bluuebunny/crossref_metadata_2025 huggingface dataset:
ChemInform Abstract: Copper‐Catalyzed Azide—Alkyne Cycloaddition (CuAAC) in Liquid Ammonia.
Authors: Ji Pengju , Atherton John H. , Page Michael I.
Published: March 2013

The title reaction performed in liquid ammonia requires less catalyst than that in conventional solvents and provides the product triazoles (III) in excellent yields.
ChemInform Abstract: Synthesis and Molecular Structure of Novel 2‐(Alkylthio)‐4‐chloro‐N‐ (4,5‐dihydro‐5‐oxo‐1H‐1,2,4‐triazol‐3‐yl)‐5‐methylbenzenesulfonamides with Potential Anticancer Activity.
Authors: Slawinski Jaroslaw , Zolnowska Beata , Orlewska Czeslawa , Chojnacki Jaroslaw
Published: March 2013

New compound (Ie) shows high activities against 13 human tumor cell lines representing lung, colon, CNS, melanoma, ovarian, renal, prostate, and breast.
ChemInform Abstract: Design, Synthesis and Biological Activity Evaluation of 2,5‐Diphenyl‐1,3,4‐oxadiazole Derivatives as Novel Inhibitors of Fructose‐1,6‐bisphosphatase.
Authors: He Hai‐Bing , Gao Li‐Xin , Zhou Yue‐Yang , Liu Ting , Tang Jie , Gong Xue‐Ping , Qiu Wen‐Wei , Li Jing‐Ya , Li Jia , Yang Fan
Published: March 2013

Compound (Ia) is discovered as a potential FBPase inhibitor by high‐throughput screening of a library of 56,000 lead‐like compounds.
ChemInform Abstract: Organocatalytic Asymmetric anti‐Selective Michael Reactions of Aldehydes and the Sequential Reduction/Lactonization/Pauson—Khand Reaction for the Enantioselective Synthesis of Highly Functionalized Hydropentalenes.
Authors: Hong Bor‐Cherng , Dange Nitin S. , Yen Po‐Jen , Lee Gene‐Hsiang , Liao Ju‐Hsiou
Published: March 2013

In the presence of DBU and the prolinol derivative, unsaturated aldehydes undergo asymmetric anti‐selective Michael addition to malonates of type (VI).
ChemInform Abstract: Facile Assembly of Indeno[1,2‐c]chromenes via a Palladium‐Catalyzed Reaction of 2‐Alkynylhalobenzene.
Authors: Pan Xiaolin , Nie Hongming , Luo Yong , Gao Yueqiu , Wu Jie
Published: March 2013

2‐Alkynylbromobenzenes (I) react with 2‐alkynylphenols (IV) in the presence of a Pd catalyst, leading to title compounds (V) in high yields.
ChemInform Abstract: Rhodium/Diene‐Catalyzed Asymmetric Arylation of N‐Boc‐Protected α,β‐Unsaturated δ‐Lactam with Arylboronic Acids: Enantioselective Synthesis of 4‐Aryl‐2‐piperidinones.
Authors: He Zhi‐Tao , Wei Ya‐Bing , Yu Hong‐Jie , Sun Cai‐Yun , Feng Chen‐Guo , Tian Ping , Lin Guo‐Qiang
Published: March 2013

Title compounds (III) and (V) are prepared in high yields and enantioselectivities.
ChemInform Abstract: Novel Synthesis of Some New Fluorescent 2‐Amino‐3‐cyanopyridines
Authors: Zonouzi Afsaneh , Izakian Zakieh , Ng Seik Weng
Published: March 2013

via one‐pot three‐component condensation of acetylacetone, malononitrile, and different amines in the presence of N‐hydroxybenzamide or p‐toluenesulfonic acid
ChemInform Abstract: Facile Synthesis of Dispirooxindole‐Fused Heterocycles via Domino 1,4‐Dipolar Addition and Diels—Alder Reaction of in situ Generated Huisgen 1,4‐Dipoles.
Authors: Sun Jing , Sun Yan , Gong Hui , Xie Ya‐Jing , Yan Chao‐Guo
Published: March 2013

Treatment of the aminopyridine (I) with acetylenedicarboxylates and N‐substituted acylidineoxindoles allows an efficient and stereoselective access to novel spirocyclic compounds of type (IV) and (VI).
ChemInform Abstract: An Efficient Synthesis of Pyrrolo[3′,2′:4,5]thiopyrano[3,2‐b]pyridin‐2‐one: A New Ring System of Pharmaceutical Interest.
Authors: Barraja Paola , Diana Patrizia , Spano Virginia , Montalbano Alessandra , Carbone Anna , Parrino Barbara , Cirrincione Girolamo
Published: March 2013

Derivatives of the title ring system are screened for their inhibitory activity against 60 human cancer cell lines.
ChemInform Abstract: Synthesis and Physicochemical Characterization of Novel 6‐Aminopyrido[3,4‐c][1,9]phenanthrolines as Aza‐Analogues of Benzo[c]phenanthridines.
Authors: Meier Christopher , Kotthaus Joscha , Stenzel Lars , Girreser Ulrich , Heber Dieter , Clement Bernd
Published: March 2013

This work contains information on lipophilicity, solubility, drug‐likeness, and cytotoxicity of the synthesized compounds.
ChemInform Abstract: Three‐Component Heterocyclization of gem‐Bromofluorocyclopropanes with NOBF4: Access to 4‐Fluoropyrimidine N‐Oxides.
Authors: Sedenkova Kseniya N. , Averina Elena B. , Grishin Yuri K. , Kutateladze Andrei G. , Rybakov Victor B. , Kuznetsova Tamara S. , Zefirov Nikolay S.
Published: March 2013

The reaction in nitrile solvents results in a new, unexpected formation of 4‐fluoropyrimidine N‐oxides.
ChemInform Abstract: Route Selection in the Synthesis of C—4 and C—6 Substituted Thienopyrimidines.
Authors: Bugge Steffen , Kaspersen Svein Jacob , Sundby Eirik , Hoff Baard Helge
Published: March 2013

