bluuebunny/crossref_metadata_2025 huggingface dataset:
Direct determination of the enantiomeric purity of (R)‐ and (S)‐2‐hydroxy‐4‐phenylbutyric acid
Authors: Chilmonczyk Zdzisław , Ksycińska Hanna , Kruszewska Hanna , Cybulski Jacek
Published: January 2005

The determination of enantiomeric purity of (R)‐ and (S)‐2‐hydroxy‐4‐phenylbutyric acid by chiral HPLC is described. Good resolution has been obtained on covalently bonded L‐hydroxyproline saturated with Cu(II) ions. The method makes possible the determination of enantiomeric purity in media containing growing cells. © 1994 Wiley‐Liss, Inc.
Optically active analogues of ebastine: Synthesis and effect of chirality on their antihistaminic and antimuscarinic activity
Authors: Zhang Ming‐Qiang , Walczynski Krzysztof , Ter Laak Anton M. , Timmerman Henk
Published: January 2005

A series of optically active analogues of the H1‐antihistamine ebastine, with chiral center(s) at the benzhydryl and/or phenylbutyl part of the molecule, have been synthesized. Their in vitro antihistaminic and antimuscarinic activities were investigated, along with a molecular modelling study. It was found that introduction of the benzhydryl chiral center yielded significant stereoselectivity for both antihistaminic and antimuscarinic activities. The steric preferences of the benzhydryl chiral center for antihistaminic and antimuscarinic actions were mirror images of each other. The (−)‐isomer of 4‐methylebastine (6d) showed more than 10‐fold higher in vitro antihistaminic potency than ebastine. Meanwhile the selectivity of 6d for histamine H1‐receptors was also increased by more than 20 times in comparison with ebastine. The chirality at the phenylbutyl part of the molecule does not significantly alter the antihistaminic or antimuscarinic activity of the compounds although the (S)‐isomers showed slightly but unanimously higher antihistaminic activity than the (R)‐isomers. These results have been discussed with existing stereoselectivity data of antihistamines and an asymmetric pharmacophore model for H1‐antagonists has been described. © 1994 Wiley‐Liss, Inc.
Successive optical resolution by replacing crystallization of DL‐threonine
Authors: Shiraiwa Tadashi , Miyazaki Hideya , Kurokawa Hidemoto
Published: January 2005

DL‐Threonine [DL‐Thr; (2RS,3SR)‐2‐amino‐3‐hydroxybutanoic acid] was optically resolved by replacing crystallization using L‐serine (L‐Ser) and 4‐hydroxy‐L‐proline (L‐Hyp) as optically active cosolutes. D‐Thr was allowed to crystallize preferentially from racemic aqueous solutions in the presence of these L‐α‐amino acids. The optical resolution of DL‐Thr was more successfully achieved by using L‐Ser, whose structure is more similar to that of DL‐Thr than L‐Hyp, and successively gave D‐ and L‐Thr of 87—92% optical purities. The D‐ and L‐Thr obtained were then recrystallized from water to give optically pure D‐ and L‐Thr. © 1994 Wiley‐Liss, Inc.
Analysis of warfarin enantiomers: Chromatographic separation of six stereoisomeric esters prepared from (−)‐(1S,2R,4R)‐endo‐1,4,5,6,7,7‐hexachlorobicyclo[2.2.1]hept‐5‐ene‐2‐ carboxylic acid
Authors: Duke Colin C. , Carter Stephen R. , Hambley Trevor W. , Holder Gerald M. , Cutler David J.
Published: January 2005

Reaction of rac‐warfarin, (−)‐(1S,2R,4R)‐endo‐1,4,5,6,7,7‐hexachlorobicyclo[2.2.1]hept‐5‐ene‐2‐ carboxylic acid [(−)‐HCA] and carbodiimide reagents gave two noncyclic ketonic diastereoisomeric derivatives whereas rac‐warfarin and (−)‐HCA acid chloride with 4‐(dimethylamino)pyridine gave four cyclic hemiketal diastereoisomeric ester derivatives. The structure and stereochemistry of diastereoisomeric esters prepared from warfarin and p‐chlorowarfarin were determined from 1H‐ and 13C‐NMR spectra, mass spectra, and hydrolysis to warfarin and p‐chlorowarfarin enantiomers. The structure and stereochemistry of one of the cyclic hemiketal diastereoisomeric derivatives of warfarin are supported by an X‐ray crystallographic determination. Mechanisms for the formation of all products are proposed. © 1994 Wiley‐Liss, Inc.
Synthesis and enantiomeric purity determination of chiral 3‐benzylglycidol, a key synthon for hiv protease inhibitors
Authors: Shum Wilfred P. , Chen Jian , Cannarsa Michael J.
Published: January 2005

The detailed synthesis of (2R,3R)‐3‐benzylglycidol by the Sharpless asymmetric epoxidation route is described. The enantiomeric purity determination of this compound is complicated by the presence of small quantities of the diastereometric (2R,3S)‐3‐benzylglycidol from the asymmetric epoxidation of the cis‐allylic alcohol, and the unreacted allylic alcohols that are not removed in the product isolation steps. We have developed a direct chiral HPLC method that can resolve all these components for the precise determination of enantiomeric excesses of chiral 3‐benzylglycidols. © 1994 Wiley‐Liss, Inc.
K‐Opioid activity of the four stereoisomers of the peripherally selective κ‐agonists, EMD 60 400 and emd 61 753
Authors: Gottschlich Rudolf , Krug Michael , Barber Andrew , Devant Ralf M.
Published: January 2005

The four stereoisomers of the two peripherally selective κ‐opioid agonists EMD 60 400 and EMD 61 753 were synthesized, tested for stereoisomeric purity, and examined for affinity to the κ opioid receptor. The relationships between the configuration of these molecules and their biological activity are discussed. © 1994 Wiley‐Liss, Inc.
Retention model for the resolved enantiomers of felodipine on chiral‐AGP using micellar mobile phases
Authors: Haupt Dan , Pettersson Curt , Westerlund Douglas
Published: January 2005

