.8 and 2.58 Ma based on bio‐magnetostratigraphic analyses. The overall stratigraphic framework indicates deposition and erosion during the progressive uplift of the Alps/Apennines system. The frequency of unconformities and sedimentary changes, compared to other coeval successions of other syn‐orogenic basins of northern and central Italy, suggests the interaction between high‐amplitude global cold stages and tectonic deformation. Tectonic climax occurred in the Gelasian, as revealed by the 450‐ to 600‐ka‐long hiatus associated with the S3 unconformity, whereas the subsequent deposition of the MRZ3 unit (meandering alluvial system) including a Gelasian magnetic reversal points to the fading of tectonic activity. The stratigraphic reconstruction provided in this study enriches the current knowledge of the European continental biota: the absence of thermophilous elements in the MRZ1 carpoflora reflects the late Piacenzian cooling phase after 2.8 Ma, whereas the persistence of several extra‐European taxa in MRZ3 (e.g. Ampelopsis cf. ludwigii, Boehmeria lithuanica, Cryptomeria rhenana) rules out an age younger than 1.4 Ma. The freshwater mollusc assemblage of MRZ2 shows the occurrence of Pomatias elegans and Tournouerina belnensis, identified for the first time in the Pliocene of northern Italy. Copyright © 2015 John Wiley & Sons, Ltd.
Rare earth elements (REEs) geochemistry of Sinian–Cambrian reservoir solid bitumens in Sichuan Basin, SW China: potential application to petroleum exploration
Authors: Gao Ping , Liu Guangdi , Wang Zecheng , Jia Chengzao , Wang Tongshan , Zhang Pengwei
Published: December 2015

In order to evaluate rare earth elements (REEs) as a potential proxy for solid bitumen classification, we employed traditional correlation approaches, such as carbon isotopes and V/(V + Ni) ratios, to infer the source rocks of Sinian–Cambrian reservoir solid bitumens in the Sichuan Basin and analyse solid bitumens for their REE compositions by inductively coupled plasma–mass spectrometry. Our data suggested that Sinian–Cambrian reservoir solid bitumens were primarily sourced from the lower Cambrian shales deposited under anoxic–euxinic conditions. REE and their associated parameters seemed to be more sensitive to classify solid bitumens than traditional correlation approaches. REE concentrations played a dominant role and fractionation degree between light and heavy REE and played a secondary role in solid bitumen classification. REE concentration and pattern in solid bitumens might be controlled by two processes, including inheritance from source rocks and water–rock interaction. The major factor controlling REE concentrations in solid bitumens was the type of organic matter of source rocks. Authigenic minerals in solid bitumens formed by water–rock interaction appeared to have little influence on REE compositions of solid bitumens because of their trace contents. Overall, REE could be used as a novel complementary approach to solid bitumen classification in complicated petroleum systems. Copyright © 2015 John Wiley & Sons, Ltd.
The Interviewer Interviewed: An Interview with Richard Simon
Authors: Martin Graham
Published: December 2015

The Second International Family Therapy Conference, organised in New York in October 1985 by the American Association of Marriage and Family Therapy, proved to be an invigorating watershed of ideas old and new attended by 3500 family therapists (old and new, famous, infamous and unknown) from over 20 countries. Richard Simon, the Editor of The Family Therapy Networker, was extremely busy with his own interviews and running, almost single handed (it seemed), an exhibit for The Networker. Nevertheless, he made time for the following interview which traces briefly the origins of The Networker, its creator and editor, and its influence on family therapy in the United States and elsewhere.
Long‐Term Outcomes of Lesbian, Gay, Bisexual, and Transgender Recalled School Victimization
Authors: Greene Darrell C. , Britton Paula J. , Fitts Brian
Published: December 2015

The authors examined relationships among recalled and current bullying, shame‐focused coping, and fear of negative evaluation in an adult lesbian, gay, bisexual, and transgender (LGBT) sample. Findings indicated that attack self, withdrawal, and attack other shame‐focused coping fully mediated the relationship between recalled bullying and fear of negative evaluation. Fear of negative evaluation and current bullying victimization were predicted by shame‐focused coping. Findings suggested the importance of addressing histories of school‐related bullying and shame‐focused coping when counseling LGBT persons.
Influence of Relationship Education on Relationship Satisfaction for Low‐Income Couples
Authors: Carlson Ryan G. , Barden Sejal M. , Daire Andrew P. , Greene Jennifer
Published: December 2015

