bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis, Characterization and Cytotoxicity of Diam(m)‐ineplatinum(II) Complexes Containing β‐phenylisosuccinate Ligand
Authors: Ye Qing‐Song , Lou Li‐Guang , Liu Zuo‐Yan , Liu Wei‐Ping , Hou Shu‐Qian , Chen Xi‐Zhu , Yu Yao
Published: October 2007

Four diam(m)ineplatinum(II) complexes containing β‐phenylisosuccinate as the leaving groups were prepared, characterized, and evaluated for their cytotoxicity against A549/ATCC human lung cancer cell line and SGC‐7901 human gastric cancer cell line. One of the complexes, (trans‐1R,2R‐diaminocyclohexane)‐β‐phenylisosuccinatoplatinum(II) 4, was much more active than cisplatin and carboplatin.
Synthesis and In Vitro Protozoocidal Evaluation of Novel Diazabicyclic Tropolone Derivatives
Authors: Khrizman Alexander , Slack Rachel D. , Remsing Richard C. , Little Susan , Yardley Vanessa , Moyna Guillermo
Published: October 2007

The synthesis and in vitro antiparasitic activity of twenty‐seven novel diazabicycles based on tropolone ethers is presented. The compounds can be readily prepared by means of a high‐yielding hetero Diels–Alder reaction using simple and readily available starting materials. Several of the new diazabicycles have in vitro activities against Trypanosoma cruzi, Leishmania donovani, Trypanosoma brucei rhodesiense, and chloroquine‐resistant Plasmodium falciparum that are comparable or superior to those of currently employed protozoocidal agents.
Design and Synthesis of Isocyanide Ligands for Catalysis: Application to Rh‐Catalyzed Hydrosilylation of Ketones
Authors: Ito Hajime , Kato Takayuki , Sawamura Masaya
Published: October 2007

New isocyanide ligands with meta‐terphenyl backbones were synthesized. 2,6‐Bis[3,5‐bis(trimethylsilyl)phenyl]‐4‐methylphenyl isocyanide exhibited the highest rate acceleration in rhodium‐catalyzed hydrosilylation among other isocyanide and phosphine ligands tested in this study. 1H NMR spectroscopic studies on the coordination behavior of the new ligands to [Rh(cod)2]BF4 indicated that 2,6‐bis[3,5‐bis(trimethylsilyl)phenyl]‐4‐methylphenyl isocyanide exclusively forms the biscoordinated rhodium–isocyanide complex, whereas less sterically demanding isocyanide ligands predominantly form tetracoordinated rhodium–isocyanide complexes. FTIR and 13C NMR spectroscopic studies on the hydrosilylation reaction mixture with the rhodium–isocyanide catalyst showed that the major catalytic species responsible for the hydrosilylation activity is the Rh complex coordinated with the isocyanide ligand. DFT calculations of model compounds revealed the higher affinity of isocyanides for rhodium relative to phosphines. The combined effect of high ligand affinity for the rhodium atom and the bulkiness of the ligand, which facilitates the formation of a catalytically active, monoisocyanide–rhodium species, is proposed to account for the catalytic efficiency of the rhodium–bulky isocyanide system in hydrosilylation.
Economic impacts of bio‐refinery and resource cascading systems: An applied general equilibrium analysis for Poland
Authors: Ignaciuk Adriana M. , Sanders Johan
Published: October 2007

Due to more stringent energy and climate policies, it is expected that many traditional chemicals will be replaced by their biomass‐based substitutes, bio‐chemicals. These innovations, however, can influence land allocation since the demand for land dedicated to specific crops might increase. Moreover, it can have an influence on traditional agricultural production. In this paper, we use an applied general equilibrium framework, in which we include two different bio‐refinery processes and incorporate so‐called cascading mechanisms. The bio‐refinery processes use grass, as one of the major inputs, to produce bio‐nylon and propane‐diol (1,3PDO) to substitute currently produced fossil fuel‐based nylon and ethane‐diol. We examine the impact of specific climate policies on the bioelectricity share in total electricity production, land allocation, and production quantities and prices of selected commodities. The novel technologies become competitive, with an increased stringency of climate policies. This switch, however, does not induce a higher share of bioelectricity. The cascade does stimulate the production of bioelectricity, but it induces more of a shift in inputs in the bioelectricity sector (from biomass to the cascaded bio‐nylon and 1, 3PDO) than an increase in production level of bioelectricity. We conclude that dedicated biomass crops will remain the main option for bioelectricity production: the contribution of the biomass systems remains limited. Moreover, the bioelectricity sector looses a competition for land for biomass production with bio‐refineries.
Biobutanol: An attractive biofuel
Authors: Dürre Peter
Published: October 2007

Biofuels are an attractive means to prevent a further increase of carbon dioxide emissions. Currently, gasoline is blended with ethanol at various percentages. However, butanol has several advantages over ethanol, such as higher energy content, lower water absorption, better blending ability, and use in conventional combustion engines without modification. Like ethanol, it can be produced fermentatively or petrochemically. Current crude oil prices render the biotechnological process economic again. The best‐studied bacterium to perform a butanol fermentation is Clostridium acetobutylicum. Its genome has been sequenced, and the regulation of solvent formation is under intensive investigation. This opens the possibility to engineer recombinant strains with superior biobutanol‐producing ability.
Monolayer cell expansion conditions affect the chondrogenic potential of adipose‐derived stem cells
Authors: Estes Bradley T. , Diekman Brian O. , Guilak Farshid
Published: October 2007

