bluuebunny/crossref_metadata_2025 huggingface dataset:
Feasibility and safety of concomitant left internal mammary arteriography at the setting of the right transradial coronary angiography
Authors: Cha Kwang Soo , Kim Moo Hyun
Published: October 2002

We investigated the feasibility and safety of concomitant left internal mammary artery (LIMA) angiography at the setting of the right transradial coronary angiography (TRCA). LIMA angiography was performed using a 5 Fr Simmons‐type catheter with a newly modified tip in 184 consecutive patients. The catheter was reformed in the descending (new method) or ascending (traditional method) aorta and manipulated to cannulate the left subclavian artery and LIMA orifice. LIMA angiography was performed selectively in 164 patients (89%) and semiselectively (when the catheter tip reached and was directed to the mammary artery orifice) in 20 patients. There were no procedure‐related complications. The image quality of all the semiselective angiograms was also determined satisfactory. Total procedural time was 223 ± 168 sec. The catheter was reformed using the new method in 160 patients (87%). The catheter reformation time and total procedure time were significantly shorter with the new method than with the traditional method (18 ± 8 vs. 117 ± 115 sec, p = 0.000; 204 ± 191 vs. 309 ± 139 sec, p = 0.021, respectively). In conclusion, LIMA angiography can be performed readily and safely at the setting of the right TRCA using a Simmons‐type catheter. The image quality of the LIMA angiograms is sufficient to obviate the need of the second preoperative angiography via another route. Cathet Cardiovasc Intervent 2002;56:188–195. © 2002 Wiley‐Liss, Inc.
Retinal embolization during carotid angioplasty and stenting: Mechanisms and role of cerebral protection systems
Authors: Wilentz James R. , Chati Zukai , Krafft Veronique , Amor Max
Published: October 2002

Carotid stenting has become an accepted alternative to endarterectomy, but fear of embolic stroke has impeded its generalized application. The retina provides a unique observatory for the study of emboli, which may occur either directly or indirectly via collaterals to the ophthalmic artery. Systems under development for cerebral protection differ in their capacity to trap small emboli and in their protection of the collateral circulation. We evaluated 118 sequential patients undergoing carotid stenting using fundoscopy, fluorescein retinal angiography, and visual field examination. The site and size of emboli was assessed, and degree of edema estimated. All patients were treated using distal protection during carotid stent implantation: 38 patients with the Théron system (using routine flushing toward the external carotid) and 80 patients with the Percusurge® system (aspiration only). Retinal embolization occurred in 6 of the 118 patients (4%), of whom 2 were symptomatic (1.7%). Using the Théron system, 5 of 38 patients (13.2%) had emboli while 1 of 80 (1.25%) had emboli using the Percusurge system (P = 0.019). Symptoms occurred only with emboli >20 μm. Symptomatic retinal embolization is uncommon during carotid stenting, but is more likely when external to internal carotid collaterals are not protected. Cerebral protection system designs should take into consideration the existence of collaterals and the need to protect against smaller sized emboli, which may cause blindness in the retinal circulation. Cathet Cardiovasc Intervent 2002;56:320–327. © 2002 Wiley‐Liss, Inc.
Initial and late results after catheter intervention for neonatal critical pulmonary valve stenosis and atresia with intact ventricular septum: A technique in continual evolution
Authors: Weber Howard S.
Published: October 2002

Critical pulmonary valve stenosis or atresia with intact ventricular septum is a rare congenital cardiac defect that can be technically difficult to alleviate in the catheterization laboratory. Over the past 10 years, several techniques and modifications with variable results have been advocated to facilitate the valvuloplasty procedure. This report describes a single operator's experience using various techniques in 28 neonates with critical pulmonary stenosis or atresia who were considered candidates for transcatheter intervention. The first two patients underwent a gradational balloon valvuloplasty approach that resulted in prolonged fluoroscopy exposure. Thereafter, a “snare assisted” umbilical artery approach was developed which facilitated the valvuloplasty procedure and resulted in significantly fewer balloons used and shorter fluoroscopy times. Early in our experience, stiff guidewire perforation of atretic pulmonary valves was used, whereas in our last two patients, a simplified perforation technique with a new 0.9‐mm excimer laser catheter was used. Late echocardiographic and clinical follow‐up evaluation in 27 patients demonstrates persistent gradient relief, resolution of tricuspid valve insufficiency, and elimination of right to left shunting at the atrial level. Balloon valvuloplasty is the treatment of choice for critical pulmonary valve stenosis or atresia with intact ventricular septum. When necessary, the use of umbilical artery “snare assistance” facilitates the valvuloplasty technique and shortens procedure time while laser perforation is currently preferable for perforation of the atretic pulmonary valve. Cathet Cardiovasc Intervent 2002;56:394–399. © 2002 Wiley‐Liss, Inc.
Multivariate image segmentation based on geometrically guided fuzzy C‐means clustering
Authors: Noordam J. C. , van den Broek W. H. A. M.
Published: October 2002