The authors randomly assigned 54 ethnically diverse, low‐income married couples with children to receive relationship education either immediately or in 6 months. Couples attended 12 hours of relationship education using the Prevention and Relationship Enhancement Program curriculum. The authors collected pre‐ and postassessment data and compared differences in relationship satisfaction between treatment and wait‐list control couples. Results indicated significant differences in relationship satisfaction between the 2 groups. Findings support relationship education as an efficacious intervention for low‐income couples.
Aminoglutethimide: Review of Pharmacology and Clinical Use
Authors: Santen Richard J. , Misbin Robert I.
Published: December 2015

Aminoglutethimide blocks several cytochrome P‐450 mediated steroid hydroxylation steps, including those required for conversion of cholesterol to pregnenolone and for the aromatization of androgens to estrogens. Through these actions it blocks adrenal steroidogenesis and the production of estrogens in extraglandular tissues. Aminoglutethimide is indicated for treatment of certain patients with Cushing's syndrome and breast cancer. Other potential uses (prostate carcinoma, low renin hypertension, etc.) remain investigational. For treatment of Cushing's syndrome, aminoglutethimide is usually given alone or in combination with metyrapone. In women with breast carcinoma, replacement hydrocortisone must be administered with aminoglutethimide to prevent reflex ACTH hypersecretion from overcoming adrenal inhibition. Administration of aminoglutethimide to patients with Cushing's syndrome results in improvement in clinical status in 56% of cases. Results are most favorable in patients with adrenal tumors and patients with ectopic ACTH production. Aminoglutethimide and replacement glucocorticoid produce objective disease regression in 32% of unselected postmenopausal patients with metastatic breast carcinoma and in 52% of women whose tumors are estrogen receptor positive. Reponses are similar in duration and frequency to those produced by surgical adrenalectomy and hypophysectomy and the antiestrogen, tamoxifen.
Pharmacology, Clinical Uses, and Adverse Effects of Ceruletide, A Cholecystokinetic Agent
Authors: Vincent Miriam E. , Wetzner Steven M. , Robbins Alan H.
Published: December 2015

Ceruletide, a decapeptide, is a potent cholecystokinetic agent with a direct spasmogenic effect on the gallbladder muscle and bile ducts in humans and animals. It was recently approved by the Food and Drug Administration for use as an adjunct in x‐ray examination of the gallbladder and small bowel. The drug causes a coordinated propulsive activity from the duodenum to the ileum and segmenting activity in the colon. Because of this stimulatory effect, ceruletide is useful not only diagnostically as an aid in x‐ray examination of the small bowel, but also therapeutically for treatment of postoperative ileus, intestinal atonia, and chronic fecal stasis. Because of its pancreatic stimulatory action, it is useful in evaluation of exocrine pancreatic function. In therapeutic doses the adverse effects noted are mild, transient extensions of the drug's pharmacologic actions and are manifest as nausea, vomiting, abdominal pain, and rarely hypotension and tachycardia. On the basis of current evidence, ceruletide is a safe and effective cholecystokinetic agent and small bowel and exocrine pancreatic stimulant.
Oxprenolol Hydrochloride: A Long‐Term Study of Efficacy, Safety, and Tolerability
Authors: Tarpley Edward L.
Published: December 2015

Thirty‐five patients whose hypertension was not adequately controlled with optimum doses of hydrochlorothiazide (50–200 mg) entered a long‐term study to evaluate the efficacy, safety, and tolerability of oxprenolol hydrochloride (60–480 mg). All patients were included in the analysis of safety and tolerability, while the data of 26 patients studied for at least 22 months were used for a parametric analysis of efficacy. Mean standing systolic/diastolic blood pressure was significantly (p < 0.001) reduced from 171/106 mm Hg to 142/85 mm Hg within three weeks of treatment. There was a similar reduction in supine blood pressure. All 26 patients were normotensive at the end of the titration period and blood pressure control was maintained for at least 22 months of therapy. Oxprenolol produced no serious adverse effects. The results of this long‐term study suggest that oxprenolol is effective, well tolerated, and safe in the treatment of thiazide‐resistant hypertension.
Effect of Dose and Ointment Application Technique on Nitroglycerin Plasma Concentrations
Authors: Iafrate R. Peter , Yost Richard L. , Curry Stephen H. , Gotz Vincent P. , Caranasos George J.
Published: December 2015