A retention model for the chiral separation of an uncharged solute, felodipine, on CHIRAL‐AGP, using a micellar mobile phase is proposed. The model assumes the presence of two stereoselective sites and each enantiomer was found to interact with different sites. Addition of a chiral aliphatic alcohol, (+)‐(S)‐2‐octanol, preferentially interacted with the binding site for (−)‐(S)‐felodipine. The monomeric form of the micellar agent (Tween® 20) competed with the enantiomers for the adsorption sites, and the formation of a 1:1 complex between the enantiomers and the micelles was assumed. The retention of the solutes was effectively controlled by adding small quantities (<1.63 × 10−3 M) of the nonionic detergent Tween 20 to the mobile phase. Baseline separation was achieved by addition of 1.0 mM n‐octylamine to the mobile phase; 8.14 × 10−4 M Tween 20 in phosphate buffer pH 7.0. The separation factor (α = 1.74) was unaffected by the detergent concentration in the presence of 1.0 mM n‐octylamine. © 1995 Wiley‐Liss, Inc.
Stereoselectivity in acid‐catalyzed heteronucleophilic substitution of enantiomeric 3‐O‐methyloxazepam and 3‐O‐ethyloxazepam
Authors: Yang Shen K.
Published: January 2005

Kinetics of acid‐catalyzed heteronucleophilic substitution and racemization of enantiomeric MeOX in ethanol and enantiomeric EtOX in methanol were studied by quenching reaction products at various times by neutralization. Enantiomeric contents of remaining substrate and reaction product were determined by chiral stationary phase high‐performance liquid chromatography. The experimental procedure allowed the determination of the stereoselectivity (i.e., the enantiomeric ratio of a substitution product formed from an enantiomerically pure substrate) involved in the heteronucleophilic substitution reactions. The stereoselectivity was found to vary between 58:42 and 87:13, depending on the acid concentration, substrate, solvent, and temperature. The enantiomeric purity of remaining substrates was identical to that of the starting substrate, indicating that the enantiomeric substrates did not undergo a ring‐opening reaction. The results provided additional evidence supporting the mechanism proposed earlier in acid‐catalyzed stereoselective heteronucleophilic and homonucleophilic substitutions and the resulting racemization of enantiomeric 3‐alkoxy‐1,4‐benzodiazepines in alcoholic solvents. © 1995 Wiley‐Liss, Inc.
Structural features affecting chiral resolution of cannabimimetic enantiomers by amylose 3,5‐dimethylphenylcarbamate chiral stationary phase
Authors: Levin Shulamit , Sterin Marina , Abu‐lafi Saleh
Published: January 2005

The effect of structural features of six pairs of enantiomers of cannabimimetic compounds on their chromatographic resolution on an amylose tris(3,5‐dimethylphenylcarbamate) chiral stationary phase was studied using various compositions of n‐hexane with 2‐propanol and ethanol. Structural analysis by molecular mechanics was also performed to verify that the 3D conformation within this family of compounds was preserved with substitution. The homologous enantiomeric pairs showed better resolution when there was an additional OH group near the chiral centers (position 7 on the cannabinoid structure). Better resolution was observed also for the enantiomeric pair that had the smaller alkyl side chain. These differences indicated that the additional OH group contributed to a better discrimination of the enantiomers by the chiral sites of the stationary phase and that the bulkier alkyl side chain reduced it. The chromatographic resolution of two enantiomeric pairs of nonclassical cannabinoids HU‐249 and HU‐250, HU‐255 and HU‐256, was compared both in ethanol and 2‐propanol. Both enantiomeric pairs showed relatively high resolution and selectivity, but the rigid benzofuran analogs (HU‐249 and HU‐250) exhibited better resolution using 2‐propanol, in spite of the flexibility of the open chain analog (HU‐255 and HU‐256) and its additional OH group. The elution order of all the cannabinoids was (+)/(−) using both solvents. Unusual solvent effects were displayed by one enantiomeric pair, Δ6‐THC, which was resolved easily using 2‐propanol, but whose elution order reversed with 1% ethanol in the mobile phase. Partial separation was obtained at 5% ethanol [elution order (+)/(−)] and full separation was obtained at 0.5% ethanol [elution order (−)/(+)]. © 1995 Wiley‐Liss, Inc.
Chiral aspects of the metabolism of ethosuximide
Authors: Millership Jeffrey S. , Collier Paul S. , Hamilton John T. G. , McRoberts W. Colin , Mifsud Janet
Published: January 2005

Ethosuximide is a chiral drug substance primarily indicated for the treatment of absence seizures. This drug is used clinically as the racemate. The urinary metabolites of ethosuximide (following i.p. administration of the racemate or individual enantiomers to rats) have been studied using chiral gas chromatography (GC) and gas chromatography‐mass spectroscopy (GCMS). The metabolites identified were unchanged ethosuximide enantiomers, all four stereoisomers of 2‐(1‐hydroxyethyl)‐2‐methylsuccinimide, and a single stereoisomer of 2‐ethyl‐3‐hydroxy‐2‐methylsuccinimide [derived from (R)‐ethosuximide]. Preliminary quantitative studies indicate a degree of stereoselectivity in the fate of ethosuximide since the ratio of (R)‐ to (S)‐ethosuximide in the urine was found to be 0.77:1 (0–24 h sample), 0.64:1 (24–48 h sample), and 0.83:1 (48–72 h sample). This would suggest that the (R)‐isomer is preferentially metabolised. Results obtained following the administration of individual enantiomers of ethosuximide indicate that the 2‐(1‐hydroxyethyl)‐2‐methylsuccinimide diastereoisomers derived from (R)‐ethosuximide are produced in approximately equal proportions [ratio 1.05:1 (0–24 h sample), 1.10:1 (24–48 h sample)], whilst those from (S)‐ethosuximide are produced in unequal proportions [ratio 1.65:1 (0–24 h sample), 1.74:1 (24–48 h sample)]. © 1995 Wiley‐Liss, Inc.
Solvent selectivity in chiral chromatography using a β‐cyclodextrin‐bonded phase
Authors: Piperaki Stavroula , Tsantili‐Kakoulidou Anna , Parissi‐Poulou Maria
Published: January 2005