Adipose‐derived stem cells (ASCs) are an abundant, readily available population of multipotent progenitor cells that reside in adipose tissue. Isolated ASCs are typically expanded in monolayer on standard tissue culture plastic with a basal medium containing 10% fetal bovine serum. However, recent data suggest that altering the monolayer expansion conditions by using suspension culture plastic, adding growth factors to the medium, or adjusting the seeding density may affect the self‐renewal rate, multipotency, and lineage‐specific differentiation potential of the ASCs. We hypothesized that variation in any of these expansion conditions would influence the chondrogenic potential of ASCs. ASCs were isolated from human liposuction waste tissue and expanded through two passages with different tissue culture plastic, feed medium, and cell seeding densities. Once expanded, the cells were cast in an agarose gel and subjected to identical chondrogenic culture conditions for 7 days, at which point cell viability, radiolabel incorporation, and gene expression were measured. High rates of matrix synthesis upon chondrogenic induction were mostly associated with smaller cells, as indicated by cell width and area on tissue culture plastic, and it appears that expansion in a growth factor supplemented medium is important in maintaining this morphology. All end‐point measures were highly dependent on the specific monolayer culture conditions. These results support the hypothesis that monolayer culture conditions may “prime” the cells or predispose them towards a specific phenotype and thus underscore the importance of early culture conditions in determining the growth and differentiation potential of ASCs. Biotechnol. Bioeng. 2008; 99; 986–995. © 2007 Wiley Periodicals, Inc.
Study of Modification Pattern–RNAi Activity Relationships by Using siRNAs Modified with 4′‐Thioribonucleosides
Authors: Hoshika Shuichi , Minakawa Noriaki , Shionoya Aki , Imada Keiko , Ogawa Naoki , Matsuda Akira
Published: October 2007

A detailed study of the modification pattern–RNAi activity relationships by using siRNAs that are modified with 4′‐thioribonucleosides has been carried out against photinus luciferase and renilla luciferase genes in cultured mammalian NIH/3T3, HeLa, and MIA PaCa‐2 cell lines. When the photinus luciferase gene was targeted, all of the modified siRNAs showed activity equal to, or less than the unmodifed siRNA. In contrast, all modified siRNAs that have a similar modification pattern showed activity equal to or much higher than the unmodified siRNA when tested with the renilla luciferase gene. These results indicated that siRNAs such as RNA33 and RNA53, which each have four residues of the 4′‐thioribonucleoside unit on both ends of the sense strand and four residues on the 3′‐end of the antisense strand, were the most effective. Accordingly, we succeeded in developing modified siRNAs that have the greatest number of 4′‐thioribonucleosides without loss of RNAi activity, and that exhibit potent RNAi activity against two target genes in three different cell lines. Our findings also indicate the significance of target sequences and cell lines when RNAi activity is compared with that of the unmodified siRNA.
Randomized, double‐blind, multicenter study of the polymer‐based 17‐β estradiol‐eluting stent for treatment of native coronary artery lesions: Six‐month results of the ETHOS I trial
Authors: Abizaid Alexandre , Chaves Áurea J. , Leon Martin B. , Hauptmann Karl , Mehran Roxana , Lansky Alexandra J. , Baumbach William , Shankar Hari , Muller Ralf , Feres Fausto , Sousa Amanda G.M.R. , Sousa J. Eduardo , Grube Eberhard
Published: October 2007

Objectives: The ETHOS I trial was the first in‐human experience evaluating the safety and efficacy of two different release formulations of the 17‐β estradiol‐eluting R‐Stent™ versus uncoated control stents for the treatment of patients with single de novo native coronary lesions. Background: Estrogens were reported to inhibit neointimal proliferation and to accelerate endothelial regeneration after coronary angioplasty and thus could be an ideal compound to deliver on a stent for the purpose of reducing in‐stent restenosis. Methods: Ninety‐five patients were randomized to receive a slow‐release (n = 32) or the moderate release (n = 31) formulations or the bare metal stent (n = 32). The primary end point was the 6‐month percent in‐stent volume obstruction by intravascular ultrasound (IVUS). Results: Diabetes was present in 29.5% of patients; the mean reference vessel diameter was 2.90 mm; and the mean lesion length was 13.5 mm. Primary endpoint, 6‐month percent in‐stent volume obstruction by IVUS, did not differ significantly between the 3 groups (31% ± 14%, 33% ± 11%, and 31% ± 14%, P = 0.83). Secondary endpoints also did not differ significantly between the groups including 6‐month rates of in‐lesion binary angiographic restenosis (13.3%, 14.3%, and 12.5%, P = 0.98), in‐stent late loss (0.82 ± 0.49 mm, 0.86 ± 0.53 mm, and 0.84 ± 0.46 mm, P = 0.97), target lesion revascularization (12.5%, 6.9%, and 6.5%, P = 0.64), and major adverse cardiac events (18.8%, 10.3%, and 6.5%, P = 0.31). Conclusions: In this first‐in‐man randomized trial, the 17‐β estradiol‐eluting R‐Stent™, in either slow‐ or moderate‐release formulations, was well‐tolerated, but showed no benefit for treatment of coronary lesions when compared to controls. © 2007 Wiley‐Liss, Inc.
Dislodged caval stent in right pulmonary artery
Authors: Chiu Kuan‐Ming , Chu Shu‐Hsun , Chan Chih‐Yang
Published: October 2007

Percutaneous intervention for central vein occlusion is getting popular. Self‐expandable stent is user‐friendly in this field, however, jump‐out displacement may happen. An 82‐year‐old woman with end‐stage renal disease and central vein occlusion underwent central vein stenting. Dislodgement of the self‐expandable stent was encountered. Migration into right ventricle and subsequently right pulmonary artery was noted. Chest films of this rare condition were reported. © 2007 Wiley‐Liss, Inc.
Long‐term effects of balloon angioplasty on left ventricular hypertrophy in adolescent and adult patients with native coarctation of the aorta. Up to 18 years follow‐up results
Authors: Hassan Walid , Awad Mahmoud , Fawzy Mohamed Eid , Omrani Ahmad Al , Malik Shahid , Akhras Nathem , Shoukri Mohamed
Published: October 2007

Background:

Little is known regarding the long‐term follow‐up results of balloon angioplasty (BA) for patients with native aortic coarctation (AC) on left ventricular hypertrophy (LVH) regression.