Each of ten non‐smoking, healthy male volunteers between the ages of 20 and 30 and within 10% of their ideal body weight received four nitroglycerin ointment (NTG‐O) treatments: ½″ NTG‐O over 3.94 in2 and 7.88 in2, and 1″ NTG‐0 over 3.94 in2 and 7.88 in2 in a randomized order. Eleven blood samples and 22 determinations of heart rate and blood pressure were obtained over each 6‐hour study period. Nitroglycerin plasma concentrations were determined by gas‐liquid chromatography with electron capture detection. Area under the nitroglycerin plasma concentration‐time curve (AUC), peak plasma concentration (Cmax), and time to peak concentration (Tmax) were determined for each study. Cmax and AUC values were corrected for the actual dose applied. Differences between AUC, Cmax and Tmax were tested using repeated measures analysis of variance. Change in surface area had no statistically significant effect on AUC, Cmax and Tmax. Mean AUC for the ½″ and 1″ doses differed (648 vs 2003 ng.ml−1 min, p = 0.016), as did Cmax (4.6 vs 12.4 ng.ml−1, p = 0.022); however, there was no correlation between individual doses and AUCs. Generally, NTG plasma concentrations within the proposed therapeutic range of 1.2–11.1 ng.ml−1 were detectable throughout each study interval. These data suggest that continuous absorption occurred throughout the 6‐hour dosing interval, that a trend toward increased AUC and Cmax occurred with the larger surface area, and that, in general, doubling the dose of NTG‐O doubles the AUC.
Pharmacology and Hypnotic Efficacy of Triazolam
Authors: Roth Thomas , Roehrs Timothy A. , Zorick Frank J.
Published: December 2015

Triazolam is a new triazolobenzodiazepine drug that is indicated for the treatment of insomnia. The usual adult dosage is 0.25 to 0.5 mg; for geriatric patients a dose of 0.125 to 0.25 mg is recommended. Triazolam is readily absorbed and quickly eliminated with a half‐life of 2–5 hours, making it the shortest acting benzodiazepine available in the United States. Sleep laboratory and non‐laboratory clinical trials found triazolam 0.25 and 0.5 mg effective in inducing and maintaining sleep. It remained effective in laboratory studies of up to one month duration and non‐laboratory studies of up to six months duration when the drug was administered nightly. On discontinuation disturbed sleep for one or two nights was observed in some studies. Triazolam impairs performance for several hours after administration. However, unlike benzodiazepines with long‐acting metabolites, triazolam is relatively free of daytime residual effects, which is attributable to its short half‐life. Overall, triazolam is an effective and safe compound for the symptomatic treatment of insomnia complaints.
Cutaneous Administration of Nitroglycerin: A Review
Authors: Olivari Maria‐Teresa , Cohn Jay N.
Published: December 2015

Chronic administration of nitroglycerin may have important therapeutic effects in patients with angina, acute myocardial infarction, congestive heart failure and peripheral vascular disease. Because of unpredictable oral absorption and short duration of action, topical preparations provide an alternative mode of administration. New controlled release transdermal preparations appear to produce constant plasma nitroglycerin concentrations of 0.2–0.3 ng/ml that persist for up to 24 hours. Additional clinical trials of the therapeutic response to this drug form are necessary, particularly in regard to the relative hemodynamic efficacy and side‐effect profile of sustained vs. fluctuating plasma nitroglycerin concentrations.
Erythrityl Tetranitrate Compared with Isosorbide Dinitrate: Effects on Systolic Time Intervals and Nitrate Modification of Effects of Food
Authors: Nakamura Yasuyuki , Haffty Bruce G. , Long Robert A. , Hull Heyward J. , Starbuck Robert R. , Spodick David H.
Published: December 2015

The pharmacologic effects of erythrityl tetranitrate (ETN) and isosorbide dinitrate (ISDN) were compared to placebo using systolic time intervals (STI) in a randomized, double‐blind study in 15 fasted male volunteers. Sublingual doses of ETN 5 mg, ISDN 5 mg, and placebo were administered to each volunteer at weekly intervals, and measurements of heart rate and STI [pre‐ejection period (PEP), left ventricular ejection time (LVET), and PEP/LVET ratio] were made serially for up to 6 hours after each dose. STI were determined using ear densitography. Evaluation of the pharmacologic effects of ETN and ISDN were based on placebo‐corrected changes from baseline values. Ejection time index (ETI) [LVET corrected for heart rate] was shortened, but the changes were not statistically significant for either drug. However, after ETN and ISDN, statistically significant (p < 0.05) changes in PEP and PEP/LVET ratio were demonstrated for up to 240 minutes after dosing. Unexpected marked changes in the baseline corrected PEP/LVET ratio were observed following food at 4 hours after dosing. This suggests increased inotropy during the postprandial period.
Naloxone‐Responsive Hypotension in a Patient with an ACTH‐Secreting Tumor
Authors: Young Mark J. , Strom Brian L. , Gibson Gene A. , Barnathan Elliot S. , Coplan Neil
Published: December 2015

