bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic delay in breast cancer
Authors: Barber M D , Jack W , Dixon J M 
Published: January 2004

Abstract

Background
Delay in the diagnosis of breast cancer has important clinical and medicolegal implications. This study assessed the frequency, causes and effects of delay in the diagnosis of breast cancer in a specialist breast unit.

Methods
Details of women who attended the breast clinic between 1988 and 1999 inclusive, and for whom the interval between first attendance and diagnosis of invasive breast cancer was greater than 2 months, were reviewed. Potential causes of delay were identified and the consequence of the delay assessed. The clinical features were compared with those of patients diagnosed with breast cancer during a 2-year period from 1999 and 2001.

Results
Breast cancer was diagnosed in 5283 women during the interval reviewed; delay in diagnosis was suggested in 72 women (1·4 per cent). Women with a delayed diagnosis were younger (P &lt; 0·001) and had a smaller tumour at diagnosis (P = 0·011) compared with all women diagnosed with breast cancer between 1999 and 2001. There were no differences in the rate of axillary node positivity or the need for mastectomy. Women unsuitable for conservation therapy in the delayed group had a significantly longer interval to diagnosis (P = 0·006).

Conclusion
The likelihood that conservation therapy will be appropriate is reduced when the hospital delay in the diagnosis of breast cancer is more than 240 days. All patients with a palpable mass require triple assessment to minimize delay in diagnosis of breast cancer.
Interleukin 7 induces the growth of breast cancer cells through a wortmannin-sensitive pathway
Authors: Al-Rawi M A A , Rmali K , Mansel R E , Jiang W G 
Published: January 2004

Abstract

Background
Interleukin (IL) 7 is a growth factor able to induce the growth and development of certain haematopoietic malignancies including lymphoma and leukaemia. Its effects on solid tumours, including breast cancer, are unknown. This report concerns the effect of IL-7 on the growth of breast cancer cells.

Methods
Reverse transcription–polymerase chain reaction, western blotting and immunoprecipitation were used to detect to detect IL-7 and its receptor (IL-7R) in breast cancer cell lines MDA MB-231 and MCF-7. These cells were treated with various concentrations of human recombinant IL-7 over specified intervals. Changes in growth were assessed using colorimetric and fluorescence-based technologies. Selective IL-7 downstream signalling inhibitors (wortmannin, JAK-3 inhibitor 1, piceatanol and AG 490) were use to clarify the pathways through which IL-7 may affect breast cancer growth.

Results
IL-7 significantly accelerated the growth of MDA MB-231 cells and MCF-7 cells (P = 0·004 and P = 0·012, respectively, in PicoGreen® assay). The maximum effects were observed after incubation for 72 h. The stimulatory effect of IL-7 on cell growth was completely eliminated in the presence of wortmannin (P = 0·001 and P = 0·003 versus no inhibitor in MDA MB-231 and MCF-7 cells, respectively) and JAK-3 inhibitor 1 (P &lt; 0·001 versus no inhibitor in both cell lines), but not in the presence of piceatanol and AG 490.

Conclusion
IL-7 induced the growth of breast cancer cells in vitro through a wortmannin-sensitive pathway. This may have an important impact on research into breast cancer development and progression.
Increased vascular endothelial growth factor production in fibroblasts isolated from strictures in patients with Crohn's disease
Authors: Beddy D , Watson R W G , Fitzpatrick J M , O'Connell P R 
Published: January 2004

Abstract

Background
Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that is implicated in early wound healing and fibrosis. Fibroblasts may initiate stricture formation in Crohn's disease through overexpression of VEGF. The aim of this study was to examine VEGF expression and regulation in fibroblasts isolated from patients with Crohn's disease.

Methods
Fibroblasts were isolated by a primary explant technique from serosal biopsies of non-strictured and strictured segments of bowel from eight patients undergoing resection for Crohn's disease, and normal colon from six patients undergoing resection for benign and malignant colorectal disease. Fibroblasts were cultured with transforming growth factor (TGF) β and corticosteroids. After 24 h the culture supernatant was collected for VEGF assay by enzyme-linked immunosorbent assay.