A β‐cyclodextrin‐bonded phase has been used to investigate the separation of the enantiomers of atenolol, oxprenolol, celiprolol, tertatolol, terbutaline, fluoxetine, norfluoxetine, and zopiclone, focusing on the importance of solvent selectivity. With cyclodextrin (CD)‐bonded phases, chiral discrimination occurs because the two enantiomers of a racemate form inclusion complexes of different strengths within the CD cavity. The organic modifier molecules tend to compete with solutes for a definite number of adsorption sites on the stationary phase. Moreover, the ternary complex formation may play an important role in chiral recognition. In this study, it was of interest to estimate the influence of mobile phase modifiers with respect to solvent type (i.e., ACN, MeOH, EtOH, THF, i‐PrOH, PrOH and t‐BuOH), size and shape, and concentration. Solvent selectivity has been investigated by using different organic modifiers in mobile phases with the same polarity, and relationships were established between the logarithm of solvent partition coefficient (log Ps) and the three most important chromatographic parameters: retention time (t), resolution (R), and enantioselectivity (α). Thus, it seems that the hydrophobicity of the organic modifier becomes one of the dominant factors affecting the inclusion process phenomena. Further, the apparent partition coefficients of the compounds under study have been determined and a comparison has been attempted regarding the degree of their enantiomeric resolution. © 1995 Wiley‐Liss, Inc.
Lack of metabolic racemisation of ropivacaine, determined by liquid chromatography using a chiral AGP column
Authors: Arvidsson Torbjörn , Bruce Heidi Forsmo , Halldin Magnus M.
Published: January 2005

Ropivacaine hydrochloride monohydrate (ropivacaine) is a new local anaesthetic agent which is administered exclusively as the (‐)‐(S)‐form. The aim of the study was to determine whether metabolic racemisation of (‐)‐(S)‐ropivacaine occurs. This was tested in man, rat, dog, and sheep after different routes of administration. The enantiomers of ropivacaine and two of the major metabolites, 3‐hydroxy‐ropivacaine and 2′,6′‐pipecoloxylidide (PPX), were determined in urine samples by liquid chromatography on a Chiral AGP column after liquid–liquid extraction. It was possible to detect <1% of the (+)‐(R)‐enantiomer of both ropivacaine and the two major metabolites. In the samples examined, no trace of metabolic racemisation was observed. In pharmacokinetic, pharmacodynamic, toxicological, and metabolic studies, therefore, nonchiral assays are considered to be adequate. © 1995 Wiley‐Liss, Inc.
Comparative toxicity of (+)‐(R)‐ and (−)‐(S)‐1,2‐dibromo‐3‐chloropropane
Authors: Kouzi Samir A. , Søderlund Erik J. , Dybing Erik , Meerman John H. N. , Nelson Sidney D.
Published: January 2005

The haloalkane 1,2‐dibromo‐3‐chloropropane (DBCP), an environmental pollutant that was widely used as a soil fumigant, is a carcinogen and a mutagen and displays target‐organ toxicity to the testes and the kidneys. Because little is known about effects of stereochemistry on the metabolism and toxicity of halogenated alkyl compounds and because DBCP, which has a chiral center at C‐2, may show enantioselectivity in its metabolism and/or toxicities, the optically pure enantiomers of DBCP were tested in vivo in rats for organ toxicity as well as for bacterial mutagenicity. Organ toxicity studies showed that (S)‐DBCP was slightly more renal toxic than (R)‐DBCP but was not significantly more toxic than the racemate, and that no significant differences were observed in the extents of testicular necrosis and atrophy caused by either enantiomer or the racemate. In contrast, (R)‐DBCP was more mutagenic than either (S)‐DBCP or the racemate to Salmonella typhimurium (S. typhimurium) strains TA 100 and TA104. However, there was little or no enantioselectivity in glutathione S‐transferase (GST)‐catalyzed conjugation reactions of glutathione with DBCP based on the lack of selectivity in the rates of disappearance of the enantiomers of DBCP in the presence of glutathione (GSH) and GSTs as monitored by chiral gas chromatography (GC). © 1995 Wiley‐Liss, Inc.
Determination of the enantiomers of citalopram, its demethylated and propionic acid metabolites in human plasma by chiral HPLC
Authors: Rochat B. , Amey M. , Van Gelderen H. , Testa B. , Baumann P.
Published: January 2005

A stereoselective HPLC assay has been developed to analyze the enantiomers of citalopram and of its three main metabolites in plasma after their separation on a Chiracel OD column. Using a fluorescence detector, the limit of quantification in plasma samples was 15, 4, 5, and 2 ng/ml for the enantiomers of citalopram (CIT), desmethylcitalopram (DCIT), didesmethylcitalopram (DDCIT), and for the citalopram propionic acid derivative (CIT‐PROP), respectively. Except for CIT, all metabolites were derivatized with achiral reagents. Identification of the enantiomers was realized with an optical rotation detector which showed that the enantiomers invert their rotation depending on the polarity and nature of the solvent. Under varying conditions, a racemization study has shown that the pure enantiomers of CIT and its demethylated metabolites are configurationally stable. Preliminary results obtained with five patients treated with CIT show a mean S/R ratio of 0.7 for both CIT and its active metabolite DCIT and of 3.6 for CIT‐PROP in plasma. This suggests that the pharmacologically relevant (+)‐(S)‐isomers of CIT and DCIT could be preferentially and steroselectively metabolized to CIT‐PROP. © 1995 Wiley‐Liss, Inc.
Racemization, enantiomerization, diastereomerization, and epimerization: Their meaning and pharmacological significance
Authors: Reist Marianne , Testa Bernard , Carrupt Pierre‐Alain , Jung Martin , Schurig Volker
Published: January 2005