We report a case in which hypotension was corrected by the administration of naloxone in a patient with an ACTH‐secreting mediastinal tumor. According to previous reports, reversal of hypotension would not be expected in patients with suppressed central ACTH secretion. The implications of this patient's response on the possible mechanisms for naloxone's action in reversing septic shock are discussed.
The Effects of Antacid and Propantheline on the Absorption of Oral Ranitidine
Authors: Donn Karl H. , Eshelman Fred N. , Plachetka John R. , Fabre Louis , Powell J. Robert
Published: December 2015

The effects of propantheline bromide and an aluminum hydroxide/magnesium hydroxide suspension on absorption of ranitidine were evaluated in 12 healthy volunteers according to a Latin square design. Ranitidine 150 mg was administered alone, with 30 ml antacid or preceded by 15 mg propantheline. Ten serum samples were obtained over 12 hours during each treatment period for measurement of ranitidine concentration. The antacid had no significant effect on ranitidine absorption, but propantheline increased the relative bioavailability of ranitidine by 22%. In addition, there was a trend, although not statistically significant, for propantheline to increase the maximum ranitidine serum concentration and the time to maximum serum concentration. Ranitidine can be administered concomitantly with the evaluated doses of antacid and propantheline without a clinically significant alteration in its absorption.
Theophylline QID, TID, BID and Now QD?
Authors: Weinberger Miles M.
Published: December 2015

Dosing intervals for slow‐release theophylline preparations depend on the rate of formulation absorption, the rate of patient elimination, and clinically acceptable fluctuations in serum concentration. Three products, two new to the United States market, have received approval by the Food and Drug Administration (FDA) for 24‐hour dosing claims. Data submitted to the FDA for Theo‐24 (Searle) suggest slow but incomplete absorption in single‐dose studies, and multiple‐dose studies confirm incomplete absorption relative to plain theophylline tablets. Fluctuations in serum concentration expressed as a percentage of the trough value at steady state with Theo‐24 given once daily in the morning ranged from 48 to 1371% among 18 subjects; 13 of the 18 had greater than 100% fluctuation, which is the upper limit for fluctuations that can stay within the 10‐ to 20‐μg/ml therapeutic range. Among another 18 subjects with somewhat slower and less variable rates of elimination, fluctuations ranged from 40–168% at steady state, with 4 of 18 greater than 100% during daily dosing with Theo‐24; all subjects had fluctuations less than 100% (39–92%) when they were given Theo‐durà tablets every 12 hours. Theo‐dur tablets have also received FDA approval for once daily administrations, but only 1 of 14 subjects in a submitted study had fluctuations less than 100% and thus was able to stay within the therapeutic range. No data were available on the absorption of Uniphyl, also approved for once‐daily dosing, but large fluctuations in serum concentration are apparent from advertisements for the European product Uniphyllin, and are also suggested by presentations on Uniphyl at a recent scientific meeting. Current standards for receiving FDA approval for 24‐hour dosing appear to be inconsistent with the pharmacodynamics and pharmacokinetics of theophylline and fail to consider the greater risks from variability in absorption when a single, large daily dose is taken.
Corticosteroid Aerosols in the Treatment of Asthma
Authors: Tse C. S. Ted , Bernstein I. Leonard
Published: December 2015

Since the 1950s, corticosteroid aerosols have proved useful in the treatment of asthma. Although their precise mechanism of action is not known, these topical agents have beneficial antiinflammatory and decongestive effects on the bronchial tree in both the allergic and nonallergic forms of this disease. Four of the newer aerosolized steroids — beclomethasone dipropionate, triamcinolone acetonide, flunisolide and budesonide — have been evaluated in clinical trials. The last drug is still investigational. Their side effects are minimal, the major ones being oral candidiasis and dysphonia. They are most effective when used prophylactically and should not be administered during acute asthmatic attacks, as insufficient amounts of drug are inhaled when the airways are obstructed. Patients must be instructed in the correct techniques of administering steroid aerosols to ensure optimal therapy.
Long‐term Follow‐up Study of Cimetidine
Authors: Porter Jane B. , Jick Hershel , Perera David R. , Ylvisaker J. Thomas , Hunter Judith R.
Published: December 2015

In a 5‐year follow‐up study of 8553 recipients of cimetidine at Group Health Cooperative of Puget Sound, we examined the frequency of uncommon serious illness requiring hospitalization that may have been drug induced. With the possible exception of one patient with probable drug‐induced liver disease, we did not find any instances of serious illness requiring hospitalization that could be attributed with reasonable certainty to cimetidine. This large study provides reassurance that cimetidine is a relatively safe medication.
Pharmacology and Clinical Efficacy of Terfenadine, a New H1‐receptor Antagonist
Authors: Connell John T.
Published: December 2015