Different routes towards title compounds (III) and (VI) starting from dihalogenated thienopyrimidine (I) are developed.
ChemInform Abstract: Palladium‐Catalyzed Direct C—H Arylation of Thieno[3,4‐b]pyrazines: Synthesis of Advanced Oligomeric and Polymeric Materials.
Authors: Abdo Nabiha I. , El‐Shehawy Ashraf A. , El‐Barbary Ahmed A. , Lee Jae‐Suk
Published: March 2013

Compounds (I) can be synthesized from easily available starting materials via established C—C coupling reactions.
ChemInform Abstract: Syntheses of Novel Diaryl[d,f][1,3]diazepines via One‐Pot Suzuki Coupling Followed by Direct Ring Closure with Carboxylic Acids.
Authors: Yan Longjia , Che Xin , Bai Xu , Pei Yazhong
Published: March 2013

Several diazepines are synthesized starting from bromoanilines, chloronitropyridines, and carboxylic acids.
ChemInform Abstract: Gold(I)‐Catalyzed Cyclodehydration Enabled by the Triisopropylsilyl Group: A Synthetically Versatile Methodology.
Authors: Usanov Dmitry L. , Naodovic Marina , Brasholz Malte , Yamamoto Hisashi
Published: March 2013

The mild, robust, and operationally convenient method provides an easy access to a library of polycyclic systems including minimally functionalized benzofulvenes of type (XI).
ChemInform Abstract: Synthesis and Biological Evaluation of Novel 3′‐Difluorovinyl Taxoids.
Authors: Ojima Iwao , et al. et al.
Published: March 2013

A series of 3′‐difluorovinyl taxoids (I) with C10 modifications, as well as those with C2 and C10 modifications, are designed and synthesized.
ChemInform Abstract: Novel Cytotoxic Phenanthrenequinone from Odontioda Marie Noel “Velano”.
Authors: Masuda Yuko , Suzuki Ryuichiro , Sakagami Hiroshi , Umemura Naoki , Shirataki Yoshiaki
Published: March 2013

A new phenanthrenequinone (I) is isolated together with known ephemeranthoquinone B.
ChemInform Abstract: Solid State Thermochromic Materials
Authors: Kiri Pragna , Hyett Geoff , Binions Russell
Published: March 2013

Review: 147 refs.
ChemInform Abstract: Clay Crystal‐Chemical Adaptability and Transformation Mechanisms
Authors: Cuadros J.
Published: March 2013

Review: 76 refs.
ChemInform Abstract: TiO2—SnO2 Composites and Solid Solutions for Chemical Nanosensors
Authors: Zakrzewska K. , Radecka M.
Published: March 2013

Review: 13 refs.
ChemInform Abstract: Integrated Approaches to the Configuration Assignment of Marine Natural Products
Authors: Molinski Tadeusz F. , Morinaka Brandon I.
Published: March 2013

Review: 391 refs.
ChemInform Abstract: Organocatalyzed Enantioselective Desymmetrization of Diols in the Preparation of Chiral Building Blocks
Authors: Diaz‐de‐Villegas Maria D. , Galvez Jose A. , Badorrey Ramon , Lopez‐Ram‐de‐Viu M. Pilar
Published: March 2013

Review: 49 refs.
ChemInform Abstract: Aziridine‐2‐carboxylates: Preparation, Nucleophilic Ring Opening, and Ring Expansion
Authors: Ishikawa Tsutomu
Published: March 2013

Review: 151 refs.
ChemInform Abstract: Nucleoside Triphosphates — Building Blocks for the Modification of Nucleic Acids
Authors: Hollenstein Marcel
Published: March 2013

Review: 139 refs.
ChemInform Abstract: Glycofunctionalized Quantum Dots
Authors: Weingart Jacob J. , Sun Xue‐Long
Published: March 2013

Review: 75 refs.
ChemInform Abstract: Synthesis of Glyconanomaterials via Photoinitiated Coupling Chemistry
Authors: Wang Xin , Norberg Oscar , Deng Lingquan , Ramstrom Olof , Yan Mingdi
Published: March 2013

Review: 79 refs.
ChemInform Abstract: Development of Metal Ion Containing Catalysts for the Decomposition of Phosphorothioate Esters
Authors: Edwards David R. , Brown R. Stan
Published: March 2013

Review: 75 refs.
ChemInform Abstract: Recent Developments in the Synthesis of 1,4,5‐Trisubstituted Triazoles
Authors: Mignani S. , Zhou Y. , Lecourt T. , Micouin L.
Published: March 2013

Review: 156 refs.
ChemInform Abstract: Combinatorial Libraries of Porphyrins — Chemistry and Applications
Authors: Drain Charles Michael , Singh Sunaina
Published: March 2013

Review: 241 refs.
ChemInform Abstract: Synthesis of Fluorinated Neurotransmitter Analogues
Authors: Winkler Margit , O'Hagan David
Published: March 2013

Review: 85 refs.
ChemInform Abstract: DNA‐Based Soft Phases
Authors: Bellini Tommaso , Cerbino Roberto , Zanchetta Giuliano
Published: March 2013

Review: 174 refs.
ChemInform Abstract: Ruthenium‐Catalyzed Selective Hydrogenation for Flavor and Fragrance Applications
Authors: Dupau Philippe
Published: March 2013

Review: 41 refs.
ChemInform Abstract: Pincer Complexes as Catalysts in Organic Chemistry
Authors: Szabo Kalman J.
Published: March 2013

Review: 146 refs.
ChemInform Abstract: Fluorine: The New Kingpin of Drug Discovery
Authors: Prakash G. K. Surya , Wang Fang
Published: March 2013

Review: 47 refs.
ChemInform Abstract: Alkane C—H Oxygenation Catalyzed by Transition Metal Complexes
Authors: Company Anna , Lloret Julio , Gomez Laura , Costas Miquel
Published: March 2013

Review: 332 refs.
ChemInform Abstract: Interactions of Anticancer Pt Compounds with Proteins: An Overlooked Topic in Medicinal Inorganic Chemistry?
Authors: Casini Angela , Reedijk Jan
Published: March 2013

Review: 162 refs.
ChemInform Abstract: Chemical Synthesis of Glycosylphosphatidylinositol Anchors
Authors: Swarts Benjamin M. , Guo Zhongwu
Published: March 2013