Objectives:

The purpose of this study was to define the long‐term effect of BA of AC on LVH in adolescent and adult patients.

Methods:

Follow‐up data of 53 patients (36 male) mean age 24 ± 9 years undergoing BA for discrete AC at median interval of 11.8 years (range 4–18 years) including cardiac catheterization, magnetic resonance imaging, and Echocardiography form the basis of this study. Patients were divided into two groups at 1 year after BA based on absence (group A) or presence (group B) of persistent hypertension and need for medication.

Results:

Forty‐nine patients had baseline LVH, BA produced an immediate reduction in peak AC gradient from 66 ± 23 mm Hg (95% confidence interval [CI]: 59.5–72.7) to 10.8 ± 7 mm Hg (95% CI: 8.8–12.5) (P < 0.0001). Follow‐up catheterization 12 months later revealed a residual gradient of 6.2 ± 6 mm Hg (95% CI: 4.4–7.9) (P < 0.001). The blood pressure had normalized without medication in 38 of the 49 patients (165 ± 17 to 115 ± 10 mm Hg). Left ventricular mass index (LVMI) decreased significantly (>20% decrease LVMI from baseline) in 48 patients (98%) at median interval 1.4 years (range 0.5–3 years) post BA, group A (38 patients) LVMI decreased from 132 ± 30.7 g/m2 (95% CI: 122–141.9) to 86 ± 19.9 g/m2 (95% CI: 79.5–92.5) (P < 0.0001). Similarly, in 10 patients (group B) the LVMI decreased from 157 ± 38.7 g/m2 (95% CI: 127–185) to 102 ± 29 g/m2 (95% CI: 105–151) (P < 0.0001) at follow‐up. Mild (<20% decrease in LVMI) regressions were noted in one patient from group B. There was no progression to LVH in the four patients who had normal baseline LVMI.

Conclusion:

(1) Long‐term results of BA for discrete AC are excellent and should be considered as first option for treatment of this disease; (2) Regression of LVH (≥20% reduction in LVMI) occurred in 98% of patients after BA. © 2007 Wiley‐Liss, Inc.
Living Photolytic Ring‐Opening Polymerization of Amino‐Functionalized [1]Ferrocenophanes: Synthesis and Layer‐by‐Layer Self‐Assembly of Well‐Defined Water‐Soluble Polyferrocenylsilane Polyelectrolytes
Authors: Wang Zhuo , Masson Georgeta , Peiris Frank C. , Ozin Geoffrey A. , Manners Ian
Published: October 2007

Facile synthetic routes have been developed that provide access to cationic and anionic water‐soluble polyferrocenylsilane (PFS) polyelectrolytes with controlled molecular weight and narrow polydispersity. Living photolytic ring‐opening polymerization of amino‐functionalized [1]ferrocenophane (fc) monomers [fcSiMe{CCCH2N(SiMe2CH2)2}] (3), [fcSi{CCCH2N(SiMe2CH2)2}2] (10), [fcSiMe(CCCH2NMe2)] (14), and [fcSiMe(p‐C6H4CH2NMe2)] (20) yielded the corresponding polyferrocenylsilanes [(fcSiMe{CCCH2N(SiMe2CH2)2})n](5), [(fcSi{CCCH2N(SiMe2CH2)2}2)n] (11), [{fcSiMe(CCCH2NMe2)}n] (15), and [{fcSiMe(p‐C6H4CH2NMe2)}n] (21) with controlled architectures. Further derivatization of 5, 15, and 21 generated water‐soluble polyelectrolytes [(fcSiMe{CCCH2N(CH2CH2CH2SO3Na)2})n] (6), [{fcSiMe(CCCH2NMe3OSO3Me)}n] (7), and [{fcSiMe(p‐C6H4CH2NMe3OSO3Me)}n] (22), respectively. The polyelectrolytes were readily soluble in water and NaCl aqueous solutions, with 6 and 22 exhibiting long‐term stability in aqueous media. The PFS materials 6 and 22, have been utilized in the layer‐by‐layer (LbL) self‐assembly of electrostatic superlattices. Our preliminary studies have indicated that films made from controlled low molecular‐weight PFSs possess a considerably thinner bilayer thickness and higher refractive index than those made from PFSs that have an uncontrolled high molecular‐weight. These results suggest that the structure and optical properties of LbL ultra‐thin films can be tuned by varying polyelectrolyte chain length. The water‐soluble low molecular weight PFSs are also useful materials for a range of applications including LbL self‐assembly in highly confined spaces.
Reinforced Self‐Assembly of Hexa‐peri‐hexabenzocoronenes by Hydrogen Bonds: From Microscopic Aggregates to Macroscopic Fluorescent Organogels
Authors: Dou Xi , Pisula Wojciech , Wu Jishan , Bodwell Graham J. , Müllen Klaus
Published: October 2007

Hexa‐peri‐hexabenzocoronene derivatives (HBCs) that have hydrogen‐bonding functionalities (either amido or ureido groups) adjacent to the aromatic cores have been synthesized to study the effects of intracolumnar hydrogen bonds on the self‐assembly behavior of HBCs. The hydrogen bonds effectively increased the aggregation tendency of these compounds in solution. In the bulk state, the typical columnar supramolecular arrangement of HBCs was either stabilized substantially (1 a, 1 b, 2 a, and 2 b), or suppressed by dominant hydrogen‐bonding interactions (3). For some of the compounds (1 a, 2 a, and 2 b), the supramolecular arrangement adopted in the liquid‐crystalline state was even retained after annealing, presumably owing to the reinforcement of the π‐stacking interactions by the hydrogen bonds. Additionally, the combined effect of the hydrogen bonds and π‐stacking of the aromatic moieties led to the formation of fluorescent organogels, whereby some derivatives were further investigated as novel low molecular‐mass organic gelators (LMOGs).
Synthesis of 4‐Aminotropones from [(Sulfinyl or Sulfonyl)methyl]‐Substituted p‐Quinamines
Authors: Carreño M. Carmen , Ortega‐Guerra Montserrat , Ribagorda María , Sanz‐Cuesta M. Jesús
Published: October 2007