Terfenadine is the first of a new class of non‐sedating H1 antihistamines. It differs from chlorpheniramine in its lower anticholinergic activity in rabbit salivation tests. In animal model distribution studies, the drug is not found in the brain. In most clinical studies sedation attributed to terfenadine was on the order of that observed with placebo. Clinical trials of efficacy show that at best terfenadine is slightly less effective than or as effective as chlorpheniramine.
Antimicrobial Activity, Pharmacokinetics, Therapeutic Indications and Adverse Reactions of Ceftazidime
Authors: Gentry Layne O.
Published: December 2015

Ceftazidime is an aminothiazolyl cephalosporin with potent activity against gram‐negative bacteria including multiresistant strains of Pseudomonas aeruginosa. It has limited activity against gram‐negative anaerobes, is less active against some gram‐positive cocci than other newer beta‐lactam compounds and is inactive against Streptococcus faecalis and methicillin‐resistant Staphylococcus aureus. Ceftazidime is stable against common plasmid and chromosomally mediated beta‐lactamase produced by Enterobacteriaceae and Pseudomonas sp. Its pharmacokinetic properties are similar to those of moxalactam and ceftizoxime, and it has a half‐life of 1.9 hours. Excretion is by glomerular filtration. It is not metabolized. Ceftazidime penetrates into most body tissue and fluids, including cerebrospinal fluid, and produces therapeutic levels against most of the pathogenic gram‐negative bacteria, including P. aeruginosa. Ceftazidime accumulates during renal failure, but is removed by hemodialysis and peritoneal dialysis. As a single agent it has been shown effectively to treat meningitis; urinary tract infections; gram‐negative pneumonia; bone, joint and skin infections; and obstetric and gynecologic infections due to susceptible organisms. When combined with an agent that is effective against gram‐positive organisms, it is also beneficial in the treatment of infections in seriously ill neonates. Different investigators have used ceftazidime alone or in combination with other agents in the successful treatment of infections in immuno‐suppressed patients. Adverse reactions have been few and are mostly reversible laboratory findings. The effects of ceftazidime on prothrombin synthesis and platelet function have been minimal, and no drug‐induced clinical bleeding has been reported.
Certain Nonsteroidal Antiinflammatory Drugs and Hospitalization for Upper Gastrointestinal Bleeding
Authors: Jick Hershel , Feld Andrew D. , Perera David R.
Published: December 2015

In this follow‐up study we attempted to estimate the risk of hospitalization for upper gastrointestinal bleeding (exclusive of bleeding from duodenal ulcer) caused by taking certain nonsteroidal antiinflammatory drugs (NSAIDs) in people below the age of 65 years. The final figures represent our best estimate, taking into account all of the available information, and suggest that NSAIDs (excluding aspirin) rarely cause gastrointestinal bleeding from the stomach that requires hospitalization in this age group. A formal analysis of the data according to classic techniques was not feasible since numerous important confounding factors could not be controlled. Indeed, the results indicated that such formal analysis is unnecessary. The data as they stand are of considerable value in providing a reasonable estimate of attributable risk for the drugs studied.
Comparison of Buspirone and Diazepam in Generalized Anxiety Disorder
Authors: Jacobson Alan F. , Dominguez Roberto A. , Goldstein Burton J. , Steinbook Richard M.
Published: December 2015

A total of 66 outpatients meeting Diagnostic and Statistical Manual (DSM‐III) criteria for generalized anxiety disorder began treatment in a randomized double‐blind study that compared the efficacy and safety of buspirone and diazepam. Thirty‐nine outpatients completed the 4‐week trial. Both drugs were administered in a 1:1 dosage ratio; the daily prescribed dose did not exceed 40 mg. The mean daily dose of buspirone prescribed thoughout the study was significantly higher than that of diazepam. Diazepam had a significantly earlier onset of efficacy than buspirone, although both drugs were equivalent after 4 weeks of treatment. Adverse reactions were more frequent in the diazepam group. Total scores from the Hamilton anxiety scale and physician's global ratings show that diazepam was significantly superior to buspirone during the initial 2 weeks of treatment. These findings are further corroborated by the results of patients' self‐rated scales.
Steady‐state Disposition of Diflunisal: Once‐ versus Twice‐daily Administration
Authors: Mojaverian Parviz , Rocci Mario L. , Swanson Brian N. , Vlasses Peter H. , Chremos Athanassios N. , Lin Jiunn H. , Yeh Juang C. , Ferguson Roger K.
Published: December 2015