Results
VEGF production was significantly higher in fibroblasts isolated from strictures (mean(s.e.m.) 1980(260) pg/ml) than from non-strictured segments (1116(165) pg/ml) in patients with Crohn's disease or control fibroblasts (898(93) pg/ml). TGF-β increased VEGF production in normal and non-strictured Crohn's fibroblasts. Corticosteroids suppressed unstimulated VEGF production in all groups.

Conclusion
Enhanced serosal fibroblast VEGF production might play a role in initiating stricture formation in Crohn's disease. VEGF production in serosal fibroblasts is sensitive to stimulation with TGF-β. Corticosteroids may reduce stricturing through suppression of VEGF.
Systematic review of survival after acute mesenteric ischaemia according to disease aetiology
Authors: Schoots I G , Koffeman G I , Legemate D A , Levi M , van Gulik T M 
Published: January 2004

Abstract

Background
Differentiation of acute mesenteric ischaemia on the basis of aetiology is of great importance because of variation in disease progression, response to treatment and outcome. The aim of this study was to analyse the published data on survival following acute mesenteric ischaemia over the past four decades in relation to disease aetiology and mode of treatment.

Method
A systematic review of the available literature from 1966 to 2002 was performed.

Results
Quantitative analysis of data derived from 45 observational studies containing 3692 patients with acute mesenteric ischaemia showed that the prognosis after acute mesenteric venous thrombosis is better than that following acute arterial mesenteric ischaemia; the prognosis after mesenteric arterial embolism is better than that after arterial thrombosis or non-occlusive ischaemia; the mortality rate following surgical treatment of arterial embolism and venous thrombosis (54·1 and 32·1 per cent respectively) is less than that after surgery for arterial thrombosis and non-occlusive ischaemia (77·4 and 72·7 per cent respectively); and the overall survival after acute mesenteric ischaemia has improved over the past four decades.

Conclusion
There are large differences in prognosis after acute mesenteric ischaemia depending on aetiology. Surgical treatment of arterial embolism has improved outcome whereas the mortality rate following surgery for arterial thrombosis and non-occlusive ischaemia remains poor.
Enantioselectivity of inhibition of cytochrome P450 3A4 (CYP3A4) by ketoconazole: Testosterone and methadone as substrates
Authors: Dilmaghanian Shahrzad , Gerber John G. , Filler Scott G. , Sanchez Angela , Gal Joseph 
Published: January 2004

AbstractRacemic ketoconazole (KTZ) was the first orally active azole antifungal agent used in clinical practice and has become widely used in the treatment of mucosal fungal infections associated with AIDS immunosuppression and cancer chemotherapy. However, the use of KTZ has been limited because of adverse drug–drug interactions. KTZ blocks ergosterol biosynthesis by inhibiting the fungal cytochrome P450 (CYP51). KTZ is also a potent inhibitor of human cytochrome P450 3A4 (CYP3A4) enzyme, the major drug‐metabolizing CYP isozyme in the human liver. We examined the enantioselective differences of KTZ in the inhibition of human CYP3A4 and in antifungal action. Dextro‐ and levo‐KTZ exhibited modest enantioselective differences with respect to CYP3A4 inhibition of testosterone and methadone metabolism. For both substrates levo‐KTZ was approximately a 2‐fold more potent inhibitor. We examined the enantioselective differences in the in vitro activity of KTZ against medically relevant species of Candida and Aspergillus, as well as Cryptococcus neoformans. Overall, levo‐KTZ was 2–4‐fold more active than dextro‐KTZ. Therefore, levo‐KTZ is a more potent inhibitor of CYP3A4 and has stronger in vitro antifungal activity. Chirality 16:79–85, 2004. © 2004 Wiley‐Liss, Inc.
NMR studies of chiral recognition by cyclodextrins
Authors: Dodziuk Helena , Koźmiński Wiktor , Ejchart Andrzej 
Published: January 2004