An efficient synthesis of 4‐aminotropones has been achieved in excellent yields by simple treatment of 4‐amino‐4‐[(p‐tolylsulfinyl)methyl]‐2,5‐cyclohexadienones (p‐quinamines) with NaH. The method allowed regiocontrolled access to 3‐methyl, 5‐methyl‐ and 3,5‐dimethyl‐substituted derivatives starting from p‐quinamines with adequate substituents at the cyclohexadienone moiety and/or at the carbon linked to the sulfur function. The p‐quinamines in turn were easily accessible from N‐Boc p‐anisidines (Boc=tert‐butoxycarbonyl) by electrochemical oxidation in MeOH to quinone imine monoketals, followed by addition of a α‐lithium sulfinyl carbanion to the imino group, and ketal hydrolysis. Oxidation of the sulfoxide gave the sulfonyl‐substituted p‐quinamines that, upon basic treatment, behave similarly. The p‐quinamine 55 and bis‐p‐quinamine 56, resulting in the addition of the anion derived from dimethyl sulfone to the p‐quinonimine ketal 14, also gave the 4‐aminotropone. The mechanism involves the initial formation of a α‐sulfonyl carbanion, which intramolecularly attacks the cyclohexadienone giving a norcaradiene‐like enolate intermediate, the evolution of which through a ring‐expansion process, pushes off a methyl sulfinate anion or SO2. This efficient process fulfils the criteria of atom economy. The introduction of a proline substituent in the nitrogen of the starting p‐quinamine allowed the synthesis of an enantiopure 4‐aminotropone, the asymmetric Diels–Alder reactions of which with maleimide occurred in a highly endo and π‐facial diastereoselective manner.
The use of circular dichroism spectroscopy for studying the chiral molecular self‐assembly: An overview
Authors: Gottarelli Giovanni , Lena Stefano , Masiero Stefano , Pieraccini Silvia , Spada Gian Piero
Published: October 2007

Self‐assembly plays an important role in the formation of many chiral biological structures and in the preparation of chiral functional materials. Therefore the control of chirality in synthetic or biological self‐assembled systems is important either for the comprehension of recognition phenomena or to obtain materials with predictable and controllable properties. Circular dichroism was developed to study molecular chirality, however, because of its outstanding sensitivity to chiral perturbations of the system under investigation; it has been extended more recently to supramolecular chemistry. In particular, self‐assembly processes leading to the formation of chiral supramolecular architectures (and eventually to gels or liquid crystal phases) can be monitored by CD. Furthermore, CD spectroscopy often allows one to obtain structural information on the assembled structures. This review deals with representative contributions to the study of supramolecular chirality by means of circular dichroism. Chirality, 2008. © 2007 Wiley‐Liss, Inc.
The use of X‐ray crystallography to determine absolute configuration
Authors: Flack H. D. , Bernardinelli G.
Published: October 2007

Essential background on the determination of absolute configuration by way of single‐crystal X‐ray diffraction (XRD) is presented. The use and limitations of an internal chiral reference are described. The physical model underlying the Flack parameter is explained. Absolute structure and absolute configuration are defined and their similarities and differences are highlighted. The necessary conditions on the Flack parameter for satisfactory absolute‐structure determination are detailed. The symmetry and purity conditions for absolute‐configuration determination are discussed. The physical basis of resonant scattering is briefly presented and the insights obtained from a complete derivation of a Bijvoet intensity ratio by way of the mean‐square Friedel difference are exposed. The requirements on least‐squares refinement are emphasized. The topics of right‐handed axes, XRD intensity measurement, software, crystal‐structure evaluation, errors in crystal structures, and compatibility of data in their relation to absolute‐configuration determination are described. Characterization of the compounds and crystals by the physicochemical measurement of optical rotation, CD spectra, and enantioselective chromatography are presented. Some simple and some complex examples of absolute‐configuration determination using combined XRD and CD measurements, using XRD and enantioselective chromatography, and in multiply‐twinned crystals clarify the technique. The review concludes with comments on absolute‐configuration determination from light‐atom structures. Chirality, 2008. © 2007 Wiley‐Liss, Inc.
Why is it important to simultaneously use more than one chiroptical spectroscopic method for determining the structures of chiral molecules?
Authors: Polavarapu Prasad L.
Published: October 2007

In recent years, four different chiroptical spectroscopic methods, namely vibrational circular dichroism, vibrational Raman optical activity, electronic circular dichroism, and optical rotatory dispersion, have become popular for establishing the absolute configuration and predominant conformations of chiral molecules in solution state. Many individual laboratories normally utilize only one of these methods to derive the molecular structural information. Although that approach may be satisfactory for most of the molecules studied, it is to be noted that in some instances a single method can give ambiguous conclusions or may not give complete structural information. This article summarizes the situations where simultaneous use of more than one chiroptical spectroscopic method is required to obtain molecular structural information and recommends the routine application of more than one chiroptical spectroscopic method for any given molecule. Chirality, 2008. © 2007 Wiley‐Liss, Inc.
Absolute configuration of tropane alkaloids bearing two α,β‐unsaturated ester functions using electronic CD spectroscopy: Application to (R,R)‐trans‐3‐hydroxysenecioyloxy‐6‐senecioyloxytropane
Authors: Humam Munir , Christen Philippe , Muñoz Orlando , Hostettmann Kurt , Jeannerat Damien
Published: October 2007