To evaluate the steady‐state bioequivalence of the nonsteroidal antiinflammatory analgesic agent, diflunisal, administered once versus twice daily, 13 healthy volunteers received diflunisal as follows: (1) 1000 mg at 8:00 am and (2) 500 mg at 8:00 am and 8:00 pm, each for 14 days in a randomized crossover study. The mean (± SD) steady‐state peak plasma concentrations were significantly greater after once‐daily dosing (186 ± 25 μg/ml vs 150 ± 37 μg/ml; p < 0.01). The time to peak concentration was also longer after the single‐dose regimen (2.5 ± 0.8 vs 1.9 ± 0.9 hr; p < 0.05). The regimens were similar with respect to the mean 24‐hour area under the plasma concentration‐time curve at steady state (2839 ± 612 vs 2782 ± 778 μg·hr·ml−1), steady‐state plasma concentrations (118 ± 25 vs 116 ± 32 μg/ml), trough plasma concentration (85 ± 27 vs 92 ± 28 μg/ml) as well as 24‐hour urinary excretion (776 ± 79 vs 771 ± 89 mg) of diflunisal. Based on urinary recoveries, the bioequivalence ratio (once vs twice daily) was 1.01 ± 0.08. These results indicate that diflunisal administered once daily might offer comparable therapeutic effects but be more convenient than a twice‐daily regimen.
N‐Acetylprocainamide Kinetics During Intravenous Infusions and Subsequent Oral Doses in Patients with Coronary Artery Disease and Ventricular Arrhythmias
Authors: Ludden Thomas M. , Crawford Michael H. , Kennedy Gemma T.
Published: December 2015

The kinetics of N‐acetylprocainamide (NAPA) were studied in 5 patients (all men, mean age = 62) with coronary artery disease and ventricular arrhythmias during loading infusions of 0.22–0.45 mg/kg/min, prolonged (19–48 hrs) intravenous infusions 2.5–5.2 mg/min, and in 4 of the patients, during subsequent oral doses 1.5–3 g every 8 hrs. Serum, concentrations of NAPA were determined by high‐performance liquid chromatography. The individual concentration‐time profiles could, with one exception, be described by a two‐compartment, open, kinetic model with apparent first‐order elimination. The kinetic variables were: initial distribution volume (Vc) 0.20 ± 0.11 l/kg (mean ± SD); steady‐state distribution volume (Vss) 1.58 ± 0.55 l/kg; distributional clearance (Cle) 133 ± 23 ml/(kg·hr); absorption rate constant (Ka) 0.354 ± 0.173 hr−1; and fraction of dose reaching systemic circulation (F) 1.00 ± 0.14. The data for one patient who had received increasing oral dosages of 1.5, 2, 2.5 and 3 g every 8 hours resulted in systematic underprediction of observed concentrations at the two highest oral dosing rates. This suggests the possibility of some degree of nonlinearity or time‐dependent change in the kinetic behavior of NAPA. Only low concentrations of procainamide, < 1 mg/L, were found at the end of the infusions.
The Absolute Bioavailability of Oral Theophylline in Patients with Spinal Cord Injury
Authors: Segal Jack L. , Brunnemann Sherry R. , Gordon Stanley K. , Eltorai Ibrahim M.
Published: December 2015

The absolute bioavailability of oral theophylline in five tetraplegic, five paraplegic and three control (intact neuraxes) subjects was studied. All were healthy nonobese males between 20 and 60 years of age, with normal renal and hepatic function. More than 1 year had elapsed from the date of injury in all of the patients with spinal cord injury. None of the study subjects was taking medications known to interfere with theophylline metabolism or the analytic methodology. Each received theophylline in an equivalent amount orally, and by intravenous infusion on 2 occasions separated by not less than 2 weeks. The time course of serum theophylline concentration was followed for up to 24 hours and the area under each oral and intravenous curve extrapolated to infinity (AUCO→∞) was compared using a linear, least‐squares, best‐fit BASIC program (ESTRIP). A statistically significant difference between means and variances of the absolute bioavailability of oral theophylline, AUCOralO→∞/AUCIVO→∞, (AUCratio ± SD) was demonstrated in the tetraplegic subjects who showed decreased bioavailability (AUCratio = 0.67 ± 0.04, range 0.63–0.73) as compared to the paraplegic (AUCratio = 0.95 ± 0.09, range 0.84–1.08) and control subjects (AUCratio = 0.90 ± 0.12, range 0.78–1.02). A decrease in the bioavailability of oral theophylline in tetraplegic subjects has not previously been described and may be caused by impaired gastric emptying, which frequently characterizes high myelopathy. Diminished bioavailability could result in underestimation of loading and maintenance doses in tetraplegic humans.
Ketoprofen: A Review of Its Pharmacologic and Clinical Properties
Authors: Kantor Thomas G.
Published: December 2015