This paper describes a new approach to geometrically guided fuzzy clustering. A modified version of fuzzy C‐means (FCM) clustering, conditional FCM, is extended to incorporate a priori geometrical information from the spatial domain in order to improve image segmentation. This leads to a new algorithm (GGC‐FCM) where the cluster guidance is determined by the membership values of neighbouring pixels. GGC‐FCM is tested on synthetic and real images to demonstrate the improved image segmentation compared to traditional FCM. Copyright © 2002 John Wiley & Sons, Ltd.
A phenomenological study of ripening of salted herring. Assessing homogeneity of data from different countries and laboratories
Authors: Bro Rasmus , Nielsen Henrik Hauch , Stefánsson Guðmundur , Skåra Torstein
Published: October 2002

Data from ripening experiments of herring carried out at three Nordic fishery research institutions in the period 1992–1995 were collected and analyzed by multivariate analysis. The experiments were carried out at different times, with different stocks as raw material, using different types of treatments and analyzed in different laboratories. The question considered here is whether these data can be assumed to be one homogeneous set of data pertaining to ripening of salted herring or whether data from different labs, stocks, etc. must be considered independently. This is of importance for further research into ripening processes with these and similar data. It is shown in this paper that all data can be considered as one homogeneous data set. This is verified using resampling where latent structures are compared between different sample sets. This is done indirectly by testing regression models, that have been developed on one sample set, on other sample sets. It is also done directly by monitoring the deviation in latent structure observed between different sample sets. No formal statistical test is developed for whether samples can be assumed to stem from the same population. Although this can easily be envisioned, it was exactly the need for a more intuitive and visual test that prompted this work, developing different exploration tools that visually make it clear how well the data can be assumed to derive from the same population. Subsequently analyzing the data as one homogeneous group provides new information about factors that govern the ripening of salted herring and can be used in new strategic research as well as in industrial practice. Copyright © 2002 John Wiley & Sons, Ltd.
Modelling near‐infrared signals for on‐line monitoring in cheese manufacture
Authors: Mertens B. J. A. , O'Donnell C. P. , O'Callaghan D. J.
Published: October 2002

This paper considers the analysis of a continuously monitored near‐infrared reflectance signal at a single wavelength for the calibration of a process parameter in an application to food engineering for quality control. We describe how we may summarize the information in the observed signals by postulating an explicit statistical model on the signal. An exploratory data analysis may then be carried out on the profile summaries to evaluate whether and how the functional data provide information on the parameter which we would like to calibrate. From a conceptual point of view, such an approach is not dissimilar to principal component regression methods which use an intermediate decomposition through which information is summarised for calibration of a response. The paper demonstrates how the approach leads to important insights into the manner in which the functional data provide the required information on the desired outcome variable, in the context of the practical application in quality control which is discussed and by using a designed experiment. Calculations are implemented through the Gibbs sampler. Calibration of the prediction equation takes place through meta‐analysis of the summarized profile data in order to take the uncertainty inherent in the summaries into account. Copyright © 2002 John Wiley & Sons, Ltd.
Evaluation of mass spectra from organic compounds assumed to be present in cometary grains. Exploratory data analysis
Authors: Werther W. , Demuth W. , Krueger F. R. , Kissel J. , Schmid E. R. , Varmuza K.
Published: October 2002

From about 60 organic compounds, mass spectra have been measured by 252Cf ionization mass spectrometry (PDMS). The substances and the data are relevant for future experiments near a comet by the space research project COSIMA (a time‐of‐flight mass spectrometer for secondary ions) on board of the ESA mission ROSETTA. The spectra have been transformed into a set of appropriate spectral features (x‐variables); the corresponding chemical structures have been characterized by binary substructure descriptors (y‐variables). PLS‐2 mappings exhibit good correlations between the x‐ and the y‐components. PLS spectrum–substructure mappings supported the detection of structural classes that are well reflected by spectral data. PCA with spectral data was less efficient for this purpose. The found structural classes are candidates for the development of spectral classifiers for the COSIMA project. Interpretation of the loading plots indicated spectral properties which are characteristic for substance classes. Copyright © 2002 John Wiley & Sons, Ltd.
An investigation of orthogonal signal correction algorithms and their characteristics
Authors: Svensson O. , Kourti T. , MacGregor J. F.
Published: October 2002

Six different algorithms for orthogonal signal correction (OSC) are studied and compared both from an algorithmic point of view and from a prediction and analysis point of view. The algorithms have appeared under the names OSC (three alternative algorithms), direct orthogonalization (DO) and orthogonal projection to latent structures (OPLS). These algorithms can be divided into two groups. The first group has the ability to reduce the number of PLS components in the calibration models significantly by removing only one orthogonal component. The second group reduces the complexity of the calibration model by one PLS component for each orthogonal component removed. The methods are evaluated and compared using both simulated and real calibration data sets. In some cases the OSC algorithms can have quite different behaviors, such as when non‐linearities are present. However, in all cases we have studied, none of the OSC algorithms provided a significant improvement in the calibration models over using PLS on the raw data. The main advantage with OSC may lie in the possibly easier interpretation and understanding from the analysis of corrected data. Analysis of the orthogonal information removed with OSC might also be beneficial. Copyright © 2002 John Wiley & Sons, Ltd.
Multivariate calibration stability: a comparison of methods
Authors: Marx Brian D. , Eilers Paul H. C.
Published: October 2002