The absolute configuration of heterocyclic natural products substituted with two mobile α,β‐unsaturated esters was studied using electronic circular dichroism (CD) spectroscopy. The conformational flexibility of the side chains imposed the use of density functional theory calculation to determine the set of the most probable conformations in solution. The electronic CD and UV spectra were calculated by Boltzmann‐weighted average of the simulated spectra using the results of the excited states calculation of a set of simplified structures. Comparison with the experimental CD spectrum allowed to determine whether the calculations were made with the right enantiomer. The method was applied to the determination of the absolute configuration of (R,R)‐trans‐3‐hydroxysenecioyloxy‐6‐senecioyloxytropane. Chirality, 2007. © 2007 Wiley‐Liss, Inc.
Structure–chiroptical properties relationship in clavams: An experimental and theoretical study
Authors: Chmielewski Marek , Cierpucha Maciej , Kowalska Patrycja , Kwit Marcin , Frelek Jadwiga
Published: October 2007

It is well known that the biological activity of clavams depends strongly on the absolute configuration at the ring junction carbon atom. Therefore, development of the efficient stereo‐controlled synthetic methods for the new oxygen analogs of penams, and the structure−activity relationship studies call for a reliable determination of the absolute stereochemistry of newly synthesized compounds. Recently, we proposed an empirical helicity rule relating the configuration of the bridgehead carbon atom to the sign of the 240 nm band observed in the electronic circular dichroism (ECD) spectrum of clavams. In the present work, we investigate the validity of this structure–property relationship for several enantiomeric pairs of model compounds possessing an additional, interfering chromophore in the molecule. For this purpose a combination of the ECD spectroscopy and the time‐dependent density functional theory (TD‐DFT) is used. A comparison of the ECD spectra with the theoretical ones obtained by the TD‐DFT calculations gives a reasonable interpretation of the Cotton effects observed in the 250–220 nm spectral range. Moreover, the calculations confirm validity of the helicity rule for systems studied here and demonstrate that ECD spectroscopy may be used as a highly sensitive probe of the three‐dimensional molecular structure of clavams. Chirality, 2008. © 2007 Wiley‐Liss, Inc.
Mu Opioid Receptor Antagonists: Recent Developments
Authors: Goodman Allan J. , Le Bourdonnec Bertrand , Dolle Roland E.
Published: October 2007

For thousands of years mu opioid agonists such as morphine have been utilized for their analgesic properties. Today, morphine and related compounds are still used as a first line therapy in the treatment of moderate to severe pain. However, despite the clear benefits of mu agonists in pain management, severe side effects such as dependence and respiratory depression are associated with use of these drugs. To date, there are only two approved mu opioid antagonists for use in the treatment of these adverse effects, that is, naloxone and naltrexone. However, many other clinical and therapeutic areas have been linked to mu opioid receptor antagonism. These include treatment of opioid induced pruritis of the skin, obesity, and Parkinson‐induced tardive dyskinesia. Currently there are two compounds,N‐methylnaltrexone and alvimopan, under FDA review as possible treatments for opioid induced bowel dysfunction and postoperative ileus. These compounds are of special interest as they are peripherally restricted. This attribute enables treatment of peripheral side effects induced by opioid agonists without reversal of the centrally mediated analgesia of the agonist. In this article we discuss the structural classes of mu opioid antagonists, their potential clinical applications, and review the relevant patents of the last ten years.
Organometallic Ruthenium Inhibitors of Glutathione‐S‐Transferase P1‐1 as Anticancer Drugs
Authors: Ang Wee Han , De Luca Anastasia , Chapuis‐Bernasconi Catherine , Juillerat‐Jeanneret Lucienne , Lo Bello Mario , Dyson Paul J.
Published: October 2007

Ruthenium–arene complexes conjugated to ethacrynic acid were prepared as part of a strategy to develop novel glutathione‐S‐transferase (GST) inhibitors with alternate modes of activity through the organometallic fragment, ultimately to provide targeted ruthenium‐based anticancer drugs. Enzyme kinetics and electrospray mass spectrometry experiments using GST P1‐1 and its cysteine‐modified mutant forms revealed that the complexes are effective enzyme inhibitors, but they also rapidly inactivate the enzyme by covalent binding at Cys 47 and, to a lesser extent, Cys 101. They are highly effective against the GST Pi‐positive A2780 and A2780cisR ovarian carcinoma cell lines, are among the most effective ruthenium complexes reported so far, and target ubiquitous GST Pi overexpressed in many cancers.
The medicare modernization act and reimbursement for outpatient chemotherapy
Authors: Friedman Joeëlle Y. , Curtis Lesley H. , Hammill Bradley G. , Dhillon Jatinder K. , Weaver Charles H. , Biswas Sugata , Abernethy Amy P. , Schulman Kevin A.
Published: October 2007

BACKGROUND.

The primary objectives were to measure and compare time to initiation of chemotherapy for patients undergoing treatment either before or after the enactment of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA), and to measure and compare the location of care for patients undergoing chemotherapy either before or after the enactment of the MMA.

METHODS.

A Web‐based survey was conducted of a convenience sample of patients with cancer.

RESULTS.

A total of 1421 respondents completed the survey, 684 in the pre‐MMA group and 737 in the post‐MMA group. Respondents aged ≥65 years in both the pre‐MMA and post‐MMA groups had a median waiting time to chemotherapy of 3.0 weeks (P = .74). Most respondents aged ≥65 years received chemotherapy in outpatient hospital infusion centers or centers affiliated with private practices (73% in the pre‐MMA group vs 62% in the post‐MMA group; P = .02). However, in multivariate analysis there was no statistically significant difference in treatment location between the pre‐MMA and post‐MMA cohorts.

CONCLUSIONS.