Ketoprofen (Orudis), a highly potent and safe nonsteroidal antiinflammatory drug of the propionic acid derivative group, was synthesized in France by Rhône‐Poulenc chemists in 1967, 3 years after the prototype ibuprofen. Ketoprofen was introduced in 1973 in France and the United Kingdom for antiinflammatory use. Today the drug is available in about 80 countries and has recently been approved in the United States for treatment of rheumatoid arthritis and osteoarthritis. The therapeutic experience with ketoprofen is estimated to have exceeded 3 million patient‐years. Double‐blind trials have established its therapeutic equivalence with aspirin, indomethacin, and ibuprofen in rheumatoid arthritis and with aspirin in osteoarthritis. Ketoprofen has a short half‐life, a simple metabolism, and a broad therapeutic window, and does not accumulate with multiple doses. These features contribute to a rapid onset of action, flexible dosing, and a reliable tolerance profile.
Comparison of Intramuscular Ketorolac Tromethamine and Morphine Sulfate for Analgesia of Pain After Major Surgery
Authors: Yee James P. , Koshiver John E. , Allbon Carolyn , Brown Colin R.
Published: December 2015

Ketorolac tromethamine is a new injectable nonnarcotic analgesic. In a parallel, double‐blind study, the analgesic efficacies of single intramuscular doses of ketorolac 10, 30 and 90 mg were compared with those of morphine sulfate 6 and 12 mg. Two hundred forty‐one patients were categorized according to type of surgical procedure and severity of pain. Pain intensity and pain relief were assessed for 6 hours by scoring standard verbal and visual analog scales. Patients receiving ketorolac 10, 30 or 90 mg or morphine (MS) 12 mg all had significantly better pain relief in almost all measurements performed than those receiving MS 6 mg (p < 0.05). Ketorolac 10 and 30 mg were as effective as morphine 12 mg during the entire 6‐hour observation period, and ketorolac 90 mg was more effective than morphine 12 mg during the entire 6 hours. Patients with pain related to major surgery (e.g., cholecystectomy and abdominal hysterectomy) were better able to distinguish analgesic potency of morphine than those having less traumatic procedures (e.g., tendon and ligament repairs)
Venous Thrombosis: An Overview
Authors: Peterson Carl W.
Published: December 2015

Venous thromboembolic disease contributes to morbidity and mortality in certain groups of hospitalized patients, particularly those who have undergone surgery. Although principles of treatment have changed relatively little during the past 20 years, significant advances have been made in the diagnosis of deep vein thrombosis (DVT). Venography, once the only reliable diagnostic technique, has been largely replaced by noninvasive tests: impedance plethysmography, venous Doppler, 125I‐radiofibrinogen‐uptake test, and phleborheography. Virchow's triad of stasis, vessel injury, and hypercoagulability remains a valid explanation of the pathogenesis of thrombus formation, but laboratory and clinical data have refined our knowledge of how these factors interact to result in clinically significant disease. Knowledge of the natural history of venous thrombosis, plus heightened awareness of the long‐term morbidity and expense associated with the postphlebitic syndrome, have led to increased interest in preventing DVT. Clinically and economically, venous thrombosis is best managed by prevention.
HLA: Its Role in Pathogenesis of Disease
Authors: Bach Fritz H.
Published: December 2015

The complexity of the HLA system, the major histocompatibility complex in man, is reviewed with regard both to the isotypic complexity (the number of loci) as well as the polymorphism of the individual loci. Different methods used to define polymorphism, including serological analysis and T lymphocyte response analysis, are considered. The possible role of HLA antigens in association with a variety of diseases is discussed.
Intravenous Immune Globulin: Dosage and Administration
Authors: Wordell Cindy J.
Published: December 2015

Intravenous immune globulin (IV‐IgG) is approved for use in substitution therapy of immunodeficiency syndromes and treatment of idiopathic thrombocytopenic purpura (ITP). The initial dose for substitution therapy is 0.2 g/kg body weight repeated monthly. If necessary, the dose may be increased to 0.3 g/kg and the frequency to every 2–3 weeks. The approved dosage for ITP is 0.4 g/kg daily for 2 to 5 consecutive days. Repeat doses of 0.4 g/kg have been used as maintenance therapy. The initial infusions of IgG to immunodeficient patients who have not been treated during the previous 8 weeks or never treated at all should proceed with caution. These patients are at risk of potentially serious complement‐mediated adverse reactions. Adverse reactions due to IgG administration are less frequent and less severe for patients with ITP. Currently available preparations are contraindicated in patients with a selective IgA deficiency and detectable IgA antibodies.
Ganciclovir Hepatotoxicity
Authors: Shea Brian F. , Hoffman Stephen , Sesin G. Paul , Hammer Scott M.
Published: December 2015