Review: 146 refs.
ChemInform Abstract: Recent Biotechnological Applications of Glyconanomaterials
Authors: Hong Sung You , Green Malcolm L. H. , Davis Benjamin G.
Published: March 2013

Review: 63 refs.
ChemInform Abstract: The Procedure, Principle, and Instrumentation of Antioxidant Phytochemical Analysis
Authors: White Brittany , Rice Lydia , Howard Luke R.
Published: March 2013

Review: 153 refs.
ChemInform Abstract: Methane Storage in Advanced Porous Materials
Authors: Makal Trevor A. , Li Jian‐Rong , Lu Weigang , Zhou Hong‐Cai
Published: March 2013

Review: 311 refs.
ChemInform Abstract: Thio Effects as a Tool for Mechanistic Studies of the Cleavage of RNA Phosphodiester Bonds: The Chemical Basis
Authors: Ora Mikko , Lonnberg Tuomas , Lonnberg Harri
Published: March 2013

Review: 92 refs.
ChemInform Abstract: Polymer Adsorption at Solid Surfaces: Theoretical Aspects
Authors: Kislenko V. N.
Published: March 2013

Review: 70 refs.
ChemInform Abstract: Electrochemical Detection of DNA Hybridization: Use of Latex to Construct Metal‐Nanoparticle Labels
Authors: Somasundrum Mithran , Surareungchai Werasak
Published: March 2013

Review: 134 refs.
Synthesis and Characterization of Azidobipyridyl Ruthenium Complexes and Their “Click” Chemistry Derivatives
Authors: Uppal Baljinder S. , Zahid Adam , Elliott Paul I. P.
Published: March 2013

The ligand 4‐azido‐2,2′‐bipyridyl (1) has been used to prepare 1,2,3‐triazole‐substituted ligands through copper‐catalyzed alkyne/azide cycloaddition (CuAAC or “click” chemistry) with phenylacetylene, ethynylferrocene and 2‐ethynylpyridine to yield 4‐(4‐phenyl‐1,2,3‐triazol‐1‐yl)‐2,2′‐bipyridyl (2a), 4‐(4‐ferrocenyl‐1,2,3‐triazol‐1‐yl)‐2,2′‐bipyridyl (2b) and 4‐[4‐(pyridyl‐2‐yl)‐1,2,3‐triazol‐1‐yl]‐2,2′‐bipyridyl (2c). Complexes of the form [Ru(p‐cymene)(Cl)(L)]PF6 (3, L = 1; 4a, L = 2a; 4b, L = 2b) were then prepared and characterized. We also report the synthesis of the complex of the analogous ligand 4,4′‐bisazido‐2,2′‐bipyridyl (1′), [Ru(p‐cymene)(Cl)(1′)]PF6 (3′). Complexes 4a and 4b were also prepared by an alternative route, whereby 3 undergoes CuAAC coupling with phenylacetylene and ethynylferrocene respectively. Complexes prepared with ligands that are pre‐assembled or “clicked” at the metal show identical 1H NMR spectra. CuAAC coupling of 3 and 2‐ethynylpyridine results in the formation of the complex [Ru(p‐cymene)(Cl)(2c)]PF6 (4c), which contains a coordinatively vacant pyridyltriazole moiety. The reaction of [Ru(p‐cymene)(Cl)2]2 with pre‐assembled 2c results in the formation of the dinuclear complex [{Ru(p‐cymene)(Cl)}2(2c)]·2PF6 (5), which incorporates ruthenium atoms at both bipyridyl and pyridyltriazole binding domains. The 1H NMR spectrum of the complex shows two signals for the triazole ring proton as well as duplicate signals for other protons of the bridging ligand, which indicates that 5 is produced as a mixture of diastereoisomers. The complex [{Ru(p‐cymene)Cl}2{di‐4‐([1‐{2,2′‐bipyrid‐4‐yl}triazol‐4‐yl]methyl)ether}][PF6]2 (7) was also prepared through the coupling of 3 with dipropargyl ether.
Organoaluminum and ‐gallium Formamidinate Complexes
Authors: Hamidi Shima , Dietrich H. Martin , Werner Daniel , Jende Lars N. , Maichle‐Mössmer Cäcilia , Törnroos Karl W. , Deacon Glen B. , Junk Peter C. , Anwander Reiner
Published: March 2013

Dialuminum formamidinate complexes [Me2Al(μ‐Form)(μ‐Me)AlMe2] [Form (ArNCHNAr) = EtForm (Ar = 2,6‐Et2C6H3) or DippForm (Ar = 2,6‐iPr2C6H3)] were obtained in good yields by treatment of formamidines (FormH) with trimethylaluminum in a 1:3 stoichiometry. The products contain both a bridging Form ligand and a bridging methyl group between the two aluminum centers. [M(Form)Me2] (M = Al, Form = DippForm, EtForm; M = Ga, Form = DippForm) were prepared in high yields by the protonolysis reactions of MMe3 (M = Al, Ga) with formamidines (FormH) in a 1:1 stoichiometry. [Al(DippForm)Me2] was also synthesized by other methods including concentration of the tetrahydrofuran/n‐hexane solution of [Me2Al(μ‐DippForm)(μ‐Me)AlMe2] to dryness and also by reaction of AlMe3 with [Ga(DippForm)Me2] in a 1:1 ratio. Partial dissociation of the dialuminum to monoaluminum complexes was detected in the 1H NMR spectra of [Me2Al(μ‐Form)(μ‐Me)AlMe2] complexes. All complexes exhibit a distorted tetrahedral stereochemistry of the Group 13 metal atoms.
Synthesis of Pure Lithium Amide Nanoparticles
Authors: Baldissin Gael , Boag Neil M. , Tang Chiu C. , Bull Daniel J.
Published: March 2013