In the multivariate calibration framework we revisit and investigate the prediction performance of three high‐dimensional modeling strategies: partial least squares, principal component regression and P‐spline signal regression. Specifically we are interested in comparing the stability and robustness of prediction under differing conditions, e.g. training the model under one temperature and using it to predict under differing temperatures. An example illustrates stability comparisons. Copyright © 2002 John Wiley & Sons, Ltd.
Hard‐modelled trilinear decomposition (HTD) for an enhanced kinetic multicomponent analysis
Authors: Neuhold Yorck‐Michael , Maeder Marcel
Published: October 2002

We present a novel approach for kinetic, spectral and chromatographic resolution of trilinear data sets acquired from slow chemical reaction processes via repeated chromatographic analysis with diode array detection. The method is based on fitting rate constants of distinct chemical model reactions (hard‐modelled, integrated rate laws) by a Newton–Gauss–Levenberg/Marquardt (NGL/M) optimization in combination with principal component analysis (PCA) and/or evolving factor analysis (EFA), both known as powerful methods from bilinear data analysis. We call our method hard‐modelled trilinear decomposition (HTD). Compared with classical bilinear hard‐modelled kinetic data analysis, the additional chromatographic resolution leads to two major advantages: (1) the differentiation of indistinguishable rate laws, as they can occur in consecutive first‐order reactions; and (2) the circumvention of many problems due to rank deficiencies in the kinetic concentration profiles. In this paper we present the theoretical background of the algorithm and discuss selected chemical rate laws. Copyright © 2002 John Wiley & Sons, Ltd.
Multivariate data analysis and bivariate regression studies applied to comparison of two multi‐elemental methods for analysing wine samples
Authors: Sagrado S. , Pérez‐Jordan M. Y. , Pastor A. , Salvador A. , de la Guardia M.
Published: October 2002

Two inductively coupled plasma mass spectrometry (ICP‐MS) methods which permit multi‐elemental analysis in wine samples have been compared following two strategies. First, a multivariate tool based on principal component analysis (PCA) was employed for a global (all analytes) qualitative comparison of the two methods. A single plot based on the confidence limits of the Q and T2 PCA model statistics corresponding to the ‘standard’ method results (calibration set) was used to check the comparability of the ‘candidate’ method (test samples). The residual matrix (after test matrix interpolation into the PCA model) gives qualitative information about the nature of the main errors. This approach is compatible with the presence of missing data. Second, comparison of the methods, analyte by analyte, based on bivariate least squares (BLS) regression was used. This approach, which uses the uncertainty information from both methods and performs a joint test for the intercept and slope parameters, permits appropriate comparison when the two methods have non‐constant standard deviations. Copyright © 2002 John Wiley & Sons, Ltd.
Children with severe learning disabilities: needs, services and costs
Authors: Beecham Jennifer , Chadwick Oliver , Fidan Dogan , Bernard Sarah
Published: October 2002

This study looks at how services are used by children with severe learning disabilities living at home and explores the associated total and component costs. Multivariate and bivariate analyses are employed and the results interpreted alongside information on parents' perceptions of their children's needs for healthcare. There is some evidence to suggest costs were associated with greater needs but there is also evidence of under‐provision of formal care supports, particularly mental health services. Copyright © 2002 John Wiley & Sons, Ltd.
Mechanism of asymmetric hydrogenation by rhodium complexes with unsymmetrical P‐chirogenic bisphosphine ligands
Authors: Ohashi Atsushi
Published: October 2002

Using a series of the rhodium complexes with (1S,2S)‐1‐(R1)methylphosphino‐2‐(R2)(R3)phosphinoethane (R1, R2 and R3 = 1‐adamantyl, t‐butyl, cyclohexyl, cyclopentyl, methyl; abbreviated as unsymmetrical BisP*), very high enantioselectivities were observed when the di‐ or tri‐ substituted and tetra‐substituted dehydro‐α‐amino acid derivatives were used as the substrates. The main factor to give high enantioselectivity is the repulsive interaction between the functional groups of the substrate and the bulky substituents of the unsymmetrical BisP*. Since the unsymmetrical BisP* has two independent chiral phosphorous atoms in the vicinity of the active site, the higher enantioselectivity than those by the C2 symmetric BisP* complexes can be obtained. Moreover, the fine‐tuning to obtain extremely high enantioselectivity may be possible by changing the combination of the substituents on the two phosphorous atoms of the unsymmetrical BisP*. Chirality 14:573–577, 2002. © 2002 Wiley‐Liss, Inc.
Enantioselectivity in the steady‐state pharmacokinetics and transplacental distribution of pindolol at delivery in pregnancy‐induced hypertension
Authors: Gonçalves Paulo Vinicius Bernardes , Matthes Ângelo Do Carmo Silva , Da Cunha Sérgio Pereira , Lanchote Vera Lucia
Published: October 2002