AbstractChiral recognition by cyclodextrins is of considerable importance, especially for pharmaceutical industry, in view of the possible side effects of the second enantiometer of chiral drugs. In general, it manifests itself in all NMR parameters (chemical shifts, coupling constants, NOE and ROE effects, and relaxation rates) on one hand. On the other hand, it allows one to determine the thermodynamic parameters characterizing diastereomeric complexes formed by cyclodextrins with enantiomeric guests. After an introduction and a general discussion of NMR manifestations of chiral recognition by cyclodextrin, the existing literature data on this problem will be discussed herein. Chirality 16:90–105, 2004. © 2004 Wiley‐Liss, Inc
Stereospecific synthesis of “para‐hydroxymexiletine” and sodium channel blocking activity evaluation
Authors: Catalano Alessia , Carocci Alessia , Fracchiolla Giuseppe , Franchini Carlo , Lentini Giovanni , Tortorella Vincenzo , De Luca Annamaria , De Bellis Michela , Desaphy Jean‐Francois , Conte Camerino Diana 
Published: January 2004

AbstractBoth enantiomers of “para‐hydroxymexiletine” (PHM), one of the main metabolites of mexiletine, were synthesized and fully characterized. Properties of (R)‐ and (S)‐PHM, in terms of blocking potency and stereoselectivity on frog skeletal muscle Na+ channels, were evaluated. The presence of a hydroxy group on the aryloxy moiety in the 4‐position, as in PHM, reduced potency with respect to mexiletine in reducing INa max. However, PHM showed clear use‐dependent behavior similar to that of mexiletine and, in contrast with what is observed with the parent compound, maintained its stereoselectivity during the use‐dependent block. Chirality 16:72–78, 2004. © 2004 Wiley‐Liss, Inc.
Stereoselectivity in the placental transfer and kinetic disposition of racemic bupivacaine administered to parturients with or without a vasoconstrictor
Authors: Papini Olga , Do Carmo Silva Mathes Ângelo , Pereira Da Cunha Sergio , Lucia Lanchote Vera 
Published: January 2004

AbstractThe aim of the present study was to investigate the stereoselectivity in the kinetic disposition and the transplacental distribution of bupivacaine in term parturients during labor. Maternal age ranged from 18–37 years and fetal gestational age from 37.6–41.5 weeks. Healthy parturients (n = 23) received epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine (group B). Maternal venous blood was sampled at regular intervals until 8 h after drug administration and umbilical venous blood was obtained at delivery. Bupivacaine enantiomers were determined in plasma samples by HPLC using a Chiralcel® OD‐R column and a UV detector. One‐ or two‐compartment models were fitted to data and differences between the (+)‐(R) and (–)‐(S) enantiomers were compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine was evaluated using the unpaired Mann‐Whitney test (P< 0.05). The disposition of bupivacaine in maternal plasma was stereoselective, with higher Vd/f (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and Cl/f (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t1/2β (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being observed for (+)‐(R)‐bupivacaine. The combined administration of epinephrine resulted in higher Vd/f (197.86 vs. 140.60 L for (+)‐(R) and 169.46 vs. 132.81 L for (–)‐(S)) and t1/2β values (4.36 vs. 3.24 h for (+)‐(R) and 4.45 vs. 3.30 h for (–)‐(S)). The transplacental distribution of bupivacaine was stereoselective only when bupivacaine was administered without epinephrine (group B), with a higher cord blood/maternal blood ratio being observed for (–)‐(S)‐bupivacaine (0.40 vs. 0.35). Chirality 16:65–71, 2004. © 2004 Wiley‐Liss, Inc.
Enantioselective reactions of α‐lithiated allyl aryl sulfides using chiral bis(oxazoline)s
Authors: Nakamura Shuichi , Kato Toru , Nishimura Haruka , Toru Takeshi 
Published: January 2004