The configurational lability of enantiomers can be characterized by different terms, each defining a specific process. Racemization relates to the macroscopic and statistical process of the irreversible transformation of one of the enantiomers into the racemic mixture. Enantiomerization refers to the microscopic and molecule process of the reversible conversion of one enantiomer into the other. Methods allowing the experimental determination of rate constants of racemization (krac) and enantiomerization (kenant) are discussed, and it is shown that kenant = 1/2 krac. Neglect of this fact is a source of some confusion in the literature. When two or more elements of chirality are present in a molecule and one of them is configurationally labile, epimerization occurs, a particular case of diastereomerization. These processes of interconversion between diastereomers are kinetically more complicated than racemization and enantiomerization since the rate constants of the forward and reverse reactions are always different (kdiast/A‐to‐B ≠ kdiast/B‐to‐A), however small the difference. An important aspect of the configurational lability of stereoisomeric drugs is the time scale of the phenomenon. When interconversion occurs to a significant extent during the residence time of a drug in the body, a pharmacological time scale is implied. In contrast, the pharmaceutical time scale refers to slower rates of interconversion that affect the configurational purity of a drug during its shelf‐life. © 1995 Wiley‐Liss, Inc.
In vitro fenoprofenyl–coenzyme a thioester formation: Interspecies variations
Authors: Soraci A. , Benoit E.
Published: January 2005

In vitro coenzyme A thioester formation from (−)‐(R)‐fenoprofen (FPF) and palmitic acid has been studied using liver microsomes from rat, guinea pig, sheep, and dog. In every species with both palmitic acid or (−)‐(R)‐fenoprofen, the Lineweaver–Burk plot was linear in the substrate concentration range used and as a consequence agrees with the involvement of only one isoenzyme (or different isoenzymes of similar Km values). The Vmax values for the thioesterification of (−)‐(R)‐fenoprofen present large species variations from 2.1 ± 1.0 with sheep liver microsomes to 60.6 ± 11 nmol/min/mg with dog liver microsomes. These values statistically significantly correlate (r = 0.94) to the Vmax values observed when palmitic acid was used as a substrate. Furthermore palmitic acid inhibited (−)‐(R)‐fenoprofen–CoA formation in the same extent in all animal species. The stereoselectivity of the thioesterification was also species dependent. © 1995 Wiley‐Liss, Inc.
Enantioselective influence of cyclodextrins on cleavage of chiralic esters
Authors: Beyrich Thorsten , Jira Thomas , Beyer Christine
Published: January 2005

Assessing the reactivity of optical antipodes is of central importance in drug research. Using the model of 2‐methoxy‐2‐phenylacetic acid‐4‐nitrophenylester (MPE), the rate of hydrolysis in the presence of β‐cyclodextrin (CD), hydroxyethyl‐ and hydroxypropyl‐β‐CD, as well as methyl‐β‐CD is studied photometrically and by means of HPLC (Chiralcel‐OD‐R‐column). Both β‐CD and hydroxyalkylated‐β‐CD catalyze (−)‐(R)‐enantiomers to a larger extent than (+)‐(S)‐enantiomers, resulting in an enrichment of the latter. Methyl‐β‐CD stabilizes the ester trifold, thus abolishing chiral discrimination. © 1995 Wiley‐Liss, Inc.
Bevantolol hydrochloride (nc‐1400): Absolute configuration and direct separation of the enantiomers
Authors: Yamamoto Masao , Takayanagi Yukiko , Nihashi Susumu , Nomura Yutaka , Nohira Hiroyuki
Published: January 2005

Synthesis of (−)‐bevantolol hydrochloride from 3,4‐dimethoxyphenethylamine and (S)‐(+)‐m‐tolyl glycidyl ether derived from (R)‐(−)‐epichlorohydrin established the absolute configuration of the (+) and (−) enantiomer as R and S, respectively. The purity of the enantiomers was determines using a chiral cellulose column (CHIRALCEL OD®) which allowed direct separation of the enantiomers. A separation factor (α) of 4.20 and a resolution factor (Rs) of 9.21 were obtained. © 1995 Wiley‐Liss, Inc.
Stereoselective disposition of hydroxychloroquine and its metabolites in rats
Authors: Wei Yimin , Nygard Gloria A. , Ellertson Shari L. , Khalil Shoukry K.W.
Published: January 2005

Racemic hydroxychloroquine‐sulfate (HCQ‐sulfate) was administered to rats orally. Groups of 9 male and 9 female rats received doses of 0, 8, 16, or 24 mg/kg/day for 6 weeks, followed by a reduction of the higher doses to 8 mg/kg/day for the duration of the study. Whole blood samples were collected at 0, 3, 6, 8, and 10 weeks, and eleven tissues were harvested after the tenth week. The concentrations and enantiomer ratios of the parent drug and three metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ), were determined. The highest concentration of HCQ was found in the intestinal smooth muscle, and the lowest in the brain and adipose tissue. The highest concentrations of the metabolites were found in the liver, adrenals, and lung tissue.

The metabolism of HCQ in the rats was found to be stereoselective with R/S > 1 for the drug and < 1 for the metabolites. Gender‐specific differences in the proportions of the drug and its metabolites and their enantiomers in blood and tissue were found. Varying dosages appeared to have only a temporary influence on blood concentrations and not to effect the enantiomer ratios in blood. Only a limited number of tissues exhibited significant differences between dose groups. There were no observed differences in enantiomer ratios among the blood collection times. © 1995 Wiley‐Liss, Inc.
A pilot clinical trial of vaccination with dendritic cells pulsed with autologous tumor cells derived from malignant pleural effusion in patients with late‐stage lung carcinoma
Authors: Chang Gee‐Chen , Lan Haw‐Chang , Juang Shin‐Hun , Wu Yu‐Chen , Lee Hui‐Chen , Hung Yi‐Mei , Yang Hui‐Yu , Whang‐Peng Jacqueline , Liu Ko‐Jiunn
Published: January 2005

BACKGROUND

The authors conducted a pilot clinical trial to explore the vaccination of patients with late‐stage lung carcinoma with dendritic cells (DCs) pulsed with necrotic tumor cells derived from malignant pleural effusion specimens, and to evaluate the antitumor immune response induced by this therapy.