Nine patients taking oral doses of 10 mg/12 h rac‐pindolol as part of their treatment for hypertension in pregnancy were recruited for the study. Maternal and fetal gestational age ranged from 20–38 years and 28–41 weeks, respectively. Blood was collected from the umbilical cord vein and from the mother from zero to 12 h after drug administration. Urine was collected for 12 h after rac‐pindolol administration at the following intervals: 0–3, 3–6, 6–9, and 9–12 h. Plasma and urine concentrations of the pindolol enantiomers were determined by HPLC using a Chiralpak® AD chiral column and fluorescence detection. The data were fitted to a one‐compartment model and differences between (+)‐R and (−)‐S enantiomers were compared by the pairedt‐test (P< 0.05). Mean results are reported. The disposition of pindolol in maternal plasma was stereoselective, with higher AUC(84.34 vs. 95.69 ng.h/ml) and ClRvalues (9.16 vs. 10.85 L/h) and lower Vd/f (251.38 vs. 225.17 L) and Cl/f (62.48 vs. 55.74 L/h) for the (+)‐R pindolol. The transplacental distribution of pindolol was not stereoselective. Cord, plasma, and presumably fetal, concentrations of the pindolol enantiomers were 56% of the maternal plasma concentrations up to 6 h after the last dose. Chirality 14:683–687, 2002. © 2002 Wiley‐Liss, Inc.
Arabidopsis thaliana protein, ATK1, is a minus‐end directed kinesin that exhibits non‐processive movement
Authors: Marcus Adam I. , Ambrose J. Christian , Blickley Lisa , Hancock William O. , Cyr Richard J.
Published: October 2002

The microtubule cytoskeleton forms the scaffolding of the meiotic spindle. Kinesins, which bind to microtubules and generate force via ATP hydrolysis, are also thought to play a critical role in spindle assembly, maintenance, and function. The A. thaliana protein, ATK1 (formerly known as KATA), is a member of the kinesin family based on sequence similarity and is implicated in spindle assembly and/or maintenance. Thus, we want to determine if ATK1 behaves as a kinesin in vitro, and if so, determine the directionality of the motor activity and processivity character (the relationship between molecular “steps” and microtubule association). The results show that ATK1 supports microtubule movement in an ATP‐dependent manner and has a minus‐end directed polarity. Furthermore, ATK1 exhibits non‐processive movement along the microtubule and likely requires at least four ATK1 motors bound to the microtubule to support movement. Based on these results and previous data, we conclude that ATK1 is a non‐processive, minus‐end directed kinesin that likely plays a role in generating forces in the spindle during meiosis. Cell Motil. Cytoskeleton 52:144–150, 2002. © 2002 Wiley‐Liss, Inc.
Diverse chemotactic responses of Dictyostelium discoideum amoebae in the developing (temporal) and stationary (spatial) concentration gradients of folic acid, cAMP, Ca2+ and Mg2+
Authors: Korohoda Włodzimierz , Madeja Zbigniew , Sroka Jolanta
Published: October 2002

The responses of Dictyostelium discoideum amoebae to developing (temporal) and stationary (spatial) gradients of folic acid, cAMP, Ca2+, and Mg2+ were studied using the methods of computer‐aided image analysis. The results presented demonstrate that the new type of experimental chambers used for the observation of single cells moving within the investigated gradients of chemoattractants permit time lapse recording of single amoebae and determination of the trajectories of moving cells. It was found that, besides folic acid and cAMP (natural chemoattractants for Dictyostelium discoideum amoebae), also extracellular Ca2+ and Mg2+ are potent inducers of these cells' chemotaxis, and the amoebae of D. discoideum can respond to various chemoattractants differently. In the positively developing gradients of folic acid, cAMP, Ca2+, and Mg2+ oriented locomotion of amoebae directed towards the higher concentration of the tested chemoattractants was observed. However, in the negatively developing (temporal) and stationary linear (spatial) gradients, the univocal chemotaxis of amoebae was recorded only in the case of the Mg2+ concentration gradient. This demonstrates that amoebae can respond to both developing and stationary gradients, depending upon the nature of the chemoattractant. We also investigated the effects of chosen inhibitors of signalling pathways upon chemotaxis of D. discoideum amoebae in the positively developing (temporal) gradients of tested chemoattractants. Verapamil was found to abolish the chemotaxis of amoebae only in the Ca2+ gradients. Pertussis toxin suppressed the chemotactic response of cells in the gradients of folic acid and cAMP but did not prevent chemotaxis in those of Ca2+ and Mg2+, while quinacrine inhibited chemotaxis in the gradients of folic acid, cAMP, and Ca2+ but only slightly affected chemotaxis in the Mg2+ gradient. None of the tested inhibitors causes inhibition of cell random movement, when applied in isotropic solution. Also EDTA and EGTA up to 50 mM concentration did not inhibit locomotion of amoebae in control isotropic solutions. Cell Motil. Cytoskeleton 53:1–25, 2002. © 2002 Wiley‐Liss, Inc.
Significance of secondary ultrasonographic endometrial thickening in postmenopausal tamoxifen‐treated women
Authors: Cohen Ilan , Azaria Ron , Shapira Jeremiah , Yigael Dror , Tepper Ron
Published: October 2002

BACKGROUND

Ultrasonography has a limited value in endometrial assessment for identification of endometrial pathologies in postmenopausal tamoxifen‐treated patients.

METHODS

We compared the rate of endometrial pathologies and the mean ± SD of endometrial thickness diagnosed after the first and second transvaginal ultrasonographic studies performed on 55 postmenopausal tamoxifen‐treated patients with secondary endometrial thickening (Group I). This rate was also compared with 46 similar patients without secondary thickening (Group II). We also compared the mean ± SD of endometrial thickness detected in various ultrasonographic studies, as well as various clinical features.