AbstractThe reaction of α‐lithio allyl aryl sulfides, generated by treatment with n‐BuLi and chiral ligands at −78°C, with ketones was examined. The α‐addition products were formed in preference to the γ‐addition products. The enantioselectivity of the α‐addition products varied depending on the chiral ligand, and bis(oxazoline)‐tBu showed the highest enantioselectivity. Chirality 16:86–89, 2004. © 2004 Wiley‐Liss, Inc.
Allylation and propargylation of chiral cyanopropanoates: An efficient route to long chain α‐substituted α‐methyl α‐amino acids
Authors: Cativiela Carlos , Díaz‐De‐Villegas María D. , Gálvez José A. , Ronco Eva 
Published: January 2004

Abstractα‐Methyllysine and 2‐amino‐2‐methylundecanoic acid, two α,α‐disubstituted unnatural glycines, were synthesized using highly diastereoselective allylation or propargylation of chiral (1S,2R,4R)‐10‐dicyclohexylsulfamoylisobornyl 2‐cyanopropanoate as the key step to introduce the long side chain. Chirality 16:106–111, 2004. © 2004 Wiley‐Liss, Inc.
2‐(2,3‐Dihydro‐1H‐indol‐3‐yl)ethanol: Synthesis, separation of enantiomers, and assignment of absolute stereochemistry by X‐ray structure analysis
Authors: Frydenvang Karla , Bech Sommer Michael , Heckmann Dieter , Nielsen Ole , Bang‐Andersen Benny 
Published: January 2004

AbstractThe first direct resolution of racemic 2‐(2,3‐dihydro‐lH‐indol‐3‐yl)ethanol—prepared by catalytic hydrogenation of 2‐(lH‐indol‐3‐yl)ethanol—has been accomplished by chiral simulated moving bed (SMB) chromatography. The single enantiomers were isolated as their dihydrogen phosphate salts. Single‐crystal X‐ray analyses were successful, revealing that the (+)‐enantiomer of 2‐(2,3‐dihydro‐lH‐indol‐3‐yl)ethanol has the (S) configuration. Chirality 16:126–130, 2004. © 2004 Wiley‐Liss, Inc.
In vitro release and stereoselective disposition of flurbiprofen loaded to poly(D,L‐lactide‐ co‐glycolide) nanoparticles in rats
Authors: Radwan Mahasen A. , Aboul‐Enein Hassan Y. 
Published: January 2004

AbstractFlurbiprofen (FL) is a chiral 2‐arylpropionate used clinically as the racemate (rac‐FL). This study was undertaken to investigate the influence of sustained release formulation on the pharmacokinetics of flurbiprofen enantiomers (−) ‐R‐FL and (+)‐S‐FL. Therefore, a stereoselective high‐performance liquid chromatographic (HPLC) method was developed and validated for the rapid, quantitative determination of (−)‐R‐FL and (+)‐S‐FL in rat plasma. Flurbiprofen‐loaded poly(D,L‐lactide‐co‐glycolide) nanoparticles (rac‐FL‐PLGA) were prepared by in emulsion–solvent evaporation technique. Optimum conditions for rac‐FL‐PLGA nanoparticle preparation were considered, and the in vitro release of rac‐FL, R‐FL, and S‐FL were followed up to 48 h in phosphate buffer (pH 7.4). The three tested formulations revealed approximately zero‐order release of either (−)‐R‐FL or S‐FL up to 24 h with r ≥ 0.97.Surprisingly, there was no significant difference between t50% of the three formulations (21.6 ± 1.1 h). The stereoselective disposition of the sustained release rac‐FL deliverv system was investigated in rats. There was a rapid release of R‐FL, S‐FL, or rac‐FL followed by a slower one and Cmax values were observed after 2.5 ± 2.5, 8.3 ± 3.4 and 8.86 ± 3.6 h of (−)‐R‐FL, (+)‐S‐FL, and rac‐FL, respectively, after nanoparticle administration. PLGA nanoparticles increased the mean retention time (MRT) of S‐FL by 2.7‐fold, from 6.8 to 16.3 h, compared to rac‐FL. Although the dose of rac‐FL‐PLGA nanoparticles was only 2.5 times higher than that of the drug in the suspension, the mean (+)‐S‐FL concentration after 12 h was 3.4 times higher in the case of nanoparticles than after the free form, 10.35 ± 1.6 and 3.04 ± 1.1 mg/l, respectively. The area under the concentration‐time curve (AUC) values of (+)‐S‐FL and rac‐FL were about 2.5‐fold higher after the nanoparticles compared to suspension, while the AUC of the (−)‐R‐FL was about 3.5 times higher. This difference may indicate that the two enantiomers have different absorption kinetics. The present study provides evidence that the sorption of racemic flurbiprofen to PLGA nanoparticles was successful in maintaining (at least up to 12 h) elevated plasma drug concentrations of (+)‐S‐FL in rats. Chirality 16:119–125, 2004. © 2004 Wiley‐Liss, Inc.
Chiral symmetry‐breaking transition in growth front of crystal phase of 1,1′‐binaphthyl in its supercooled melt
Authors: Asakura Kouichi , Nagasaka Yasushi , Hidaka Masashi , Hayashi Masato , Osanai Shuichi , Kondepudi Dilip K. 
Published: January 2004