METHODS

Autologous DCs were generated by culturing adherent mononuclear cells with interleukin‐4 and granulocyte‐macrophage–colony‐stimulating factor for 7 days. Day‐7 DCs were cocultured overnight with autologous necrotic tumor cells derived from pleural effusion specimens to allow internalization of tumor antigens. DCs were then treated with tumor necrosis factor‐alpha for 16 hours. The antigen‐loaded DCs were injected into each patient's inguinal lymph nodes under sonographic guidance. Eight patients with late‐stage nonsmall cell lung carcinoma were treated in this manner. Patients were vaccinated once weekly for 4 weeks and then boosted twice biweekly.

RESULTS

The authors found that there was no Grade II/III toxicity and autoimmune response in all patients after intranodal injection of the DC vaccine. Minor to moderate increases in T‐cell responses against tumor antigens were observed after DC vaccination in six of eight patients. Five patients had progressive disease. One patient had minor tumor response and two patients had stable disease. The two patients who had longer disease control also had better T‐cell responses.

CONCLUSIONS

The results indicated that it was feasible to immunize patients with lung carcinoma intranodally with DCs pulsed with necrotic tumor cells enriched from pleural effusion specimens, and this approach may generate T‐cell responses and provide clinical benefit in some patients. Cancer 2005. © 2005 American Cancer Society.
Predictors of breast conservation therapy
Authors: Hiotis Karen , Ye Wei , Sposto Richard , Skinner Kristin A.
Published: January 2005

BACKGROUND

Despite the National Institutes of Health consensus statement in 1991 that breast‐conserving surgery (BCS) followed by radiotherapy is an appropriate approach to the treatment of early‐stage breast carcinoma, studies have shown a relatively low rate of BCS in the United States. The current study investigated predictors of breast conservation therapy in a large, diverse patient population.

METHODS

Between 1990 and 1998, 43,111 patients underwent surgery for breast carcinoma and were entered into the Cancer Surveillance Program database for Los Angeles County. Of these, 29,666 (68.3%) had complete data on patient demographics, staging, surgeon, type of surgery, and hospital. Data were collected regarding extent of disease, lymph node status, tumor size, age, race, socioeconomic status (SES), surgeon specialization, surgeon volume, hospital specialization, and hospital volume. Univariate and multivariate analyses were performed.

RESULTS

Univariate analysis showed that extent of disease, lymph node status, tumor size, age, race, SES, surgeon and hospital specialization, and surgeon and hospital volume all were significantly associated with surgery type (P < 0.0001). Multivariate analysis showed that not only did extent of disease impact choice of surgery, but so did race, SES, hospital volume, surgeon volume, and surgeon specialization (P < 0.0001).

CONCLUSIONS

These results suggest that not only does the extent of locoregional disease play a role in the likelihood of a woman undergoing breast conservation therapy, but patient age, socioeconomic status, racial/ethnic factors, and the experience of both the surgeon and hospital have an effect. Cancer 2005. © 2005 American Cancer Society.
Phase II study of transdermal estradiol in androgen‐independent prostate carcinoma
Authors: Bland Lisa B. , Garzotto Mark , DeLoughery Thomas G. , Ryan Christopher W. , Schuff Kathryn G. , Wersinger Emily M. , Lemmon Dianne , Beer Tomasz M.
Published: January 2005

BACKGROUND

Oral estrogen therapy has activity in patients with hormone‐naive and androgen‐independent prostate carcinoma (AIPC), but its utility is limited by the associated risk of thromboembolic toxicity. Parenteral administration may be safer as it avoids “first pass” liver exposure to estrogen. The authors tested the safety and efficacy of transdermal estradiol (TDE), as well as the effect of therapy on hot flashes, sex hormones, the procoagulant cascade, and bone turnover in patients with AIPC.

METHODS

Patients with prostate carcinoma progressing after primary hormonal therapy received TDE 0.6 mg per 24 hours (administered as six 0.1 mg per 24‐hour patches replaced every 7 days). Serum prostate‐specific antigen (PSA) and hormone levels, coagulation factors, markers of bone turnover, bone density measurements, and a hot flash diary were collected at regular intervals.

RESULTS

Three of 24 patients (12.5%; 95% confidence interval [CI], 0–26%) had a confirmed PSA reduction > 50%. The Kaplan–Meier estimate of median time to disease progression was 12 weeks (95% CI, 4.6–19.4 weeks). Toxicity was modest and no thromboembolic complications occurred. The mean (±95% CI) serum estradiol level increased from 17.2 pg.mL (range, 14.8–19.6 pg/mL) to 460.7 pg/mL (range, 334.6–586.7 pg/mL). The total testosterone level remained stable in the anorchid range during treatment, but the free testosterone level decreased as a result of increased sex hormone binding globulin. No change in factor VIII activity, F 1.2, or resistance to activated protein C was observed, whereas a modest decrease in the protein S level was observed.

CONCLUSIONS

In patients with APIC, TDE was well tolerated and produced a modest response rate, but was not associated with thromboembolic complications or clinically important changes in several coagulation factors. Cancer 2005. © 2005 American Cancer Society.
Split sample comparison of ThinPrep and conventional smears in endoscopic retrograde cholangiopancreatography‐guided pancreatic fine‐needle aspirations
Authors: Siddiqui Momin T. , Gokaslan Sefik T. , Saboorian M. Hossein , Ashfaq Raheela
Published: January 2005