RESULTS

A significantly higher rate of endometrial pathologies, including two cases of endometrial cancer identified in gynecologically asymptomatic patients (3.6%), was diagnosed in Group I after the second study compared with the first study (52.7% and 9.1%, respectively; P = 0.001) and compared with those diagnosed after the second study in Group II (30.4%; P = 0.03). There was a significant increase (74.7 ± 115%) in endometrial thickness after the second study compared with the first study performed on Group I (10.7 ± 5.53 mm and 16.59 ± 5.53 mm, respectively; P = 0.0001) and a significant difference in endometrial thickness demonstrated in the second study performed on Groups I and II (16.59 ± 5.53 mm and 11.4 ± 3.91 mm, respectively; P = 0.001).There were no significant differences in the time elapsed since the diagnosis of breast carcinoma and from the beginning of tamoxifen treatment to the performance of the first ultrasonographic study as well as the time elapsed between the first and second studies performed.

CONCLUSIONS

A significant increase (> 50%) in secondary endometrial thickening, measured ultrasonographically, in postmenopausal tamoxifen‐treated patients, is associated with a high rate of endometrial pathologies, including endometrial cancer. Cancer 2002;94:3101–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10587
Impact of thrombophilic gene mutations on thrombosis risk in patients with gastrointestinal carcinoma
Authors: Pihusch Rudolf , Danzl Gudrun , Scholz Michael , Harich Detlev , Pihusch Markus , Lohse Peter , Hiller Erhard
Published: October 2002

BACKGROUND

Patients with malignancies have an increased risk for thromboembolic events due to the release of tissue factor by the tumor, damage to the vessel wall, and immobilization. Moreover, tumors may improve their growth and metastatic spread by utilizing the coagulation system. To date, no information is available on the additional role of prothrombotic mutations in these patients.

METHODS

The prevalence of the factor V Leiden mutation (FVL) and the prothrombin G20210A mutation and of homozygosity for the methylenetetrahydrofolate reductase (MTHFR) C677T substitution has been analyzed in a cohort of 175 patients with gastrointestinal adenocarcinoma by the polymerase chain reaction‐restriction fragment length polymorphism technique.

RESULTS

6.9% of the patients were heterozygous for FVL, 5.7% were heterozygous for the prothrombin mutation, and 9.7% were homozygous for the MTHFR C677T mutation was detected in 9.7% of patients. Compared with the normal population, we found an increased prevalence of the prothrombin G20210A substitution (5.7% vs. 0.8%, P = 0.028). Thromboses were absent in 147 patients (Group A), whereas 28 of the patients suffered from thromboses during the period following tumor diagnosis (Group B). In Group A, 6.8% of the patients and 21.4% of the patients in Group B had a thrombosis before the diagnosis of cancer (P = 0.025, odds ratio [OR] 3.7). Heterozygous FVL was present in 4.8% of the patients in Group A and in 17.9% of the patients in Group B (P = 0.026, OR 4.4). In patients with thromboses before the detection of the tumor, the risk was elevated 6.3‐fold (25.0% vs 5.0%, P = 0.015). Heterozygosity for the prothrombin mutation and homozygosity for the MTHFR C677T substitution did not increase the incidence of thromboses.

CONCLUSIONS

We demonstrated a significant effect of FVL on thrombosis in patients with malignant disease. Most thromboses occurred during the first months after tumor diagnosis, implicating diagnostic and therapeutic procedures as important nongenetic risk factors for venous thromboembolism. Our data also indicate that the prothrombin G20210A mutation may be a possible cofactor in cancer pathogenesis. Cancer 2002;94:3120–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10590
Overexpression of cyclooxygenase‐2 is associated with a poor prognosis in patients with squamous cell carcinoma of the uterine cervix treated with radiation and concurrent chemotherapy
Authors: Kim Yong Bae , Kim Gwi Eon , Cho Nam Hoon , Pyo Hong Ryull , Shim Su Jung , Chang Sei Kyung , Park Hee Chul , Suh Chang Ok , Park Tchan Kyu , Kim Byung Soo
Published: October 2002

BACKGROUND

The objective of this study was to determine whether cyclooxygenase‐2 (COX‐2) overexpression was an indicator of prognosis in patients with International Federation of Gynecology and Obstetrics (FIGO) Stage IIB uterine cervical carcinoma who underwent radiation and concurrent chemotherapy.

METHODS

Seventy‐five patients with FIGO Stage IIB squamous cell carcinoma (SCC) of the uterine cervix who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996 were divided into two groups according to their COX‐2 level in an immunohistochemical study: the COX‐2 negative group (n = 54 patients) and the COX‐2 positive group (n = 21 patients). The clinicopathologic features, patterns of treatment failure, and survival data for patients in the COX‐2 positive group were compared with data from the patients in the COX‐2 negative group. Univariate and multivariate analyses were performed to determine the prognostic factors that influenced patient survival.