AbstractAlthough the theory of spontaneous chiral symmetry‐breaking in open systems was proposed some time ago, experimental realization of this phenomenon has not been achieved. In this article, we note that the crystal growth front of 1,1′‐binaphthyl shows many of the characteristics of an open system in which chiral symmetry‐breaking has occurred. We studied the temperature profiles of the crystallizing surface and obtained X‐ray diffraction data of the crystals grown from the melt under controlled conditions. The data show that, under appropriate conditions, the observed bimodal probability distribution of enantiomeric excess (ee) with maxima ∼60% is due exclusively to chiral crystals and not due to racemic crystals of 1,1′‐binaphthyl that can also form at large supercooling. The mass independence of the ee shows that the growing front maintains a constant ee, which is a clear signature of open systems in steady state. Chirality 16:131–136, 2004. © 2004 Wiley‐Liss, Inc.
Pharmacokinetics of the enantiomers of trans‐tramadol and its active metabolite, trans‐O‐demethyltramadol, in healthy male and female chinese volunteers
Authors: Hui‐chen Liu , Yang Yu , Na Wang , Ming Deng , Jian‐fang Liu , Hong‐yuan Xue 
Published: January 2004

AbstractBy using a high‐performance capillary electrophoresis method, the pharmacokinetics of the enantiomers of trans‐tramadol (trans‐T) and its active metabolite, trans‐O‐demethyltramadol (M1), was studied in healthy male and female Chinese volunteers after oral administration of 100 mg trans‐T hydrochloride. The values of Cmax for the enantiomers of trans‐T and M1, and AUC0–∞ for (–)‐trans T, (+)‐M1, and (–)‐M1 were higher in females than in males. The values of Vd/F for the enantiomers of trans‐T and CLr for (+)‐M1 were lower in females than in males. The value of t1/2 for (–)‐M1 was longer in females than in males. There were significant differences in pharmacokinetic parameters of the two enantiomers of trans‐T or M1 both in males and in females. The (+)/(–)‐enantiomeric ratios of tmax, Vd/F for trans‐T in males were significantly different from those in females and the (+)/(–)‐enantiomeric ratios of pharmacokinetic parameters for M1 in males were similar to those in females. There are gender‐related differences in the pharmacokinetics of the enantiomers of trans‐T and M1 which may be due to the greater body weights for men and/or the higher CYP2D6 activity in women. The pharmacokinetics of trans‐T and M1 is stereoselective in men and women. There is a gender‐related difference in the stereoselectivity in pharmacokinetics of trans‐T in human and the stereoselectivity in pharmacokinetics of M1 in men is similar to that in women. Chirality 16:112–118, 2004. © 2004 Wiley‐Liss, Inc.
“Viele Köche verderben den Brei” – H.Koch, H. P. G.Koch, K.Koch, W.Kochund W. D. J.Kochals Gefäßpflanzen‐Autoren in europäischen Basisfloren und Standardlisten
Authors: Raus Th. 
Published: December 2003