Deprotonation of ammonia with n‐butyllithium offers a facile synthetic route to produce pure lithium amide exhibiting fine granularity, which facilitates the complete thermal decomposition to lithium imide at a relatively low temperature of 600 K. Synthesised compounds were characterised by high‐resolution synchrotron X‐ray diffraction, and the particle morphology of lithium amide was studied by transmission electron microscopy. The proposed methodology readily affords the production of pure lithium amide nanoparticles at both bench‐top and commercial scale.
Selenacalix[3]triazines: Anion Versus Proton Association
Authors: Van Rossom Wim , Thomas Joice , Terentyeva Tatyana G. , Maes Wouter , Dehaen Wim
Published: March 2013

Selenacalix[3]triazines, cyclotrimeric metacyclophanes with direct Se linkages between the heteroaryl constituents, were shown to associate with various guest species. The preorganization of three electron deficient triazine rings allows for anions to bind through anion‐π interactions, and alignment of the central nitrogen lone pairs and the well‐defined size of the macroring enable association with a single proton. Extended UV/Vis titration studies indicated a clear difference in complexation behavior depending on the outer‐rim substitution pattern. The host–guest properties of analogous selena‐ and thiacalix[3]triazines were found to be notably different.
Synthesis of Axially Chiral 1,1′‐Binaphthalenes by Palladium‐Catalysed Cross‐Coupling Reactions of Triorganoindium Reagents
Authors: Mosquera Ángeles , Pena Miguel A. , Pérez Sestelo José , Sarandeses Luis A.
Published: March 2013

1,1′‐Binaphthalenes and heterocyclic analogues can be efficiently prepared by palladium‐catalysed cross‐coupling reactions between tri(1‐naphthyl)indium reagents and 1‐halonaphthalenes and haloisoquinolines. The reactions were usually carried out in THF at 80 °C with a slight excess of the indium reagent (40 mol‐%) and a low catalyst loading (4 mol‐% Pd) to afford the cross‐coupling products in good yields (45–99 %). The method allows the synthesis of sterically hindered 2‐substituted and 2,2′‐disubstituted 1,1′‐binaphthalenes and naphthylisoquinolines. In addition, the coupling reactions can be performed enantioselectively and the best enantiomeric excesses were obtained by using the chiral amino‐phosphane ferrocenyl ligand (R,S)‐PPFA.
Residual drift demands in moment‐resisting steel frames subjected to narrow‐band earthquake ground motions
Authors: Bojórquez Edén , Ruiz‐García Jorge
Published: March 2013

This paper presents the main results of the evaluation of residual inter‐story drift demands in typical moment‐resisting steel buildings designed accordingly to the Mexican design practice when subjected to narrow‐band earthquake ground motions. Analytical 2D‐framed models representative of the study‐case buildings were subjected to a set of 30 narrow‐band earthquake ground motions recorded on stations placed in soft‐soil sites of Mexico City, where most significant structural damage was found in buildings as a consequence of the 1985 Michoacan earthquake, and scaled to reach several levels of intensity to perform incremental dynamic analyses. Thus, results were statistically processed to obtain hazard curves of peak (maximum) and residual drift demands for each frame model. It is shown that the study‐case frames might exhibit maximum residual inter‐story drift demands in excess of 0.5%, which is perceptible for building's occupants and could cause human discomfort, for a mean annual rate of exceedance associated to peak inter‐story drift demands of about 3%, which is the limiting drift to avoid collapse prescribed in the 2004 Mexico City Seismic Design Provisions. The influence of a member's post‐yield stiffness ratio and material overstrength in the evaluation of maximum residual inter‐story drift demands is also discussed. Finally, this study introduces response transformation factors, Tp, that allow establishing residual drift limits compatible with the same mean annual rate of exceedance of peak inter‐story drift limits for future seismic design/evaluation criteria that take into account both drift demands for assessing a building's seismic performance. Copyright © 2013 John Wiley & Sons, Ltd.
Inorganic–organic hybrid coating‐encapsulated ammonium polyphosphate and its flame retardancy and water resistance in epoxy resin
Authors: Qu Hongqiang , Wu Weihong , Hao Jianwei , Wang Chunzheng , Xu Jianzhong
Published: March 2013

A novel encapsulated ammonium polyphosphate (APP) with an inorganic–organic hybrid coating (MAPP) was prepared by a sol–gel method using tetraethoxysilane and octyltriethoxysilane as precursors. The properties of MAPP were investigated by water solubility, hydrophobicity, and morphological determination. The structure of MAPP was characterized by X‐ray photoelectron spectroscopy. The flame retardancy of epoxy resin composite with MAPP was evaluated by limiting oxygen index, UL‐94 test, and cone calorimetry test. The results showed that both tetraethoxysilane and octyltriethoxysilane hydrolyze and condense to form a dense polysiloxane layer structure on the surface of APP. The water solubility of MAPP was reduced from 0.64 to 0.13 g/100 mL of water, and the water resistance of epoxy resin composites filled with MAPP was also greatly improved. The limiting oxygen index, UL‐94 test, and cone calorimeter results showed that the epoxy resin composites filled with MAPP had better flame retardancy, probably because of a synergistic effect between polysiloxane and APP. Copyright © 2013 John Wiley & Sons, Ltd.
Safety of robotic thyroidectomy approaches: Meta‐analysis and systematic review
Authors: Jackson Nicole R. , Yao Lu , Tufano Ralph P. , Kandil Emad H.
Published: March 2013

Background

This study compared the efficacy of robotic thyroidectomy via a gasless, axillary approach with conventional cervical and endoscopic techniques by meta‐analysis.

Methods

Articles were identified from the following keyword searches: robotic/robot‐assisted thyroidectomy/thyroid surgery. Outcomes included operative time, hospital stay, complications, and cosmetic satisfaction after surgery. Between‐group outcome differences were calculated using random‐effects models.

Results

In all, 87 publications were identified and 9 studies met inclusion criteria, totaling 2881 patients, 1122 of whom underwent robotic thyroidectomy. Those who underwent robotic surgery reported greater cosmetic satisfaction, with a pooled net mean difference of −1.35 (95% confidence interval [CI]: −1.69, −1.09). Robotic approach operative time was longer than that of the conventional approach (95% CI: 29.23, 54.87), with a trend to be shorter than the endoscopic approaches. Robotic surgery had similar risks to open and endoscopic approaches.