RESULTS

In the immunohistochemical study, COX‐2 overexpression was observed in approximately 30% of patients with FIGO Stage IIB SCC of the uterine cervix. With delayed regression to the initial treatment, the treatment failure rate of patients in the COX‐2 positive group was much higher compared with the treatment failure rate of patients in the COX‐2 negative group. The higher incidence of central failure and lymph node failure for patients in the COX‐2 positive group was statistically significant (48% for the COX‐2 positive group vs. 13% for the COX‐2 negative group). However, there was no difference in the incidence of hematogenous metastases between the two groups (5% for the COX‐2 positive group vs. 7% for the COX‐2 negative group). In addition, increased COX‐2 expression in tumor cells also was correlated with a shorter interval to tumor recurrence (median interval to recurrence, 9 months in the COX‐2 positive group vs. 26 months in the COX‐2 negative group). Compared with patients in the COX‐2 negative group, patients in the COX‐2 positive group had lower overall actuarial and disease free survival rates (overall 5‐year actuarial survival rates: 56% for the COX‐2 positive group vs. 94% for the COX‐2 negative group; P = 0.003). Univariate and multivariate analyses showed that COX‐2 overexpression was an independent prognostic factor that surpassed other well‐known clinicopathologic parameters.

CONCLUSIONS

COX‐2 overexpression can be used as a potent molecular risk factor in patients with FIGO Stage IIB SCC of the uterine cervix who are treated with radiotherapy and concurrent chemotherapy. Cancer 2002;95:531–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10684
The relevance of prostatectomy findings for brachytherapy selection in patients with localized prostate carcinoma
Authors: Pisansky Thomas M. , Blute Michael L. , Hillman David W. , Davis Brian J. , Haddock Michael G. , Suman Vera J. , Wilson Torrence M. , Zincke Horst
Published: October 2002

BACKGROUND

The efficacy of brachytherapy for patients with localized prostate carcinoma depends on adequate radiotherapeutic coverage of the primary tumor and its subclinical extraprostatic extensions. Predictive models based on pretherapy factors may be useful to estimate the likelihood for clinically relevant extraprostatic disease and may be incorporated into selection criteria for this procedure.

METHODS

Multivariate logistic regression model building was performed using pretherapy factors in 2905 surgically staged patients with localized prostate carcinoma to estimate the probability of seminal vesicle and/or lymph node involvement. Bootstrap methods were employed to assess the stability of the final model parameters and to determine the sensitivity and specificity of the final model.

RESULTS

Clinical tumor classification, biopsy Gleason score groupings, and serum prostate specific antigen (PSA) levels were associated with seminal vesicle and/or pelvic lymph node involvement. These factors were incorporated into a multivariate model that predicted for these adverse histopathologic features. Allowing for up to a 10% likelihood for seminal vesicle and/or pelvic lymph node involvement, patients with tumors classified as T1c–T2a, Gleason scores of 2–6, and PSA ≤ 16 ng/mL; or with tumors classified as T1c–T2a, Gleason scores of 7–10, and PSA ≤ 4 ng/mL; or with tumors classified as T2b–T2c, Gleason scores of 2–6, and PSA ≤ 6 ng/mL would be potential candidates for brachytherapy alone.

CONCLUSIONS

The predictive model presented may provide criteria whereby an adequately performed prostate brachytherapy procedure is expected to encompass the intraprostatic and adjacent extraprostatic disease. Prostate brachytherapy alone may be considered in these circumstances, whereas the addition of external beam radiotherapy may be reserved for patients with disease that is apt to extend beyond the brachytherapy target volume. Cancer 2002;95:513–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10697
Decreased Smad4 expression in the transforming growth factor‐β signaling pathway during progression of esophageal squamous cell carcinoma
Authors: Fukuchi Minoru , Masuda Norihiro , Miyazaki Tatsuya , Nakajima Masanobu , Osawa Hidenobu , Kato Hiroyuki , Kuwano Hiroyuki
Published: October 2002

BACKGROUND

Transforming growth factor‐β (TGF‐β) has antiproliferative effects in various cells, and inactivation of the TGF‐β signaling pathway contributes to tumor progression or development. Smad4, a tumor suppressor gene, is a central mediator in the signaling pathways of the TGF‐β superfamily. This study was undertaken to clarify the correlation between Smad4 expression and the clinicopathologic characteristics of patients with esophageal squamous cell carcinoma (SCC). The authors also investigated the expression of components of the TGF‐β signaling pathway in seven established cell lines derived from esophageal SCC.

METHODS

Immunohistochemistry for Smad4 using monoclonal anti‐Smad4 antibody was performed on surgical specimens obtained from 80 patients with esophageal SCC. In seven cell lines, the authors examined the expression of components of the TGF‐β signaling pathway using Western and Northern blot analyses.

RESULTS

There was a significant inverse correlation between Smad4 expression and both depth of invasion (P = 0.0008) and pathologic stage (P = 0.0079). The expression of Smad4 proteins could be detected in five of seven cell lines. The expression of TGF‐β type II receptor protein was decreased in two of seven cell lines, and the expression of both Smad2 and Smad3 proteins was decreased in only one cell line. The level of expression of Smad4 mRNA did not differ dramatically between cell lines and was not correlated with the quantity of Smad4 protein.

CONCLUSIONS

In this study, the expression of Smad4 protein appeared to be correlated with the depth of invasion of esophageal SCC. The loss of Smad4 expression was not regulated at the level of transcription. Cancer 2002;95:737–43. © 2002 American Cancer Society.