Overall, the findings do not support generalizations from anecdotal reports that patients have been affected by the change in reimbursement to oncologists for chemotherapy as a result of the MMA. The analysis may be confounded by payments to physicians in the concurrent Centers for Medicare and Medicaid Services cancer demonstration project because these payments may have delayed changes in care. Moreover, research is needed to examine the effects of the legislation on vulnerable populations. Cancer 2007 © 2007 American Cancer Society.
Decision analysis to assess the efficacy of routine sentinel lymphadenectomy in patients undergoing prophylactic mastectomy
Authors: Boughey Judy C. , Cormier Janice N. , Xing Yan , Hunt Kelly K. , Meric‐Bernstam Funda , Babiera Gildy V. , Ross Merrick I. , Kuerer Henry M. , Singletary Sonja E. , Bedrosian Isabelle
Published: October 2007

BACKGROUND.

Patients who have invasive breast cancer identified after prophylactic mastectomy (PM) require axillary lymph node dissection (ALND) for lymph node staging (ie, directed ALND). Because the majority of these patients will be lymph node negative, sentinel lymphadenectomy (SLND) has been advocated at the time of PM to avoid the sequelae of unnecessary ALND. The objective of this study was to compare the efficacy of 2 surgical strategies, routine SLND versus directed ALND, in PM patients.

METHODS.

A decision‐analytic model was created to compare the 2 surgical strategies. Model estimates were derived from a systematic literature review. The endpoints that were examined to compare the 2 strategies were the number of SLNDs performed per breast cancer detected, the number of SLNDs attempted to avoid 1 ALND in a lymph node‐negative patient with occult invasive cancer, and the number of axillary complications associated with each strategy.

RESULTS.

The prevalence of invasive cancer in patients undergoing PM was estimated at 1.9%. At this rate, 37 SLNDs were performed per 1 breast cancer detected, and 73 SLNDs were required to avoid 1 ALND in a lymph node‐negative PM patient. In 1 model scenario, the probability of complications per breast cancer detected was 9‐fold greater with the SLND strategy than with the directed ALND strategy (2.7 vs 0.3). The complication rates for the 2 strategies become equivalent in the model scenario when the prevalence of occult invasive cancer was projected to 28%.

CONCLUSIONS.

Routine SLND for patients undergoing PM is not warranted given the large number of procedures required to benefit 1 patient and the potential complications associated with performing SLND in all patients. Cancer 2007. Published 2007 by the American Cancer Society.
Expression of vascular endothelial growth factor in early cutaneous melanocytic lesion progression
Authors: Einspahr Janine G. , Thomas Tracy L. , Saboda Kathylynn , Nickolof Brian J. , Warneke James , Curiel‐Lewandrowski Clara , Ranger‐Moore James , Duckett Laura , Bangert Jerry , Fruehauf John P. , Alberts David S.
Published: October 2007

BACKGROUND.

A considerable body of evidence supports the concept that a significant number of cutaneous malignant melanomas progress through a precursor lesion or dysplastic melanocytic nevi (DN). Tumor angiogenesis likely plays a critical role in early development of melanoma, and intermediate biomarkers of angiogenesis could be useful as chemoprevention and prognostic markers.

METHODS.

Markers of angiogenesis that included expression of the vascular endothelial growth factor A (VEGF‐A) and microvessel density counts (MVD) were evaluated in 13 prospectively collected benign nevi (BN) and 19 DN from 16 individuals and in a comparison group of 17 primary melanomas (16 archival samples and 1 prospective melanoma).

RESULTS.

VEGF expression in melanocytic cells (mean ± standard error [SE]) was low or absent in BN (3.4 ± 1.4), increased significantly in DN (41.0 ± 10.1; P = .0003 for BN vs DN), and increased further in primary melanoma (119.9 ± 28.3; P = .06 for DN vs melanoma). MVD using CD31 (mean ± SE [percentage × intensity]) followed a similar pattern with similarity between BN (2.6 ± 0.7; N = 13) and DN (2.2 ± 0.8; N = 19; P = .4 for BN vs DN), whereas primary melanomas were significantly higher (39.4 ± 6.4; N = 17; P = .0001 for BN or DN vs melanoma).

CONCLUSIONS.

In a prospective setting, the current data suggested that increased VEGF‐A expression in DN may be a good indicator of preneoplastic change in melanocytic lesions with the potential for improving the understanding and prevention of the transformation of DN to melanoma. Cancer 2007. © 2007 American Cancer Society.
Energy flow and the organization of life
Authors: Morowitz Harold , Smith Eric
Published: October 2007

Understanding the emergence and robustness of life requires accounting for both chemical specificity and statistical generality. We argue that the reverse of a common observation—that life requires a source of free energy to persist—provides an appropriate principle to understand the emergence, organization, and persistence of life on earth. Life, and in particular core biochemistry, has many properties of a relaxation channel that was driven into existence by free energy stresses from the earth's geochemistry. Like lightning or convective storms, the carbon, nitrogen, and phosphorus fluxes through core anabolic pathways make sense as the order parameters in a phase transition from an abiotic to a living state of the geosphere. Interpreting core pathways as order parameters would both explain their stability over billions of years, and perhaps predict the uniqueness of specific optimal chemical pathways. © 2007 Wiley Periodicals, Inc. Complexity, 2007
Sinusoidal shaping of the ISF in LC oscillators
Authors: Jannesari Abumoslem , Kamarei Mahmoud
Published: October 2007