A 33‐year‐old male with acquired immunodeficiency syndrome received ganciclovir for presumed cytomegalovirus retinitis. Although results of baseline liver function tests were abnormal, marked elevations of transaminases and alkaline phosphatase occurred when the drug was first instituted, as well as after rechallenge. These elevated laboratory values declined on each occasion that the drug was withdrawn. As no other toxic or infectious insults could clearly be incriminated in these acute, self‐limited episodes of hepatic function abnormalities, ganciclovir was most likely responsible for the toxicity observed in this patient.
Silent Myocardial Ischemia: Pathophysiology and Clinical Recognition
Authors: Morris James J.
Published: December 2015

Silent myocardial ischemia is reported to account for approximately one‐fifth of all myocardial infarctions and to be very common in patients with a history of angina pectoris. It may also play an important role in sudden cardiac death. Detection of silent ischemia is best accomplished by treadmill testing, electrocardiogram, or Holter monitoring. When detected, it should be treated vigorously in high‐risk patients and all postinfarction patients. Recommendations regarding to the ideal therapy still await the results of controlled clinical testing, although preliminary reports indicate that topical nitrates are effective.
The Relative Predictive Performance of Two Theophylline Pharmacokinetic Dosing Programs
Authors: Hoon Timothy J. , Wood Charles A. , Whidden Margaret A. , Greene William L. , Bottorff Michael B.
Published: December 2015

The predictive performance of 2 theophylline pharmacokinetic dosing programs (Abbott and Simkin) was evaluated using a group of 44 inpatients who had 2 serum concentrations (TSC) measured during hospitalization. Bias was assessed with the median prediction error (PE) and precision was assessed with the median absolute PE. The Abbott program was significantly less biased than the Simkin program in predicting the first TSC (PEs 0.1 and −1.3 μg/ml, respectively; p < 0.05). No significant difference in bias was observed in predicting the second TSC, or in precision in predicting either the first or second TSC. Both programs exhibited small improvements in prediction precision when the first TSC was used to predict the second. Correlations of predicted versus measured TSC also improved with the second prediction. These programs may be useful in dosing theophylline; however, TSC monitoring and the application of sound clinical judgment are warranted.
DDAVP in the Treatment of Bleeding Disorders
Authors: Salva Kathryn M. , Kim Hugh C. , Nahum Kenneth , Fallot Paul L.
Published: December 2015

Hemophilia A and von Willebrand's disease are hereditary disorders associated with qualitative and quantitative abnormalities of clotting factor VIII. A major clinical feature is excessive or abnormal bleeding often necessitating the use of transfusions of pooled blood products to achieve hemostasis. Exposure to blood products places the recipient at risk for infection by the hepatitis B virus or the human immunodeficiency virus. A synthetic analog of arginine vasopressin, 1‐desamino‐8‐d‐arginine vasopressin, has been shown to increase the plasma levels of factor VIII coagulant activity and von Willebrand's factor, and clinically to improve abnormal bleeding, obviating the need to use blood products.
Buspirone: An Update on a Unique Anxiolytic Agent
Authors: Jann Michael W.
Published: December 2015

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5‐HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5‐HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5‐HT‐containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle‐relaxant properties, and causes only mimimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half‐life is 2.1 hours. Buspirone is mainly bound to albumin and oxacid glycoprotein. It is metabolized to an active metabolite 1‐(2‐pyrimidinyl) piperazine (1‐PP). The mean elimination half‐life of 1‐PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.
Conservation, Ethnobotany, and the Search for New Jungle Medicines: Pharmacognosy Comes of Age … Again
Authors: Plotkin Mark J.
Published: December 2015

Through most of man's history, botany and medicine were, for all practical purposes, synonymous fields of knowledge, and the shaman, or witch‐doctor — usually an accomplished botanist — represents probably the oldest professional man in the evolution of human culture.
Genital Necrosis Secondary to Warfarin Therapy
Authors: Kandrotas Robert J. , Deterding James
Published: December 2015

Several adverse dermatologic effects have been reported with the use of warfarin. Among these is the rare complication of drug‐induced necrosis. Approximately 150 cases had been reported by 1976, and a review of the literature since 1943 revealed only 4 reported cases of penile necrosis. We present the fifth case of genital necrosis reported with coumarin anticoagulants and the third such case associated with warfarin.