Fine‐needle aspiration (FNA) of pancreatic lesions is a common procedure to establish a tissue diagnosis before chemotherapy or surgery. In this study, the authors attempt to compare the diagnostic value of the ThinPrep (TP) method with conventional smears (CSs) in samples obtained by endoscopic retrograde cholangiopancreatography (ERCP)‐guided pancreatic FNAs. Material obtained, prospectively, from ERCP‐guided pancreatic FNAs was split to prepare CSs (2–5 slides) first, the remainder being rinsed in PreservCyte, and in the laboratory, 1 TP slide was prepared. The diagnostic categories of unsatisfactory, benign, reactive, suspicious for malignancy, and malignant were compared. Fifty‐one pancreatic FNAs prepared by split sample method yielded the following results: TP yielded unsatisfactory, 6 cases; benign, 3 cases; reactive, 5 cases; suspicious for malignancy, 11 cases; and malignant, 26 cases; in contrast, CS yielded unsatisfactory, 13 cases; benign, 4 cases; reactive, 3 cases; suspicious for malignancy, 13 cases; and malignant, 18 cases. Histological follow‐up was available in 21 cases (reactive, 8 cases; suspicious for malignancy, 1 case, and malignant, 12 cases). The foregoing data indicate a higher sensitivity in detection of pancreatic adenocarcinoma by the TP method (TP, 91% vs. 58% CS) with equivalent specificity (100%). In addition, TP provides better preservation and cytological detail. Diagn. Cytopathol. 2005;32:70–75. © 2005 Wiley‐Liss, Inc.
Patient with immunoproliferative disease and lung carcinoma: A case report
Authors: Radman Ivo , Sučić Mirna , Serventi‐Seiwerth Ranka , Boban Dubravka , Marković‐Glamočak Mirjana , Ries Sunčica , Gjadrov‐Kuveždić Koraljka , Petković Dražen , Jakić‐Razumović Jasminka , Šćukanec‐Špoljar Mira , Seiwerth Sven , Sučić Zvonimir , Papa Jurica
Published: January 2005

There are a number of reports on collision occurrance of non‐hematologic cancers and Non‐Hodgin's lymphoma (NHL) and multiple myeloma. In this report we present a case of patient with immunoproliferative disease, extramedullary plasmocytoma and NHL‐lymphoplasmocytoid lymphoma (LPL) and squamous cell carcinoma of the lung. After diagnosis of extramedullary plasmocytoma cytostatic therapy was commenced and the patient was well. Five years after patient was clinically worse and diagnostic evaluation this time revealed lymphoplasmocytoid cells in bone marrow. Five months later malignant morphologically undifferentiated cells were found in bone marrow which were by immunocytochemistry established as CD38 positive. After the patient's death, disseminated NHL‐LPL and squamous cell carcinoma of lung was confirmed. In the report, we compared clinical course and diagnostic findings of our patient with literature data. We have also discussed the possible relationship of multiple B‐cell lymphoid tumors and squamous cell carcinoma concluding that multidiscplinary diagnostic tools are essential not only for carcinoma diagnosis and follow‐up, but also for further understanding of carcinogenesis. Diagn. Cytopathol. 2005;32:97–102. © 2005 Wiley‐Liss, Inc.
Unusual finding in a nipple discharge of a female dog: Dirofilariasis of the breast
Authors: Manuali E. , Eleni C. , Giovannini P. , Costarelli S. , Ciorba A.
Published: January 2005

We report a case of dirofilariasis of the breast occurring in a 6‐yr‐old Bernese female dog living in central Italy presenting with a breast lump, diagnosed on cytological examination of nipple secretion fluid smears. The direct smears of nipple discharge revealed clusters of glandular cells characterized by mild pleomorphic appearance and the presence of some nematodes of about 350 μm in length in the background. The smears also contained several inflammatory cells, including eosinophils. Both the Knott and the antigen tests were negative for Dirofilaria immitis. The morphological features of this round worm is compatible with that of Dirofilaria repens. The case describes an unusual finding of dirofilariasis presenting as a breast lump, simulating an inflammatory breast carcinoma. Diagn. Cytopathol. 2005;32:108–109. © 2005 Wiley‐Liss, Inc.
Fine‐needle aspiration of a pleomorphic lipoma of the head and neck: A case report
Authors: Yong Mona , Raza Anwar S. , Greaves Timothy S. , Cobb Camilla J.
Published: January 2005

Pleomorphic lipoma is a rare soft‐tissue tumor, most commonly seen in the head and neck regions of middle‐aged men. Fine‐needle aspiration (FNA) of these lesions can present a diagnostic challenge. Its large, hyperchromatic cells and multinucleated forms (floret cells) can easily be mistaken for a malignancy. A patient with a round, well‐circumscribed, painless, soft, subcutaneous posterior neck mass for 6 yr presented to our FNA clinic. Aspiration of the mass showed a hypocellular specimen with atypical large and floret cells with fragments of mature fibroadipose tissue in the background. Based on the clinical and cytomorphological findings, a diagnosis of pleomorphic lipoma was suggested, and it was confirmed on excision. This case highlights the need to be aware of unusual benign lesions that may arise in the head and neck region. Knowledge of these benign lesions will help in making the correct cytological diagnosis when these lesions are sampled by FNA. Diagn. Cytopathol. 2005;32:110–113. © 2005 Wiley‐Liss, Inc.
[Re6Q7O(3,5‐Me2PzH)6]Br2·3,5‐Me2PzH (Q = S, Se) − New Octahedral Rhenium Cluster Complexes with Organic Ligands: Original Synthetic Approach and Unexpected Ligand Exchange in the Cluster Core
Authors: Mironov Yuri V. , Shestopalov Michael A. , Brylev Konstantin A. , Yarovoi Spartak S. , Romanenko Galina V. , Fedorov Vladimir E. , Spies Hartmut , Pietzsch Hans‐Juergen , Stephan Holger , Geipel Gerhard , Bernhard Gert , Kraus Werner
Published: January 2005