AbstractBei Namen von Gefäßpflanzentaxa mit bibliographischem Zitat wird die AutorbezeichnungKochin hohem Maße unklar und verwirrend verwendet. Rund 67 % von 1121 in fünf zeitgenössischen Basisfloren und Standardlisten exemplarisch nachgeprüftenKoch‐Zitaten entsprechen nicht dem empfohlenen internationalen Standard des Autorenlexikons vonBrummitt&Powell(Authors of Plant Names, Kew 1992). Zahlreiche Taxa werden dadurch scheinbar, einige tatsächlich nicht dem zutreffenden Beschreiber bzw. Kombinationsautor zugeschrieben. In tabellarischer Form werden Hilfen zur Überprüfung unkritischerKoch‐Zitate geboten.
Seedling diversity in Araceae and its systematic implications
Authors: Tillich H.‐J. 
Published: December 2003

AbstractThe paper gives a detailed morphological analysis of seedlings of 45 genera of Araceae. Including all seedling descriptions in the literature, informations for 60 genera are available now.Generally, the cotyledon is subdivided into a bifacial hypophyll and a unifacial hyperphyll. The presumably most ancestral seedling type is characterised by a compact cotyledon, the cotyledonary hyperphyll is a haustorium inside the copious endosperm. Furthermore, it has a well growing primary root, the plumule gives rise to one to several cataphylls until the first eophylls develop. Starting from this type, two very different evolutionary lines can be followed. The first one leads to a seedling of which the cotyledonary hypophyll is transformed to an assimilating, blade‐like organ, while the minute unifacial hyperphyll is haustorial and hidden in the seed (e.g. Philodendron, Colocasia, Sauromatum ). The second line leads to endospermless seeds, the cotyledonary hyperphyll is transformed to a voluminous storage organ, hypocotyl and primary root are completely missing (e.g. Aglaonema, Arophyton, Nephthytis ). Many tribes are characterised by one or by two closely related seedling types, but a few tribes encompass a surprising diversity of seedlings (e. g. Caladieae, Spathicarpeae, Areae). The possible adaptive value of different seedlings is discussed.
Vegetationskundliche Untersuchungen im Dornod Aimak (Ost‐Aimak) der Mongolei
Authors: Hilbig W. 
Published: December 2003

AbstractWährend einer im Sommer 2002 durchgeführten botanischen Exkursion in den Dornod Aimak (Ost‐Aimak) der Mongolei wurden in den pflanzengeographischen Bezirken Ostmongolei und Chingan‐Vorgebirge Vegetationsuntersuchungen durchgeführt.Vor allem den weitverbreiteten Steppen und Wiesensteppen, den Ulmen‐Buschwäldern mit Paeonio‐lactiflorae‐Ulmetum pumilae ass. nov., Dünenkiefernwäldern, Spiraea‐, Cotoneaster‐ und Armeniaca‐ Gebüschen und der Salzvegetation wurde Aufmerksamkeit geschenkt. Aber auch Weidengebüsche, Weiderasen und Wiesen sowie Hochstaudenbestände, Röhrichte und andere Pflanzenbestände der Flussauen wurden wie die Ruderalbestände der Siedlungen in die Beobachtungen und Untersuchungen einbezogen.Als Besonderheit der Gehölzvegetation konnte in einer kleinen Schlucht im Chingan‐Vorgebirge ein Laubwaldvorkommen mit Padus avium und Malus baccata erfasst werden. Auf die Beziehungen der angetroffenen Pflanzengesellschaften zu entsprechenden Beständen in der chinesischen Barga und der Inneren Mongolei wird hingewiesen.