Conclusions

Our meta‐analysis suggests that robotic thyroidectomy is as safe, feasible, and efficacious as conventional cervical and endoscopic thyroidectomy, showing superior cosmetic satisfaction than that of conventional thyroidectomy. © 2012 Wiley Periodicals, Inc. Head Neck 36: 137–143, 2014
Decision making in the management of recurrent head and neck cancer
Authors: Ho Allen S. , Kraus Dennis H. , Ganly Ian , Lee Nancy Y. , Shah Jatin P. , Morris Luc G. T.
Published: March 2013

Despite substantial improvements in head and neck squamous cell carcinoma (HNSCC) treatment, the major obstacle to long‐term survival remains disease recurrence. Salvage options are often limited due to prior therapy and the escalated morbidity of retreatment. The costs of treatment must be measured against the anticipated quality and quantity of life recovered, even with resectable disease. This review surveys the recurrent HNSCC literature to better guide decision making. Across multiple studies, negative prognostic factors include impaired performance status, advanced recurrent stage, brief disease‐free interval, previous chemotherapy, and nonlaryngeal sites of recurrence. When possible, surgical salvage remains the principal option for durable disease control, quality of life preservation, and cure. Nonsurgical therapies have also demonstrated measurable improvements in locoregional control. Interpretation of salvage literature must be tempered by recognition of significant selection bias. The decision for salvage therapy must be individualized, with management that involves well‐informed patients resulting in the best outcomes. © 2013 Wiley Periodicals, Inc. Head Neck 36: 144–151, 2014
Book Reviews
Authors: PROCITA LEONARD , Pelton E. Williams
Published: March 2013

Book reviewed in this article:

Clinical and Experimental Neurology. Proceedings of the Australian Association of Neurologists. J. H. Tyrer and M. J. Eadie

Psychopharmacology Update: New and Neglected Areas. J. M. Davis and D. Greenblatt
Adverse Effects of Commonly Ordered Oral Narcotics
Authors: KANTOR T. G. , HOPPER M. , LASKA E.
Published: March 2013

Abstract: Approximately equianalgesic oral doses of codeine, an oxycodone compound resembling Percodan, and pentazocine were compared for adverse effects in a double‐blind, randomized study of four doses of each drug given over two days to 247 postsurgical patients with pain. Placebo and parenteral morphine were also treated as negative and positive controls, respectively. Approximately 50 patients each received one of the five drugs. Codeine, pentazocine, and morphine had the same incidence of adverse effects (22 to 28 per cent). One capsule of oxycodone compound was the analgesic equivalent of 12.5 mg morphine with an adverse effect incidence of 4 per cent (placebo 8 per cent). Smoking made no difference in analgesic effect or adverse effects. Analgesics given in the evening intervening between the two days may have affected the analgesic performance of placebo.
The Effectiveness of Antihistamines in the Common Cold
Authors: CRUTCHER JAMES E. , KANTNER THEODORE R.
Published: March 2013

Abstract: A randomized, double‐blind, placebo‐controlled study was done on 106 volunteers to assess the effectiveness of chlorpheniramine maleate against the common cold. The results suggest that this antihistamine is significantly effective in relieving the symptoms of a cold if used four times daily for one week, and that relief was gained with no significant increase in side effects.
Multiple‐Dose Phase I Trials—Normal Volunteers or Patients? One Viewpoint
Authors: WEISSMAN LESTER
Published: March 2013

Abstract: Traditionally, Phase I tolerance trials have been done with normal volunteers to establish single‐ and multiple‐dose tolerance. We feel that the justification for doing multiple‐dose tolerance studies in normals is open to question and that, in fact, more pertinent data can be generated by using the appropriate patient populations for these studies.
Chenodeoxycholic Acid and Ursodeoxycholic Acid Effects in Endogenous Hypertriglyceridemias. A Controlled Double‐Blind Trial
Authors: CARULLI N. , de LEON M. PONZ , PODDA M. , ZUIN M. , STRATA A. , FRIGERIO G. , DIGRISOLO A.
Published: March 2013

Abstract: A double‐blind controlled trial was carried out to compare the effects of chenodeoxycholic acid (CDCA), ursodeoxycholic acid (UDCA), and placebo on cholesterol and triglyceride levels in patients with endogenous hypertriglyceridemias. The dose of both bile acids was four 150‐mg capsules a day. Total serum cholesterol levels did not show appreciable changes with any of the treatments. HDL cholesterol was significantly increased after CDCA but not after UDCA or placebo. CDCA feeding was associated with a significant decrease in serum triglyceride levels, whereas the other treatments failed to show an effect. It is concluded that UDCA does not affect serum lipid levels, whereas CDCA lowers serum triglycerides and may be useful in the treatment of endogenous hypertriglyceridemia.
Potentiation of Ampicillin Skin Reactions by Allopurinol or Hyperuricemia
Authors: JICK HERSHEL , PORTER JANE B.
Published: March 2013

Abstract: Of 4434 hospitalized medical patients who received ampicillin in the absence of allopurinol, 251 (5.9 per cent) developed a rash within 21 days of exposure. Of 252 patients who received ampicillin and allopurinol together, 35 (13.9 per cent) developed a rash. The present data confirm the previously reported increase in rash frequency in patients who receive both ampicillin and allopurinol.
Serum Binding of Diltiazem in Humans
Authors: BLOEDOW D. C. , PIEPHO R. W. , NIES A. S. , GAL J.
Published: March 2013

Abstract: Diltiazem binding was measured by equilibrium dialysis in the serum of five healthy male subjects, aged 22 to 34 years, at seven serum diltiazem concentrations ranging from 0.03 to 2.06 μg/ml. The percentage of unbound diltiazem ranged from 19.6 ± 3.1 to 22.6 ± 4.1 (mean ± S.D.) and was independent of serum diltiazem concentration. Serum diltiazem binding was also examined in the presence of six drugs that might be used concurrently with diltiazem in patients being treated for cardiac disease. The percentage of unbound diltiazem was not influenced by digoxin, hydrochlorothiazide, phenylbutazone, propranolol, salicylic acid, or warfarin at therapeutic concentrations of these drugs over the therapeutic range of diltiazem.
The Effect of Amiloride on the Renin—Aldosterone System in Primary Hyperaldosteronism and Bartter's Syndrome
Authors: GRIFFING GEORGE T. , AURECCHIA STEVEN A. , SINDLER BRUCE H. , MELBY JAMES C.
Published: March 2013