Two new octahedral rhenium cluster complexes, [Re6S7O(3,5‐Me2PzH)6]Br2·3,5‐Me2PzH (1) and [Re6Se7O(3,5‐Me2PzH)6]Br2·3,5‐Me2PzH (2), with the organic ligand 3,5‐dimethylpyrazole (3,5‐Me2PzH), have been synthesised by reaction of rhenium chalcobromides Cs3[Re6(µ3‐Q7Br)Br6] (Q = S, Se) with molten dimethylpyrazole. During the reaction, all six apical bromine ligands of the cluster complexes are substituted by the organic ligand, which is coordinated through the aromatic nitrogen atom N2. Additionally, the inner ligand µ3‐Br in the cluster core [Re6(µ3‐Q7Br)]3+ is substituted by oxygen, giving cluster cores [Re6(µ3‐Q7O)]2+ with mixed chalcogen/oxygen ligands. Compounds 1 and 2 have been characterised by single‐crystal X‐ray diffraction analysis. They are isostructural and crystallise with four formula units in the unit cell. Absorption spectra and luminescence characteristics of these two cluster compounds have been investigated in methanol. Absorption starts below 400 nm. For both compounds, broad emissions were found. The fluorescence decays of the two compounds follow a diexponential decay behaviour. The main fluorescence intensity decays have longer fluorescence lifetimes of 3.07 ± 0.03 (1) and 3.96 ± 0.02 µs (2). Studying the thermal stability of both compounds in vacuo showed that the release of 3,5‐dimethylpyrazole ligands begins near 200 °C, and decomposition, with the removal of 7 molecules of 3,5‐Me2PzH, is complete at 330 °C. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Special meshes and domain decomposition methods for evolutionary convection–diffusion–reaction problems
Authors: Portero L. , Jorge J. C.
Published: January 2005

In this work we propose new parallel numerical methods to solve certain evolutionary singularly perturbed problems in a robust and efficient way. To get this, we firstly consider a semidiscretization in time using a simple fractional step Runge–Kutta method, where the splittings for the convection–diffusion–reaction operator and the source term are subordinated to a decomposition of the spatial domain in many smaller subdomains. Such semidiscretization procedure reduces the original problem to a set of elliptic problems (in smaller subdomains), which can be solved in parallel, and it avoids the use of Schwarz iterations. To discretize in space such problems we have considered classical linear finite elements on certain piecewise uniform meshes which have been constructed with a very simplea prioricriterion, similar to the one introduced by Shishkin for one‐dimensional stationary problems of this kind. We show that the use of these meshes permits to obtain uniformly convergent approximations even in the boundary layer regions. Copyright © 2005 John Wiley & Sons, Ltd.
Iterative solution techniques for unsteady flow computations using higher order time integration schemes
Authors: Bijl H. , Carpenter M. H.
Published: January 2005

In this paper iterative techniques for unsteady flow computations with implicit higher order time integration methods at large time steps are investigated. It is shown that with a minimal coding effort the standard non‐linear multigrid method can be combined with a Newton–Krylov method leading to speed‐ups in the order of 30%. Copyright © 2005 John Wiley & Sons, Ltd.
Tributylstibine‐mediated olefination of carbonyl compounds with bromomalonic ester and with dibromomalonic ester—A possible pathway through a stibonium ylide via halophilic initiation by tertiary stibines
Authors: Chen Chen , Huang Yao‐Zeng , Shen Yanchang , Liao Yi
Published: January 2005

Tributylstibine can mediate the olefination of carbonyl compounds with bromomalonic ester and with dibromomalonic ester. An initial halophilic attack of tributylstibine on the bromine of bromomalonic or dibromomalonic ester forming an ion pair of bromotributylstibonium cation and malonic (A) or bromomalonic ester carbanion (B), respectively, is proposed. These ion pairs react with carbonyl compounds to achieve subsequent olefination. Alternatively, 2 equiv of A collapse, with elimination of malonic ester, to form stiborane D, and the ion pair B reacts with another equivalent of tributylstibine to form stiborane D. This last undergoes a Wittig‐type reaction with carbonyl compound to achieve olefination.
Organoboranes. 52. The successful ring enlargement of boracyclanes via sequential one‐carbon homologation: The first synthesis of boracyclanes in the strained medium‐ring range
Authors: Brown Herbert C. , Phadke Avinash S. , Rangaishenvi Milind V.
Published: January 2005

Previous attempts to synthesize boracyclanes in the medium‐ring range (9‐, 10‐, 11‐, and 12‐ring members) via cyclic hydroboration of α,ω‐dienes have failed. However, their synthesis via the sequential one‐carbon homologation of B‐methoxyboracyclanes has been achieved utilizing the successive reaction of B‐methoxyboracyclanes with in situ generated (chloromethyl)lithium (LiCH2Cl): MeOB(CH2)5 → MeOB(CH2)6 → MeOB(CH2)7 → MeOB(CH2)8 → MeOB(CH2)9 → MeOB(CH2)10 → MeOB(CH2)11. The yields achieved are in the range of 75–85%. In each case the products are identified by conversion via the DCME reaction into the known cycloalkanones. This development provides the first entry into boracyclanes of the strained medium ring range.
α‐Alkenyl analogs of phosphorylcholines
Authors: Gololobov Yuri G. , Oganesyan Anush S. , Kolomnikova Galina D. , Kuznetsova Svetlana A. , Kasukhin Leonid F.
Published: January 2005

The new type of α‐alkenyl esters of phosphorus acids containing ammonium or phosphonium groups in unsaturated radicals as well as carbonyl or other complexes of Mo, Cr, W, Mn, or Pt with such organophosphorus ligands have been described. The alkenyl phosphates undergo dealkylation upon heating to give betaines. This conversion results in a substantial decrease of an anticholinesterase activity of the compounds and in a sharp rise of their hydrolytic stability. The prototropic rearrangement is observed for the phosphonium betaines.
Thermolysis of disubstituted 1,2‐dioxetanes: Activation parameters and chemiexcitation yields
Authors: Baumstark Alfons L. , Moghaddari Mehrdad , Chamblee Myra L.
Published: January 2005