DOI 10.1002/cncr.10727
Predicting the survival of patients with breast carcinoma using tumor size
Authors: Michaelson James S. , Silverstein Melvin , Wyatt John , Weber Griffin , Moore Richard , Halpern Elkan , Kopans Daniel B. , Hughes Kevin
Published: October 2002

BACKGROUND

Tumor size has long been recognized as the strongest predictor of the outcome of patients with invasive breast carcinoma, although it has not been settled whether the correlation between tumor size and the chance of death is independent of the method of detection, nor is it clear how tumor size at the time of treatment may be translated into a specific expectation of survival. In this report, the authors provide such a method.

METHODS

A Kaplan–Meier survival analysis was carried out for a population of 1352 women with invasive breast carcinoma who were treated at the Van Nuys Breast Center between 1966 and 1990, and the data were analyzed together with survival data published by others.

RESULTS

The authors found that the survival of patients with invasive breast carcinoma was a direct function of tumor size, independent of the method of detection. The results showed that the correlation between tumor size and survival was well fit by a simple equation, with which survival predictions could be made from information on tumor size. For example, a comparison of three large populations studied over the last 5 decades revealed a marked improvement (≈ 35% absolute) in the survival of patients with invasive breast carcinoma diagnosed on clinical grounds that could be ascribed to a reduction in tumor size. However, the capacity of screening mammography to find smaller tumors remains the best way reduce breast carcinoma deaths, with the potential for adding an additional ≈ 20% absolute reduction in breast carcinoma deaths. The mathematic correlation between tumor size and survival is consistent with a biologic mechanism in which lethal distant metastasis occurs by discrete events of spread such that, for every invasive breast carcinoma cell in the primary tumor at the time of surgery, there is approximately a 1‐in‐1‐billion chance that a lethal distant metastasis has formed.

CONCLUSIONS

The correlation between tumor size and lethality is well captured by a simple equation that is consistent with breast carcinoma death as the result of discrete events of cellular spread occurring with small but definable probabilities. Cancer 2002;95:713–23. © 2002 American Cancer Society.

DOI 10.1002/cncr.10742
Effect of service screening mammography on population mortality from breast carcinoma
Authors: Feig Stephen A.
Published: October 2002

Breast cancer deaths have been reduced as much as 44% in Swedish counties that offer service screening mammography. In the United States, death rates from breast cancer are now approximately 39 percent lower than expected given the increased incidence of invasive carcinoma. This estimated reduction may be attributed to heightened awareness of breast cancer, increased utilization of screening mammography, and improved treatment. See also pages 458–69.
Onset of Tlx‐3 expression in the chick cerebellar cortex correlates with the morphological development of fissures and delineates a posterior transverse boundary
Authors: Logan Cairine , Millar Cassie , Bharadia Vinay , Rouleau Katherine
Published: October 2002

Recent studies have shown that the mammalian cerebellar cortex can be subdivided into a reproducible array of zones and stripes. In particular, discontinuous patterns of gene expression together with mutational analysis suggest that there are at least four distinct transverse zones along the rostrocaudal axis in mouse: the anterior zone (lobules I–V), the central zone (lobules VI and VII), the posterior zone (lobules VIII and IX), and the nodular zone (lobule X). Here we show that the divergent homeobox‐containing transcription factor, Tlx‐ 3 (also known as Hox11L2 or Rnx) is transiently expressed in external granule cells in a distinct transverse domain of the developing chick cerebellar cortex. Expression is first detected at Hamburger and Hamilton (HH) stage 35. Interestingly, Tlx‐3 mRNA expression is initially confined to, and coincident with, the morphological development of fissures. Slightly later, at HH stage 38, expression extends throughout the developing external granular layer (EGL) of lobules I–IXab. Notably, no Tlx‐3 expression was detected in lobules IXc and X at any developmental time point examined. Expression is noticeably stronger in nonproliferating cells located in the deep layer of the EGL. Tlx‐3 expression is downregulated as granule cells migrate inward to form the internal granule layer and is undetectable shortly after birth. These results suggest that Tlx‐3 is expressed as granule cells become postmitotic and suggest that Tlx‐3 may play a role in the differentiation of distinct neuronal populations in the cerebellum. J. Comp. Neurol. 448:138–149, 2002. © 2002 Wiley‐Liss, Inc.
Synaptic vesicle recycling at two classes of release sites in giant nerve terminals of the embryonic chicken ciliary ganglion
Authors: Nguyen Don , Sargent Peter B.
Published: October 2002

Rapid synaptic transmission in the embryonic chicken ciliary ganglion occurs through the activation of two distinct classes of nicotinic acetylcholine receptors (AChRs): those containing α3 subunits (α 3*‐AChRs) and those containing α7 subunits (α 7*‐AChRs). α3*‐AChRs are found on ciliary neurons in clusters at synaptic sites on the cell body, whereas α7* ‐AChRs are found on somatic spines, which historically were thought not to have release sites in the embryo. However, Shoop et al. (Shoop et al. [1999] J. Neurosci. 19:692–704) recently described release sites having pre‐ and postsynaptic densities on somatic spines. We used transmission electron microscopy to compare the structure of synaptic sites on spines with those on the smooth surfaced part of the cell. We find that the two populations of sites are similar in active zone length, number of vesicles, and distance between vesicles and active zone. To study the functional properties of these sites, we examined their stimulation‐dependent uptake and release of the extracellular tracer horseradish peroxidase (HRP). We found that each class of release sites both took up and released HRP in a stimulation‐ and calcium‐dependent manner. The mean fraction of synaptic vesicles labeled with tracer was similar for the two populations, both after loading (∼45%) and after unloading (∼ 7%). Thus we detect no differences between these two anatomically distinct classes of release sites, other than their incidence: sites on spines occurred only 12% as often as those on the cell body. The release sites on somatic spines presumably underlie synaptic responses attributable to α7*‐AChRs. J. Comp. Neurol. 448:128–137, 2002. © 2002 Wiley‐Liss, Inc.
Application of adjunct techniques in cytologic material in the diagnosis of rhabdomyosarcoma: Case report and review of the literature
Authors: Bhattacharya Baishali , Sariya Dinesh , Reddy Vijaya B. , Kluskens Larry , Gould Victor E. , Gattuso Paolo
Published: October 2002