Abstract: Amiloride is a potassium‐sparing diuretic which has been advocated for the treatment of hypokalemic disorders. This agent was prospectively evaluated in hypokalemic patients with either primary hyperaldosteronism (ten patients) or Bartter's syndrome (five patients). Vital signs, electrolytes, and ambulatory hormonal studies were assessed during a control period and treatment period with amiloride therapy at 10 to 40 mg/day over two to 24 weeks. During the treatment period the systolic and diastolic blood pressure fell significantly in primary hyperaldosteronism but remained unchanged in Bartter's syndrome. In summary, amiloride therapy (1) increased plasma potassium in both diseases; (2) increased plasma renin activity (PRA) in primary hyperaldosteronism but decreased PRA in Bartter's syndrome; and (3) increased plasma aldosterone in both diseases. Since potassium is known to suppress renin production and stimulate aldosterone secretion, correction of the hypokalemia in this study probably accounts for the decreased PRA and increased plasma aldosterone observed in Bartter's syndrome. The increase in both PRA and plasma aldosterone in primary hyperaldosteronism, however, may be evidence of either a direct activation of the renin‐aldosterone system or, alternatively, may be due to the mild natriuretic effects of amiloride.
Slow‐Release Furosemide and Hydrochlorothiazide in Congestive Cardiac Failure: A Controlled Trial
Authors: VERMEULEN A. , CHADHA DEV R.
Published: March 2013

Abstract: Thirty‐eight ambulatory patients with congestive cardiac failure took part in a double‐blind clinical trial of 50 mg hydrochlorothiazide orally daily and slow‐release formulation of 60 mg furosemide orally daily. Following a one‐week period of placebo administration, patients were randomly allocated to the treatment which they continued for six weeks. Other diuretic drugs were discontinued at entry, but antihypertensive drugs and digoxin were continued during the study at constant dosage. A controlled sodium diet was prescribed. Clinical observations and biochemical and hematologic measurements were made before, during, and at the end of the study. There was an improvement in the clinical condition of patients in both treatment groups, but no significant difference between treatments (with or without digitalis) was detected. Both treatments were clinically well tolerated; however, the tendency of hypokalemia was more pronounced in the hydrochlorothiazide group. This could be hazardous in patients who receive a concomitant cardiac glycoside, especially when no clear‐cut benefit of concomitant digitalis therapy is demonstrated.
Quantitative Differences in Aspirin Analgesia in Three Models of Clinical Pain
Authors: LASKA EUGENE M. , SUNSHINE ABRAHAM , WANDERLING JOSEPH A. , MEISNER MORRIS J.
Published: March 2013

Abstract: An analysis was made of data from over 4000 postepisiotomy, uterine cramping, and postsurgical patients complaining of moderate or severe pain. They had received 325, 650, or 1300 mg aspirin or placebo while they were subjects in 10 analgesic clinical trials. On the average, for the same verbally expressed pain intensity level and the same treatment, more relief was obtained by a patient with uterine cramping than one with episiotomy pain, who in turn obtained more relief than a patient with surgical pain. A new mathematical model which characterizes the probability that an analgesic provides complete relief as a function of dose, severity of pain intensity, and pain etiology is developed. The model utilizes the data itself to estimate the numerical score corresponding to verbal pain intensities. The results indicate that the numerical score quantifying severe surgical pain is 1.4 times greater than the score for severe episiotomy pain, which in turn is 3.2 times greater than the score for severe uterine cramping. Clinical trials must be designed to take these differences into account. Also, clinicians must be cognizant of such differences when choosing among drugs and dosages for patients with different pain intensity and etiology.
Influence of Alcohol on the Pharmacokinetics of Diazepam Controlled‐Release Formulation in Healthy Volunteers
Authors: WILLS ROBERT J. , CROUTHAMEL WILLIAM G. , IBER FRANK L. , PERKAL MARK B.
Published: March 2013

Abstract: Twelve normal volunteers were empanelled in an open‐label, three‐way crossover study to evaluate the influence of alcohol on the pharmacokinetics of controlled‐release diazepam capsules. Each volunteer received one 15‐mg diazepam controlled‐release capsule alone, concomitantly with alcohol or followed by alcohol 2 hours later. The mean plasma concentration—time profiles following both alcohol treatments were superimposable on the profile from the control. The mean plateau concentrations were observed to endure from 2 through 12 hours in all cases. The mean ± S.D. areas under the plasma concentration—time curves from time zero to infinity were similar indicating no difference in the extent of absorption of diazepam in the presence of alcohol. The harmonic mean elimination half‐lives were also similar. Overall, the pharmacokinetics and the release properties of control led‐release diazepam capsule were not influenced by alcohol in normal volunteers.
Pharmacokinetic Equivalence of Stable—Isotope‐Labeled and Unlabeled Drugs. Phenobarbital in Man
Authors: BROWNE THOMAS R. , VAN LANGENHOVE AGNES , COSTELLO CATHERINE E. , BIEMANN KLAUS , GREENBLATT DAVID J.
Published: March 2013

Abstract: Stable isotope labeling of drugs has been used in human metabolism studies because it eliminates the risk of radiation exposure accompanying use of radioactive tracers. The labeled drug can be measured by gas‐chromatographic mass spectrometry (GCMS). However, if reliable pharmacokinetic data are to be obtained, one has to be certain the rate of metabolism of labeled and unlabeled drug is the same, i.e., there is no kinetic isotope effect. To evaluate this for phenobarbital (PB), three humans were infused with a 1:1 mixture of phenobarbital and 1,3‐15N2‐2‐13C‐PB. Serum was collected at regular intervals. Concentrations of labeled and unlabeled phenobarbital were determined by GCMS. Within each subject, there was no trend for concentrations of labeled phenobarbital to be higher or lower than concentrations of unlabeled phenobarbital (P > 0.90 for all three subjects). There was no difference in the zero time intercepts, distribution and elimination time constants and half‐lives, volumes of distribution and central compartment, or clearance of the two forms of phenobarbital. Thus, no isotope effect was found. Published data on other labeled drugs and the likelihood of encountering an isotope effect based on type of isotope and its location in the molecule are discussed.
Pharmacokinetics of Erythromycin in Normal and Alcoholic Liver Disease Subjects
Authors: HALL KEVIN W. , NIGHTINGALE CHARLES H. , GIBALDI MILO , NELSON EDWARD , BATES THEODORE R. , DISANTO ANTHONY R.
Published: March 2013