trans‐3‐Methyl‐4‐(p‐anisyl)‐1,2‐dioxetane 1, trans‐3‐methyl‐4‐(o‐anisyl)‐1,2‐dioxetane 2, 3‐methyl‐3‐benzyl‐1,2‐dioxetane 3, and 3‐methyl‐3‐p‐methoxybenzyl‐1,2‐dioxetane 4 were synthesized in low yield by the β‐bromo hydroperoxide method. The activation parameters were determined by the chemiluminescence method (for 1 ΔG≠ = 22.8 ± 0.3 kcal/mol, Δ≠ = 22.2, ΔS≠ = −1.7 e.u., k60 = 7.6 × 10−3s−1; for 2 ΔG≠ + 23.6 ± 0.3 kcal/mol, ΔH≠ = 22.8, ΔS≠ = −2.2 e.u., k60 = 2.5 × 10−3S−1; for 3 ΔG≠ = 24.0 ± 0.4 kcal/mol, ΔH≠ = 23.1, ΔS≠ = −2.7 e.u., k60 = 1.2 × 10−3S−1; for 4 ΔG≠ = 24.0 ± 0.2 kcal/mol, ΔH≠, = 23.2, ΔS≠, = −2.4 e.u., k60 = 1.2 × 10−3s−1). Thermolysis of 1–4 produced excited carbonyl fragments (direct production of high yields of triplets relative to excited singlets) [chemiexcitation yields ϕT, ϕS, respectively: for 1 0.02, 0.0001; for 2 0.02, 0.0001; for 3 0.03, 0.0002; for 4 0.02, 0.0001]. The effect of paramethoxyaryl substitution was consistent with electronic effects. The ortho substitution in 2 resulted in an increase in stability of the dioxetane, opposite that observed for an electronic effect. The results are discussed in relation to a diradical‐like mechanism.
Evidence for formation of diphenylphosphinic peroxy radical intermediate: Spin trapping and chemical reactivity of the new phosphorus radical generated from diphenylphosphinic chloride and superoxide
Authors: Lim Sang Chul , Kim Yong Hae
Published: January 2005

Diphenylphosphinic chloride reacts with the superoxide anion radical in acetonitrile under mild conditions to form a peroxyphosphorus radical intermediate which shows strong oxidizing abilities for the epoxidation of olefins, oxidation of sulfides to sulfoxides, desulfurization of thioamides to amides, and oxidation of triarylphosphines to phosphine oxides. The radical can be trapped using a spin trapping method.
The photochemical reaction of (E,E)‐dibenzylidenesuccinic thioanhydride: A spectroscopic and structural study
Authors: Davidse P. Adriaan , Dillen Jan L. M.
Published: January 2005

The first photochromic thioanhydride, (E,E)‐2,3‐dibenzylidenesuccinic thioanhydride (1b), was synthesized. Irradiation of (1b) in benzene, dichloromethane, or chloroform gives isomerization and cyclization products similar to those obtained for the anhydride analogue (1a). The crystal structure of (1b) was determined (X‐rays) and compared to the structures of the anhydridge (1a) and N‐phenylimide (1c). 1H and 13C NMR spectra were recorded, and the electron charge densities of the carbon atoms were calculated with AM1. These results are discussed and compared with those for the compounds 1a–1c. The thioanhydride (1b) ring is much more twisted than either the anhydridge (1a) or the imide (1c) rings. The linear relationship between the 13C NMR chemical shifts and the electron charge density on the given atom has been investigated. The C(carbonyl) and C(α) carbon atoms of 1b were found to be greatly deshielded relative to the corresponding atoms in 1a and 1b. The increase in corresponding atoms in 1a and 1b. The increase in sensitivity toward cyclization of the thioanhydridge (1b) is attributed to the marked change in the charge distribution.

Crystal data. Thioanhydride (1b): space group P21/c with a = 12.956(3) Å, b = 14.843(6) Å, c = 7.512(6) Å, β = 98.05(2)°, Rw = 0.085 and R = 0.089.
Charge transfer complexes of some N‐methylated thiohydantoins with molecular iodine
Authors: Cristiani Franco , Devillanova Francesco A. , Diaz Angelo , Isaia Francesco , Verani Gaetano
Published: January 2005

Using a series of N‐methylated thiohydantoins as substrates, the donor properties of the sulfur atom are measured by determining the stability constants (K) of their adducts with molecular iodine. The K's have been determined by recording the UV‐visible spectra of several CH2Cl2 solutions with different amounts of the reagents. The experimental data fit the 1:1 adduct model for all the compounds. The K values, compared with those previously found for the unsubstituted hydantoins and with those obtained for 5‐methyl‐2‐thiohydantoin, show that the hydrogen‐bonding interaction between the NH hydrogen and the S‐bonded iodine plays an important role in determining the stability of the adduct.

The K values obtained for several pentaatomic rings, all containing the thioureido group HNC()NH, are discussed on the basis of the influence of the substituents at C‐4 and C‐5 on the donor properties of the sulfur atom.
Conformational analysis of 1,4,7‐trithiacyclodecane and related compounds: Synthesis and complexation studies of mesocyclic and macrocyclic polythioethers VI
Authors: Setzer William N. , Guo Qin , Meehan Edward J. , Grant Gregory J.
Published: January 2005

Molecular mechanics (MM2) calculations have been carried out on the ten‐membered ring trithioethers, 1,4,7‐trithiacyclodecane (10S3) and 1,4,7‐trithiacyclodecan‐9‐one (keto‐10S3). The lowest energy conformations according to these calculations are a [1333] and a [2233] conformation, respectively. The crystal and molecular structure of the ketone, 1,4,7‐trithiacyclodecan‐9‐one, has been determined by a single‐crystal X‐ray study. The compound crystallizes in the monoclinic space group P21, with two molecules per unit cell of dimensions a = 7.176(1) Å, b = 5.3447(6) Å, c = 12.0914(6) Å, and β = 96.486(7)0, and R = 0.048. The conformation adopted by the compound in the crystalline state is a [2323] or boat‐chair‐boat conformation with two sulfur atoms endodentate and one sulfur atom exodentate.
Synthesis and X‐ray crystal structure analysis of (−)‐1‐menthoxygermatrane
Authors: Zaitseva G. S. , Mohammed Nasim , Livantsova L. I. , Tafeenko V. A. , Aslanov L. A. , Petrosyan V. S.
Published: January 2005

A solvate complex of (−)‐1‐menthoxygermatrane with chloroform (1) was obtained by reaction of (−)‐menthoxytriethylstannane with 1‐bromogermatrane in chloroform. The crystal and molecular structure of 1 was established by X‐ray analysis.