A new method to decrease the phase noise of the sinusoidal oscillators is proposed. The proposed method is based on using a dynamic transistor biasing in a typical oscillator topology. This method uses the oscillator impulse sensitivity function (ISF) shaping to reduce the sensitivity of the oscillator to the transistor noise and as a result reducing the oscillator phase noise. A 1.8 GHz, 1.8 V designed oscillator based on the proposed method shows a phase noise of −130.3dBc/Hz at 1 MHz offset frequency, thereby showing about 6 dB phase noise decreasing in comparison with the typical constant bias topology. This result is obtained from the simulation based on 0.18u CMOS technology and on‐chip spiral inductor with a quality factor equal to 8. Copyright © 2007 John Wiley & Sons, Ltd.
Outcome of “Atypical squamous cells” in a cervical cytology screening program: Implications for follow up in resource limited settings
Authors: Gupta Sanjay , Sodhani Pushpa , Chachra Krishan Lal , Singh Veena , Sehgal Ashok
Published: October 2007

(1) To study the incidence and outcome of “Atypical squamous cells (ASC)” diagnosis in a hospital based cytology screening programme. (2) To work out a feasible strategy for follow up of Atypical squamous cells–undetermined significance (ASC‐US) and Atypical squamous cells–cannot exclude high grade squamous intraepithelial lesion (ASC‐H) in resource limited settings. A total of 29,475 women were screened cytologically through Pap tests. The epithelial cell abnormalities (ECA) detected on screening were reviewed by the cytopathologists and classified according to Bethesda 2001 system. The women with ASC‐US reports were followed up by two repeat cytology tests at 3 and 6 months of the initial visit. The persistent ASC‐US cases or the cases which revealed squamous intraepithelial lesion (SIL) on follow up smears; as well as all ASC‐H and above cases were referred for coloposcopic evaluation. ASC diagnosis comprised 3.6% of all reports. These were qualified as ASC‐US (3.36%) and ASC‐H (0.22%). On follow up, only 7 CIN 2 or worse (3.2%) lesions were detected on 218 biopsies in ASC‐US category while in ASC‐H qualifier 16 CIN 2 and above lesions (30.8%) were picked up on 52 colposcopic biopsies. The difference between ASC‐US and ASC‐H categories for a CIN 2 or worse outcome was highly significant (P < 0.001). ASC‐H qualifier has a high likelihood for an ominous histological outcome and warrants an immediate colposcopic evaluation. On the other hand, ASC‐US cases can be managed conservatively by repeat cytology tests at regular intervals without a significant risk of missing a high grade lesion. Diligent screening of cervical smears can judiciously downgrade some cases overcalled as ASC because of inflammatory atypia and thereby reduce referrals in geographic settings with high prevalence of reproductive tract infections. High risk HPV (HR HPV) testing may be a useful adjunct to further reduce referrals by selecting the women who require colposcopic evaluation. Diagn. Cytopathol. 2007; 35:677–680. © 2007 Wiley‐Liss, Inc.
Aspiration cytology of brain abscess from a fatal case of cerebral phaeohyphomycosis due to Ramichloridium mackenziei
Authors: Amr Samir S. , Al‐Tawfiq Jaffar A.
Published: October 2007

Ramichloridium mackenziei is a dematiaceous fungus that usually causes cerebral phaeohyphomycosis. We describe the aspiration cytology findings of a case of cerebral abscess caused by R. mackenziei in a 66‐yr‐old Saudi woman who had a long standing history of diabetes mellitus and a recent diagnosis of systemic lupus erythematosus. She was on long‐term corticosteroid therapy. The patient developed rapidly progressive multiple brain abscesses and died despite aspiration of the abscess and administration of intravenous amphotericin B lipid complex and voriconazole. Diagn. Cytopathol. 2007;35:695–699. © 2007 Wiley‐Liss, Inc.
Diagnosis of Schistosomiasis japonica infection coincident with hepatocellular carcinoma by fine‐needle aspiration
Authors: Chen Hui‐Zhu , Chuang Shih‐Chang , Hsieh Fu‐Chiao , Lin Le‐Jie , Hung Ruei‐Mei , Lee King‐Teh
Published: October 2007

Schistosomiasis japonica is not an endemic parasite in Taiwan. Previously, there have been no primarily infected cases reported with the exception of Chinese war veterans who had immigrated from Mainland China. We reported a 79‐year‐old patient who was diagnosed as having non‐B, non‐C liver cirrhosis complicated with a 1.2 × 1.2 × 1.2 cm liver tumor in the S5 of the liver. For a definitive diagnosis, we performed ultrasonographic‐guided fine needle (21 gauge) aspiration biopsy. In the smear of liver aspiration, a calcified fragment of a parasite egg with foreign body reaction adjacent to the crowding cancer cells of hepatocellular carcinoma was found. To our knowledge, parasite eggs are difficult to find within the fibrotic bands using fine needle aspiration biopsy. The etiologic relationship between Schistosomiasis japonica infection and the hepatocellular carcinoma is also discussed in this report. Diagn. Cytopathol. 2007;35:722–724. © 2007 Wiley‐Liss, Inc.
Granular cell tumor of the breast
Authors: El Aouni Nadra , Laurent Isabelle , Terrier Philippe , Mansouri Dhouha , Suciu Voichita , Delaloge Suzette , Vielh Philippe
Published: October 2007

We report a case of a 43‐yr‐old woman with a granular cell tumor of the breast. She presented with a palpable mass of the left breast of 2‐yr duration. On physical examination, a firm, painless, well‐defined mass located at the union of the upper quadrants was observed and a palpable homolateral axillary lymph node. The tumor was dense with ill‐defined borders at mammography and hypoechoic, hypovascular, and poorly limited at ultrasonography. Fine needle aspiration cytology of the lesion was performed. Cytologic examination revealed the presence of highly cellular material, composed of both large cohesive groups and single cells often admixed with connective tissue. These cells had ill‐defined abundant granular cytoplasm and bland regular small nuclei. Nucleoli were inconspicuous. Neither mitoses nor necrosis were noted. The cytological diagnosis of granular cell tumor of the breast was confirmed by histological examination of the surgical specimen following a breast lumpectomy. Diagn. Cytopathol. 2007;35:725–727. © 2007 Wiley‐Liss, Inc.
Systemic mastocytosis associated with small lymphocytic lymphoma: An incidental finding in a patient with invasive gastric adenocarcinoma
Authors: Steinmetz Caron , Shabaik Ahmed , Hasteh Farnaz
Published: October 2007