A 4½‐yr‐old female presented with right‐sided pleural effusion and a retroperitoneal mass. Cytologic analysis of the pleural fluid yielded malignant small round blue cells, which were noncohesive, 3–4 times the size of lymphocytes. The malignant cells had hyperchromatic, pleomorphic nuclei with moderate amounts of vacuolated cytoplasm. A few fiber‐shaped cells were also seen. Immunostains for desmin, muscle‐specific actin were positive; ultrastructural findings of thick and thin actin‐myosin filaments confirmed the diagnosis of embryonal rhabdomyosarcoma. This case illustrates the importance of performing appropriate immunohistochemical stains and ultrastructural studies on cytological material to arrive at a definitive diagnosis. Diagn. Cytopathol. 2002;26:384–386. © 2002 Wiley‐Liss, Inc.
Cytohistologic correlations of 24 malignant peripheral nerve sheath tumor (MPNST) in 17 patients: The Institut Curie experience
Authors: Klijanienko Jerzy , Caillaud Jean‐Michel , Lagacé Réal , Vielh Philippe
Published: October 2002

Cytomorphological patterns of malignant peripheral nerve sheath tumor (MPNST) are insufficiently documented in the literature. Cytological and histological specimens in 24 tumors in 17 patients were correlated. The review of the original cytology reports showed that four (16.6%) tumors were correctly diagnosed, eight (33.3%) were diagnosed as sarcoma not otherwise specified, four (16.7%) as fibrosarcoma, three (12.5%) as synovial sarcoma, three (12.5%) as leiomyosarcoma, and one (4.2%) case each as malignant fibrous histiocytoma and rhabdomyosarcoma. At the review tumors were histologically reclassified as well‐differentiated MPNST in 11 (45.9%) cases, anaplastic MPNST in 11 (45.9%) cases, and epithelioid MPNST and malignant Triton tumor in one (4.2%) case each. Cytologically, well‐differentiated MPNST were composed of polymorphous oval to round cells, small spindle‐shaped cells with wavy and comma‐like naked nuclei, and a fibrillary, delicate stroma. Anaplastic MPNST, moreover, were composed of anaplastic giant and polymorphous cells. The malignant Triton tumor was composed of oval to round rhabdomyoblastic cells with eccentric nuclei and the epithelioid MPNST of polymorphous and round, epithelial‐like cells. The cytological diagnosis of MPNST may be difficult, especially in anaplastic tumors. The correlation between the cytological features and the clinical information—origin of the tumor from a nerve trunk, a preexisting neurofibroma, patients with known history of neurofibromatosis 1—could be indicative of an MPNST diagnosis. Diagn. Cytopathol. 2002;27:103–108. © 2002 Wiley‐Liss, Inc.
Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice
Authors: McFadyen Melanie P. , Brown Richard E. , Carrey Normand
Published: October 2002

Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been conducted to determine its potential long‐term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD‐1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear‐ and anxiety‐related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.). © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 123–132, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10059
Relative right versus left frontal EEG in neonates
Authors: Field Tiffany , Diego Miguel , Hernandez‐Reif Maria , Schanberg Saul , Kuhn Cynthia
Published: October 2002

Although infants have been noted to have greater relative right or left frontal EEG as early as the neonatal period, other ways in which these newborns differ have not been reported. In this study, 48 newborns were divided on the basis of greater relative right versus greater relative left frontal EEG to determine whether these groups differed in other ways at the neonatal period including behavior, physiology, and biochemistry. We also were interested in whether these EEG patterns were related to any prenatal maternal variables including mood states (depression, anxiety, anger) and biochemistry as well as fetal activity. The greater relative right frontal EEG newborns had mothers with lower prenatal and postnatal serotonin and higher postnatal cortisol levels. The mothers of the greater relative right frontal EEG newborns also had greater relative right frontal EEG activation and lower vagal tone. The greater relative right frontal EEG newborns themselves had elevated cortisol levels, showed a greater number of state changes during sleep/wake behavior observations, and performed less optimally on the Brazelton Neonatal Behavior Assessment (T. B. Brazelton, 1973) including the habituation, motor, range of state, excitability, and depressive symptoms scales. These data suggest that greater relative right frontal EEG newborns may be at greater risk for developmental problems than those with greater relative left frontal EEG activation. In addition, a discriminant function analysis correctly classified 67% of the newborns' EEGs by prenatal maternal variables, suggesting that these might be used to target pregnant women for prenatal intervention. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 41: 147–155, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/dev.10061