Abstract: The objective of this study was to compare the pharmacokinetic behavior of erythromycin in normal volunteers with that in subjects with alcoholic liver disease. Six normal volunteers received 500 mg erythromycin as an intravenous infusion or as two 250‐mg enteric‐coated tablets in a crossover fashion. The pharmacokinetics of erythromycin after intravenous administration was best described as a two‐compartment model. The elimination half‐life was 1.6 ± 0.7 hours (mean ± S.D.) after the intravenous dose and 2.0 ± 0.7 hours after the oral dose. In patients with alcoholic liver disease the elimination half‐life after oral administration of two 250‐mg enteric‐coated tablets was 3.2 ± 0.5 hours, significantly different from that in normal subjects, probably due to impaired metabolism. The difference in half‐life does not require dosage adjustment in this patient population. The systemic availability of erythromycin was 33.5 per cent (range 10.5 to 79.3 per cent).
Is Phosphodiesterase Inhibition Arrhythmogenic? Electrophysiologic Effects in Pithed Rats and in Normoxic and Hypoxic Rabbit Atria of Enoximone, a New Cardiotonic Agent
Authors: Williams E. M. Vaughan
Published: March 2013

The positive inotropic and chronotropic actions of enoximone were confirmed. At concentrations within the clinical range, enoximone prolonged the chronotropic and hypotensive action of isoproterenol in pithed rats. Very high doses of both enoximone and isoproterenol caused ventricular fibrillation in only one of six rats. In isolated rabbit atria, the maximum frequency at which pacing stimuli were followed 1:1 was increased by enoximone, and atrial flutter was consistently induced, then terminated by greatly suprathreshold stimulation. Enoximone significantly shortened action potential duration (APD), but did not exacerbate the APD‐shortening induced by hypoxia. Since such hypoxia‐induced shortening occurred in the presence of glucose 11 mmol/L and oxygen 20%, it was concluded that it was unlikely to have been caused by the opening of ATP‐regulated potassium channels. These animal experiments suggest that enoximone, at concentrations encountered clinically in humans, does not have any electrophysiologic actions that would be likely to increase the probability of arrhythmias.
Effect of a Sustained‐Release Formulation of Trimazosin in Mild to Moderate Hypertension
Authors: Byyny Richard L. , Nies Alan S. , LoVerde Mary E. , Mitchell Wayne D.
Published: March 2013

A single‐blind study was conducted to evaluate the blood pressure (BP) reduction and side effects of a sustained‐release (SR) formulation of trimazosin in patients with mild to moderate hypertension. Eighteen individuals (age, 21–65 yr; mean diastolic BP, >95 mm Hg) with essential hypertension were enrolled into the study. Each patient's dose was titrated to a range of 150–900 mg/d, with polythiazide added as necessary to achieve BP control Four hours following the maximum titrated dose of trimazosin, mean standing and supine diastolic BPs were significantly lower than baseline readings. Supine systolic BP and supine and standing heart rate were not significantly lower than baseline. At 24 hours after administration of the maximum dose, there were no significant differences in heart rate or BP compared with baseline readings. Five of 16 patients responded to trimazosin therapy alone. Of the 11 treatment failures with trimazosin alone, five were therapeutic failures and six discontinued because of side effects. Only two of these 11 patients achieved satisfactory results with the combination therapy. Trimazosin SR acutely lowers BP three to six hours after administration. It appears to have a duration of action longer than six hours, but it is not sustained for 24 hours. The proportion of patients failing to respond in this sample was very high and suggests that for similar patients, the drug does not appear to be a very useful antihypertensive agent.
Pharmacokinetics and Pharmacodynamic Effects of Aqueous Diltiazem in Healthy Humans
Authors: Fu Morgan , Hung Jui‐Sung , Yeh San‐Jou , Lin Fun‐Chung , Hsu Robert S. , Wu Delon
Published: March 2013

Aqueous diltiazem was given to ten healthy male volunteers in a single oral dose of 2.5 mg/kg body weight. Serum diltiazem levels were measured at various intervals up to 24 hours after administration of the drug as were blood pressure, heart rate, and PR interval. The pharmacokinetics followed a one‐compartment model in six and two‐compartment model in four subjects. The mean distribution half‐life in the latter four subjects was 15.8 ± 3.7 minutes (range, 10.4–18.8 min). In the ten subjects, the peak serum diltiazem level was attained in 20 to 45 minutes (mean, 32.5 ± 9.5 min) and ranged from 136 to 701 ng/mL (mean, 332 ± 180 ng/mL). The elimination half‐life ranged from 2.8 to 4.8 hours (mean, 3.8 ± 0.6 hr). The area under the concentration‐time curve varied from 508 to 2,245 ng‐hr/mL, indicating differing bioavailability. Slight but significant blood pressure reduction was seen only at one to three hours. Changes in heart rate were not significant at any measurement. Transient facial flushing, beginning at ten to 20 minutes after administration, was noted in nine subjects, reflecting the vasodilatory effect of the drug. Significant prolongation (>10%) of PR intervals began at ten minutes in three, at 20 minutes in six, and at 30 minutes in one participant, and progressed to second‐degree Wenckebach atrioventricular (AV) block in six subjects 20 to 60 minutes after administration and third‐degree AV block in one person 45 minutes after dosing. These AV blocks resolved by the third hour without treatment, and PR prolongation resolved by the fifth to seventh hours. Significant PR prolongation was not observed in any subject when the serum diltiazem level was less than 30 ng/mL. In each subject, suppressive effects on the AV node correlated well with the serum diltiazem level. However, there was individual variability in response of the AV node to diltiazem.
Pharmacokinetics of Nilvadipine in Healthy Volunteers
Authors: Terakawa Masato , Tokuma Yoji , Shishido Akira , Noguchi Hideyo
Published: March 2013