Mastocytosis comprises a heterogeneous group of disorders characterized by the abnormal growth and accumulation of mast cells in various tissues. We report an interesting case of systemic mastocytosis diagnosed incidentally in an omental lymph node in the setting of an invasive gastric adenocarcinoma. The Diff‐Quick touch preparation of the lymph node revealed abundant single cells and loose aggregates of cells with round to oval nuclei and deeply basophilic granules. Monotonous proliferation of small mature lymphocytes and many eosinophils were also present in the background. No evidence of metastatic carcinoma was seen. The frozen section and permanent sections of lymph node showed partial to complete replacement of lymph node by neoplastic mast cells. We present the cytologic findings of this unique case in addition to a brief discussion of systemic mastocytosis in the setting of another malignancy. Diagn. Cytopathol. 2007;35:728–733. © 2007 Wiley‐Liss, Inc.
Diagnostic accuracy of image‐guided percutaneous fine needle aspiration biopsy of the mediastinum
Authors: Assaad Margaret W. , Pantanowitz Liron , Otis Christopher N.
Published: October 2007

Interpreting a fine needle aspiration biopsy (FNAB) from the mediastinum is challenging as this location may harbor many lesions, including primary and metastatic tumors. Image‐guided transthoracic (percutaneous) FNAB is less invasive than mediastinoscopy or endoscopic‐guided FNAB. The aim of this study was to determine the diagnostic accuracy of FNAB performed percutaneously for evaluating mediastinal lesions.

A retrospective study of 157 consecutive CT‐guided transthoracic FNAB of the mediastinum was performed (1988–2004). Direct smears (N = 145; average 13 slides/case), ThinPrep™ slides (N = 25), and adequate cell blocks (N = 131) were prepared from procured cytologic material. When needed, ancillary studies included immunocytochemistry (N = 53) and flow cytometry (N = 8). Subsequent histologic tissue diagnoses available for 68 cases were also reviewed.

Patients were of average age 57 yr (range 1–88 yr), including 75 males and 82 females. A definitive diagnosis was rendered in 128 (82%) cases. Primary neoplasms (N = 38) included 24 lymphomas (6 Hodgkin and 18 non‐Hodgkin), 7 thymomas, 1 thymic carcinoma, and 6 peripheral nerve sheath tumors. Metastases (N = 72) were mainly carcinomas (N = 71) and 1 melanoma. There were 4 non‐neoplastic lesions (1 granulomatous process; 2 bronchogenic and 1 pericardial cyst), 1 case of undifferentiated malignant large cell neoplasm, 13 cases negative for malignancy, and 29 (18%) that were indeterminate, due largely to insufficient cellularity. Subsequent histologic diagnoses were concordant with FNAB diagnoses in 53/68 cases (78%). Nine FNAB were inadequate/nondiagnostic. There were 6 discordant cases, including 5 FNAB that were of adequate cellularity but interpreted as negative for malignant cells (on subsequent histology 2 turned out to be Hodgkin lymphoma, 2 carcinomas, and 1 diffuse large cell lymphoma), and 1 diagnosed as thymoma that on histologic evaluation was a thymic large cell lymphoma.

Adequate diagnostic cytologic material was obtained by image‐guided percutaneous FNAB of mediastinal lesions in 82% of our cases. Sufficient material was available to make cell blocks and perform ancillary studies when necessary. These data also show a high proportion of agreement (78%) between FNAB and subsequent histologic diagnoses for a wide variety of mediastinal lesions. The majority of discordant cases were primarily interpretive, with a final cytologic diagnosis negative for malignancy. Only one problematic case misdiagnosed on FNAB as thymoma was found on subsequent surgical excision to be a thymic large B cell lymphoma. Cases with nondefinitive FNAB diagnoses were largely due to sampling error and/or insufficient cellularity. Therefore, percutaneous FNAB of the mediastinum is a diagnostically helpful, minimally invasive procedure that can be performed in patients of all ages as part of the evaluation of a mediastinal mass lesion. Diagn. Cytopathol. 2007;35:705–709. © 2007 Wiley‐Liss, Inc.
Expression of K homology domain Containing protein Overexpressed in cancer in pancreatic FNA for diagnosing adenocarcinoma of pancreas
Authors: Zhao Huicong , Mandich Daniza , Cartun Richard W. , Ligato Saverio
Published: October 2007

We evaluated the immunocytochemical (ICC) expression of K homology domain containing protein overexpressed in cancer (KOC) in pancreatic endoscopic ultrasound‐guided fine needle aspirates (EUS‐FNAs) to assess its potential use as an adjunct in differentiating nonneoplastic (GI epithelium) and benign neoplastic epithelia (benign epithelial pancreatic neoplasms) from pancreatic adenocarcinoma cells. Forty‐eight cases of EUS‐FNAs with histological and/or clinical follow‐up data were selected for this study. Alcohol‐fixed and PAP‐stained slides were stained with monoclonal antibody to KOC/L523S (clone 69.1). Results were recorded as negative or positive. KOC expression was present in 35/40 (88%) of adenocarcinomas (Ac) and was negative in all eight benign cases. The sensitivity and specificity were as follows: cytology 85 and 100%, KOC 88 and 100%; combination of cytology and KOC 95 and 100%. We conclude that KOC ICC expression on alcohol‐fixed smears along with cytology improves the sensitivity of EUS‐FNAs in the diagnosis of pancreatic Ac, and KOC reactivity is especially useful in differentiating Ac from nonneoplastic gastrointestinal epithelium and benign neoplastic epithelia. Diagn. Cytopathol. 2007;35:700–704. © 2007 Wiley‐Liss, Inc.