The pharmacokinetics of nilvadipine, a new antihypertensive and antianginal drug, were examined in healthy male volunteers. In a Latin square, three‐way crossover design with a one‐day run‐in period, six subjects in three groups of two each were given single 2‐, 4‐, or 6‐mg oral doses of nilvadipine after overnight fasting. Nilvadipine plasma concentrations up to 32 hours after drug treatment were determined by capillary column gas chromatography‐negative‐ion chemical ionization mass spectrometry (detection limit, 0.01 ng/mL). Nilvadipine urinary concentrations were determined by capillary column gas chromatography with electron capture detector (detection limit, 0.5 ng/mL). Nilvadipine plasma concentrations declined in a bi‐ or triexponential pattern after reaching the maximum plasma concentrations. The mean ± standard deviation maximum plasma concentrations of 1.48 ± 0.47, 3.48 ± 0.53, and 6.69 ± 1.54 ng/mL were attained from 1.08 to 1.50 hours after doses of 2, 4, and 6 mg, respectively. The elimination half‐life was dose‐independent and averaged 11.0 ± 2.3 hours. The area under the plasma concentration‐time curve increased in proportion to the dose. Nilvadipine was not detected in the urine. The pharmacokinetics of nilvadipine were generally linear over the dosage range studied. Besides the above model‐independent pharmacokinetic parameters, model‐dependent parameters were also obtained by curve‐fitting the plasma data to a bi‐ or triexponential equation with zero‐order absorption. Nilvadipine decreased blood pressure slightly and in a dose‐dependent fashion.
Bioavailability Evaluation of a Controlled‐Release Dextromethorphan Liquid
Authors: Woodworth James R. , Dennis Susana R. K. , Hinsvark Orville N. , Amsel Lewis P. , Rotenberg Keith S.
Published: March 2013

A randomized, two‐way, steady‐state crossover study was performed in 24 healthy male volunteers to evaluate the bioavailability of a controlled‐release (CR) dextromethorphan (DM) suspension. Only slow and intermediate DM metabolizers were allowed to participate in the study; determination of metabolizer status was performed before study enrollment Each volunteer was administered 30 mg of an immediate‐release (IR) DM solution qid or 60 mg DM as a CR suspension bid for two weeks, for a total daily dose of 120 mg. After a two‐week washout period, the subjects were administered the alternate treatment. Blood samples were collected over a 12‐hour dosing period on the last day of each treatment and analyzed for DM and its active metabolite, dextrorphan (DP). In addition, urine was collected oyer the 12‐hour steady‐state dosing interval and measured for DM and two metabolites. Pharmacokinetic determinations were made from plasma DM and DP data, and total urinary excretion was determined. All comparisons made between the two formulations indicated that the CR DM suspension was bioequivalent to the IR DM solution at steady state, while producing a prolonged release of the drug over time.
The Acute Effects of the Enkephalin Analogue BW 942C in Humans
Authors: Boucher Bradley A. , Foster Thomas S. , Phillips Barbara A. , Fleck Richard J. , Kirksey Donny F. , Cato Allen E.
Published: March 2013

BW 942C hydrochloride is an enkephalin analogue that has exhibited a wide separation between antidiarrheal dosages and dosages inducing adverse effects in animals. This has likewise been the case in humans when administered orally. In this study, the safety and tolerance of single 0.5‐mg doses of intravenous BW 942C compared with placebo were assessed in humans. Four healthy male volunteers received BW 942C, and two received placebo. The effects of BW 942C on serum growth hormone (GH), luteinizing hormone (LH), prolactin (PR), and follicle‐stimulating hormone (FSH) were assessed in three of these volunteers. No significant changes were apparent in vital signs, in clinical chemistry, hematologic and urine studies following BW 942C administration. BW 942C did not appear to alter mood as assessed by two psychologic mood scales. Prolactin levels tended to increase in volunteers receiving BW 942C two hours postinfusion. Luteinizing hormone concentrations decreased slightly at two and six hours. No trends in FSH or GH could be identified. Pulmonary function testing did not reveal any significant changes in oximetry, spirometry, or plethysmography in any of the subjects. A marked decrease in CO2 responsiveness in two subjects may indicate that BW 942C has mild ventilatory depressant effects. Untoward effects experienced in volunteers receiving BW 942C included heaviness in the limbs, nasal stuffiness, mouth dryness, facial flushing, skin rash, and prickling sensations. These effects bear a striking similarity to those experienced after parenteral administration of other enkephalin analogues. Intravenous administration of BW 942C up to 0.5 mg appears safe from a laboratory, physiologic, and clinical perspective with unusual untoward effects that may preclude rational use of the drug by the parenteral route.
Management of Cancer Pain With Oral Controlled‐Release Morphine Sulfate
Authors: Meed Steven D. , Kleinman Phyllis M. , Kantor Thomas G. , Blum Ronald H. , Savarese John J.
Published: March 2013

Morphine sulfate Contin (MSC) is an investigational matrix delivery system for oral morphine sulfate that allows for prolonged blood levels of morphine. Twenty‐six patients with inadequately controlled cancer‐related pain were examined in an open but controlled study using MSC. Initially, all patients were converted from the prestudy analgesic regimen to an equianalgesic amount of immediate‐release morphine sulfate (IRMS) on a q4h dose schedule that was in turn titrated to the level of adequate pain relief. Patients then were switched to MSC q8h and eventually to q12h, starting at doses representing the same total daily amount of morphine that was in the final IRMS dose. Of the 18 patients who completed the study, all achieved satisfactory levels of analgesia on MSC, seven at q8h and 11 at q12h dosing intervals. All patients reported better analgesia while taking MSC compared with their previous regimen. Side effects associated with MSC included sedation and constipation but not nausea or respiratory difficulty. Significant drug tolerance did not develop during a mean follow‐up period of four weeks (range, 1–18 weeks). MSC is an effective oral opioid analgesic that allows an increased dose interval without increased side effects or decreased potency. It can improve the quality of life of cancer patients by allowing them to be maintained without frequent dosing or parenteral medication.